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ObjectivesJanus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety.MethodsExisting data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration.ResultsThe Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale.ConclusionThe consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.

ObjectivesDespite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte–macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA.MethodsIn a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)−C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28−CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24).Results326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012–June 2013). Mavrilimumab treatment significantly reduced DAS28−CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: −1.90 (0.14), 100 mg: −1.64 (0.13), 30 mg: −1.37 (0.14), placebo: −0.68 (0.14); pSignificantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (pConclusionsMavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential.Trial registration numberNCT01706926; results.

Background:Understanding the durability of response to biologics and factors associated with failure to maintain response in a real-world setting can inform treatment decisions for patients with rheumatoid arthritis (RA).Objectives:To evaluate the durability of response and identify factors associated with decreased durability in US patients with RA initiating tocilizumab (TCZ) in routine clinical practice.Methods:TCZ-naïve patients enrolled in the Corrona RA registry who initiated TCZ (subcutaneous [SC] or intravenous [IV]) after January 1, 2010 and had ≥1 follow-up visit were included. Durability of response was defined as maintaining continuous TCZ and: (a) a minimum clinically important difference (MCID) in clinical disease activity index (CDAI) (defined as an improvement in CDAI compared to baseline of: ≥2 if baseline CDAI ≤10; ≥6 if baseline >10 to ≤22; ≥11 if baseline >22) or (b) low disease activity (LDA; CDAI ≤10). Patient response was no longer durable upon the first: discontinuation of TCZ or failure to maintain MCID or LDA. Secondary analyses estimated durability after including only patients: (a) with reported reasons for discontinuation (patients with non-medical reasons for discontinuation [eg, insurance coverage] were censored) or (b) who initiated TCZ-IV. Durability was calculated with Kaplan-Meier survival analysis. Cox proportional hazards modeling identified factors associated with durability.Results:A total of 1789 TCZ initiators (TCZ-IV, n=1284) were identified; 861, 483, and 298 patients were persistent and had follow-up visits at 1, 2, and 3 years, respectively. At baseline, the mean (SD) age was 58.5 (12.6) years, duration of RA was 12.0 (9.6) years and CDAI score was 23.2 (14.2). Most patients (93.4%) had prior biologic use and 67.4% had received ≥2 prior biologics. Among patients with follow-up data available at 1, 2 and 3 years, MCID in CDAI was achieved by 56.3% (261/464), 67.3% (183/272) and 69.8% (113/162), respectively. Overall, MCID durability remained above 50% after 36 months of follow-up, and the same is true when including only patients with reported reasons for discontinuation (Fig 1). For TCZ-IV initiators, median MCID durability was 26 months (Fig 1). For all MCID durability analyses, factors associated with reduced hazard of failure included increased duration of RA and higher baseline CDAI, while higher hazard of failure was associated with history of malignancy or diabetes (Fig 2). Among patients with follow-up data available, LDA was achieved in 53.7% (249/464), 60.3% (164/272) and 67.3% (109/162) at 1, 2 and 3 years, respectively. The overall median (95% CI) LDA durability was 13.0 (12.0, 20.0) months; when including only patients with reported reasons for discontinuation it was 13.0 (9.0, 29.0) months; among TCZ-IV initiators it was 13.0 (10.0, 19.0) months. Factors associated with an increased hazard of failing to maintain LDA included history of malignancy and, in contrast to MCID, higher baseline CDAI.Conclusion:In this real-world RA population who initiated TCZ, most patients received ≥2 prior biologics. Median durability of response (MCID) was >3 years. Among factors associated with shorter durability of response, history of malignancy was significant in all analyses.Acknowledgments:This study was sponsored by Corrona, LLC. Corrona is supported through contracted subscriptions with multiple pharmaceutical companies. The abstract was a collaborative effort between Corrona and Genentech, Inc., with financial support provided by Genentech, Inc.Disclosure of Interests:Dimitrios A Pappas: None declared, Taylor Blachley Employee of: Corrona, LLC, Jennie H. Best Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Steve Zlotnick Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., William Reiss Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Kelechi Emeanuru Employee of: Corrona, LLC – employment, Joel M Kremer Shareholder of: May own stocks and opinions, Grant/research support from: Research and consulting fees from AbbVie Inc., Consultant of: AbbVie, Amgen, BMS, Genentech, Inc., Gilead, GSK, Lilly, Pfizer, Regeneron and Sanofi, Employee of: Corrona, LLC employee

Background:Understanding the persistence of biologic therapies and factors associated with discontinuation can help inform treatment decisions for patients with rheumatoid arthritis (RA).Objectives:To evaluate the persistence of tocilizumab (TCZ) therapy and identify factors associated with its discontinuation among US patients with RA in routine clinical practice.Methods:Eligible participants were TCZ-naïve patients enrolled in the Corrona RA registry who initiated TCZ after January 1, 2010 and had ≥ 1 follow-up visit. Persistence of therapy was defined as maintaining continuous TCZ treatment with no interruptions; patients were considered no longer persistent upon the first discontinuation of TCZ. Persistence was calculated using Kaplan-Meier survival analysis for the overall population; secondary analyses evaluated persistence excluding patients who stopped TCZ with no reported reason for discontinuation (patients with non-medical reasons for discontinuation [eg, insurance] were censored) and in only those patients who initiated intravenous (IV) TCZ. Cox proportional hazards modeling was used to identify factors associated with persistence.Results:A total of 1789 TCZ initiators were included; 81.0% were female, 85.0% were white and 75.4% were overweight or obese. The mean (SD) age was 58.5 (12.6) years and mean (SD) disease duration was 12.0 (9.6) years. Most patients (93.4%) had prior biologic use and 67.4% had received ≥ 2 prior biologics. Overall, 28.8% initiated TCZ as monotherapy. Among all TCZ initiators, the median (95% CI) duration of persistence was 20 (18 to 22) months (Fig 1). Factors associated with an increased hazard of TCZ discontinuation included smoking and higher baseline CDAI, whereas prior tumor necrosis factor inhibitor (TNFi) use was associated with a reduced hazard (Fig 2A). After excluding patients with no reported reason for discontinuation (remaining n = 1303), the median (95% CI) duration of persistence was 46 (38 to 55) months (Fig 1); smoking, use of 1 prior non-TNFi and higher baseline patient pain score were associated with an increased hazard of discontinuation (Fig 2B). Among the 1284 patients who initiated TCZ IV, median (95% CI) duration of persistence was 22 (19 to 25) months (Fig 1); smoking, lack of insurance and higher baseline patient fatigue score were associated with an increased hazard of discontinuation, whereas use of 1 prior TNFi was associated with a decreased hazard (Fig 2C).Conclusion:In this real-world population of US patients with RA, TCZ was most frequently initiated after an inadequate response to ≥ 2 biologics. Overall median duration of persistence was approximately 20 months and was higher (46 months) when patients with no reported reason for TCZ discontinuation were excluded. As expected, factors indicative of higher baseline disease activity were associated with shorter persistence.Acknowledgments:This study was sponsored by Corrona, LLC. Corrona is supported through contracted subscriptions with multiple pharmaceutical companies. The abstract was a collaborative effort between Corrona and Genentech, Inc., with financial support provided by Genentech, Inc.Disclosure of Interests:Dimitrios A Pappas: None declared, Taylor Blachley Employee of: Corrona, LLC, Jennie H. Best Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Steve Zlotnick Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Kelechi Emeanuru Employee of: Corrona, LLC – employment, Joel M Kremer Shareholder of: May own stocks and opinions, Grant/research support from: Research and consulting fees from AbbVie Inc., Consultant of: AbbVie, Amgen, BMS, Genentech, Inc., Gilead, GSK, Lilly, Pfizer, Regeneron and Sanofi, Employee of: Corrona, LLC employee

Background:Rheumatoid arthritis (RA) patients who fail therapy may be switched to any of the five classes of biological disease-modifying antirheumatic drugs (DMARDs) and targeted synthetic DMARDs, to meet treatment goals. Physicians may hesitate to switch between Janus Kinase inhibitors (JAKi) and interleukin-6 receptor inhibitors (IL-6Ri) since they both impact IL-6 signalling and due to limited data on switching between the two classes.Objectives:This retrospective, observational study based on the real-world Corrona RA registry aimed to describe the response in RA patients switching between IL-6Ri and JAKi.Methods:Adult RA patients who initiated either IL-6Ri or JAKi after November 2012 and had a six-month post-initiation follow-up visit were eligible. Patients in ‘Cohort A’ initiated an IL-6Ri following discontinuation of a JAKi and those in ‘Cohort B’ initiated a JAKi following discontinuation of an IL-6Ri. Disease activity measures and patient-reported outcomes (PROs) were evaluated at baseline and at six-month follow-up. Within each group, change from baseline was assessed for Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire (HAQ), pain, fatigue, tender joint count (TJC), swollen joint count (SJC), physician global assessment (MDGA), patient global assessment (PtGA) and morning stiffness duration. Proportion of patients achieving CDAI low disease activity (LDA), CDAI remission and minimal clinically important difference (MCID) for HAQ, pain, fatigue, MDGA, PtGA were assessed. Adjusted linear and logistic regression models were performed for between-group comparisons (Cohort A vs Cohort B) excluding initiators who switched therapy prior to six-month visit.Results:Cohorts A and B included 122 and 144 initiators, respectively. Patients who switched toIL-6Ri (vs JAKi) were younger (mean [SD] age, 56.2 [11.3] vs 58.9 [12.6] years), had higher baseline CDAI (23.2 [12.9] vs 20.2 [12.8]), had higher prior use of ≥2 csDMARDs (75% vs 65%), and were less likely to initiate therapy as monotherapy (44% vs 50%).In Cohort A, significant changes from baseline were observed for all continuous outcomes except HAQ and fatigue. In Cohort B, a significant improvement was observed only for patient-reported pain (Table 1).Table 1.Unadjusted Within-Group Change from Baseline to Six Months, Mean (95% CI), nOutcomesCohort A, N = 122Cohort B, N = 144CDAI-4.7 (-7.6, -1.9), 109-2.4 (-5.2, 0.4), 116HAQ-0.0 (-0.1, 0.1), 105-0.1 (-0.1, 0.0), 118Patient-reported pain-8.2 (-13.4, -3.0), 109-5.9 (-11.5, -0.2), 120Patient-reported fatigue-4.4 (-9.0, 0.2), 109-1.7 (-6.6, 3.3), 117TJC-1.6 (-3.0, -0.1), 112-1.2 (-2.6, 0.3), 117SJC-1.5 (-2.5, -0.4), 112-0.4 (-1.3, 0.6),117MDGA-10.9 (-15.6, -6.3), 112-4.3 (-8.7, 0.2), 117PtGA-6.0 (-11.2, -0.8), 109-4.8 (-10.5, 0.8), 120Morning stiffness durationa-1.3 (-2.2, -0.5), 109-0.1 (-1.1, 0.8), 118aAmong those reporting morning stiffness at baseline.In the adjusted between-group comparison (data not shown) of change from baseline, there were no significant differences in clinical outcomes between Cohorts A and B.In both cohorts, patients achieved CDAI LDA, CDAI remission, and MCIDs across other PROs (Figure 1). In the adjusted between-group comparison (data not shown), the results were similar with the exception of achievement of CDAI LDA among patients with moderate to high disease activity at baseline.Figure 1.Rates of CDAI LDA, CDAI Remission, and MCID for PROsa at Six MonthsConclusion:In general, in both cohorts a substantial proportion of patients achieved CDAI LDA and MCID across PROs. Despite some overlap of JAKi and IL-6Ri therapies’ on the IL-6 pathway, there are some distinct mechanisms of action which may result in meaningful improvements for a subset of patients.Acknowledgements:Amy Praestgaard (Sanofi) contributed to the interpretation of the statistical analysis for this abstract. Medical writing support for this abstract was provided by Nupur Chaubey (Sanofi).Disclosure of Interests:Anisha Dua Speakers bureau: AbbVie, Consultant of: Consulting/advisory board for AbbVie, Novartis, and Chemocentryx, Employee of: Board member of Vasculitis foundation and Chicago Rheumatism Society, Kerri Ford Shareholder of: Sanofi, Employee of: Sanofi, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi. In addition, Stefano Fiore has a patent EP 19306553.9; USPTO #s 62/799,698; 62/851,474; 62/935,395 issued, Dimitrios A Pappas Shareholder of: Corrona LLC, Consultant of: Sanofi, AbbVie, Gtech, Roche Hellas, and Novartis, Employee of: Corrona LLC. Board of directors, Corrona Research Foundation, Judson Janak: None declared, Taylor Blachley: None declared, Carla Roberts-Toler: None declared, Kelechi Emeanuru: None declared, Joel Kremer Consultant of: AbbVie, Lilly, Novartis, Pfizer, BMS, Genentech, Regeneron, Sanofi, and Corrona, Grant/research support from: AbbVie, Lilly, Novartis, and Pfizer, Alan Kivitz Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., and Novartis, Speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Flexion, and AbbVie, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc. In addition, Alan Kivitz reports other from Altoona Center for Clinical Research, PC, during the conduct of the study.

Background:Upadacitinib (UPA) has demonstrated efficacy in randomized controlled trials1-3; however, few data are available from patients with rheumatoid arthritis (RA) who have been treated with UPA in real-world clinical practice.Objectives:Describe the characteristics and 6-month outcomes in patients with RA initiating UPA in a real-world setting.Methods:We identified adults with RA enrolled in the Corrona RA Registry through October 31, 2020 who initiated UPA during or after August 2019 and had a follow-up visit 6 (±3) months after initiation of UPA. Descriptive statistics were used to summarize characteristics in all patients initiating UPA who had a 6-month follow-up visit. Outcomes (CDAI, modified HAQ-DI, pain, and fatigue) were described at the 6-month visit for all UPA initiators regardless of UPA use at 6 months and for the subset of patients who continued UPA through the 6-month visit. Patients who discontinued UPA before the 6-month visit were considered non-responders for dichotomous variables and were assigned the value at the time of discontinuation for continuous variables. Mean change from baseline in continuous variables was analyzed with one-sample t tests or one-sample Wilcoxon rank sum tests. Minimum clinically important difference (MCID) in HAQ-DI is defined as an improvement of 0.22 units or more. MCID in CDAI is an improvement of at least 2, 7, and 13 units for patients in low, moderate and severe disease at initiation, respectively. MCID for 100-point VAS is an improvement of ≥10 points. Percentages of patients achieving MCID thresholds were calculated.Results:We identified 181 patients who initiated UPA and had a 6-month follow-up visit. Mean±SD age was 58.6±12.1 years, 81% were female. Patients had RA for a mean of 11.5±9.8 years. At UPA initiation, 45% of patients were on monotherapy. Prior use of one or more TNFi and JAKi was 79% and 52%, respectively. Seventy-two percent of patients (n=130) initiated UPA as the third or higher line of therapy. Mean CDAI was 18.7±11.6 and mean HAQ-DI was 1.1±0.8 at initiation. Based on CDAI (n=155), 29%, 52%, and 15% of patients had high, moderate, and low disease activity, respectively; 4.5% were in remission at initiation. At 6 months (n=158), 22%, 39%, and 28% had high, moderate, and low disease activity, respectively; 11% were in remission. Among 138 initiators with valid CDAI measures at initiation and 6 months, mean change in CDAI was –4.8±11.8, P=MCID in CDAI, HAQ-DI, pain, and fatigue were achieved in 36–44% of UPA initiators. Improvements were similar, but larger in the subset of patients (n=122) who continued UPA through the 6-month visit (Table 1).Conclusion:Among patients in the Corrona RA Registry, UPA is frequently started in those who failed multiple previous therapies. UPA initiators responded to therapy in the first 6 months with improvements in several disease activity measures including CDAI and HAQ-DI, as well as patient-reported pain and fatigue.References:[1]Fleischmann R. Arthritis Rheumatol. 2019;71:1788–800.[2]Smolen JS. Lancet. 2019;393:2303–11.[3]Burmester GR. Lancet. 2018;382:2505–12.Outcomes at 6-month follow-upAll initiators(n=181)Subset remainingon UPA (n=122)nValueanValueaRemission (CDAI 15818 (11)10512 (11)Low (CDAI >=2.8 and 15844 (28)10538 (36)Moderate (CDAI >=10 and 15862 (39)10536 (34)High (CDAI >=22)15834 (22)10519 (18)Improvement in any CDAI category13854 (39)8940 (45)Maintenance of CDAI category13863 (46)10539 (44)Mean change in CDAI138–4.8±11.8*89–7.1±12.0* HAQ-DI154–0.1±0.5*101–0.2±0.5* Pain154–9.3±25.1*101–13.5±25.8* Fatigue153–7.6±27.3*100–12.5±27.5*MCID achievement in CDAI13857 (41)8943 (48) HAQ-DI15455 (36)10139 (39) Pain15468 (44)10153 (52) Fatigue15365 (42)10049 (49)aMean±SD or n (%).*PAcknowledgements:This study was sponsored by Corrona, LLC. Corrona has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Crescendo, Eli Lilly and Company, Genentech, Gilead, GSK, Janssen, Merck, Momenta Pharmaceuticals, Novartis, Pfizer, Regeneron, Roche, Sun, UCB, and Valeant. The design, study conduct, and financial support for the study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. No honoraria or payments were made for authorship.Medical writing services were provided by Joann Hettasch of Fishawack Facilitate Ltd., part of Fishawack Health, and funded by AbbVie.Disclosure of Interests:Joel M Kremer Shareholder of: Corrona, Consultant of: AbbVie, Grant/research support from: AbbVie, Employee of: Corrona, Namita Tundia Shareholder of: AbbVie, Employee of: AbbVie, Robert McLean Employee of: Corrona, Taylor Blachley Employee of: Corrona, anna maniccia Shareholder of: AbbVie, Employee of: AbbVie, Dimitrios A Pappas Shareholder of: Corrona, Consultant of: AbbVie, Genentech, Novartis, Regeneron, and Roche Hellas, Employee of: Corrona

