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Secondary immunodeficiency (SID) occurs when the immune system is weakened by external factors, including certain medical treatments. It can leave a person with an increased risk of potentially serious or even fatal infections, as they no longer have adequate defenses against bacteria. Some patients with this condition require treatment to boost their immune system, including supplementation of their antibodies, known as immunoglobulin replacement therapy (IgRT). In this study, we explored whether: (1) patients with conditions that are at risk of SID and associated infections received IgRT; and (2) whether receiving the IgRT reduced the incidence of infections. We found that patients who had IgRT were much less likely to experience infections than those who did not receive IgRT, suggesting that IgRT may be an effective treatment option for preventing infections in patients with compromised immune systems caused by SID.

Objective This open-label 12-week study was conducted to evaluate the efficacy and safety of tofacitinib, a JAK inhibitor, in treatment-refractory active dermatomyositis (DM). Methods Tofacitinib in extended-release doses of 11 mg was administered daily to 10 subjects with DM. Prior to treatment, a complete washout of all steroid-sparing agents was performed. The primary outcome measure was assessment of disease activity improvement based on the International Myositis Assessment and Clinical Studies group definition of improvement. Response rate was measured as the total improvement score according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. Secondary outcome measures included Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, chemokine levels, immunohistochemical analysis of STAT1 expression in the skin, RNA sequencing analysis, and safety. Results At 12 weeks, the primary outcome was met in all 10 subjects. Five (50%) of 10 subjects experienced moderate improvement in disease activity, and the other 50% experienced minimal improvement according to the 2016 ACR/EULAR myositis response criteria. The secondary outcome of the mean change in the CDASI activity score over 12 weeks was statistically significant (mean ± SD 28 ± 15.4 at baseline versus 9.5 ± 8.5 at 12 weeks) (P = 0.0005). Serum chemokine levels of CXCL9/CXCL10 showed a statistically significant change from baseline. A marked decrease in STAT1 signaling in association with suppression of interferon target gene expression was demonstrated in 3 of 9 skin biopsy samples from subjects with dermatomyositis. The mean ± SD level of creatine kinase in the 10 subjects at baseline was 82 ± 34.8 IU/liter, highlighting that disease activity was predominantly located in the skin. Conclusion This is the first prospective, open-label clinical trial of tofacitinib in DM that demonstrates strong clinical efficacy of a pan-JAK inhibitor, as measured by validated myositis response criteria. Future randomized controlled trials using JAK inhibitors should be considered for treating DM.

We previously demonstrated that tofacitinib was effective in treating skin-predominant refractory dermatomyositis (DM) at 12 weeks in a prospective open label clinical trial, Study of Tofacitinib In Refractory dermatomyositis (STIR) (1). Here, we report the long-term extension results of up to 96 weeks to investigate the treatment durability of tofacitinib in refractory DM. Inclusion criteria and outcome measures were the same as the parent study (1). Assessments were conducted at weeks 20, 72, and 96. The baseline demographic features of all 10 trial patients were reported previously (1).

