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Dose escalation of infliximab in both primary and secondary nonresponders is widely reported; however, the usefulness of dose escalation has been disputed. The objective of this analysis is to evaluate trends in clinical efficacy following multiple infliximab dose escalations in patients with rheumatoid arthritis (RA). Patients enrolled in a US RA registry were included if they initiated infliximab at 3 mg/kg every 8 weeks, received ≥ 1 infliximab dose escalation within 12 months of initiation, and had ≥ 1 visit following dose escalation. Trends in mean Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores from visits following dose escalations were evaluated. In patients who received 2 or 3 dose escalations, the initial (1 or 2) dose escalations resulted in reduced mean CDAI scores, but subsequent escalations did not further reduce disease activity. In patients who received ≥ 4 dose escalations, mean CDAI scores did not further reduce disease activity over time. Mean HAQ scores were stable over time in patients who received 2 or 3 dose escalations. In patients who received ≥ 4 dose escalations, mean HAQ scores decreased following 1 dose escalation but progressively increased following subsequent dose escalations. Initial dose escalations (from 3 mg/kg to the equivalent of approximately 5 to 7 mg/kg) may be useful in controlling disease activity; however, there may be diminishing clinical benefit of further escalations, which can also increase the potential risk for infection and increase incremental drug costs. • Initial infliximab dose escalations (1 to 2) may be useful in lowering disease activity in patients with rheumatoid arthritis. • There does not appear to be a clinical benefit in infliximab dose escalations above the equivalent of 5 to 7 mg/kg.

Objective To assess the feasibility and efficacy of implementing a treat‐to‐target approach versus usual care in a US‐based cohort of rheumatoid arthritis patients. Methods In this behavioral intervention trial, rheumatology practices were cluster‐randomized to provide treat‐to‐target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score >10) were followed for 12 months. Both treat‐to‐target and usual care patients were seen every 3 months. Treat‐to‐target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score >10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score >10, and achievement of low disease activity (LDA; CDAI score ≤10) by an intent‐to‐treat analysis. Results A total of 14 practice sites per study arm were included (246 patients receiving treat‐to‐target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat‐to‐target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat‐to‐target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat‐to‐target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration. Conclusion This study is the first to examine the feasibility and efficacy of a treat‐to‐target approach in typical US rheumatology practice. Treat‐to‐target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified.

Objective To assess whether the time between the last rituximab infusion and initiation of a different biologic agent influenced infection risk in patients with rheumatoid arthritis (RA). Methods Patients with RA who newly initiated rituximab within the Consortium of Rheumatology Researchers of North America registry were included if they switched to a nonrituximab biologic agent and had ≥1 followup visit within 12 months of switching. Patients were categorized by duration of time between their last rituximab infusion and initiation of a subsequent biologic agent (≤5 months, 6–11 months, and ≥12 months). The primary outcome was time to first infectious event. Adjusted Cox regression models estimated the association between time to starting a subsequent biologic agent and infection. Results A total of 44 overall infections (7 serious, 37 nonserious) were reported during the 12-month followup in the 215 patients included in this analysis (104 switched at ≤5 months, 67 at 6–11 months, and 44 at ≥12 months). Median (interquartile range) time to infection was 4 (2–5) months. Infection rates per patient-year in the ≤5-month, 6–11-month, and ≥12-month groups were 0.34 (95% confidence interval [95% CI] 0.22–0.52), 0.30 (95% CI 0.17–0.52), and 0.41 (95% CI 0.22–0.77), respectively. After adjustment, time to switch to a subsequent biologic agent was not associated with infection, which remained unchanged when number and rate of rituximab retreatments were included in the models. Conclusion In this real-world cohort of patients with RA, infection rates ranged from 0.30 to 0.41 per patient-year, with no significant difference in the rate between patients who initiated a subsequent biologic agent earlier versus later after rituximab treatment.