ObjectivesTo evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX).MethodsIn this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12.ResultsOverall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, pConclusionsOver 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated.Trial registration numberNCT01894516.

Background:Clinical studies have demonstrated the efficacy of tocilizumab (TCZ) administered with methotrexate (MTX) in improving rheumatoid arthritis (RA) disease activity in patients who have had an inadequate response to tumor necrosis factor inhibitors (TNFis).Objectives:To compare the effectiveness of TCZ + MTX with that of TNFis + MTX in patients with RA who had prior exposure to TNFis in routine clinical practice.Methods:Eligible participants were TCZ-naïve patients from the Corrona RA registry who initiated TCZ + MTX or a TNFi + MTX after January 1, 2010 and had a 6-month follow-up visit. Patients in both groups must have used ≥ 1 TNFi, had a Clinical Disease Activity Index (CDAI) score available at initiation (baseline) and 6 months and had a CDAI score > 10 at baseline. The primary outcome was mean change in CDAI from baseline to 6 months. Secondary outcomes included achievement of low disease activity (LDA; CDAI ≤ 10) and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients were grouped by baseline MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes were compared between patients initiating TCZ and those initiating a TNFi overall and within each MTX dose group using propensity score (PS)-trimmed populations. As a sensitivity analysis, TCZ and TNFi initiators in each group were PS-matched 1:1 and outcomes were assessed in the matched populations. Linear and logistic regression models were estimated in the trimmed and matched populations, adjusting for covariates not balanced after PS trimming or matching, respectively.Results:A total of 415 TCZ + MTX initiators and 725 TNFi + MTX initiators met the inclusion criteria prior to PS trimming or matching. The overall trimmed population included 402 TCZ + MTX initiators and 703 TNFi + MTX initiators. In the trimmed population, patient demographics were generally comparable between TCZ + MTX and TNFi + MTX initiators; the mean age was 57.1 years in the TCZ + MTX group and 57.7 years in the TNFi + MTX group, the majority of patients in both groups were female (≥ 80%) and white (≥ 82%) and the mean duration of RA was 11.8 and 10.5 years in the TCZ + MTX and TNFi + MTX groups, respectively. Higher proportions of patients initiating TCZ had received ≥ 2 prior biologics (66.0% to 76.3%) compared with those initiating a TNFi (33.2% to 42.2%) across all MTX dose groups. Patients initiating TCZ had higher mean baseline CDAI scores (26.5 to 29.3) than those initiating a TNFi (24.7 to 27.5). Patients in both cohorts had improvements in CDAI and mHAQ scores and achieved LDA in similar proportions at 6 months regardless of baseline MTX dose (Fig 1). Results were comparable between TCZ and TNFi initiators across all MTX groups in the trimmed population after adjustment for potential confounding variables. Similar results were observed in the PS-matched cohorts.Conclusion:In this real-world population of US patients with RA who had prior TNFi exposure, there was no statistically significant or clinically meaningful difference in the effectiveness of therapy in patients who initiated TCZ + MTX compared with TNFi + MTX.Acknowledgments :This study was sponsored by Corrona, LLC. Corrona is supported through contracted subscriptions with multiple pharmaceutical companies. The abstract was a collaborative effort between Corrona and Genentech, Inc., with financial support provided by Genentech, Inc.Disclosure of Interests: :Dimitrios A Pappas: None declared, Taylor Blachley Employee of: Corrona, LLC, Steve Zlotnick Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jennie H. Best Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Kelechi Emeanuru Employee of: Corrona, LLC – employment, Joel M Kremer Shareholder of: May own stocks and opinions, Grant/research support from: Research and consulting fees from AbbVie Inc., Consultant of: AbbVie, Amgen, BMS, Genentech, Inc., Gilead, GSK, Lilly, Pfizer, Regeneron and Sanofi, Employee of: Corrona, LLC employee

Background:Targeting remission (REM) or low disease activity (LDA) is a widely accepted treatment strategy for RA. However, there are limited data on the proportion of pts who achieve these targets, or remain in moderate (MDA) or high disease activity (HDA) following advanced therapy.Objectives:To estimate the proportion of RA pts in disease activity states (REM, LDA, MDA, and HDA) who were biologic-naïve at initiation and had continuous treatment with a TNFi for 6–12 months in the Corrona RA registry.Methods:Eligible pts were aged ≥18 years, biologic-naïve, initiated TNFi treatment between January 1, 2010 and July 31, 2019, and had continuous use of a TNFi for 6–12 months. Disease activity was defined based on Clinical Disease Activity Index (CDAI) at the visit closest to 6-month follow-up: REM, ≤2.8; LDA, >2.8–10; MDA, >10–22; and HDA, >22. Disease characteristics, disease activity measures, and pt-reported outcomes (PROs) were reported at TNFi initiation and at the 6-month follow-up visit.Results:2586 biologic-naïve pts who initiated a TNFi and had continuous use for 6–12 months were included. At TNFi initiation, 167 (6%) were in REM, 479 (19%) had LDA, 907 (35%) had MDA, and 1033 (40%) had HDA. After 6–12 months of treatment, 563 (21.8%) were in REM, 923 (35.7%) had LDA, 674 (26.1%) had MDA, and 426 (16.5%) had HDA. Pts with HDA/MDA at 6–12 months were more likely to have a history of hypertension (32.7% HDA; 34.0% MDA; vs 23.6% REM) and had higher mean body mass index (BMI) (30.9 HDA; 31.1 MDA; vs 29.0 REM) at baseline compared with pts in REM. Disease activity measures and PROs were worse in pts with MDA and HDA vs LDA and REM after 6–12 months (Table). Pt Global Assessment was higher than Physician Global Assessment across all groups.Conclusion:While 57.4% of pts who initiated a TNFi experienced a favorable outcome, >40% required additional or alternative intervention to achieve REM/LDA. Pts who remained in MDA/HDA continued to have an inadequate response to TNFi (as measured by disease activity measures and PROs) after 6–12 months of treatment compared with those who achieved REM/LDA.TableSummary of disease activity measures and PROs in previously biologic-naïve pts at the 6–12-month follow-up visit, stratified by disease activity category at the 6–12-month follow-up visitCharacteristics at 6–12 months, mean (standard deviation)Disease activity category at 6–12 monthsREM (n=563)LDA (n=923)MDA (n=674)HDA (n=426)CDAI1.2 (0.8)6.2 (2.1)15.4 (3.4)32.7 (9.2)Tender joint count (28)0.1 (0.3)1.0 (1.3)4.3 (3.3)13.4 (7.0)Swollen joint count (28)0.1 (0.3)1.1 (1.6)4.0 (3.6)9.1 (5.9)C-reactive protein6.4 (22.7)7.0 (10.6)11.1 (19.9)12.6 (22.1)Modified health assessment questionnaire0.1 (0.2)0.3 (0.4)0.5 (0.5)0.8 (0.5)Pt global assessment6.6 (6.8)28.6 (20.9)43.7 (25.7)58.0 (22.7)Physician global assessment3.6 (4.3)12.1 (10.4)27.4 (15.9)44.9 (19.8)Pt pain assessment8.7 (11.0)30.3 (23.5)46.1 (27.0)59.9 (24.4)Pt fatigue assessment15.7 (19.2)34.5 (26.6)48.3 (28.0)59.4 (27.5)Morning stiffness (min)16.5 (36.5)55.4 (146.3)96.9 (197.5)143.6 (260.0)Disclosure of Interests:Joel M Kremer Shareholder of: May own stocks and opinions, Grant/research support from: Research and consulting fees from AbbVie Inc., Consultant of: AbbVie, Amgen, BMS, Genentech, Inc., Gilead, GSK, Lilly, Pfizer, Regeneron and Sanofi, Employee of: Corrona, LLC employee, Anne Winkler Consultant of: AbbVie, Pfizer, and Novratis, Speakers bureau: AbbVie, Janssen, Sanofi, Genentech, Celgene, Eli Lilly, and Novartis., Laura Anatale-Tardiff Employee of: Corrona, LLC employee, Robert McLean Employee of: Corrona, LLC, Ying Shan Employee of: Corrona, LLC employee, Page Moore Employee of: Corrona, LLC employee, Namita Tundia Shareholder of: May own stocks and options, Employee of: AbbVie employee, Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., John Tesser Consultant of: Sanofi/Regeneron, Speakers bureau: Sanofi/Regeneron

Methotrexate (MTX) is known to improve blood levels and clinical outcome to anti-tumour necrosis factor (anti-TNF) therapy by reducing the formation of antidrug antibodies.1 Recent findings indicate that MTX prevents immunisation against TNF inhibitors through de novo purine biosynthesis inhibition and generation of immunosuppressive adenosine.2 This effect is mediated by activation of MTX prodrug to MTX polyglutamates (MTXPG), and we previously reported that MTXPG levels were associated with improved steady state levels of infliximab.3 In this study, we extended these observations and evaluated the impact of MTXPG on adalimumab and etanercept levels. The study was cross-sectional by design, multicentred (three sites) and enrolled 169 consecutive consented adult rheumatoid arthritis subjects under MTX in combination with adalimumab (83 subjects) or etanercept (86 subjects). All patients enrolled were inadequate responders to MTX prior to starting anti-TNF therapy and had received MTX with anti-TNF therapy for least 3 months. At the time of a single visit, anticoagulated blood was collected randomly …

BackgroundThere is increasing interest in discontinuing biological therapies for patients with rheumatoid arthritis (RA) achieving good clinical responses, provided patients maintain clinical benefit.MethodsWe assessed patients with RA from the Corrona registry who discontinued treatment with their first tumour necrosis factor inhibitor (TNFi) while in low-disease activity (LDA) or lower levels of disease activity. Patients were followed until they lost clinical benefit, defined as increased disease activity or change in RA medications. Duration of maintenance of clinical benefit was estimated using the Kaplan–Meier method. Cox proportional hazard models were assessed to identify factors related to maintenance of benefit.ResultsWe identified 717 eligible patients with RA from 35 656 in the Corrona registry. At discontinuation, patients had a median RA duration of 8 years, mean clinical disease activity score of 4.3±0.11; 41.8% were using TNFi as monotherapy. 73.4% of patients maintained benefit for >12 months after discontinuing therapy and 42.2% did so through 24 months. Factors predictive of maintaining clinical benefit in multivariate analysis included lower disease activity, less pain and better functional status at the time of TNFi discontinuation. Among 301 patients initiating their first TNFi within the registry, faster responders (ie, those who achieved LDA in 4 months or less) did better than slower responders (HR 1.54 (95% CI 1.17 to 2.04)). RA disease duration did not affect maintenance of clinical benefit.ConclusionsDiscontinuation of a first course of TNFi may be associated with persistent clinical benefit. Half of patients maintained response through 20 months. Several patient characteristics may help predict persistent benefit.

Objective We compared the effectiveness of abatacept (ABA) versus a subsequent anti-tumour necrosis factor inhibitor (anti-TNF) in rheumatoid arthritis (RA) patients with prior anti-TNF use. Methods We identified RA patients from a large observational US cohort (2/1/2000–8/7/2011) who had discontinued at least one anti-TNF and initiated either ABA or a subsequent anti-TNF. Using propensity score (PS) matching (n:1 match), effectiveness was measured at 6 and 12 months after initiation based on mean change in Clinical Disease Activity Index (CDAI), modified American College of Rheumatology (mACR) 20, 50 and 70 responses, modified Health Assessment Questionnaire (mHAQ) and CDAI remission in adjusted regression models. Results The PS-matched groups included 431 ABA and 746 anti-TNF users at 6 months and 311 ABA and 493 anti-TNF users at 12 months. In adjusted analyses comparing response following treatment with ABA and anti-TNF, the difference in weighted mean change in CDAI (range 6–8) at 6 months (0.46, 95% CI −0.82 to 1.73) and 12 months was similar (−1.64, 95% CI −3.47 to 0.19). The mACR20 responses were similar at 6 (28–32%, p=0.73) and 12 months (35–37%, p=0.48) as were the mACR50 and mACR70 (12 months: 20–22%, p=0.25 and 10–12%, p=0.49, respectively). Meaningful change in mHAQ was similar at 6 and 12 months (30–33%, p=0.41 and 29–30%, p=0.39, respectively) as was CDAI remission rates (9–10%, p=0.42 and 12–13%, p=0.91, respectively). Conclusions RA patients with prior anti-TNF exposures had similar outcomes if they switched to a new anti-TNF as compared with initiation of ABA.

To determine the relationship of disease activity to infections in patients with rheumatoid arthritis (RA).From the CORRONA database, the incidence of physician-reported infections in RA patients on stable disease-modifying antirheumatic drug, biological, and corticosteroid therapy for at least 6 months was ascertained. Two composite measures of disease activity were defined: clinical disease activity index (CDAI) and disease activity score 28 (DAS28). Incident rate ratios (IRR) were calculated using generalised estimating equation Poisson regression models adjusted for demographics, medications and clinical factors.Of 1 6242 RA patients, 6242 were on stable therapy for at least 6 months and were eligible for analysis. 2282 infections were reported in the cohort, followed over 7290 patient-years. After controlling for possible confounders, disease activity was associated with an increased rate of infections. Each 0.6 unit increase in DAS28 score corresponded to a 4% increased rate of outpatient infections (IRR 1.04, p=0.01) and a 25% increased rate of infections requiring hospitalisation (IRR 1.25, p=0.03). There was a dichotomy in the relationship between infections and CDAI scores. For CDAI10 (mild disease activity) patients had a 12% increased rate of outpatient infections with each 5 unit increase in CDAI score (IRR 1.12, p=0.003). At CDAI scores ≥10, there was no further increase in the rate of outpatient infections associated with higher disease activity. The relationship of CDAI to hospitalised infections showed similar trends to outpatient data but did not reach statistical significance after multivariate analysis (CDAI10: IRR 1.56, p=0.08).In this large cohort of RA patients, higher disease activity was associated with a higher probability of developing infections.