Secondary immunodeficiency (SID) is an acquired condition caused by several factors including, but not limited to, B-cell malignancies, and may result in frequent, burdensome, and possibly life-threatening infections. Treatment guidelines recommend immunoglobulin replacement therapy (IgRT) in certain settings to prevent recurrent, persistent, or major (severe) infections. This retrospective analysis of a US healthcare database characterized patients (pts) with suspected SID, who experienced infections, and were or were not treated with IgRT (IgPro10 [Privigen ®]). Data were collected from 26 US healthcare organizations from TriNetX DataWorks™ Network between 1/1/09 - 1/31/20. Pts were required to have the following: suspected SID (defined as ≥1 underlying conditions related to SID such as: solid organ transplant [SOT], non-Hodgkin lymphoma [NHL], multiple myeloma [MM], and chronic lymphocytic leukemia [CLL]), ≥1 severe infection (defined as requiring hospitalization and/or treatment with intravenous antibiotics or anti-viral medication) or ≥2 non-severe infections between underlying condition diagnosis date and the index date, the absence of diagnosed primary immunodeficiency, and an available medical history of ≥12 months pre-index and ≥3 months post-index. The index date refers to first IgPro10 use or the corresponding date for pts not receiving IgPro10 (unexposed cohort). In the IgPro10 cohort, pts were required to have had ≥2 consecutive IgPro10 administrations within 90 days. Between the pre- and post-index periods, the following variables were compared for both cohorts: pts' treatment, underlying conditions, baseline characteristics, and change in annualized infection rate (for infections of any severity and severe infections). Pre-index immunoglobulin G (IgG) (or calculated globulin [CG]) levels were recorded as: hypogammaglobulinemia (HGG) (IgG The final sample comprised 222 IgPro10 pts and 11,226 unexposed pts. In the IgPro10 cohort, 143 pts were on IgPro10 for 12 months. In both the IgPro10 and the unexposed cohorts, SOT was the most frequent underlying condition (45.5% and 44.6%, respectively), followed by NHL (21.6% and 28.2%, respectively), MM (14.4% and 10.1%, respectively), and CLL (11.3% and 7.6%, respectively). Age (mean [SD], 57.2 [13.9] vs 57.9 [17.0] years old, respectively) and sex distribution (male:female, 56.3%:43.7% vs 51%:48.8%, respectively) were similar in the IgPro10 and unexposed cohort. During the pre-index period, the IgPro10 cohort, compared with the unexposed cohort, received a greater number of antibiotic courses (median [interquartile range], 7 [20] vs 1 [5], respectively), had a substantially higher proportion of pts with HGG (HGG: 34.7% vs 3.0%; normal IgG: 43.7% vs 57.8%; missing: 21.6% vs 39.2%, respectively), and a lower proportion of pts with an annualized infection rate of zero (for infections of any severity and severe infections) (Figure 1). There was an approximate four-fold increase in the proportion of pts with no infections of any severity following IgPro10 administration; this increase was significantly larger than in the unexposed cohort (p This real-world study found that compared with pts not receiving IgRT, pts who subsequently went on to receive IgPro10 experienced more infections pre-treatment. Following IgPro10 administration, more pts had an annualized infection rate of zero (for infections of any severity or severe infections) compared with the pre-index period. Moreover, the increase in the proportion of pts with no infections was greater in the IgPro10 cohort than in the unexposed cohort, for both infections of any severity and severe infections. Taken together, these findings suggest effectiveness of IgPro10 in pts with SID, but further study, such as a prospective randomized controlled trial, is needed to confirm these initial findings. Figure 1 Figure 1. Disclosures Lahue: CSL Behring: Consultancy; Alkemi Health: Current Employment, Current holder of stock options in a privately-held company. Mallick: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Zhang: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Koenig: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Espinoza: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. OffLabel Disclosure: IgPro10 (Privigen®, CSL Behring, King of Prussia, PA, U.S.), a type of immunoglobulin replacement therapy, is currently approved in the U.S. to treat patients with primary immunodeficiency (PI), chronic inflammatory demyelinating polyneuropathy (CIDP), and chronic immune thrombocytopenic purpura (ITP).

Background The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA). Methods This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression. Results Data from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p p p p Conclusions MRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures. Trial registration ClinicalTrials.gov, NCT01164579.

Real-world data comparing tofacitinib with biologic disease-modifying antirheumatic drugs (bDMARDs) are limited.To compare characteristics, treatment patterns, and costs of patients with rheumatoid arthritis (RA) receiving tofacitinib versus the most common bDMARDs (adalimumab [ADA], etanercept [ETN], and abatacept [ABA]) following a single bDMARD in a U.S. administrative claims database.This study was a retrospective cohort analysis of patients aged ≥ 18 years with an RA diagnosis (ICD-9-CM codes 714.0x-714.4x; 714.81) and 1 previous bDMARD filling ≥ 1 tofacitinib or bDMARD claim in the Truven MarketScan Commercial and Medicare Supplemental claims databases (November 1, 2012-October 31, 2014). Monotherapy was defined as absence of conventional synthetic DMARDs within 90 days post-index. Persistence was evaluated using a 60-day gap. Adherence was assessed using proportion of days covered (PDC). RA-related total, pharmacy, and medical costs were evaluated in the 12-month pre- and post-index periods. Treatment patterns and costs were adjusted using linear models including a common set of clinically relevant variables of interest (e.g., previous RA treatments), which were assessed separately using t-tests and chi-squared tests.Overall, 392 patients initiated tofacitinib; 178 patients initiated ADA; 118 patients initiated ETN; and 191 patients initiated ABA. Tofacitinib patients were older versus ADA patients (P = 0.0153) and had a lower proportion of Medicare supplemental patients versus ABA patients (P = 0.0095). Twelve-month pre-index bDMARD use was greater in tofacitinib patients (77.6%) versus bDMARD cohorts (47.6%-59.6%). Tofacitinib patients had greater 12-month pre-index RA-related total costs versus bDMARD cohorts (all P0.0001) and greatest index use of monotherapy (P = 0.0080 vs. ABA). A similar (all P0.10) proportion of patients were persistent with tofacitinib (42.6%) versus ADA (37.6%), ETN (42.4%), and ABA (43.5%). Mean PDC was 0.55 for tofacitinib versus 0.57 (ADA), 0.59 (ETN), and 0.44 (ABA; P = 0.0003). Adjusted analyses generated similar findings to the unadjusted treatment patterns. Tofacitinib had lower adjusted 12-month post-index mean RA-related total costs ($23,568) versus ADA ($29,278; P0.0001), ETN ($26,885; P = 0.0248), and ABA ($30,477; P0.0001).In this study, tofacitinib was more commonly used as monotherapy and yielded at least comparable persistence and adherence with lower adjusted mean RA-related total costs versus ADA, ETN, and ABA. Further analysis is warranted given the greater 12-month pre-index bDMARD use and RA-related costs for tofacitinib versus bDMARDs.This study was sponsored by Pfizer. Harnett, Gerber, Gruben, Koenig, and Chen are employees and shareholders of Pfizer. Some data reported in this manuscript have been previously presented at the Academy of Managed Care Nexus 2015; Orlando, Florida; October 26-29, 2015, and was submitted in abstract form to the European League Against Rheumatism Congress; London, United Kingdom; June 8-11, 2016. All authors were involved in the conception and design of this study. Harnett and Gruben were involved in data collection and analysis. All authors interpreted the data, critically reviewed and revised the manuscript, and read and approved the final manuscript.