Objective.To characterize the real-world effectiveness of rituximab (RTX) in patients with rheumatoid arthritis.Methods.Clinical effectiveness at 12 months was assessed in patients who were prescribed RTX based on the Clinical Disease Activity Index (CDAI). Change in CDAI was calculated (CDAI at 12 mos minus at initiation). Achievement of remission or low disease activity (LDA; CDAI ≤ 10) among those with moderate/high disease activity at the time of RTX initiation was compared based on prior anti-tumor necrosis factor agent (anti-TNF) use (1 vs ≥ 2) using logistic regression models.Results.Patients (n = 265) were followed for 12 months with a mean change in CDAI of −8.1 (95% CI −9.8 – −6.4). Of the 218 patients with moderate/high disease activity at baseline, patients with 1 prior anti-TNF (baseline CDAI 25.0) demonstrated a mean change in CDAI of −10.1 (95% CI −13.2 – −7.0); patients with ≥ 2 prior anti-TNF (baseline CDAI 30.0) demonstrated a mean change of −10.5 (95% CI −12.9 – −8.0). The unadjusted OR for achieving LDA/remission in patients with moderate/high disease activity at baseline exposed to ≥ 2 versus 1 prior anti-TNF was 0.40 (95% CI 0.22–0.73), which was robust to 4 different adjusted models (OR range 0.38–0.44).Conclusion.A good clinical response was observed in all patients; however, patients previously treated with 1 anti-TNF, who had lower baseline CDAI and a greater opportunity for clinical improvement compared with patients previously treated with ≥ 2 anti-TNF, were more likely to achieve LDA/remission.

Background Extended observations in clinical trials have not demonstrated an increased risk of serious infection events (SIE) in patients with rheumatoid arthritis (RA) treated with rituximab.1 However, continuous surveillance using large-scale observational data is of importance. Objectives To evaluate the rate of SIEs among patients with RA who received only an initial rituximab infusion vs those retreated with ≥1 rituximab infusion during the first year of therapy, and also to describe characteristics of rituximab-treated patients who experienced an SIE vs those who did not. Methods Patients with RA enrolled in the Corrona registry and treated with rituximab were followed until their most recent Corrona registry visit, first SIE, switch to another biologic or targeted synthetic disease-modifying antirheumatic drug, or 12 months after the most recent infusion with no further retreatment – whichever occurred first. The rate of SIEs was estimated in the overall population as well as in patients retreated with ≥1 infusion every 12 months after rituximab initiation and in those who did not receive a repeat infusion in the first 12 months. Patient characteristics were compared between those who experienced an SIE and those who did not. Results A total of 1361 patients with 1821 patient-years (PY) of follow-up were included; there were 59 SIEs for a rate of 3.24 SIE/100 PYs. 637 patients (46.8%) received ≥1 rituximab retreatment during the first 12 months and 724 (53.2%) received only the initial infusion. In the retreatment population there were 40 SIEs per 1312.8 PY for a rate (95% CI) of 3.05/100 PY (2.18–4.15), and in the no retreatment population there were 19 SIEs per 508.71 PY for a rate (95% CI) of 3.73/100 PY (2.25–5.83). The Kaplan-Meier curve depicting the occurrence of SIEs in the 2 cohorts during the first year of follow-up is shown (Figure). In the 59 patients (4.3%) who experienced an SIE, the mean (SD) number of rituximab infusions was 1.88 (1.18), compared with 2.07 (1.70) in the 1302 patients (95.7%) who did not experience an SIE. Patients who experienced an SIE vs those who did not were older (mean age [SD]: 62.9 [9.9] vs 58.1 [12.55] years), had longer disease duration (19.1 [13.1] vs 13.6 [10.4] years), were more frequently diabetic (16.9% vs 8.3%) and more frequently had cardiovascular disease (25.4% vs 12.8%), prior history of SIEs (18.6% vs 5.8%) and pulmonary disease (10.2% vs 4.8%). There were no differences in other clinical, demographic and medication history characteristics; steroid therapy was similar between the groups. Conclusions Retreatment with rituximab infusions was not associated with a higher rate of SIEs in this study. Patients who experienced an SIE had a higher prevalence of risk factors for infections. References Van Vollenhoven RF et al. J Rheumatol. 2015;42:1791–6. Acknowledgements This study is sponsored by Corrona, LLC. Corrona, LLC has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, BMS, Crescendo, Eli Lilly, Genentech, GSK, Horizon Pharma USA, Janssen, Momenta Pharmaceuticals, Novartis, Pfizer, Roche and UCB. Disclosure of Interest D. Pappas Grant/research support from: AbbVie, Consultant for: AbbVie, Employee of: Corrona, LLC, G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, S. Zlotnick Employee of: Genentech, Inc., J. Best Employee of: Genentech, Inc., R. Magner: None declared, G. Persuitte Employee of: Corrona, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: Genentech; Janssen; Novartis; Pfizer; Eli Lilly, Employee of: Corrona, LLC