ObjectiveTo examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA).MethodsThe study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death.ResultsThere were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74).ConclusionTNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA.

BackgroundCardiovascular (CV) disease has a major impact on patients with rheumatoid arthritis (RA), however, the relative contributions of traditional CV risk factors and markers of RA severity are unclear. The authors examined the relative importance of traditional CV risk factors and RA markers in predicting CV events.MethodsA prospective longitudinal cohort study was conducted in the setting of the CORRONA registry in the USA. Baseline data from subjects with RA enrolled in the CORRONA registry were examined to determine predictors of CV outcomes, including myocardial infarction, stroke or transient ischemic attack. Possible predictors were of two types: traditional CV risk factors and markers of RA severity. The discriminatory value of these variables was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) in logistic regression. The authors then assessed the incidence rate for CV events among subjects with an increasing number of traditional CV risk factors and/or RA severity markers.ResultsThe cohort consisted of 10 156 patients with RA followed for a median of 22 months. The authors observed 76 primary CV events during follow-up for a composite event rate of 3.98 (95% CI 3.08 to 4.88) per 1000 patient-years. The c-statistic improved from 0.57 for models with only CV risk factors to 0.67 for models with CV risk factors plus age and gender. The c-statistic improved further to 0.71 when markers of RA severity were also added. The incidence rate for CV events was 0 (95% CI 0 to 5.98) for persons without any CV risk factors or markers of RA severity, while in the group with two or more CV risk factors and three or more markers of RA severity the incidence was 7.47 (95% CI 4.21 to 10.73) per 1000 person-years.ConclusionsTraditional CV risk factors and markers of RA severity both contribute to models predicting CV events. Increasing numbers of both types of factors are associated with greater risk.

Objectives:To determine the efficacy of CP-690,550 in improving pain, function and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a tumour necrosis factor α inhibitor.Methods:Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks’ follow-up. The patient’s assessment of arthritis pain (pain), patient’s assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded.Results:At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (⩾0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components.Conclusions:CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

Objective: Assess the effect of abatacept on progression of structural damage over 2 years in patients with rheumatoid arthritis who had an inadequate response to methotrexate. Methods: 539 patients entered an open-label extension of the AIM (Abatacept in Inadequate responders to Methotrexate) trial and received abatacept. Radiographic assessment of the hands and feet was performed at baseline, year 1 and year 2. At year 2, each patient’s radiographs were scored for progression blinded to sequence and treatment allocation. Results: In patients treated with abatacept for 2 years, greater reduction in progression of structural damage was observed in year 2 than in year 1. The mean change in total Genant-modified Sharp scores was reduced from 1.07 units in year 1 to 0.46 units in year 2. Similar reductions were observed in erosion and joint space narrowing scores. Following 2 years of treatment with abatacept, 50% of patients had no progression of structural damage as defined by a change in the total score of ⩽0 compared with baseline. 56% of patients treated with abatacept had no progression during the first year compared with 45% of patients treated with placebo. In their second year of treatment with abatacept, more patients had no progression than in the first year (66% vs 56%). Conclusions: Abatacept has a sustained effect that inhibits progression of structural damage. Furthermore, the mean change in radiographic progression in patients treated with abatacept for 2 years was significantly lower in year 2 versus year 1, suggesting that abatacept may have an increasing disease-modifying effect on structural damage over time.

The phase III RADIATE study examined the efficacy and safety of tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with rheumatoid arthritis (RA) refractory to tumour necrosis factor (TNF) antagonist therapy.499 patients with inadequate response to one or more TNF antagonists were randomly assigned to receive 8 mg/kg or 4 mg/kg tocilizumab or placebo (control) intravenously every 4 weeks with stable methotrexate for 24 weeks. ACR20 responses, secondary efficacy and safety endpoints were assessed.ACR20 was achieved at 24 weeks by 50.0%, 30.4% and 10.1% of patients in the 8 mg/kg, 4 mg/kg and control groups, respectively (less than p0.001 both tocilizumab groups versus control). At week 4 more patients achieved ACR20 in 8 mg/kg tocilizumab versus controls (less than p = 0.001). Patients responded regardless of most recently failed anti-TNF or the number of failed treatments. DAS28 remission (DAS282.6) rates at week 24 were clearly dose related, being achieved by 30.1%, 7.6% and 1.6% of 8 mg/kg, 4 mg/kg and control groups (less than p = 0.001 for 8 mg/kg and p = 0.053 for 4 mg/kg versus control). Most adverse events were mild or moderate with overall incidences of 84.0%, 87.1% and 80.6%, respectively. The most common adverse events with higher incidence in tocilizumab groups were infections, gastrointestinal symptoms, rash and headache. The incidence of serious adverse events was higher in controls (11.3%) than in the 8 mg/kg (6.3%) and 4 mg/kg (7.4%) groups.Tocilizumab plus methotrexate is effective in achieving rapid and sustained improvements in signs and symptoms of RA in patients with inadequate response to TNF antagonists and has a manageable safety profile.NCT00106522.

Duran et al 1 present the results of a literature search performed on a very large number of publications comparing methotrexate (MTX) with a biologic agent. Their literature review eventually yielded 13 published trials for their analysis. The authors were particularly interested in the dose, and route of administration, of MTX. As the efficacy of the new agent studied was being compared with MTX, it is reasonable to determine if the dose of the latter drug was adequate. If it was not, there could indeed have been a bias in the study design, which favoured the new agent. As these trials were all sponsored by the pharmaceutical manufacturers of the new drug, there would certainly be a motive for bias. As any reader of detective novels knows, there must be both a motive and an opportunity to commit the crime being investigated. Following this line of investigative reasoning, pharmaceutical manufacturers have both. However, a review of the authors' findings raises some troubling questions regarding their methodology and the implications of their findings. First, the recommendations for the maximal dosage of MTX are from a consensus document published in 2009.2 The recommendations for the total dose of MTX …

Background Little is known about the relationship between adherence to the treat-to-target (T2T) paradigm and clinical outcomes in US patients with rheumatoid arthritis (RA). Objectives To evaluate the relationship between adherence to T2T care and achievement of low disease activity (LDA) using a post hoc analysis of a cluster-randomized behavioral intervention trial evaluating a T2T implementation approach vs usual care (UC) in patients with RA. Methods Twenty-eight rheumatology practices from the Corrona network recruited patients with RA between July 29, 2011, and July 30, 2013. Eligible patients with moderate or high disease activity (Clinical Disease Activity Index [CDAI >10]) were followed for 12 months. Regardless of randomization in the trial (T2T vs UC), sites were categorized based on rate of acceleration (e.g., initiation or dose increase of cDMARD or biologic at visits with CDAI >10 and no treatment acceleration in the prior 3 months). Sites that accelerated therapy at ≥60% of eligible visits (top tertile) were considered high acceleration (HA) sites; sites with 0.10. As a sensitivity analysis, logistic regression models were fitted using acceleration rates as a linear association. The first model was as a continuous covariate (1 unit representing a 10% change in acceleration). The second model allowed for a threshold effect and used a linear spline with a knot at 60% acceleration. Results Overall, there were 10 HA sites (195 patients) and 18 LA sites (337 patients). The groups were similar in terms of sex, race, ethnicity and baseline disease activity. However, HA site patients were younger (mean age, 56 vs 58 years) and had shorter disease duration (mean, 6 vs 9 years). Over the study period, 17% of HA site patients (34/195) and 18% of LA site patients (62/337) dropped out (P=0.832). The rates of achievement of LDA at the last visit were 60.5% in the HA group vs 52.5% in the LA group (odds ratio [OR] 1.78; 95% CI 0.96–3.27) in multivariable models adjusting for demographics and disease characteristics. In the sensitivity analyses, use of acceleration rate as a continuous covariate was associated with an OR of 1.15 (95% CI 0.99–1.24). In the model with the spline (Figure), acceleration rates Conclusions Increased site adherence to a T2T approach was associated with a greater likelihood of achieving LDA. Evidence suggests there may be a threshold effect, indicating a lack of benefit with inconsistent adherence to the T2T approach. Acknowledgement The Corrona T2T study is sponsored by Corrona, LLC, with support from a development and subscription agreement/contract with Genentech and additional support from AbbVie and Crescendo. Disclosure of Interest L. Harrold Grant/research support from: Corrona, LLC, Employee of: Corrona, LLC, G. Reed Employee of: Corrona, LLC, A. John Employee of: Genentech, Inc, C. Barr Employee of: Corrona, LLC, K. Saunders Employee of: Corrona, LLC, K. Soe Employee of: Corrona, LLC, R. Magner: None declared, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Genentech, Janssen, Novartis, Pfizer, Employee of: Corrona, LLC, J. Kremer Shareholder of: Corrona, LLC, Grant/research support from: Genentech, Inc, Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, LLC

Background It is unclear whether anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) status are predictive of response to rheumatoid arthritis (RA) therapy. Objectives To assess whether baseline anti-CCP/RF status is associated with treatment response in patients with RA initiating abatacept (ABA) or a tumour necrosis factor-alpha inhibitor (TNFi). Methods Patients who initiated ABA or a TNFi within the Corrona RA registry between June 2002 and January 2015 were eligible if they had: anti-CCP and RF testing at or prior to initiation; a follow-up visit 6 months after initiation (±3 months); and Clinical Disease Activity Index (CDAI) measured at or within 4–6 months prior to initiation and after 6 months9 treatment. Seropositivity was identified for anti-CCP (≥20 U/mL) and RF (≥40 U/mL). At 6 months, the primary outcome was ΔCDAI, with secondary outcomes being achievement of remission (CDAI ≤2.8 in those with low, moderate or high baseline disease activity) and low disease activity (LDA; CDAI ≤10 in those with moderate or high baseline disease activity). Unadjusted and adjusted linear and logistic regression analyses were performed by baseline anti-CCP/RF status: double positive (anti-CCP+/RF+), single positive (anti-CCP+/RF– or anti-CCP–/RF+) and double negative (anti-CCP–/RF–). Adjusted models controlled for baseline age, sex, BMI, CDAI score, co-morbidity index and number of prior biologic DMARDs. Results 566 patients starting ABA (244 double positive; 167 single positive; 155 double negative) and 1715 starting a TNFi (774 double positive; 470 single positive; 471 double negative) were identified. Most patients were female (ABA: 79–83%; TNFi: 74–80%) and middle-aged (mean age 57–58 years in ABA, 54–57 years in TNFi), with established disease (mean disease duration 9–11 years in ABA, 6–8 years in TNFi) and moderate disease activity (mean CDAI 18–23 in ABA, 18–19 in TNFi). For patients who initiated ABA, double positive status was associated with a significantly greater response compared with double negative status on all outcomes (ΔCDAI −8.9 vs −4.5, p=0.002; LDA 43% vs 26%, p=0.002; remission 15% vs 5%, p=0.001). Additionally, single positive status was associated with a greater likelihood of remission as compared with double negative status for ABA users (12% vs 5%, p=0.018). Conversely, there were no significant differences in responses between anti-CCP/RF groups in the TNFi users (double positive vs double negative: ΔCDAI −7.5 vs −6.8, p=0.46; LDA 39% vs 35%, p=0.20; remission 16% vs 14%, p=0.38). In adjusted models, there are significant differences in the outcomes based on anti-CCP/RF status among ABA users but not TNFi users (Figure). Conclusions These real-world data demonstrate that baseline anti-CCP+/RF+ is associated with better clinical response to ABA, with the strongest association observed for double seropositivity. In contrast, no relationship was evident between anti-CCP/RF status and response to a TNFi, suggesting that the predictive value of autoantibodies is dependent on drug mechanism of action. Disclosure of Interest L. R. Harrold Grant/research support from: Pfizer, H. J. Litman Employee of: Corrona, S. E. Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Kelly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, W. Hua Employee of: Corrona, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Rebello Employee of: Corrona, J. M. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Bristol-Myers Squibb, Genentech, Lilly, Novartis, Pfizer, Employee of: Corrona, Speakers bureau: Genentech (non-branded talks only)

Background Comparative effectiveness research (CER) can inform decisions regarding the choice of biologics for the treatment of RA. Objectives To compare the efficacy of tumor necrosis factor inhibitors (TNFis) and non-TNFis (nTNFis) in real-world patients with RA previously treated with ≥1 TNFi. Methods CERTAIN was a CER study nested within the US Corrona registry. 1 Adult patients with RA with moderate to high disease activity (CDAI >10) starting a TNFi or nTNFi (physician-driven choice of agent) were enrolled. For the primary analysis, only patients previously treated with ≥1 TNFi were included. The primary outcome was achievement of low disease activity (LDA) at 12 months (CDAI ≤10). A propensity score (PS) for the probability of treatment with a TNFi vs nTNFi was generated; patients outside the common area of support in the PS were excluded. Response rate was modeled using a mixed-effect logistic regression model with start of a biologic as the unit of analysis, adjusting for a priori and imbalanced baseline factors and to account for the clustering of patients within practice sites. As a sensitivity analysis, patients were matched 1:1 on the PS within each site. Results Of the 2795 biologic starts captured, 1142 biologic naive and 562 nTNFi experienced were excluded, leaving 1091 biologic starts in 998 patients for analysis of response after a TNFi. After PS trimming, 1081 starts (566 [52.4%] nTNFi and 515 [47.6%] TNFi) remained. Patients who started nTNFis were significantly more likely to have longer disease duration, higher patient fatigue scores, Medicare insurance and more prior TNFi use. At 12 months, 29.4% of nTNFi and 24.3% of TNFi initiators were in LDA. In the adjusted analysis (Table), patients on nTNFis were significantly more likely to achieve LDA. However, when adjusting for site clustering, the results were no longer significant. Conclusions In this large, real-world study, after ≥1 TNFi failure, switch to a nTNFi was favored over treatment with a subsequent TNFi, but was not statistically significant after adjusting for site clustering. Results warrant further study. References Pappas DA, et al. BMC Musculoskeletal Disord. 2014;15:113. Acknowledgement The Corrona CERTAIN study is sponsored by Corrona, LLC, with support from the AHRQ (R01HS018517). The majority of funding for CERTAIN was derived from Genentech, with additional support for substudies from Eli Lilly, Momenta Pharmaceuticals and Pfizer. CERTAIN investigators also receive support from the NIH [JRC AR053351, JDG AR054 412]. Disclosure of Interest D. Pappas Employee of: Corrona, LLC, Paid instructor for: Novartis, A. John Employee of: Genentech, Inc, J. Kremer Shareholder of: Corrona, LLC, Consultant for: Abbvie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, LLC, G. Reed Employee of: Corrona, LLC, T. Sommers Employee of: Corrona, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Genentech, Janssen, Novartis, Pfizer, Employee of: Corrona, LLC, J. Curtis Grant/research support from: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, AbbVie, Consultant for: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie

Background Mavrilimumab, a fully human monoclonal antibody, which targets granulocyte-macrophage colony-stimulating factor receptor-α, has demonstrated efficacy and an acceptable safety profile in prior 12- and 24-week studies.1,2 Objectives This analysis evaluated all long-term (LT) safety and efficacy, through 74 weeks of treatment, of mavrilimumab. Methods This open-label extension (OLE) study (NCT01712399) enrolled adult rheumatoid arthritis (RA) patients (pts) who had completed the EARTH EXPLORER 12 and 2 (NCT01715896) Phase IIb studies or were rescued as inadequate responders (from Week 12). Pts received subcutaneous mavrilimumab 100 mg every other week (eow), consistent with data from the Phase IIa study1. The primary objective was to assess the LT risk:benefit ratio of mavrilimumab via evaluation of i) Treatment emergent adverse events (TEAEs), TE serious AEs (TESAEs), and independently adjudicated pulmonary function tests (PFTs) ii) Exploratory LT efficacy endpoints (DAS28–CRP/ACR responses). AEs with onset date after start of mavrilimumab are presented. Change from baseline (BL) in modified Total Sharp Score (mTSS) was used to explore radiographic progression in EARTH EXPLORER 1 pts. Results At the 74 week (includes original study) cutoff, 391 pts had been enrolled in the OLE study. Of these, 329 (84.1%) continued on treatment, 62 (15.9%) discontinued (due to withdrawal of consent, 9 [2.3%]; adverse event, 7 [1.8%]; non study-related site closure, 20 [5.1%]; other, 24 [6.1%]; lost-to-follow-up, 1 [0.3%]; death [sudden cardiac arrest, preferred term cardiopulmonary failure], 1 [0.3%]), and 239 (61.1%) were assessed for efficacy at Week 74. Between the Phase IIb and OLE studies, 440 pts received mavrilimumab, with a safety exposure of 603 pt years (yr) and median duration of 1.6 yr. Most common TEAEs (n [/100 pt yr]) were nasopharyngitis (51 [8.45]), bronchitis (36 [5.97]) and hypertension (32 [5.30]); the serious infection rate was 1.82/100 pt yr. Pulmonary events/defined PFT changes occurred in a few pts and were generally transient with no signal identified (Table). Mavrilimumab demonstrated sustained efficacy (DAS28–CRP/ACR responses) (Table). After 74 weeks of treatment, 68% of pts showed no radiographic progression ( Conclusions Mavrilimumab continues to demonstrate a sustained efficacy and safety profile in pts with active RA, over the 74 week treatment duration reported. Although mavrilimumab 100 mg eow is suboptimal compared with 150 mg eow in DMARD-IR pts,2 efficacy results are comparable with those of previous studies.1,2 References Burmester G, et al. Ann Rheum Dis 2013;72:1445–1452 Burmester G, et al. Arthritis Rheum 2014;66:S1231 Acknowledgement Funded by MedImmune. Editorial assistance: K Alexander, QXV Comms, an Ashfield business, UK Joint senior authors: D. Close and M. Weinblatt Disclosure of Interest G. Burmester Consultant for: MedImmune, I. McInnes Grant/research support from: Research award to University of Glasgow, Consultant for: MedImmune, AstraZeneca, J. Kremer Shareholder of: Corrona, Grant/research support from: Abbvie, Amgen, Genentech, Lilly, Pfizer, Consultant for: Abbvie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, P. Miranda Grant/research support from: Clinical trials Amgen, Medimmune, Janssen, Pfizer, Celltrion, Abbott, Sanofi, Actelion, Merck & Co, Boehringer, BMS, Consultant for: Pfizer for Etanecept (fee less than USD5000), J. Vencovský Consultant for: Pfizer, Servier, Samsumg, Eli lilley, BMS, Novartis, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, M. Albulescu Employee of: MedImmune, D. Close, Employee of: MedImmune, M. Weinblatt, Grant/research support from: BMS, UCB, Crescendo Bioscience, Consultant for: MedImmune, AstraZeneca, Amgen, Abbvie, BMS, Crescendo Bioscience, Lilly, Pfizer, UCB, Roche

Background There is a growing emphasis on treating patients to a target level of low disease activity (LDA) or remission in order to improve outcomes associated with rheumatoid arthritis (RA). Objectives Our objective was to examine trends in the achievement of LDA over the past decade among RA patients receiving their first, second and third or more biologic agent. Methods Using the Corrona registry, we identified initiators of biologic therapy (stratified by prior experience: 1st, 2nd, ≥3rd) in distinct periods of calendar time over the last decade (2002–2004, 2005–2007, 2008–2010, 2011–2013) with moderate or high disease activity at the time of the initiation based on the Clinical Disease Activity Index (CDAI >10), and a follow-up CDAI measured at 1 year (±3 months). The primary outcome was achievement of LDA (CDAI ≤10) at 12 months. Trends over time between the groups were examined using Chi square tests. Multivariable logistic regression models were performed adjusting for baseline covariate. Results We identified 6,534 biologic initiators (1st: 2,769, 2nd: 2181, ≥3rd: 1584) who met inclusion criteria. Between 2011 and 2013, LDA occurred in 51%, 42% and 35% of those initiating their 1st, 2nd and ≥3rd biologic respectively. There was a significant trend over time in achievement of LDA in those initiating their first biologic. In adjusted models, treatment in the earlier time periods for those who initiated their 1st or ≥3rd biologic was associated with a reduced likelihood of achieving LDA (Table). Conclusions In the latest time period, achievement of LDA was influenced by biologic experience (50% in 1st biologic vs. 35% ≥3rd biologic initiation). Patients who initiated their 1st or ≥3rd biologic in earlier time periods had a reduced likelihood of achieving LDA (Table). Additional investigation is needed to understand the factors contributing to the trend in improved disease as well as the barriers in order to inform efforts to further increase the proportion of patients who achieve LDA. Acknowledgement This study was funded by the Corrona Research Foundation. Disclosure of Interest L. Harrold Grant/research support from: Pfizer, Consultant for: Roche, Employee of: Corrona, LLC, J. Palmer: None declared, J. Curtis Grant/research support from: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie, Consultant for: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Genentech, Janssen, Novartis and Pfizer, Employee of: Corrona, LLC, D. Pappas Employee of: Corrona, LLC, Paid instructor for: Novartis, J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, BMS, Genentech, GSK, Lilly, Medimmune, Pfizer, Sanofi, Employee of: Corrona, LLC, Speakers bureau: Genentech (for non-branded talk only)

Background Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, has demonstrated efficacy and safety in disease-modifying antirheumatic drug (DMARD)-inadequate responder (IR) patients (pts) with rheumatoid arthritis (RA). 1 Objectives Few head-to-head studies in tumor necrosis factor antagonist (aTNF)-IR assess alternative aTNFs vs. other agents; this Phase IIb exploratory study (NCT01715896) evaluates the efficacy and safety of mavrilimumab and golimumab in aTNF-IR and DMARD-IR pts. Methods This 24-week study enrolled pts with active RA (28-joint Disease Activity Score [DAS28]–C-reactive protein [CRP]/erythrocyte sedimentation rate ≥3.2); ≥4 swollen joints; inadequate response to ≥1 DMARDs and/or 1–2 aTNFs receiving concomitant methotrexate (MTX; 7.5–25.0 mg/week). Pts received subcutaneous mavrilimumab 100 mg every other week (eow), based on data from the Phase IIa study, 2 or golimumab 50 mg alternating with placebo eow. Key endpoints were ACR20/50/70 responses, DAS28–CRP 0.22 at Week 24 and safety/tolerability. Treatment estimates for mavrilimumab and golimumab are presented with standard errors. Results Pts were randomized to mavrilimumab or golimumab (1:1) (Table). Data for pts receiving mavrilimumab 100 mg eow and golimumab 50 mg at Week 24 are shown for the aTNF-IR, DMARD-IR and overall strata (Table). The most common treatment-emergent adverse events (TEAEs) for mavrilimumab 100 mg and golimumab 50 mg were nasopharyngitis (5.7%, 1.5%), headache (4.3%, 2.9%), upper respiratory tract infection (4.3%, 2.9%), viral upper respiratory tract infection (4.3%, 2.9%), and hepatic enzyme increase (4.3%, 2.9%), respectively. Related serious TEAEs were pneumocystis pneumonia (n=1) and lung disorder (n=1) [both in golimumab-treated pts]. No deaths were reported and no significant pulmonary safety signals were identified. Conclusions In this exploratory study, mavrilimumab 100 mg eow and golimumab 50 mg demonstrated efficacy and an acceptable safety profile in DMARD-IR and aTNF-IR pts. The study was not powered to demonstrate statistical significance between mavrilimumab and golimumab. As mavrilimumab 100 mg eow has previously been shown to be suboptimal compared with 150 mg eow in DMARD-IR pts (EARTH EXPLORER 1), 1 additional studies are needed to establish the benefit of a higher dose in pts with moderate to severe RA and inadequate response to aTNF agents. References Burmester G, et al. Arthritis Rheum. 2014;66:S1231 Burmester G, et al. Ann Rheum Dis. 2013;72:1445–1452 Acknowledgement Funded by MedImmune. Editorial assistance: K Alexander, QXV Comms, an Ashfield business, UK Joint senior authors: D. Close and G. Burmester Disclosure of Interest M. Weinblatt Grant/research support from: BMS, UCB, Crescendo Bioscience, Consultant for: MedImmune, Astra Zeneca, Amgen, Abbvie, BMS, Crescendo Bioscience, Lilly, Pfizer, UCB, Roche, I. McInnes Grant/research support from: Research award to University of Glasgow, Consultant for: MedImmune, Astra Zeneca, J. Kremer Shareholder of: Corrona, Grant/research support from: Abbvie, Amgen, Genentech, Lilly, Pfizer, Consultant for: Abbvie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, P. Miranda Grant/research support from: Clinical trials: Amgen, Medimmune, Janssen, Pfizer, Celltrion, Abbott, Sanofi, Actelion, Merck & Co, Boehringer, BMS, Consultant for: Pfizer for Etanecept (fee less than USD5000), J. Vencovský Consultant for: Pfizer, Servier, Samsumg, Eli lilley, BMS, Novartis, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, M. Albulescu Employee of: MedImmune, D. Close, Employee of: MedImmune, G. Burmester, Consultant for: MedImmune

Background Anti-citrullinated protein antibodies (ACPA) are associated with more severe, erosive rheumatoid arthritis (RA), but the extent to which ACPA status predicts response to therapy is not known.1,2 Objectives To evaluate in a real-world, observational RA cohort whether baseline ACPA status is associated with response to biologics among patients with RA. Methods Using the Corrona RA registry, we identified patients with RA who initiated abatacept (ABA) or a tumour necrosis factor-alpha inhibitor (TNFi) between June 2002 and January 2015, had a follow-up visit 6 months (±3 months) after initiation and anti-cyclic citrullinated peptide (anti-CCP [a surrogate of ACPA]) measured at or prior to initiation. Anti-CCP positivity was defined as anti-CCP ≥20 U/mL. The primary outcome was mean change from baseline in Clinical Disease Activity Index (CDAI) at 6 months. Secondary outcomes at 6 months included: 1) achievement of low disease activity (LDA; CDAI ≤10) among those with moderate or high disease activity who initiated treatment; 2) achievement of remission (CDAI ≤2.8) in those with low, moderate or high disease activity who initiated treatment; 3) Minimally Important Clinical Difference (MCID) in CDAI; and 4) modified ACR20/50/70. Unadjusted and adjusted linear and logistic analyses were performed based on anti-CCP status (positive [+] vs negative [–]). Results 566 patients initiated ABA: 204 (36.0%) were anti-CCP– and 362 (64.0%) anti-CCP+. There were no differences by CCP status for age (mean 57–58 years), disease duration (median 7 years) or prior biologic use (0, 1 or ≥2 prior); however, median baseline CDAI was greater in anti-CCP– vs anti-CCP+ patients (21 vs 19, p=0.035). 1715 patients initiated a TNFi: 602 (35.1%) were anti-CCP– and 1113 (64.9%) anti-CCP+. There were no differences by CCP status for age (mean 55–56 years), prior biologic use or median baseline CDAI; however, median disease duration was greater in anti-CCP+ vs anti-CCP– patients (4 vs 3 years, p=0.021). In adjusted analyses, anti-CCP+ ABA initiators had a mean (SE) change in CDAI of –8.5 (0.6) vs –4.1 (0.8) for anti-CCP– (p Conclusions In a clinical practice setting, anti-CCP positivity was associated with a differential treatment response to abatacept, but not TNFis. These real-world data suggest that anti-CCP+ patients with RA show incremental improvements in response while receiving abatacept therapy compared with anti-CCP– patients. References Lv Q, et al. PLoS One 2014;9:e89442. Sokolove J, et al. Ann Rheum Dis 2015; doi:10.1136/annrheumdis-2015-207942. Disclosure of Interest L. R. Harrold Grant/research support from: Pfizer, H. J. Litman Employee of: Corrona, S. E. Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Kelly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, W. Hua Employee of: Corrona, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Rebello Employee of: Corrona, J. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Bristol-Myers Squibb, Genentech, Lilly, Novartis, Pfizer, Employee of: Corrona, Speakers bureau: Genentech (non-branded talks only)

Background Some studies have suggested that efficacy of triple non-biologic disease modifying anti-rheumatic drug (nbDMARD) therapy for Rheumatoid Arthritis (RA) is similar to biologic combination therapy (1). Objectives To examine the difference in need to advance therapy after treatment with triple nbDMARD (Group 1) or TNF inhibitors in combination with methotrexate (MTX)) (Group 2). Methods RA patients enrolled in Corrona between 10/2001 – 8/2015 initiating either triple nbDMARD therapy or a biologic agent in combination with MTX and with at least 1 follow-up visit were included. Group 1 included patients who started either concurrently or sequentially MTX, hydroxychloroquine and sulfasalazine. TNF inhibitors could be started concurrently with or added to MTX in Group 2. Advancement of therapy was compared for the two groups after propensity score (PS) matching and defined as discontinuing one or more of triple nbDMARD and adding a biologic/adding another nbDMARD for Group 1 and adding a second nbDMARD/switching to a different biologic for Group 2. Index visit was defined as initiation of triple therapy for Group 1 and date of biologic initiation for Group 2. Kaplan-Meier estimates were used to determine time to advancement of therapy. Results There were 236 and 2,938 in Gp 1 and 2 respectively. After PS matching, N=221 were included in each group. Groups were well balanced with a mean age of 58.5 yrs vs 58.6 yrs, mean disease duration of 10.5 yrs vs 10.6 yrs and mean clinical disease activity index (CDAI) of 15.9 vs 16.1 for groups 1 and 2 resp. About 76% (95% CI: 69.5%, 81.3%) of the Gp 1 patients continued on initial therapy compared to 82% (95% CI: 76.4%, 86.8%) in Gp 2 at 12 months of follow-up. Median time to therapy advancement was 49 months (95% CI: 35, 59) for group 1 and 69 months (95% CI: 46, 100) for group 2. About 40% of patients in triple nbDMARD group had to advance therapy during 12 months of follow-up, vs 39% in group 2. Types of first advancement of therapy is shown in table 1. Conclusions Therapy with a biologic agent resulted in a numerically but not statistically significant prolonged time to advancement therapy compared to triple nbDMARD therapy. Future examination of the need to advance therapy with a larger sample size may provide further insights for treatment practices. References Van Vollenhoven RF et al. Lancet. 2012 May 5; 379 (9827):1712–20. doi: 10.1016/S0140-6736(12)60027-0 Acknowledgement This study is sponsored by Corrona, LLC. The Corrona, LLC. RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. The design, study conduct, and financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. Disclosure of Interest D. Pappas Employee of: Corrona, LLC, Paid instructor for: Novartis, C. Karki Employee of: Corrona, LLC, H. Litman Employee of: Corrona, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Genentech, Janssen, Novartis and Pfizer, Employee of: Corrona, LLC, J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, BMS, Genentech, GSK, Lilly, Medimmune, Pfizer, Sanofi, Employee of: Corrona, LLC, Speakers bureau: Genentech (for non-branded talk only), V. Garg Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc.