Tofacitinib is an oral Janus kinase inhibitor indicated for the treatment of rheumatoid arthritis (RA). Tofacitinib can be administered as a monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs). This study describes RA patients' characteristics, treatment patterns, and costs for those initiating tofacitinib treatment as monotherapy or combination therapy, using US claims data from clinical practice.A retrospective cohort analysis of patients aged ≥18 years with RA (International Classification of Diseases, Ninth Revision code 714.xx) and with ≥1 tofacitinib claim in the Truven Marketscan (TM) or the Optum Clinformatics (OC) database. Index was defined as the first tofacitinib fill date (November 2012-June 2014). Patients were continuously enrolled for ≥12 months before and after index. Adherence was assessed using the proportion of days covered (PDC) and medication possession ratio (MPR). Persistence was evaluated using a 1.5× days' supply gap or switch. All-cause and RA-related costs in the 12-month pre- and post-index periods were evaluated. Unadjusted and adjusted analyses were conducted on data on treatment patterns and costs stratified by monotherapy status.A total of 337 (TM) and 118 (OC) tofacitinib patients met the selection criteria; 52.2% (TM) and 50.8% (OC) received monotherapy and 83.7% (TM) and 76.3% (OC) had pre-index biologic DMARD experience. Twelve-month mean PDC values were 0.56 (TM) and 0.53 (OC), and 12-month mean MPR was 0.84 (TM) and 0.80 (OC), with persistence of 140.0 (TM) and 124.6 (OC) days. Between 12-month pre- and post-index periods, mean (SD) 12-month RA-related medical costs decreased by $5784 ($31,832) in TM and $6103 ($25,897) in OC (both, P0.05), whereas total costs increased by $3996 ($30,397) in TM (P0.05) and $1390 ($26,603) in OC. There were no significant differences in adherence, persistence, or all-cause/RA-related costs between monotherapy and combination therapy in unadjusted/adjusted analyses.This analysis adds to the existing tofacitinib knowledge base and will enable informed clinical and policy decision making based on valuable datasets independent of randomized controlled trials.

Adherence to biologic disease-modifying antirheumatic drugs (bDMARDs) among patients with rheumatoid arthritis (RA) is often suboptimal in routine clinical practice. Low or nonadherence can reduce the effectiveness of bDMARD therapies.To evaluate filling of newly prescribed initial bDMARDs for the treatment of RA and evaluate potential for characterizing treatment decisions and patient outcomes.In this retrospective cohort analysis, patients aged ≥ 18 years with an RA diagnosis (ICD-9-CM code 714.xx) were selected from a de-identified database of clinical information from the Electronic Health Record (EHR; Humedica) database linked to health care claims (Optum) from commercial and Medicare Advantage health plans (2007-2013). The first biologic prescription date in EHR was the index date. Patients were categorized as filling the prescription within 30 days (early fillers), 31-180 days (late fillers), or not at all within 180 days (nonfillers) of index date.Of 373 patients meeting inclusion criteria, 170 (45.6%), 59 (15.8%), and 144 (38.6%) were categorized as early fillers, late fillers, and nonfillers, respectively. Most prescriptions were written or ordered for tumor necrosis factor inhibitors (88.7%). Compared with late and nonfillers, early fillers were younger and more likely to be female, with higher pain scores (among those reporting pain scores) and RA severity scores pre-index, and filled more prescriptions for any reason pre-index. More nonfillers (66.0%) were Medicare patients than early (17.7%) and late (35.6%) fillers. During days 0-30 post-index, conventional synthetic DMARD use was greatest for early fillers (45.9%) and lowest among nonfillers (24.3%); however, during days 31-180 post-index, the proportion was highest for late fillers (61.0%) and lowest for nonfillers (35.4%). Of early fillers, 12.9% did not fill/receive a bDMARD after 30 days. Only 23 patients had pre/post-index pain scores, and 47 patients had a rationale for stopping or not filling a bDMARD. In patients with pharmacy and medical coverage for 180 days post-index, early fillers had greater RA-related pharmacy and medical resource use and costs than late and nonfillers combined.These findings confirm a high rate of primary nonadherence to bDMARDs among patients with RA.