Introduction Patients with active rheumatoid arthritis (RA) despite anti–tumor necrosis factor(anti-TNF)agent treatment can switch to either a subsequent anti-TNF agent or a biologic with an alternative mechanism of action, such as rituximab; however, there are limited data available to help physicians decide between these 2 strategies. The objective of this analysis was to examine the effectiveness and safety of rituximab versus a subsequent anti-TNF agent in anti-TNF–experienced patients with RA using clinical practice data from the Corrona registry. Methods Rituximab-naive patients from the Corrona registry with prior exposure to ≥1 anti-TNF agent who initiated rituximab or anti-TNF agents (2/28/2006-10/31/2012) were included. Two cohorts were analyzed: the trimmed population (excluding patients who fell outside the propensity score distribution overlap) and the stratified-matched population (stratified by 1 vs ≥2 anti-TNF agents, then matched based on propensity score). The primary effectiveness outcome was achievement of low disease activity (LDA)/remission (Clinical Disease Activity Index ≤10) at 1 year. Secondary outcomes included achievement of modified American College of Rheumatology (mACR) 20/50/70 responses and meaningful improvement (≥0.25) in modified Health Assessment Questionnaire (mHAQ) score at 1 year. New cardiovascular, infectious and cancer events were reported. Results Estimates for LDA/remission, mACR response and mHAQ improvement were consistently better for rituximab than for anti-TNF agent users in adjusted analyses. The odds ratio for likelihood of LDA/remission in rituximab versus anti-TNF patients was 1.35 (95 % CI, 0.95-1.91) in the trimmed population and 1.54 (95 % CI, 1.01-2.35) in the stratified-matched population. Rituximab patients were significantly more likely than anti-TNF patients to achieve mACR20/50 and mHAQ improvement in the trimmed population and mACR20 and mHAQ in the stratified-matched population. The rate of new adverse events per 100 patient-years was similar between groups. Conclusions In anti-TNF–experienced patients with RA, rituximab was associated with an increased likelihood of achieving LDA/remission, mACR response and physical function improvement, with a comparable safety profile, versus subsequent anti-TNF agent users. Trial registration ClinicalTrials.gov NCT01402661. Registered 25 July 2011. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0776-1) contains supplementary material, which is available to authorized users.

Background Dose escalation is a common strategy for patients (pts) having an inadequate response to a medication. Objectives To examine low disease activity (LDA) among pts receiving infliximab (IFX) who did and did not escalate therapy above 3mg/kg in CORRONA, a US national registry of rheumatoid arthritis (RA) pts. Methods We identified all RA pts who initiated IFX on or after 6/2009 at a dose ≤3mg/kg and with moderate or high disease activity (CDAI>10). Eligible pts required at least 6 mos of follow-up after initiation or after dose escalation. Dose escalation was defined as an increase of >1mg/kg or reduction in infusion intervals by ≥1 wk. We divided pts into 3 groups: pts achieving LDA (CDAI ≤10) without dose escalation; pts not achieving LDA and not dose escalating; pts dose escalating. The last group was further divided into pts achieving LDA after dose escalation and pts not achieving LDA after dose escalation. We compared the populations at time of initiation by demographics, BMI in categories of normal (BMI Results There were 286 pts who met inclusion criteria. 124 (43.4%) reached LDA without escalation; 50 (17.5%) either switched without escalation or had not reached LDA by at least 9 mos; 112 (39.2%) escalated. Of the escalators, 64 (57.1%) reached LDA and 48 (42.9%) switched or did not reach LDA by at least 9 mos. Pts who reached LDA without escalation were more likely to be biologic naive (67.7%) than those who escalated but did not reach LDA (45.8%, p=0.008). Pts reaching LDA without escalation had lower disease activity measures at initiation (tender joints, physician global assessment, pt global assessment, pt pain) than pts not reaching LDA with or without escalation (p Conclusions Pts more likely to reach LDA without dose escalation are biologic naive and have lower disease activity measures at initiation. Both high BMI (obese) and diabetes are associated with requiring dose escalation to achieve LDA. In this analysis, ≤25% of patients received dose escalation beyond 8mg/kg/8wks, which may have clinical relevance. Acknowledgement Study sponsored by Corrona, LLC. Corrona RA registry has been supported thru contracted subscriptions in last 2 yrs by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, & UCB. Disclosure of Interest S. Cohen Grant/research support from: Amgen, Biogen-IDEC, BMS, Centocor, Genentech, Johnson & Johnson, Pfizer, Merck, and Roche, G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, R. Magner Employee of: Corrona, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, L. Ellis Employee of: Janssen Scientific Affairs, LLC, R. DeHoratius Employee of: Janssen Scientific Affairs, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: Janssen Scientific Affairs, LLC, AstraZeneca, Celgene, Genentech, Novartis, Pfizer, Employee of: Corrona, LLC