Background While some treatment options for psoriatic arthritis (PsA) are similar to those initially developed for rheumatoid arthritis (RA), their introduction to the clinic has generally increased in the recent years. Also, there has been a perception among some that RA is perhaps associated with greater disease burden compared to PsA. Objectives The objective of this study was to determine and compare the disease activity related to peripheral arthritis and biologic use in patients with RA and PsA over the past 10 years in Corrona registry. Methods All patients between 01/2002 – 03/2013 were included and patients were grouped in 2 year intervals 2002–2003, 2004–2005, 2006–2007, 2008–2009, 2010–2011, 2012–2013. Within each time period, standardized differences were used to identify patient characteristics that were different between PsA and RA patients. Logistic regression models evaluated the likelihood of being in moderate/high clinical disease activity index (CDAI) and use of biologics in PsA patients compared to patients with RA, adjusting for covariates within each time period. Random effects logistic regression models were also considered to account for site random effects. Results A total of 20982 and 2552 RA and PsA patients respectively were studied over the six time intervals. The mean age was 59 yrs and 53 yrs for RA and PsA patients respectively. Mean CDAI and percentage of patients in moderate/severe disease activity were significantly higher in RA and PsA over the years; disease activity generally decreased over time for both (Figure). History of biologic use was similar between the two groups in 2002–03 (44% in RA vs 42.5% in PsA), however there was an upward trend in biologic use in both groups with higher use among PsA patients over the past years (figure). Similarly current biologic use also increased from 36.3% vs 36.1% in RA vs PsA in 2002–03 to 52.1% vs 62% in 2012–2013 respectively. Adjusted models showed that PsA patients were significantly less likely to be in moderate/severe disease activity defined by CDAI (OR (95% CI): 0.79 (0.72, 0.88)) over the past years and more likely to be on a biologic compared to RA patients in 2012–13 (Odds ratio (95% CI): 1.37 (1.25, 1.49)). Conclusions Although disease activity has generally decreased while biologic therapy use has increased over recent years, there continues to be a significant proportion of PsA and RA patients with moderate/severe disease. Joint burden among PsA patients is slightly lower in comparison to RA, although biologic use was higher in the PsA population. Future research should evaluate the correlation in disease activity and biologic use over time. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona, LLC. RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. The design, study conduct, and financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. Disclosure of Interest A. Kavanaugh Grant/research support from: Amgen Abbvie Jannsen Pfizer Novartis, J. Griffith Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc., C. Karki Employee of: Corrona, LLC, C. Etzel Consultant for: Merk, Employee of: Corrona, LLC, J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, BMS, Genentech, GSK, Lilly, Medimmune, Pfizer, Sanofi, Employee of: Corrona, LLC, Speakers bureau: Genentech (for non-branded talk only), J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Genentech, Janssen, Novartis and Pfizer, Employee of: Corrona, LLC, A. Ganguli Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc.

Background Limited data are available about infliximab (IFX) dose escalation. Objectives This analysis examines the frequency of dose escalation among IFX patients using data from the US CORRONA RA registry and describes the characteristics of patients who dose escalate vs those who do not. Methods RA patients initiating IFX at a dose of ≤5 mg/kg on or after 6/1/2009 with at least 1 follow-up visit with dose information were eligible for analysis. Subgroup analysis was performed among patients with follow-up at 1yr to compare characteristics between those who dose escalated vs those who did not. Dose escalation was defined as an increase of >1mg/kg in dose and/or a decrease in the frequency of dosing by at least 1 wk (e.g. q 8 wks to q7 wks). Censoring occurred if patients switched to another biologic or left the registry. Descriptive statistics were used to compare baseline characteristics of infliximab patients stratified by number of biologics, and also comparing those who dose escalated vs those who did not within the 1st yr after initiating therapy. Results A total of 716 patients initiated IFX after June 2009. Common characteristics included mean age (61yrs), women (78%), mean weight (83 kg), RF+ (70%) and CCP+ (67%), baseline CDAI (22.5), and insurance status (Medicare 46%, Medicaid 6%). Differences between those who initiated IFX as their 1st, 2nd, or 3rd biologic included RA duration (7.0, 9.6, 11.0 yrs, respectively, p Over 3 yrs follow-up, the proportions of patients escalating IFX significantly differed, ranging from a low of 21% at 1 yr for patients using IFX as 1st line to a high of 81% at 3yrs for patients using it as 3rd line (Table, p=0.0024 for between-group differences). In patients with follow-up data at 12mo (n=608), there were some baseline characteristics associated with dose escalating vs not in the 1st yr of therapy including shorter RA duration (p=0.03), greater number of prior biologics (p=0.04), monotherapy (p=0.03), greater prednisone use (p=0.01), and higher CDAI (p=0.04) and related disease activity measures. Conclusions Dose escalation of IFX is relatively frequent over time. Patients with more severe RA undergo dose escalation more commonly than those with less severe disease. Understanding long term benefits and persistence and related factors following dose escalation may help optimize dose escalation as a treatment strategy compared to switching. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest J. Curtis Grant/research support from: Janssen Scientific Affairs, LLC, Consultant for: Roche, Genentech, UCB, CORRONA, AMGEN, PFIZER, BMS, Crescendo, ABB VIE, Y. Shan Grant/research support from: Janssen Scientific Affairs, LLC, Employee of: CORRONA, LLC, K. Saunders Grant/research support from: Janssen Scientific Affairs, LLC, Employee of: CORRONA, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, J. Kremer Grant/research support from: Janssen Scientific Affairs, LLC, Consultant for: CORRONA, LLC

Background Biologic agents can help achieve low disease activity or remission in patients with rheumatoid arthritis (RA) who do not respond adequately to therapy with one or two conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) (1). Objectives To understand the prevalence of RA patients with inadequate response to therapy with 2 csDMARDs and describe time to initiation of a biologic agent for this patient population. Methods Patients enrolled in the Corrona RA registry as of January 2015 were included in this analysis. “Inadequate response” to 2 csDMARDs was defined as being on moderate or high disease activity (CDAI >10) six months after the initiation of 2 csDMARDs. The index visit was defined as the first visit after 6m of being on moderate or high CDAI after the initiation of 2 csDMARDs. The population of biologic naive patients at index visit, with at least 6 months of additional follow up were observed longitudinally to calculate the time to initiation of a biologic agent. Kaplan-Meier method was used to estimate the time to biologic initiation. Results 2723 RA patients treated with 2 csDMARDs for at least 6 months were identified. At the time of the index visit: 1774 (65.1%) patients had responded to 2 csDMARDs, 192 (7.1%) had started a biologic, and 135 (4.9%) patients with inadequate response to 2 csDMARDs and did not have at least 6 months of additional follow up post-index visit. The final number of inadequate responders to 2 csDMARDs included in this analysis was 622 (22.9%) patients (79.1% female, 60.9±12.7 mean age, 9.0±9.9 mean duration of RA, 19.5±8.9 mean CDAI at index visit). The median follow up time for this population was 32.5 months. Among the 622 patients, 227 initiated a biologic during the follow up time. The median time to initiation of a biologic was 75 months (95% CI: 53–97 months). Among the 227 patients who initiated the biologic, the mean (SD) time to initiation was 17.7 (±21.7) months (figure 1). While for some patients disease activity fluctuated between low/remission and moderate/high until the initiation of a biologic agent, for 57.3% of patients remained persistently in moderate or high disease activity over the follow-up. Conclusions A significant percentage of RA patients treated with 2 csDMARDs did not respond adequately to such therapy in the population studied. Prolonged time until the initiation of a biologic agent was noted for this patient population. References Singh JA et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care and Research DOI 10.1002/acr.22783 Acknowledgement This study is sponsored by Corrona, LLC. The Corrona, LLC. RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. The design, study conduct, and financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. Disclosure of Interest D. Pappas Employee of: Corrona, LLC, Paid instructor for: Novartis, C. Karki Employee of: Corrona, LLC, M. Liu Employee of: Corrona, LLC, J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, BMS, Genentech, GSK, Lilly, Medimmune, Pfizer, Sanofi, Employee of: Corrona, LLC, Speakers bureau: Genentech (for non-branded talk only), J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Genentech, Janssen, Novartis and Pfizer, Employee of: Corrona, LLC, V. Garg Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc.

Background Patients with long-standing RA may have more treatment-resistant disease than those with shorter disease duration. Objectives To examine whether disease duration is an independent predictor of treatment response among biologic-naive patients with RA initiating abatacept in a US national, observational cohort. Methods Using the Corrona RA registry, we identified new initiators of abatacept between Feb 2006 and Jan 2014 who were biologic naive with a follow-up visit at 1 year (±3 months) and assessment of disease activity (CDAI) at initiation and 1-year follow-up. The primary outcome was mean change from baseline in CDAI; the secondary outcomes were: 1) achievement of low disease activity (LDA; CDAI ≤10) among those who initiated abatacept in moderate or high disease activity, and 2) achievement of remission (CDAI ≤2.8) in those who initiated abatacept in low, moderate or high disease activity. Patients were stratified by disease duration (0–2, 3–5, 6–10, >10 years). For patients who switched agents before 1 year, the last observation before the switch was used to calculate mean change in CDAI. Switchers were imputed as non-responders for calculation of LDA and remission. Linear and logistic regression models were fit, as appropriate. Results In total, 281 biologic-naive patients with RA initiating abatacept met inclusion criteria (disease duration 0–2 years: n=107; 3–5 years: n=45; 6–10 years: n=50; >10 years: n=79). Baseline characteristics were similar across disease duration groups for sex (76–89% female) and disease activity (mean CDAI: 15.3–19.1). Increasing disease duration was associated with older patient age (p=0.047) and a higher number of prior conventional (c)DMARDs (p 10 years disease duration (Table). In analyses adjusted for age, sex, baseline CDAI and prior number of cDMARDs (Table), increasing disease duration was significantly associated with smaller mean change in CDAI (p=0.015) and lower likelihood of achieving LDA (p=0.048); association with decreasing likelihood of remission reached borderline significance (p=0.055). Conclusions In biologic-naive patients initiating abatacept, change in CDAI was significantly greater for shorter versus longer disease duration (unadjusted and adjusted models). After adjusting for covariates, shorter disease duration was associated with a greater likelihood of patients achieving LDA. Disclosure of Interest L. R. Harrold Grant/research support from: Pfizer, H. J. Litman Employee of: Corrona, S. E. Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Kelly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, W. Hua Employee of: Corrona, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Rebello Employee of: Corrona, J. M. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Bristol-Myers Squibb, Genentech, Lilly, Novartis, Pfizer, Employee of: Corrona, Speakers bureau: Genentech (non-branded talks only)

Background TNF inhibitors (TNFi) can be used as monotherapy (mono) or in combination (combo) with conventional DMARDS (cDMARDS). Clinical trial data and European registry data have shown evidence of better effectiveness of TNFi combo therapy than mono. Effectiveness of mono vs combo in US clinical practice, in particular among biologic naive and experienced patients, has not been assessed. Objectives This study was carried out to quantify the prevalence and effectiveness of TNFi monotherapy use in US clinical practice. A secondary objective was to contrast this with tofacitinib (tofa) monotherapy use and effectiveness. Methods RA patients initiating a TNFi (adalimumab, etanercept, infliximab, golimumab, certolizumab pegol) or tofa with a six month follow-up in Corrona US were identified. A subcohort of TNFi initiations after 11/6/2012 (market approval of tofa) were used for comparisons with tofa initiators. We defined combo therapy as TNFi or tofa used with MTX alone and mono as no use of any cDMARD. The primary outcome was achieving low disease activity (LDA) or remission based on CDAI (≤10) at 6 months. Patients switching to another biologic prior to 6 months were defined as non-responders. Secondary outcomes included modified ACR20/50/70 and mean change in CDAI. Combo and mono initiators were matched within line of therapy using a propensity score. Covariates for the model were selected if the standardized mean difference between the groups >0.1. Results There were 7076 TNFi initiations in Corrona, with 2091 (30%) mono initiations. Mono by line of therapy was 21%, 35% and 41% for 2nd, 3rd and 4th line therapy, respectively. There were 325 tofa initiations with 201 (61%) mono and mono rates of 50%, 65% and 63% for 2nd, 3rd and 4th line therapy, respectively. In the matched populations, across outcome measures (Table 1), TNFi combo was more effective than TNFi mono in 2nd line therapy (55.6% LDA vs 47.1% LDA) and similar in 3rd and 4th line therapy. Tofa combo therapy was similar to mono in the matched populations (35.4% LDA vs 32.3% LDA). Tofa mono was similar to TNFi combo therapy in the matched populations (33.3% LDA vs 33.3% LDA). Conclusions TNFi monotherapy is common in U.S. clinical practice. TNFi monotherapy is less effective than combination therapy especially in biologic naive patients. There is no evidence that tofa monotherapy is less effective than tofa combination therapy or TNFi combination therapy. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, R. Gerber Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., Y. Shan Employee of: Corrona, LLC, L. Takiya Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., K. Dandreo Employee of: Corrona, LLC, D. Gruben Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, BMS, Genentech, GSK, Lilly, Medimmune, Pfizer, Sanofi, Employee of: Corrona, LLC, Speakers bureau: Genentech (for non-branded talk only), G. Wallenstein Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc.