To determine whether C-reactive protein (CRP) level is predictive of response to tumor necrosis factor-α blocker treatment in patients with ankylosing spondylitis (AS) and whether there is an optimal CRP range for treatment initiation.In this post hoc analysis, data on etanercept-treated patients with AS were pooled from four randomized trials. Week 12 responses (ASAS20, ASAS50, ASDAS-CRP 1.3, and ASDAS-CRP ∆ ≤ 1.1) were evaluated in relationship to baseline CRP levels (normal, defined as ≤ upper limit of normal [≤ ULN]; elevated, ULN; high, ULN and ≤ 3xULN; and very high, 3xULN), baseline levels of patient-reported outcomes (PROs), and CRP levels at weeks 2, 4, and 8, using univariate and stepwise predictor analyses. In addition, relationships between baseline CRP and other baseline predictors were analyzed using stepwise models of response.Among 867 patients, baseline CRP levels were normal in 371 (43%) patients, high in 299 (34%), and very high in 197 (23%). Very high baseline CRP was a significant predictor for all four week-12 outcomes, compared with normal CRP. Conversely, normal CRP at weeks 2, 4, and 8 was a stronger predictor of week 12 response than elevated CRP. PROs were less consistent predictors of response. In addition, there was a significant association between higher baseline CRP and lower age of disease onset ( 40 years) and between normal CRP and lower disease burden.In patients with AS, both baseline and post-baseline CRP levels can be predictive of response to treatment at week 12, more consistently than PROs.NCT00421915, NCT00247962, NCT00418548, NCT00356356.

Aim: To examine the effects of three treatment scenarios in rheumatoid arthritis (RA) on work and to determine potential predictors of work impairment. Materials & methods: Moderate RA patients received etanercept 50 mg weekly plus methotrexate (E50/MTX) for 36 weeks. Those with Disease Activity Score 28 ≤3.2 at week 36 and ≤3.2 from weeks 12–36 were randomized to E50/MTX, etanercept 25 mg weekly/MTX or placebo/MTX for 52 weeks. Results: Work-related components of the Work Productivity Activity Impairment questionnaire significantly improved with E50/MTX, which were maintained at week 88. Age, overall work impairment, disease duration, Health Assessment Questionnaire-Disability Index score >0.5, and pain visual analog scale were significantly predictive of overall work impairment. Conclusion: E50/MTX maintained significant improvements in Work Productivity Activity Impairment:RA. Prediction of potential work impairment may help improve RA work-related issues.

Objective.Investigate the role and relation of disease duration of different factors for achieving clinical remission with anti-tumor necrosis factor (TNF) treatment in patients with active ankylosing spondylitis (AS).Methods.Data pooled from 4 large (n = 1281) clinical trials were used to compare disease duration subgroups for placebo or sulfasalazine (SSZ) versus etanercept (ETN), which, in turn, were analyzed by age of diagnosis ≤ 40 versus > 40 years, HLA-B27 status, and baseline C-reactive protein (CRP) ≤ upper limit of normal (ULN) versus > ULN using chi-square tests, and ANCOVA. The primary efficacy measure was Assessments of SpondyloArthritis international Society (ASAS) partial remission (PR) after 12 weeks of treatment. Also analyzed were Bath AS Disease Activity Index and Functional Index, AS Disease Activity Scores, and ASAS response rates.Results.Overall, a larger percentage of patients achieved ASAS-PR with ETN versus SSZ or placebo. More patients with ≤ 2-year disease duration treated with ETN experienced partial remission (34%) versus longer disease duration (30%, 27%, and 22% for > 2–5, > 5–10, and > 10 yrs, respectively; all p < 0.05). In the subgroup of patients with both disease duration ≤ 2 years and aged ≤ 40 years at diagnosis, the treatment response was even more pronounced. Similar results were seen in HLA-B27–positive patients in the disease duration ≤ 2-year subgroup. Overall, patients with high CRP at baseline had better treatment responses compared with patients with normal CRP.Conclusion.Treatment response under anti-TNF treatment with ETN at 12 weeks was greatest among patients with disease duration ≤ 2 years and even more pronounced in subgroups of patients ≤ 40 years old or HLA-B27–positive at diagnosis.