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 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 Little is known regarding the treatment practices of rheumatologists with respect to biologic initiation as monotherapy versus combination therapy with nonbiologic disease modifying anti-rheumatic drugs (nbDMARDs) such as methotrexate (MTX). We explored treatment patterns at the time of biologic initiation as well as 1 year after initiation. Methods In a large US patient registry (CORRONA), we identified patients with a diagnosis of rheumatoid arthritis who were initiated on their first biologic between 10/2001-9/2012. Patients at time of initiation are divided into three therapy groups: Biologic Monotherapy - no other nbDMARD (Mono); Combination Therapy with a nbDMARD (Combo-nbDMARD) which could be MTX (Combo-MTX); or another nbDMARD (Combo-non-MTX DMARD). Patients using MTX + another nbDMARD are included in Combo-MTX. Patient demographic and clinical characteristics are estimated within each group. Within each therapy group, those initiators with a one year follow-up visit (1 year ±2 months from initiation) are divided into their current therapy at one year. Results The CORRONA registry, as of 9/3/2012, had 33,959 RA patients with at least one clinical visit. There were 3,987 patients who initiated their first biologic among biologic naive RA patients. Of these initiations, monotherapy represented 18%, combination therapy with MTX in 69%, and combination with a non-MTX nbDMARD in 13%. Demographic and clinical characteristics were similar among the three therapy groups of Mono, Combo-MTX, Combo-non-MTX DMARD: Average Age (57.0, 57.3, 58.1), CDAI (21.4, 21.2, 20.2), mHAQ (0.51, 0.49, 0.49). Average duration of disease was higher in the Combo-nbDMARD (9.7 yrs) vs Combo-MTX (7.8 yrs, p Conclusions Rheumatologists initiate biologic agents in combination with nbDMARDs in the majority of patients with most persisting on combination therapy at 1 year. Additionally, one-quarter of monotherapy users switched to combination therapy during follow-up. Of note, a substantial number of biologic initiators, regardless of monotherapy or combination nbDMARD initiation discontinued biologic therapy. Acknowledgements The CORRONA RA registry has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Eli Lilly, Novartis, Pfizer, Vertex 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 G. Reed Employee of: CORRONA, Inc., A. Ganguli Shareholder of: AbbVie, Employee of: AbbVie, K. Saunders Employee of: CORRONA, Inc., R. Magner Employee of: UMASS Medical School, J. Greenberg Shareholder of: CORRONA, Inc., Consultant for: AstraZeneca, Pfizer, Employee of: CORRONA, Inc. DOI 10.1136/annrheumdis-2014-eular.1544

Background In a US cohort of RA patients (pts) with prior exposure to 1 or more TNF inhibitors (TNFi), use of rituximab (RTX) was associated with a higher likelihood of low disease activity or remission (based on Clinical Disease Activity Index [CDAI] ≤10) as compared with a subsequent TNFi. 1,2 However, it is not known whether the increased efficacy was due to greater use of prednisone. Objectives To examine the comparative effectiveness of RTX vs a subsequent TNFi in terms of cumulative prednisone exposure in RA pts with prior TNFi exposure using data from the Consortium of Rheumatology Researchers of North America (CORRONA), a multi-center observational registry within the US. Methods Using CORRONA data spanning from 2/28/2006 through 10/31/2012, we identified RTX-naive RA pts with prior TNFi use who were initiating RTX or a subsequent TNFi, had a 1-year follow-up visit and had CDAI measurements at baseline and 1-year follow-up. Pts from the stratified-matched cohort of the previously described comparative effectiveness analysis were assessed in the current analysis. 1,2 A propensity score for TNFi vs RTX was estimated using baseline clinical characteristics with matching of pts stratified based on 1 vs ≥2 prior TNFi use. The primary outcome was area under the curve (AUC) for cumulative prednisone dose divided by time. The percentage of time spent at 10mg or higher of prednisone was examined as a secondary outcome. Multivariable linear mixed models were performed adjusting for age, gender, 1 vs ≥2 prior TNFi, baseline CDAI, baseline prednisone use and baseline methotrexate use. Results There were 205 RTX pts and 205 TNFi matched pts who met the inclusion criteria. Patients were mostly female (81-83%), with a mean age of 58, mean disease duration of 15 years, and mean CDAI of 26-27. Baseline prednisone was used in 55.6% of RTX users and 51.5% of TNFi users. Overall there was a significant decrease in cumulative prednisone use over time ( P =0.04). The mean AUC for RTX was 3.7 vs 3.2 for TNFi ( P =0.22). In adjusted models, the mean difference in AUC over time for RTX as compared with TNFi was 0.26 (95% CI: -0.29, 0.82). The mean percentage of time at prednisone dose ≥10mg was 15.0% in RTX users vs 11.3% in TNFi users ( P =0.21). With adjustment for confounders, the mean difference in the percentage of time at prednisone dose ≥10mg for RTX compared with TNFi was 2.79 (95% CI: -2.45, 8.03). Approximately 14.0% and 22.9% of RTX and TNFi baseline prednisone users, respectively, discontinued prednisone during follow-up. Conclusions In this population of RA pts with prior exposure to TNFi, treatment with RTX was associated with a higher likelihood of achieving low disease activity and remission (OR 1.54, 95% CI 1.01-2.35) compared with subsequent TNFi users 1,2 and it was not related to greater prednisone use. Both RTX and TNFi users had a reduction in cumulative prednisone use. References Harrold LH, et al. Arthritis Rheum. 2013;65(suppl 10) [abstract 1438]. Harrold LH, et al. Ann Rheum Dis. 2013;72(suppl 3) [abstract 460]. Acknowledgements This study is sponsored by CORRONA. In the last 2 years, AbbVie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Eli Lilly, Novartis, Pfizer, Vertex, and UCB have supported CORRONA through contracted subscriptions. Disclosure of Interest L. Harrold Grant/research support: CORRONA., G. Reed Employee of: CORRONA, Inc., R. Magner Employee of: University of Massachusetts., A. Shewade Employee of: Genentech, Inc., A. John Employee of: Genentech, Inc., J. Greenberg Shareholder of: CORRONA., Consultant for: AstraZeneca, Pfizer., Employee of: CORRONA., J. Kremer Shareholder of: CORRONA., Employee of: CORRONA. DOI 10.1136/annrheumdis-2014-eular.1534