Background ABT-494 is a novel selective JAK1 inhibitor. Objectives The safety, efficacy, and dose response of ABT-494 were characterized vs placebo (PBO) in patients (pts) with moderately to severely active RA and an inadequate response to ≥1 anti-TNF biologic therapy (TNF-IR). Methods This was a phase 2b, 12-week, double-blind PBO-controlled study; TNF-IR pts receiving stable background methotrexate (MTX) were randomized 1:1:1:1:1 to ABT-494 3, 6, 12, and 18 mg twice daily (BID) or matching PBO. The primary efficacy endpoint was the proportion of pts who achieved an ACR20 response at week 12. Results All 276 pts had failed ≥1 anti-TNF therapy prior to enrollment; 28% had received ≥2 anti-TNF biologics and 20% had also received non–anti-TNF biologics. Baseline (BL) characteristics were similar in all treatment groups. The proportion of pts achieving ACR20 at week 12 was significantly higher for all ABT-494 groups vs PBO (Table 1). There was a significant (P Conclusions This phase 2b study demonstrated the clinical efficacy of ABT-494 vs PBO when dosed in combination with MTX in TNF-IR pts with active RA. ABT-494 had an acceptable safety and tolerability profile. Acknowledgement The design, study conduct, analysis, and financial support of the clinical trial (NCT01960855) were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the content. All authors had access to all relevant data. Mariana Ovnic and Michael J. Theisen of Complete Publication Solutions, LLC, provided medical writing support paid for by AbbVie. This presentation contains information on the investigational product ABT-494. Disclosure of Interest J. M. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Lilly, Novartis, and Pfizer, Consultant for: AbbVie, Lilly, Pfizer, Medimmune, Sanofi, and Regeron, Employee of: Corrona, E. C. Keystone Grant/research support from: AbbVie and Lilly, Consultant for: AbbVie and Lilly, Speakers bureau: AbbVie and Lilly, P. Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Lilly, and Takeda, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Lilly, and Takeda, H. S. Camp Shareholder of: AbbVie, Employee of: AbbVie, A. Friedman Shareholder of: AbbVie, Employee of: AbbVie, L. Wang Shareholder of: AbbVie, Employee of: AbbVie, A. A. Othman Shareholder of: AbbVie, Employee of: AbbVie, N. Khan Shareholder of: AbbVie, Employee of: AbbVie, S. Jungerwirth Shareholder of: AbbVie, Employee of: AbbVie

Objective To describe changes in immune parameters observed during long-term methotrexate (MTX) therapy in patients with active rheumatoid arthritis (RA) and explore correlations with simultaneously measured MTX pharmacokinetic (PKC) parameters.\ud \ud Design Prospective, open-label, long-term mechanism of action study.\ud \ud Setting University clinic.\ud \ud Methods MTX was initiated at a single weekly oral dose of 7.5 mg and dose adjusted for efficacy and toxicity for the duration of the study. Standard measures of disease activity were performed at baseline and every 6–36 months. Serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell (PBMC) cytokine production were assessed at each clinical evaluation.\ud \ud Results Cytokine concentrations exhibited multiple significant correlations with disease activity measures over time. The strongest correlations observed were for interleukin (IL)-6 (r=0.45, p

Background Patients with rheumatoid arthritis (RA) experience diminished quality of life, including increased disability and RA-related comorbidities. Patient-reported outcomes (PROs) are increasingly being recognized as important measures in determining response to therapy in patients with RA. Objectives To examine the impact of rituximab on PROs in the Corrona registry, a national US observational cohort of >40,000 patients with RA. Methods Between March 1, 2006, and September 1, 2015, patients with RA who had prior exposure to ≥1 tumor necrosis factor inhibitor (TNFi) and newly initiated rituximab while not in remission (Clinical Disease Activity Index [CDAI] >2.8) with a follow-up visit at 1 year (± 3 months) were identified. Changes in PROs, assessed 1 year from baseline and stratified by prior TNFi use, included patient global assessment of disease, pain and fatigue (visual analog score; 0–100); morning stiffness (hours); modified Health Assessment Questionnaire (mHAQ; 0–3) and Euro Quality of Life 5 dimensions questionnaire (EQ-5D). Improvement in EQ-5D domains was defined as patients reporting improvement or resolution of impairment among patients who reported impairment at baseline. Outcomes between the 1 and ≥2 prior TNFi groups were compared using χ 2 or t -tests, as appropriate. Results Of the 667 patients initiating rituximab included, 284 (43%) had received 1 prior TNFi and 383 (57%) had received ≥2 prior TNFis. Overall, the median (IQR) age was 59 (50–66) years; 79% of patients were female. Baseline mean (SD) CDAI was 25.6 (13.9). Baseline PROs showed that patients were substantially impaired by their disease and were mostly similar between the 1 and ≥2 prior TNFi groups, although patients in the 1 prior TNFi group tended to have longer duration of morning stiffness and greater fatigue scores. At baseline, patients reported median (IQR) global assessment, pain, fatigue and mHAQ scores of 50 (35–73), 60 (31–75), 65 (40–80) and 1 (0.6–1.6), respectively, and a median (IQR) of 1 (0.5–2) hour of morning stiffness. Of the 667 total patients, 63% received rituximab retreatment and persisted on rituximab through 1 year. At 1 year, improvements were reported in all PROs with no significant difference between patients with 1 or ≥2 prior TNFis. Median (IQR) improvements in patient global assessment, pain and fatigue were 7 (−10 to 25), 7 (−5 to 25) and 9 (−5 to 20), respectively. Improvement in EQ-5D categories is shown (Figure). 51.7% of patients reported no improvement in morning stiffness, 28.5% reported improvement of 1–60 minutes and 19.8% reported improvement of >60 minutes. Conclusions Real-world data showed that quality of life in this cohort of patients with long-standing, refractory RA was substantially impacted by the disease. One year after initiation of rituximab, improvements were reported in all PROs, such as self-care and usual activities, and were similar between patients with exposure to 1 or ≥2 prior TNFis. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer and UCB. Disclosure of Interest L. Harrold Grant/research support from: Corrona, LLC, Employee of: Corrona, LLC, A. John Employee of: Genentech, Inc., C. Karki Employee of: Corrona, LLC, Y. Li: None declared, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC, J. Kremer Shareholder of: Corrona, LLC, Grant/research support from: Genentech, Inc., Consultant for: Genentech, Inc., Employee of: Corrona, LLC

Background and objectives Baricitinib is an oral, reversible inhibitor of Janus kinase (JAK)1/JAK2 being developed as treatment for patients with RA. Previous studies have shown transient increases in total lymphocyte count within hours of dosing and return to baseline prior to the next dose. We examined changes over time in lymphocyte subsets in RA patients treated with baricitinib or placebo in the phase 3 RA-BUILD and RA-BEACON studies. Materials and methods Patients had active RA with insufficient response (IR) to conventional synthetic DMARDs (csDMARDs) (RA-BUILD; N=684) or TNF inhibitors (TNFi) (RA-BEACON; N=527). Patients were randomised 1:1:1 to placebo or 2 or 4mg baricitinib QD for 24 weeks. Lymphocyte subsets and natural killer (NK) cells were quantified by flow cytometry at baseline and Week (wk) 4, wk12, and wk24. Total lymphocyte count was measured at each visit. Results Significant improvements in disease activity were seen for baricitinib versus placebo in both studies. Total lymphocyte increases at wk4 for baricitinib were generally within normal ranges. Change in total lymphocyte count was similar at wk12 and wk24 for baricitinib versus placebo. In RA-BUILD/RA-BEACON, increased T-cells/µL (158.3/22.6 and 124.1/170.7 for 2mg and 4mg,p ≤ 0.05), B-cells/µL (66.7/36.8 and 82.9/74.3 for 2mg and 4mg,p ≤ 0.001), and NK-cells/µL (59.5/36.8 and 46.2/77.0 for 2mg and 4mg,p ≤ 0.01) versus placebo were seen at wk4. Decreased T-cells/µL (wk12= -20.9/0.7 and -87.6/-33.1 for 2mg and 4mg; wk24 = -117.2/-128.1 and -83.4/-53.8 for 2mg and 4mg,p ≤ 0.05) and NK-cells/µL (wk12 = -36.7/-22.0 and -57.0/-22.7 for 2mg and 4mg,p ≤ 0.001 in RA-BEACON; wk24 = -41.2/-45.0 and -53.4/-40.9 for 2mg and 4mg, p ≤ 0.05 in RA-BEACON) and increased B-cells/µL (wk12 = 65.0/49.3 and 75.1/70.2 for 2mg and 4mg, p ≤ 0.001; wk24= 24.3/22.6 and 55.2/65.0 for 2mg and 4mg,p ≤ 0.001 for 4mg) were seen later for baricitinib groups. Changes in other T- and B-cell populations were variable, but generally reflected these patterns. Decreased NK-cell count did not appear to be associated with an increased incidence of infection. Conclusions Baricitinib produced significant clinical improvements in disease activity in csDMARD-IR and TNFi-IR RA patients. Improvements were accompanied by a variety of changes in lymphocyte counts, predominantly within normal ranges. Similar lymphocyte subset assessments will be available in a long-term extension study.

Background Of patients with RA, ∼40% of do not achieve a minimal acceptable improvement (ACR20) despite modern biologic therapy.1,2,3 Granulocyte-macrophage colony-stimulating factor (GM–CSF) is implicated in RA pathogenesis via myeloid and granulocyte cell lineage activation. In a 12-week Phase IIa study, mavrilimumab, a first-in-class inhibitor of the GM–CSF receptor-α demonstrated a sustained effect via this novel therapeutic pathway in RA.4 Objectives To evaluate the efficacy and safety of mavrilimumab in patients with moderate to severe, adult-onset RA in a 24-week, Phase IIb study. Methods Patients (18–80 yrs; inadequate response to ≥1 DMARDs; DAS28–CRP ≥3.2; ≥4 SJC) receiving MTX were randomized to receive 1 of 3 SC mavrilimumab dosages (150, 100, 30 mg every other week [eow]) or placebo (PBO) plus MTX (7.5–25.0 mg/week). Co-primary endpoints were change in DAS28–CRP (Day 1 to Week 12) and ACR20 response rate (Week 24). Safety and tolerability were measured through assessment of AEs and pulmonary parameters. Results were analyzed using the modified ITT population. Results 326 patients from Europe, South America, and South Africa (mean [SD] age, 51.8 [11.1] yrs; female, 86.5%; mean [SD] DAS28–CRP, 5.8 [0.9]; RF+/anti-CCP+, 81.9%) received mavrilimumab 150, 100 or 30 mg eow or PBO (N=79, 85, 81 and 81, respectively). At Week 12, a statistically significant difference in DAS28–CRP change from baseline (p 90% of patients entered a long-term, open-label extension study. Conclusions This Phase IIb study demonstrated the potential benefit of inhibiting macrophage activity via the GM–CSF receptor-α pathway on RA disease activity. The study met both co-primary endpoints with a clear dosage response. Mavrilimumb was well-tolerated over the 24-week study period. References Weinblatt ME, et al. N Engl J Med 1999;340:253–9. Lipsky PE, et al. N Engl J Med 2000;343:1594–602. Weinblatt ME, et al. Arthritis Rheum 2003;48:35–45, Burmester GR, et al. Ann Rheum Dis 2013;72:1445–52. Acknowledgements Funded: MedImmune. Editorial assistance: N Panagiotaki, QXV Communications, UK †Joint senior authors. Disclosure of Interest G. Burmester Grant/research support from: AbbVie, Pfizer, UCB, Roche, Consultant for: AbbVie, BMS, Novartis, MedImmune, MSD, Pfizer, UCB, Roche, Speakers bureau: AbbVie, BMS, Novartis, MSD, Pfizer, UCB, Roche, I. McInnes Grant/research support from: MedImmune (Research award to University of Glasgow), Consultant for: MedImmune, AstraZeneca, J. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Amgen, Genentech, Lilly, Pfizer, Consultant for: AbbVie, Amgen, Genentech, Lilly, Pfizer, BMS, Employee of: Corrona, P. Miranda Grant/research support from: MedImmune (to support protocol), M. Korkosz: None declared, J. Vencovsky: None declared, A. Rubbert-Roth Grant/research support from: Pfizer, Chugai, Consultant for: MSD, USB, Abbott, Pfizer, Roche, BMS, Chugai, Speakers bureau: Roche, Pfizer, UCB, E. Mysler Grant/research support from: Medimmune, Roche, BMS, Pfizer, M. Sleeman Shareholder of: AstraZeneca, Employee of: MedImmune, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, M. Albulescu Employee of: MedImmune, D. Close Shareholder of: AstraZeneca, Employee of: MedImmune, M. Weinblatt Grant/research support from: BMS, UCB, Crescendo Bioscience, Consultant for: MedImmune, AstraZeneca, Amgen, Abbvie, BMS, Crescendo Bioscience, Lilly, Pfizer, UCB, Roche

Background Among patients who have failed a prior TNF agent, there is little data to inform prescribing decisions for the next biologic. Objectives We sought to perform a head to head comparison of the effectiveness of tocilizumab (TCZ) versus abatacept (ABA) among RA patients with previous anti-TNF exposure using data from a multi-center observational registry within the United States (Corrona, LLC). Methods We identified RA patients between 4/2/2009 through 5/2/14 who had discontinued at least 1 anti-TNF and initiated either TCZ or ABA, with no prior use of either of these two drugs, were not in remission or low disease activity based on the Clinical Disease Activity Index (CDAI) at the time of initiation, and had follow-up at 6 months (TCZ=266; ABA=663). Propensity score (PS) matching (1:1 match) based on demographics, comorbid conditions and RA disease characeristics was utilized to control for imbalances between treatment groups stratified by the number of prior anti-TNF agents. This resulted in 266 matched (TCZ:ABA) pairs of which 45% had 1 and 55% ≥2 prior TNFs. Treatment response was measured at 6 months after initiation based on mean change in disease activity using the CDAI, and change in mHAQ. Secondary analyses included achievement of low disease activity (CDAI ≤10). For any patients who switched from ABA or TCZ to a new biologic, last observation carried forward (LOCF) prior to the switch was applied. Change in prednisone use was well as initiation or discontinuation of a nonbiologic disease modifying anti-rheumatic drug (DMARD) over the study period was also examined. Regression analysis was performed with the matched pairs as a random effect. Results There were 266 TCZ initiators matched to 266 ABA initiators. Most patients were female (74-75%) with a mean age of 57 years, mean disease duration of 10-11 years and mean CDAI of 28. There were no standardized differences >0.10 between the 2 groups for demographics, insurance, comorbidities, RA disease characteristics, disease activity, functional status, medication use, concomitant prednisone use, and number of prior biologics. There were no significant differences between the two groups in terms of the primary and secondary outcomes (Table). Additionally there were no significant differences between TCZ vs. ABA in terms of prednisone use (dose escalation [14.0% vs. 12.5%]) and dose reduction [18.9% vs. 18.6%]) and nonbiologic DMARD use (rates of initiation [11.3% vs. 14.3%] and discontinuation [13.1% vs. 15.0%]). Conclusions Both TCZ and ABA were associated with substantial improvements in disease activity at 6 months and had comparable effectiveness in this difficult to treat population of RA patents. Longer term outcomes will be needed in order to determine best strategies in TNF inadequate responder patients with RA in the US. Acknowledgements This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest L. Harrold Grant/research support from: Corrona, LLC., G. Reed Employee of: Corrona, LLC., D. Solomon Grant/research support from: Amgen, Lilly and Corrona, J. Curtis Grant/research support from: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie, Consultant for: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie, M. Liu Employee of: Corrona, LLC., J. Greenberg Shareholder of: Corrona, LLC., Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC., J. Kremer Shareholder of: Corrona, LLC., Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, LLC.