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. A novel automated quantification method for RA MRI-detected pathology using statistical shape modelling technology (RAMRIQ) provides a tool that may be even more responsive than the sensitive RAMRIS semi-quantitative standard. 1 Objectives To determine if early changes in RAMRIQ were predictive of subsequent MRI and radiographic damage progression in a study of tofacitinib for the treatment of early RA in methotrexate-naive patients with minimal radiographic progression. Methods We used data from an exploratory, Phase 2 randomised controlled trial comparing tofacitinib, methotrexate and the combination (n=109) in methotrexate-naive patients with early active RA. 1 All patients met ACR classification criteria for active RA. MRI was performed at baseline and at 1, 3, 6 and 12 months. A single centralised reader read all MRI data; data for each patient were randomised by time point and read in the same sitting. We examined changes in synovitis, osteitis and erosions for RAMRIQ and RAMRIS at 1 and 3 months and performed univariate analyses on their relationship to RAMRIS, RAMRIQ and radiographic progression (modified Total Sharp Score [mTSS]) at 12 months. Results Reduction in RAMRIQ synovitis and osteitis at 1 and 3 months were significantly associated with reduction in RAMRIS erosion progression at 12 months (Table). Improvement in RAMRIQ synovitis and osteitis at 1 and 3 months were also associated with reduction in radiographic progression at 12 months, while RAMRIQ erosions at 1 and 3 months were not significantly associated with radiographic progression (Table). Early changes in RAMRIS erosion at 1 and 3 months were associated with radiographic progression at 12 months (Table). Treatment with tofacitinib alone or in combination with methotrexate was also associated with reduced progression in RAMRIS erosions (p=0.017 and p=0.007, respectively). Conclusions In this study, sensitive automated detection demonstrated that change in synovitis and osteitis predict subsequent RAMRIS erosion and radiographic progression. Treatment with tofacitinib as monotherapy or in combination with methotrexate was also highly predictive of no progression of erosive damage. Because of its enhanced sensitivity, novel quantitative imaging analysis has the potential to change RA clinical trial design where assessing structural damage is an objective. References Conaghan PG et al. Ann Rheum Dis 2016; 75: 1024–1033. Acknowledgements Previously presented at ACR 2016 and reproduced with permission. This study was sponsored by Pfizer Inc. Editorial support was provided by S Morgan of CMC and was funded by Pfizer Inc. Disclosure of Interest P. G. Conaghan Consultant for: AbbVie, Eli Lilly, Flexion, Novartis, Pfizer Inc, Roche, Speakers bureau: AbbVie, Novartis, Roche, M. A. Bowes Employee of: Imorphics Ltd, M. Ostergaard Grant/research support from: AbbVie, Centocor, Merck, Consultant for: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GSK; Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GSK; Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, G. Guillard Employee of: Stryker Co, D. Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Stein Employee of: Quintiles, J. Andrews Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Z. Xie Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Koenig Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, B. Wilkinson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Aims: We compared etanercept 50 mg once weekly (ETN50)/methotrexate versus etanercept 25 mg (ETN25)/methotrexate or biologic-free methotrexate after response to ETN50/methotrexate in moderate rheumatoid arthitis patients from central/eastern Europe, Latin America and Asia. Methods: In a 36-week induction phase, methotrexate-resistant patients received ETN50/methotrexate. In a 52-week, double-blind phase, patients who achieved sustained Disease Activity Score in 28 joints low disease activity (LDA) were randomized to ETN50/methotrexate, ETN25/methotrexate or methotrexate. Results: Sustained Disease Activity Score in 28 joints LDA was achieved in 85% at week 36. LDA was achieved in 83, 81 and 50% with ETN50/methotrexate, ETN25/methotrexate and methotrexate and remission in 66, 61 and 31%, respectively, at week 88 (p < 0.0001). Conclusion: Etanercept/methotrexate therapy for 36 weeks effectively induced response in this moderate rheumatoid arthritis subpopulation. Conventional- and reduced-dose etanercept/me...