Background In patients who have failed 1 or more TNF-α inhibitors (TNFi), there is little data to guide clinical decision making in terms of changing mechanism of action or prescribing another TNFi. Objectives To compare the effectiveness of rituximab (RTX) versus a subsequent TNFi among RA patients with prior TNFi exposure using data from a multi-center observational registry within the United States (the Consortium of Rheumatology Researchers of North America: CORRONA). Methods We identified RA patients from 3/1/06 to present who had discontinued at least 1 TNFi and initiated either RTX or a subsequent TNFi, had moderate or high disease activity based on the Clinical Disease Activity Index (CDAI) at the time of initiation and had follow-up at 12 months (3 month window). A propensity score (PS) for TNFi vs. RTX was estimated using patient demographic information, disease characteristics (severity, duration, activity), comorbidities, past medication history and concurrent medications. We trimmed the PS distributions, excluding patients who fell outside the region of common support (n=2). Our primary outcome was achievement of low disease activity (CDAI ≤10). Multivariable logistic regression models with adjustment for fixed and random effects (patient and provider) were performed. Covariates with a standardized difference of Results 266 RTX users and 744 TNFi users who met inclusion criteria were included in the analyses. Baseline characteristics are described in Table 1. As compared to the TNFi users, RTX users were older, had a greater duration of RA, had prior exposure to a greater number of prior biologics and were more likely to be receiving prednisone. Achievement of low disease activity occurred in 35% of the RTX users and 28% of the TNFi users. RTX was associated with a greater likelihood of achievement of low disease activity (1.74, 95% CI 1.22-2.47) after adjustment for age, race, insurance status, comorbidity, and RA characteristics (baseline disease activity, severity and medication use [current and prior]). Results from PS matched multivariable analyses were similar. Overall reported rates in RTX users were 0.02 events per person-year (PPY) (95% CI 0.01-0.04) for cardiovascular events, 0.02 PPY (95% CI 0.01-0.05) for serious infections and 0.02 PPY (95% CI 0.01-0.04) for malignancies. The rates in TNFi users were 0.02 PPY (95% CI 0.01-0.03), 0.03 PPY (95% 0.02-0.05) and 0.02 PPY (95% 0.01-0.03), respectively. Image/graph Conclusions In RA patients who failed 1 or more TNFi agents, use of RTX was associated with a higher likelihood of achieving CDAI low disease activity than use of a subsequent TNFi. Disclosure of Interest : L. Harrold Grant/research support from: National Institute of Health - K23AR053856, Consultant for: CORRONA, G. Reed Consultant for: University of Massachusetts Medical School, Employee of: CORRONA, R. Magner Employee of: University of Massachusetts Medical School, A. Shewade Employee of: Genentech, Inc., A. John Employee of: Genentech, Inc., W. Reiss Employee of: Genentech, Inc., J. Greenberg Shareholder of: CORRONA, Consultant for: AstraZeneca, CORRONA, Novartis and Pfizer, J. Kremer Shareholder of: CORRONA, Employee of: CORRONA