Background Macrophages are pivotal to the pathogenesis of rheumatoid arthritis (RA), and their inflammatory products drive many of the signs and symptoms of disease. Mavrilimumab inhibits macrophage activation and survival via blockade of granulocyte-macrophage colony-stimulating factor receptor-α (GM–CSFR-α) and has demonstrated sustained clinical benefit in patients with RA. 1 Objectives To examine time to onset of clinical response to mavrilimumab in the EARTH EXPLORER 1 study. Methods In a 24-week, Phase IIb study (NCT01706926), patients with adult-onset RA (18–80 years; Disease Activity Score 28 C-reactive protein [DAS28–CRP] >3.2; ≥4 swollen joints; inadequate response to ≥1 disease-modifying antirheumatic drugs [DMARDs]) receiving concomitant methotrexate were enrolled. Patients received mavrilimumab (150, 100, or 30 mg every other week [eow]) or placebo, administered subcutaneously with methotrexate (7.5–25.0 mg/week). Efficacy assessments included DAS28–CRP, American College of Rheumatology (ACR)20/50/70 responses, CRP, erythrocyte sedimentation rate (ESR), swollen joint count (SJC), tender joint count (TJC), and pain assessments. Results 326 patients with mean (SD) DAS28–CRP 5.8 (0.9) were randomized to mavrilimumab (150, 100, or 30 mg eow) or placebo (N=79, 85, 81, and 81, respectively). At Week 1 (first assessment), all mavrilimumab dosages demonstrated significant reductions from baseline in DAS28–CRP ( p p =0.003 to p Conclusions By targeting activated macrophages via inhibition of GM–CSFR-α, mavrilimumab substantially reduced patients9 RA disease activity early in their treatment, from first dose (Week 1) to final assessment for many patients, as evaluated by several clinical outcomes. References Burmester GR, et al. Ann Rheum Dis. 2013;72:1445–52. Acknowledgements Funded: MedImmune Ltd. Editorial assistance: N Panagiotaki, QXV Communications, UK Disclosure of Interest I. McInnes Grant/research support from: MedImmune (Research award to University of Glasgow), Consultant for: MedImmune, AstraZeneca, G. Burmester Grant/research support from: AbbVie, Pfizer, UCB, Roche, Consultant for: AbbVie, BMS, Novartis, MedImmune, MSD, Pfizer, UCB, Roche, Speakers bureau: AbbVie, BMS, Novartis, MSD, Pfizer, UCB, Roche, J. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Amgen, Genentech, Lilly, Pfizer, Consultant for: AbbVie, Amgen, Genentech, Lilly, Pfizer, BMS, Employee of: Corrona, P. Miranda Grant/research support from: MedImmune (to support protocol), M. Korkosz: None declared, J. Vencovsky: None declared, A. Rubbert-Roth Grant/research support from: Pfizer, Chugai, Consultant for: MSD, UCB, Abbott, Pfizer, Roche, BMS, Chugai, Speakers bureau: Roche, Pfizer, UCB, E. Mysler Grant/research support from: MedImmune, Roche, BMS, Pfizer, D. Close Shareholder of: AstraZeneca, Employee of: MedImmune, M. Sleeman Shareholder of: AstraZeneca, Employee of: MedImmune, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, M. Albulescu Employee of: MedImmune, M. Weinblatt Grant/research support from: BMS, UCB, Crescendo Bioscience, Consultant for: MedImmune, AstraZeneca, Amgen, Abbvie, BMS, Crescendo bioscience, Lilly, Pfizer, UCB, Roche

Background A treat-to-target (T2T) approach to the care of patients with rheumatoid arthritis (RA) has been advocated, which involves regular assessment of disease activity using validated metrics, frequent follow-up visits for patients with moderate to high disease activity, and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores. Objectives The goal of this abstract is to examine whether cluster randomization will result in comparable patients for a behavioral intervention trial designed to assess the impact of implementing a structured T2T approach vs routine care. Methods This trial cluster-randomized 31 rheumatology practices based on practice size from the Corrona network of private and academic rheumatology sites to either the T2T intervention (n=16) or usual care (n=15) between July 29, 2011, and July 30, 2013. RA patients with moderate or high disease activity, defined as Clinical Disease Activity Index (CDAI) >10, and no contraindication to T2T were enrolled by the practices and followed for 12 months. In the T2T group, medications were to be accelerated based on disease activity levels with visits occurring as frequently as monthly in those with active disease. Treatment acceleration was defined as a new initiation or increase to the dose or frequency of a prescribed biologic or non-biologic DMARD, or changing route of methotrexate from oral to subcutaneous. In contrast, the usual care subjects were seen at least every 3 months with medication changes per the treating provider. The co-primary endpoints were achievement of low disease activity, defined as CDAI of ≤10, and an assessment of feasibility of implementing T2T in rheumatology practices (e.g., rates of treatment acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity). Results There were 249 patients enrolled from the T2T practices and 289 from usual care practices. The two groups were similar in terms of mean age, gender, and race but not for ethnicity (Table). Patients were also similar in terms of education level, employment status, insurance type and clinical features (disease duration, rheumatoid factor seropositivity, tender joint count, swollen joint count, disease activity, and patient pain); however, functional status was different. Both groups had similar proportions of subjects receiving prednisone and methotrexate as well as similar dosing for those taking these medications. Study retention at 12 months (time window is 9 to 15 months after enrollment) was 83% of the usual care subjects and 79% of the T2T subjects. Conclusions This cluster-randomized approach to implementing a behavioral intervention successfully identified similar patients for the two treatment arms for a study of T2T. Acknowledgements The Corrona T2T study is sponsored by Corrona, LLC, with support from a development and subscription agreement/contract with Genentech and additional support from AbbVie. Disclosure of Interest L. Harrold Employee of: University of Massachusetts Medical School, G. Reed Employee of: Corrona, LLC, J. T. Harrington Shareholder of: AbbVie, Amgen, BMS, GlaxoSmithKline, Johnson & Johnson, Pfizer and Roche, Consultant for: AbbVie, Amgen, Antares, AstraZeneca, Celgene, Horizon, Iroko, Pfizer, Roche and UCB, Speakers bureau: AbbVie, Amgen, Pfizer, Roche and UCB, C. Barr Employee of: Corrona, LLC, K. Saunders Employee of: Corrona, LLC, A. Gibofsky: None declared, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC, A. John Employee of: Genentech, Inc, J. Devenport Employee of: Genentech, Inc, J. Kremer Shareholder of: Corrona, LLC, Grant/research support from: Genentech, Inc, Consultant for: Genentech, Inc, Employee of: Corrona, LLC

Background The spondyloarthritides (SpA), such as ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are a group of rheumatologic diseases with shared genetic, pathophysiologic and clinical elements now known to be more prevalent than rheumatoid arthritis (RA). Disease characteristics and outcomes are less well studied than RA. Corrona has investigated over 4000 pts with PsA since 2003. The Corrona SpA registry was launched on 3/21/2013 to include all SpA including AS and other forms of axial and peripheral SpA and more deeply investigate PsA. Enrollment and 6 monthly follow-up data is ongoing. Objectives The purpose of this analysis is to provide a profile of the demographic and clinical characteristics of the initial patients in this US registry population. The registry will be a rich resource for outcomes research as follow-up time is accrued. Methods Thus far, 35 of the Corrona investigative sites have been trained to enroll, representing a diverse geographic and private/academic mix. Data at time of enrollment into the registry for a subset of 1411 patients enrolled between 3/21/2013 and 10/17/2014 are presented in this abstract. Data are gathered on demographics, clinical characteristics, referral source, disease activity, function, quality of life, work productivity, comorbid conditions, previous and current treatments, laboratory tests, and imaging. Results Sixty-nine percent (969/1411) of the patients enrolled in the PsA/SpA registry since 3/13 have a diagnosis of PsA. Median age among all subjects is 53 years. Forty-nine percent of all subjects are female (52% in PsA and 45% in SpA patients) and 51% are obese (BMI >30, as calculated by physician reported height and weight). One-tenth of the subjects have a history of iritis/uveitis, 6% have a history of IBD, but Conclusions The registry has enrolled a growing number of patients with all forms of SpA. Biologic monotherapy use is common among patients with a diagnosis of PsA or SpA. Detailed data on disease characteristics, natural history, treatment and safety outcomes will be presented. Acknowledgements This study is sponsored by Corrona, LLC. Initial funding for the Corrona SpA registry was provided by AbbVie. In the last two years, AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB have supported Corrona LLC. through contracted subscriptions. Disclosure of Interest P. Mease Grant/research support from: Celgene, Merck, Novartis, Abbvie, Amgen, BiogenIdec, BMS, Genentech, Janssen, Lilly, Pfizer, UCB, Consultant for: Celgene, Merck, Novartis, Abbvie, Amgen, BiogenIdec, BMS, Crescendo, Genentech, Janssen, Lilly, Merck, Pfizer, UCB, Vertex, Speakers bureau: Abbvie, Amgen, BiogenIdec, BMS, Crescendo, Genentech, Janssen, Lilly, Pfizer, UCB, C. Etzel Employee of: Corrona, LLC., J. Kremer Shareholder of: Corrona, LLC., Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, LLC., S. Deveikis Employee of: Corrona, LLC., Y. Li: None declared, J. O9Connor Employee of: Corrona, LLC., A. Kavanaugh Grant/research support from: AbbVie, Amgen, Janssen, L.P., UCB, E. Ruderman Consultant for: Corrona, LLC., J. Curtis Grant/research support from: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie, Consultant for: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie, C. Ritchlin Grant/research support from: Amgen, Janssen, and UCB, Consultant for: Abbvie, Amgen, Janssen, Regeneron, and UCB, D. van der Heijde Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen, Merk, Novartis, Novo-Norodisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Shering-Plough, UCB, Vertex, D. Solomon Consultant for: Amgen, Lilly and Corrona, J. Greenberg Shareholder of: Corrona, LLC., Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC.

Background Dactylitis and enthesitis are common disabling manifestations of psoriatic arthritis (PsA) that have been reported according to multiple methods of assessment. Several measures of dactylitis and enthesitis were utilized in the phase 3 FUTURE 2 secukinumab study (NCT01752634)1 and are reported here. Objectives To evaluate the effects of subcutaneous (s.c.) secukinumab on dactylitis and enthesitis through Week (Wk) 24 in FUTURE 2. Methods 397 adults with active PsA were randomized to s.c. secukinumab (300, 150 or 75 mg) or PBO at baseline, Wk 1, 2, 3, 4 and then every 4 wks thereafter. The primary endpoint was ACR20 response at Wk 24. The proportions of pts with resolution of dactylitis and enthesitis at Wk 24 (of those with these conditions at baseline) were secondary endpoints. Additional measures utilized in this study were dactylitis counts, Leeds Dactylitis Index (LDI), and Leeds Enthesitis Index (LEI). Results At baseline, 138 pts (35%) had dactylitis and 253 pts (64%) had enthesitis. At Wk 24, comparing secukinumab 300 mg and 150 mg vs PBO respectively, 56.5% and 50.0% vs 14.8% of pts had complete resolution of dactylitis, and 48.2% and 42.2% vs 21.5% had complete resolution of enthesitis. Corresponding reductions in LDI, LEI and mean dactylitis counts were observed (Table). Conclusions Across multiple methods of assessment, secukinumab 300 and 150 mg s.c. reduced the number of dactylitic digits and enthesitis sites in pts with PsA and was associated with a greater proportion of patients achieving complete resolution of dactylitis/enthesitis compared with PBO. References McInnes IB, et al. Presented at ACR 2014; L1 Acknowledgements Medical writing support was provided by Rachel Mason at Seren Communications (Tytherington, UK), and was funded by Novartis. Disclosure of Interest B. Kirkham Grant/research support from: AbbVie and UCB, Consultant for: Novartis, AbbVie, BMS, Lilly, and MSD, Speakers bureau: BMS, MSD, and UCB, I. McInnes Consultant for: Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene, and Lilly, P. Mease Grant/research support from: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Consultant for: AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, and Vertex, Speakers bureau: AbbVie, Amgen, Biogen Idec, BMS, Crescendo, Janssen, Lilly, Pfizer, and UCB, J. Kremer Grant/research support from: Novartis, Lilly, BMS, Janssen, Pfizer, and UCB, S. Kandala Employee of: Novartis, L. Pricop Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis

Background Active RA significantly impairs patients9 health-related quality of life (HRQOL) and physical function. Granulocyte-macrophage colony-stimulating factor (GM–CSF) plays a key role in macrophage activation and RA pathogenesis, including inflammatory and arthritic pain development. A Phase IIa study in active RA demonstrated that mavrilimumab produced clinically meaningful improvements across a variety of PROs. 1 Objectives To assess mavrilimumab9s effects on HRQOL and physical function in RA patients in a 24-week Phase IIb study. Methods In an RCT (NCT01706926), we evaluated the efficacy and safety of 3 subcutaneous mavrilimumab dosages (150 mg, 100 mg, and, 30 mg every other week [eow]) vs. placebo over 24 weeks. Patients with adult-onset RA (18–80 years; DAS28–CRP ≥3.2; ≥4 swollen joints; inadequate response to ≥1 DMARDs) receiving concomitant methotrexate were enrolled. Co-primary endpoints were changes in DAS28–CRP score (Day 1 to Week 12) and ACR20 response (Week 24). PRO endpoints included changes from baseline and percentage responders in patient assessments of pain, HRQOL (SF-36 Mental Component Summary [MCS] and Physical Component Summary [PCS] scores), physical function (HAQ DI), and fatigue (FACIT-F). Patients could enter a long-term, open-label extension study at Week 12 (not reported). Results 326 patients (mean [SD] age, 51.8 [11.1] years; female, 86.5%) with a mean (SD) DAS28–CRP of 5.8 (0.9) were randomized to mavrilimumab 150, 100, or 30 mg eow, or placebo (N=79, 85, 81, and 81, respectively). Both co-primary endpoints (DAS28–CRP at Week 12; ACR20 at Week 24) were met at all mavrilimumab dosages. At Weeks 12 and 24, all mavrilimumab treatment groups exhibited improvements in pain, SF-36 PCS, SF-36 MCS, HAQ DI and FACIT-F vs. placebo, with >50% of patients receiving mavrilimumab 150 mg eow achieving a clinically meaningful response. At this dosage, significant improvements were demonstrated across all PRO endpoints ( p =0.019 to p p =0.007, Week 24; p =0.187). Statistically significant improvements in pain were demonstrated for mavrilimumab beginning at Week 1. Of patients receiving mavrilimumab 150, 100, and 30 mg eow with a pain response at Week 12, 66.7% (28/42), 69.2% (27/39), and 72.2% (26/36) maintained responses at Week 24. HAQ DI responses at Week 12 were maintained at Week 24 in 78.8% (41/52), 84.0% (42/50), and 75.0% (33/44) of patients (mavrilimumab 150, 100, and 30 mg eow, respectively). Conclusions Targeting activated macrophages through inhibition of the GM–CSFR-α pathway with mavrilimumab, especially at a dosage of 150 mg eow, substantially and rapidly reduced RA disease activity. In turn, patients receiving mavrilimumab achieved significant, clinically meaningful, and sustained improvements in PROs that reflected the patients9 pain, HRQOL, physical function, and fatigue. The majority of mavrilimumab patients with improvement in pain and physical function at Week 12 sustained these improvements through Week 24 References Burmester GR, et al. Ann Rheum Dis. 2013;72:1445–52. Acknowledgements Funded: MedImmune Ltd. Editorial assistance: N Panagiotaki, QXV Communications, UK Disclosure of Interest J. Kremer Shareholder of: Corrona, Grant/research support from: AbbVie, Amgen, Genentech, Lilly, Pfizer, Consultant for: AbbVie, Amgen, Genentech, Lilly, Pfizer, BMS, Employee of: Corrona, G. Burmester Grant/research support from: AbbVie, Pfizer, UCB, Roche, Consultant for: AbbVie, BMS, Novartis, MedImmune, MSD, Pfizer, UCB, Roche, Speakers bureau: AbbVie, BMS, Novartis, MSD, Pfizer, UCB, Roche, M. Weinblatt Grant/research support from: BMS, UCB, Crescendo Bioscience, Consultant for: MedImmune, AstraZeneca, Amgen, Abbvie, BMS, Crescendo bioscience, Lilly, Pfizer, UCB, Roche, A. Williams Shareholder of: AstraZeneca, Employee of: MedImmune, N. Karlsson Shareholder of: AstraZeneca, Employee of: AstraZeneca, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, M. Albulescu Employee of: MedImmune, D. Close Shareholder of: AstraZeneca, Employee of: MedImmune

Background In ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in pts with active RA naive to biologic DMARDs (bDMARDs). 1,2 Objectives To report patient-reported outcomes (PRO) from a ph 3 study of bari in pts with active RA on 1 or 2 conventional DMARDs (cDMARDs) and an inadequate response or intolerance to ≥1 TNF inhibitors. Methods Pts were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. PROs are listed in the table. Analyses included ANCOVA, logistic regression, and nonparametric methods and compared bari 2 or 4 mg vs. PBO. Results 527 pts were randomized. Assessment of PROs at baseline revealed severe impairment of physical function (HAQ-DI: 1.7-1.8) and QoL. Bari 2 and 4 mg resulted in statistically significant improvements from baseline vs. PBO in most PROs at 24 wks (Table). Conclusions In this ph 3 study of pts with active RA on cDMARDs and an inadequate response to bDMARDs, bari was associated with significant improvement in most PROs through 24 wks compared to PBO. References Keystone et al. Ann Rheum Dis 2015;74:333-340. Tanaka et al. Arthritis Rheum 2013;65(S10):S765. Disclosure of Interest J. Smolen Grant/research support from: Abbvie, Janssen, MSD, Pfizer, Roche, UCB, Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Lilly, Pfizer and UCB, Employee of: Part time employment with Corrona, C. Gaich Employee of: Eli Lilly and Company, A. DeLozier Employee of: Eli Lilly and Company, D. Schlichting Employee of: Eli Lilly and Company, L. Xie Employee of: Eli Lilly and Company, M. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly and Company, Galapagos, Pfizer, and Vertex