Objective.The objective of these posthoc analyses was to evaluate short-term clinical outcomes as predictors of poor response after 1 year of treatment with combination etanercept/methotrexate (ETN/MTX) therapy versus MTX monotherapy in patients with early rheumatoid arthritis (RA).Methods.Participants with moderate to severe RA [28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) ≥ 3.2] of 3–24 months’ duration received ETN 50 mg weekly plus MTX or MTX monotherapy for 52 weeks. Regression analyses were performed to evaluate the likelihood of remission (DAS28-ESR < 2.6) after 1 year despite poor clinical short-term treatment effects (e.g., absolute or changes from baseline in DAS28-ESR after 4, 8, 12, 20, and 24 weeks of therapy).Results.The magnitude of disease activity and its improvement and timing influenced remission probability in both treatment groups; remission rate was diminished with higher disease activity levels and lower response levels over time from weeks 4 to 24. The rate of DAS28-ESR remission at 1 year was generally greater with ETN/MTX than with MTX alone at most timepoints from weeks 4 to 24. Despite persistent high disease activity (DAS28-ESR > 5.1) after 4, 8, 12, and 24 weeks of therapy, 35%, 27%, 25%, and 22% of patients, respectively, in the ETN/MTX group achieved DAS28-ESR remission after 1 year of continuous treatment; the respective proportions were 33%, 27%, 8%, and 13% in the MTX group.Conclusion.High disease activity and less improvement with treatment over time in the initial 24 weeks of treatment, particularly after 12 weeks, were predictive of a lower remission rate after 1 year.

The aims of this study were to investigate the short-term benefit of etanercept (ETN) + MTX vs conventional synthetic DMARDs (csDMARDs; HCQ, LEF or SSZ) + MTX in subjects with established RA. The effect of disease duration (≤2 years vs2 years) and severity (moderate vs severe) on treatment outcomes was also assessed. Methods. Data from Asian and Latin American subjects with inadequate response to MTX were pooled from the APPEAL (ETN 25 mg biweekly + MTX or csDMARD + MTX; NCT00422227) and Latin RA (ETN 50 mg/week + MTX or csDMARD + MTX; NCT00848354) studies. Endpoints included the 28-joint DAS with ESR (DAS28-ESR) low disease activity (LDA; ≤3.2), DAS28 remission (2.6) and HAQ score ≤0.5.Four hundred seventy-eight subjects received ETN + MTX, 245 subjects received csDMARD + MTX [HCQ + MTX (n = 81), LEF + MTX (n = 69), SSZ + MTX (n = 95)]. At week 16, significantly more subjects receiving ETN + MTX vs subjects on csDMARDs + MTX achieved DAS28-ESR LDA (39% vs 18%, P0.001), remission (18% vs 7%, P0.001) and HAQ ≤0.5 (48% vs 34%, P0.001). For both treatment arms, these endpoints were achieved by a greater proportion of subjects with ≤2 years vs2 years disease duration and with moderate vs severe disease activity.Overall, ETN + MTX was more effective in treating subjects with established RA than csDMARDs + MTX at 16 weeks. More subjects with shorter disease duration and moderate disease activity achieved optimal response regardless of treatment regimen.clinicaltrials.gov, NCT00422227 and NCT00848354.

Objective: To model the estimated disease-modifying effect of etanercept over sulphasalazine in patients with ankylosing spondylitis. Methods: A post hoc analysis of data from the Ankylosing Spondylitis Study Comparing ENbrel and Sulfasalazine Dosed Weekly (ASCEND) study was performed using the Natural History Staggered Start (NHSS) method. A mixed model with a linear effect over time was fitted to the ASCEND data and resampling was performed to generate confidence intervals. Results: At week 16, the total additional improvement in Bath Ankylosing Spondylitis Metrology Index of the etanercept arm over the sulphasalazine arm was 0.62 points, of which 31% (0.19 points) was estimated to be due to disease-modifying effect. Conclusions: The analysis of ASCEND data suggests that etanercept may have a larger disease-modifying effect than sulphasalazine. Further research is needed with more objective measures such as magnetic resonance imaging or X-radiography to confirm these results.