Background There are limited data describing patterns of discontinuations of biologic therapy for rheumatoid arthritis (RA) in real-world settings. Such information could help clinicians understand real-life treatment patterns and serve as a marker of effectiveness to help inform decisions. Objectives To describe the patterns and reasons for discontinuation of biologics within 1 year after initiation of treatment in the Corrona C omparative E ffectiveness R egistry to study T herapies for A rthritis and I nflammatory Co n ditions (CERTAIN) study. Methods CERTAIN is a prospective, nonrandomized, comparative effectiveness cohort study nested within the US Corrona registry and included adult patients with RA who have at least moderate disease activity (Clinical Disease Activity Index >10) and are starting or switching biologics.1 This descriptive study included all patients who initiated a biologic in CERTAIN and discontinued the biologic or switched to a different biologic before their 12-month follow-up visit. Reasons for discontinuation were evaluated based on physician's report and categorized as efficacy reasons, safety reasons, both and other reasons unrelated to safety or efficacy. Results A total of 2361 patients enrolled in CERTAIN contributed 2809 all-biologic initiations to this analysis, which included 1670 anti–tumor necrosis factor agents (aTNFs) and 1139 non-aTNFs. At the time of the analysis, data were available for 1174 biologic initiations from patients who completed CERTAIN, with 344 initiations still in follow up. Baseline characteristics at the time of biologic initiation were as follows: median age, 57 years; female, 79%; median RA duration, 5 years; and rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (ACCP) antibody seropositivity, 68%. After excluding those initiations still in follow up, 909 of 2465 initiations (37%) resulted in a discontinuation within 12 months, with reasons for discontinuation available for 635 patients (70%; [Table][1]). A higher proportion of biologics were discontinued by the 3-month follow-up visit due to safety reasons, while a higher proportion of initiations were discontinued after the 3-month follow-up visit due to efficacy reasons ( P

Background There is limited evidence comparing the types of patients initiated on different classes of biologic medications, and this information is critical when conducting comparative observational research among patients with RA. Objectives This study compared baseline characteristics of biologic naive rheumatoid arthritis (RA) patients initiating abatacept as compared to tumor necrosis factor inhibitors (TNFi), and other non-TNFi biologics and small molecules (non-TNFi/sm). Methods Biologics naive RA patients who initiated abatacept, TNFi and other non-TNFi/sm from 12/2005 to 8/2014 within the Corrona registry were identified. Initiation of first biologic or small molecule (first line use) was defined as first indication of biologic use for a patient that was previously naive to any biologic or small molecule prior to initiation of study drug. Baseline characteristics at time of biologic initiation were captured including demographics, comorbid conditions, and RA disease characteristics including age at disease onset, disease duration, prior and concomitant medication use, and disease activity. Descriptive statistics were performed including t-tests and Chi-square tests comparing abatacept initiators to TNFi and other non-TNFi/sm initiators. Results Among the 4,232 first time biologic users, 364 (9%) initiated abatacept, 3689 (87%) TNFi, and 179 (4%) other non-TNFi/sm. Abatacept initiators as compared to TNFi initiators were more likely to be older (62.8 years (yrs) vs 56 yrs; P Conclusions In a real world national cohort of biologic naive RA patients, those initiated on abatacept had a different profile than those initiating TNFi and non-TNFi/sm. Specifically abatacept users were older at the time of biologic/small molecule initiation, had onset of RA at an older age, and were more frequently using concomitant non-MTX nbDMARDS. Additionally abatacept initiators had a longer disease duration as compared to TNFi initiators. These findings are consistent with data from real-world registries in the US and Europe. Acknowledgements This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest L. Harrold Grant/research support from: Corrona, LLC., K. Gandhi Employee of: Bristol-Myers Squibb, C. Etzel Employee of: Corrona, LLC., A. Nadkarni Employee of: Bristol-Myers Squibb, K. Saunders Employee of: Corrona, LLC., S. Kelly Employee of: Bristol-Myers Squibb, J. Kremer Shareholder of: Corrona, LLC., Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, LLC.

Background The goal of treatment for patients with rheumatoid arthritis (RA) is to reduce and maintain disease activity to low disease activity (LDA) or remission. However, there is little information available regarding the likelihood of sustained response once LDA/remission has been achieved, as well as what effect rituximab retreatment has on sustained response. Objectives The objective of this analysis was to examine factors associated with sustained response in patients with RA who were treated with rituximab in the US Corrona registry. Methods Patients with RA who initiated rituximab while in moderate or high disease activity (Clinical Disease Activity Index [CDAI] >10) and who subsequently achieved LDA/remission (CDAI ≤10) within 12 months of their last rituximab infusion were identified from the Corrona registry and included in this analysis. Patients were followed until they experienced loss of response (defined as CDAI >10), initiated another biologic or small molecule or exited from the registry. Covariates identified at the index date (when LDA/remission was achieved) included demographic and clinical characteristics, prior medications and concomitant steroid and conventional synthetic disease modifying anti-rheumatic drug (csDMARD) use. Covariates ascertained at the time of rituximab initiation included functional status, baseline CDAI, patient-reported pain and time to achieve LDA/remission. Time-varying covariates of interest included the rate of rituximab retreatment, as well as number of prednisone dose increases and initiations of csDMARDs over time. Survival analyses and Cox proportional hazard regression models were performed to estimate the overall likelihood of sustained response following rituximab treatment and associations between covariates of interest and sustained response. The primary estimate of interest was the hazard ratio or loss of response for rituximab retreatment. Results Of the 1184 patients who initiated rituximab and had ≥1 follow-up appointment in Corrona, a total of 306 patients subsequently achieved CDAI LDA/remission within 12 months of the last infusion. Most patients were female (75.8%) with a median (IQR) age of 60 (52-68) years and received prior csDMARDs (median [IQR], 2 [1-3]); over 84% of patients had received ≥2 prior biologics. The median (IQR) time to achieve LDA/remission was 5 (3-10) months. Of the 306 patients included in the final study population, 104 patients received rituximab retreatments at a median (IQR) rate of 1.01 (0.71-1.36) retreatments per year. Twelve months following achievement of LDA/remission, 49.2% of patients maintained this response. In unadjusted and adjusted models (Table), rituximab retreatment was associated with a significantly reduced likelihood of loss of response (45% reduction), while prednisone dose increases ≥7.5 mg and prior non-anti–tumor necrosis factor agent use increased it. Conclusions Retreatment with rituximab was associated with a significantly greater sustained response in patients who have achieved LDA/remission on the medication, while low to moderate prednisone increases and prior non-anti–tumor necrosis factor agent use reduced it. Acknowledgements This study is sponsored by Corrona, LLC. Disclosure of Interest L. Harrold Grant/research support from: Corrona, LLC, A. John Employee of: Genentech, Inc, G. Reed Employee of: Corrona, LLC, C. Karki Employee of: Corrona, LLC, R. Magner Employee of: University of Massachusetts Medical School, J. Kremer Shareholder of: Corrona, LLC, Grant/research support from: Genentech, Inc, Consultant for: Genentech, Inc, Employee of: Corrona, LLC, A. Shewade Employee of: Genentech, Inc, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC

Background Baricitinib, a novel oral JAK1/2-inhibitor, was evaluated in a Phase 2b study in patients with moderate-to-severe RA. The primary ACR20 12-week-endpoint was met, and maintained through 24 weeks. 1 Objective To evaluate changes in serum LDL, HDL, and total cholesterol over 24 weeks of baricitinib treatment compared with placebo. Methods Patients were randomised to QD dosing with placebo (n = 98) or 1, 2, 4, or 8 mg of baricitinib with ˜50 patients per treatment arm. Serum lipids were determined at screening, baseline and at Weeks 2, 4, 8, 12, 14, 16, 20, 24, and particle size and number were determined by Nuclear Magnetic Resonance (NMR) at baseline, Weeks 12/24. Results Baricitinib treatment resulted in dose- and time-dependent increase relative to placebo in LDL, HDL and total cholesterol detectable by Week-2. The mean percent increase in total cholesterol in the combined baricitinib arms was 9.5% (p Conclusions The increase in LDL-cholesterol with baricitinib treatment is attributed to a shift towards larger particles rather than an overall increase in LDL-particle number at Week-12 and persisting through 24 weeks, while changes observed in HDL-cholesterol were associated with an increase in total number of HDL-particles. 1 Reference Genovese MC, Keystone E, Taylor P, et al . Arthritis Rheum 2012; 64 :2487.

Treatment with baricitinib (bari), an oral inhibitor of JAK1/JAK2, demonstrated improvements in signs and symptoms of RA through 52 wks in a Phase 2b study, 1 and also in dose- and time-dependent changes in serum lipids, LDL particle size and HDL and VLDL particle numbers. 2 Increases in HDL, but not LDL cholesterol, correlated with decreases in CRP at Wk 12. Changes in serum cholesterol, in apolipoprotein content of LDL, VLDL, and HDL particles were evaluated. Patients (pts) with RA were randomised to QD doses of placebo (PBO) (n = 98) or bari 1 mg (n = 49), 2 mg (n = 52), 4 mg (n = 52), or 8 mg (n = 50) for 12 wks. Pts assigned to 2-, 4-, or 8-mg bari continued blinded treatment for an additional 12 wks. Serum samples were collected through 52 wks for conventional lipid determinations (total cholesterol, LDL, HDL, and triglycerides). Apolipoprotein content was assessed at Wks 4 and 12 for PBO, 4-, and 8-mg bari groups. Pts treated with bari through 52 wks maintained a stable cholesterol and triglyceride profile with no further changes beyond Wks 12 and 24. Increases in apolipoprotein A-I, apolipoprotein B, and total apolipoprotein CIII were observed with 4- and 8-mg bari with no increase in LDL-associated apolipoprotein CIII. Bari treatment also demonstrated a significant reduction in HDL-associated SAA at the 4- and 8-mg doses compared to PBO while a significant reduction in Lp (a) was observed only in the 8-mg bari group (all p In addition to increases in serum cholesterol and lipoprotein particle number (HDL and VLDL) and size (LDL), there were changes in apolipoprotein content of these particles in pts treated with bari. The increase in HDL cholesterol with bari treatment correlated with an improvement in DAS28-CRP. References Taylor P, Genovese MC, Keystone E, et al . Ann Rheum Dis 2013; 72 :A65–A66. Kremer J, Genovese M, Keystone E, et al . Baricitinib effects on serum cholesterol and circulating lipid particles in a Phase 2b study in patients with rheumatoid arthritis [abstract]. Ann Rheum Dis 2013; 72 (Suppl 3):241.

Background Since the introduction of biological disease-modifying antirheumatic drugs (bDMARDs), treatment of rheumatoid arthritis (RA) has changed. Remission is a feasible treatment target for many patients. As a result, there is an increased interest in appropriate treatment strategies after achieving disease control, such as bDMARD discontinuation while in remission. However, its adoption in typical clinical practice has not been widely studied. Objectives We conducted a cross-national longitudinal observational study of bDMARD to describe the proportions of RA patients in remission who discontinued these agents, and to assess the potential predictors of discontinuation. Methods We utilized data from US CORRONA and Japanese NinJa registries. Patients who used bDMARDs on at least two consecutive visits and experienced remission defined by the Clinical Disease Activity Index (CDAI) ≤2.8 at least once were included. The outcome of interest was bDMARD discontinuation while in remission. Discontinuation was described with the Kaplan-Meier method as well as the cumulative incidence function method to account for competing risk events, i.e., loss of remission and switch to another bDMARD. The baseline predictors of discontinuation were assessed in the Cox regression models. Results The numbers of eligible patients were 4,382 in the CORRONA (34.4% of 12,721 bDMARD users among 22,684 total patients) and 413 in the NinJa (18.4% of 2,243 bDMARD users among 11,205 total patients). In the Kaplan-Meier analysis, discontinuation at 5 years among patient who remained in remission was observed in 28.1% in CORRONA and 22.7% in NinJa (p=0.002, log-rank test; Figure Panels A and B). In the cumulative incidence function analysis, the proportions of discontinuation at 5 years among patients who were initially in remission were 11.3% in CORRONA and 12.2% in NinJa (Figure Panels C and D). It was not significantly different (p=0.782, Gray's test) due to greater attrition to loss of remission in CORRONA (83.9%) compared to NinJa (77.2%). In Cox regression, reduced CDAI (hazard ratio for 1 point decrease: 1.49 [1.37,1.61] in CORRONA and 1.79 [1.33,2.38] in NinJa) and use of glucocorticoids (HR: 1.59 [1.19,2.12] in CORRONA and 2.11 [1.03, 4.31] in NinJa) predicted higher rates of bDMARD discontinuation in both cohorts. The overall R2 for the full models including sex, race, age, RA duration, biologic class, methotrexate use, duration of bDMARD use, and index year, was 0.074 in CORRONA and 0.168 in NinJa. ![Figure][1] Conclusions We found a slightly higher rate of bDMARD discontinuation in CORRONA than NinJa. Possible contributors to the discrepancy may include health care system differences (e.g. out of pocket cost) as well as cultural differences (e.g. patient preference vs doctor recommendation). While several variables were associated with more frequent discontinuation, they did not provide robust explanation of the variability in practice. Acknowledgements We would like to thank all CORRONA and NinJa contributors (patients, clinicians, and investigators) for maintaining such valuable sources of information. The CORRONA RA registry has been supported through contracted subscriptions in the last two years by Abbvie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Eli Lilly, Novartis, Pfizer, Vertex and UCB. All non-pharmaceutically-initiated CORRONA research activities are conducted entirely independent of any pharmaceutical input. NinJa was supported in part by a Health and Labor Sciences Research Grant from the Ministry of Health, Labor, and Welfare of Japan. Disclosure of Interest : K. Yoshida Paid instructor for: Abbott Japan, H. Radner: None declared, M. Mjaavatten: None declared, J. Greenberg Shareholder of: CORRONA, Consultant for: AstraZeneca, Pfizer, Employee of: CORRONA, A. Kavanaugh Grant/research support: Abbott, Janssen, Amgen, BMS, Roche, UCBM, M. Kishimoto Speakers bureau: Santen, Mitsubishi-Tanabe, Pfizer, Abbott Japan, K. Matsui: None declared, M. Okada Speakers bureau: Santen, Mitsubishi-Tanabe, Pfizer, Abbott Japan, G. Reed Employee of: CORRONA, Y. Saeki Grant/research support: Tanabe-Mitsubishi, Chugai, Janssen, Nippon-Kayaku, Nichi-Iko, S. Tohma Grant/research support: Pfizer Japan, Eisai, Chugai, J. Kremer Shareholder of: CORRONA, Grant/research support: Abbott, Amgen, BMS, Genetech, Novo- Nordisk, Pfizer, Novartis, Eli Lilly, Employee of: CORRONA, D. Solomon Grant/research support: Eli Lilly, Amgen, CORRONA, Consultant for: Pfizer, Novartis, Eli Lilly DOI 10.1136/annrheumdis-2014-eular.1367 [1]: pending:yes