Objectives To investigate the relationships between inflammation, nocturnal back pain and fatigue in ankylosing spondylitis (AS) and the impact of 12 weeks' etanercept treatment versus sulfasalazine or placebo. Methods Data were combined from four clinical trials for patients with AS who received at least one dose of etanercept, sulfasalazine or placebo and had at least one postbaseline assessment value. Linear regression was performed (controlling for site, protocol and demographics), to explore the relationship between inflammation (C-reactive protein [CRP]), nocturnal back pain (visual analog scale [VAS] 0–100 mm) and fatigue (VAS 0–100 mm Bath AS Disease Activity Index fatigue item). Results Out of 1283 patients (etanercept, n = 867; sulfasalazine, n = 187; placebo, n = 229), improvement in nocturnal back pain was a significant predictor of improvement in fatigue. Significant correlations were found between nocturnal back pain and fatigue, but not CRP levels. Etanercept provided significantly greater pain/fatigue improvement than sulfasalazine or placebo. Improvements in nocturnal back pain and fatigue had weak relationships with improvement in inflammation (CRP level). Conclusions AS patients treated with etanercept demonstrated superior improvement in nocturnal back pain and fatigue versus sulfasalazine or placebo. Decrease in nocturnal back pain can improve fatigue. Assessing treatment response using CRP levels alone may be misleading without also examining patient-reported outcomes such as back pain and fatigue.

The authors tested the Psoriatic Arthritis Screening and Evaluation (PASE) to assess usefulness for psoriatic arthritis (PsA) screening before and after anti-TNF treatment in a clinical trial setting.Participants of the PRISTINE trial (NCT0066305) were randomized to etanercept 50 mg once weekly or twice weekly. PASE was administered at baseline and 12 weeks of treatment. Scores were compared by a paired sample t-test. Logistic regression and receiver operating curves were used to compare disease assessments against the PASE scores.Participants (N = 273, once weekly, N = 137; twice weekly, N = 136) had a mean age of 44 years; 70% were male; mean PASI was 21. At baseline, 31% had a self-reported history of physician-diagnosed PsA (mean duration, 8 years); ∼25% had a PASE total score ≥47, indicating active PsA. At week 12, 14% had scores ≥47 (p =. 0143). PASE scores correlated with subject global assessment of joint pain.The PASE was used in a randomized controlled clinical trial in a moderate to severe psoriasis population with a high prevalence of PsA. The findings also support the use of PASE as a tool to measure treatment response for PsA.

Tofacitinib, an oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA), provides patients with an alternative to subcutaneously or intravenously administered biologic disease-modifying antirheumatic drugs (DMARDs). Little is known about patient preference for novel RA treatments.To investigate patient preferences for attributes associated with RA treatments.A choice-based conjoint survey was mailed to 1400 randomly selected commercially insured patients (aged 21-80 years) diagnosed with RA, who were continuously enrolled from May 1, 2012, through April 30, 2013, and had ≥2 medical claims for International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 714.0 and no previous biologic DMARD use. Treatment attributes included route of administration; monthly out-of-pocket cost; frequency of administration; ability to reduce daily joint pain and swelling; likelihood of serious adverse events; improvement in the ability to perform daily tasks; and medication burden. Mean attribute importance scores were calculated after adjusting for patient demographics (eg, age, sex, years since diagnosis) using a hierarchical Bayes model. Patient preferences for each treatment attribute were ranked by the importance score. Part-worth utilities (ie, preference scores) were used to perform a conjoint market simulation.A total of 380 patients (response rate, 27.1%) returned the survey. Their mean age (± standard deviation) was 54.9 (± 9.3) years. Nonrespondents were 2 years younger (mean, 52.9 years; P = .002) but did not differ significantly from respondents in known clinical characteristics. After adjustment for demographic characteristics, mean patients' ranking of treatment attribute importance, in decreasing order, was route of administration, 34.1 (± 15.5); frequency of administration, 16.4 (± 6.8); serious adverse events, 12.0 (± 9.3); cost, 10.1 (± 6.2); medication burden, 9.8 (± 8.2); joint pain reduction, 8.9 (± 3.8); and daily tasks improvement, 8.8 (± 4.7). For the route of administration attribute, the part-worth utility was highest for the oral route. Conjoint simulation results showed that 56.4% of respondents would prefer an oral route of administration.Based on this survey completed by 380 patients with RA, commercially insured patients with RA consider the route of administration to be the most important attribute of their RA treatment. In this study, the majority (56.4%) of patients preferred the oral route of administration over other routes. Understanding patient preferences may help to inform provider and payer decisions in treatment selection that may enhance patient adherence to therapy.

Discordance between patient and physician ratings of rheumatoid arthritis (RA) severity occurs in clinical practice and correlates with pain scores and measurements of joint disease. However, information is lacking on whether discordance impacts patients’ ability to work. We evaluated the discordance between patient and physician ratings of RA disease activity before and after treatment with etanercept and investigated the associations between discordance, clinical outcomes, and work productivity. In the PRESERVE clinical trial, patients with moderate RA received open-label etanercept 50 mg once weekly plus methotrexate for 36 weeks. Baseline and week-36 disease characteristics and clinical and work productivity outcomes were categorized according to week-36 concordance category, defined as positive discordance (patient global assessment – physician global assessment ≥2), negative discordance (patient global assessment – physician global assessment ≤ –2), and concordance (absolute difference between the two disease activity assessments = 0 or 1). Correlations between discordance, clinical outcomes, and predictors of discordance were determined. At baseline, 520/762 (68.2 %) patient and physician global assessment scores were concordant, 194 (25.5 %) were positively discordant, and 48 (6.3 %) were negatively discordant. After 36 weeks of therapy, 556/763 (72.9 %) scores were concordant, 189 (24.8 %) were positively discordant, and 18 (2.4 %) were negatively discordant. Patients with week-36 concordance had the best 36-week clinical and patient-reported outcomes, and overall, the greatest improvement between baseline and week 36. Baseline pain, swollen joint count, duration of morning stiffness, fatigue, and patient general health significantly correlated with week-36 discordance, p

To evaluate 12-month treatment patterns, healthcare resource use (HCRU), and costs for patients with rheumatoid arthritis (RA), following initiation of index TNF inhibitors (TNFi) and subsequent biologic DMARDs (bDMARDs).This was a retrospective cohort analysis of adults with RA newly initiating TNFi in the Truven Marketscan Commercial Claims and Encounters and Medicare Supplemental Databases during 2010-2013. A sub-group of patients who switched to a bDMARD within 12 months post-index and within 180 days of last index TNFi were subsequently evaluated over 12 months. TNFi/bDMARD treatment patterns were characterized as: continuers, no gap180 days in prescription/administration of index TNFi; discontinuers, gap180 days; switchers, initiated new bDMARD. Concomitant conventional synthetic DMARD use, co-morbid chronic illnesses, and RA severity were assessed. All-cause/RA-related HCRU and costs were evaluated 12 months post-index.Of 9567 identified patients, 67.2%, 17.3%, and 15.4% were continuers, discontinuers, and switchers, respectively. Switchers had the highest 12-month unadjusted mean all-cause costs of $34,585 vs $33,051 for continuers (p = 0.1158) and $24,915 for discontinuers (p 0.0001; discontinuers vs continuers, p 0.0001). RA-related costs comprised 82.8%, 31.4%, and 85.7% of total costs for continuers, discontinuers, and switchers, respectively. Of 764 switchers, 68.2% switched to alternative TNFi (cyclers), the rest to non-TNFi bDMARDs; 36.7% of patients who switched to TNFi switched again (to third-line bDMARD) vs 27.6% (p = 0.0313) of those who switched to non-TNFi bDMARDs. Switchers to non-TNFi bDMARDs had higher mean 12-month all-cause costs of $76,580 compared with $50,689 for switchers to alternative TNFi (p 0.0001); biologic-administration visits comprised 78.8% of the greater total RA-related costs of switchers to non-TNFi bDMARDs.Real-world TNFi discontinuation/switching rates correspond to randomized controlled trial non-response rates. TNFi cycling is common and associated with an increased likelihood of switching to third-line bDMARD. Switching to non-TNFi bDMARDs was associated with higher costs, mostly attributed to in-office administrations.

Switching among biologic therapies is common practice in patients with rheumatoid arthritis who have an inadequate response or intolerable adverse events. Evidence from observational studies and association guidelines supports the use of sequential biologic therapy for these reasons. Owing to recent economic pressures on healthcare budgets, patients with rheumatoid arthritis who are well controlled on and tolerant of their current biologic therapy may be switched to alternative biologics, despite limited evidence supporting this practice. Clinical research and experience suggest that TNF antagonists are not interchangeable, as meaningful differences have been observed in their efficacy and safety profiles. Additional research is needed to assess the risk:benefit ratio of specific sequences of biologic therapies and the validity of switching biologic therapies for nonclinical purposes.

Objective.Etanercept, a fully human tumor necrosis factor soluble receptor, is effective in treatment of ankylosing spondylitis (AS). Current guidelines suggest sulfasalazine (SSZ) treatment as initial therapy for the management of patients with AS with peripheral arthritis versus therapy with biologics. We compared the efficacy of etanercept with SSZ in patients with AS with peripheral joint involvement.Methods.The efficacy of etanercept 50 mg once weekly was compared with that of SSZ up to 3 g daily in subjects with ≥ 1 swollen peripheral joint at baseline, using data from a 16-week randomized double-blind study in subjects with AS. Efficacy was assessed by the Assessment in AS criteria and the Bath AS Disease Activity, Functional, and Metrology indices. The last observation carried forward method was used for imputation of missing values.Results.Of 566 subjects included in original study, 181 (etanercept 121; SSZ 60) had ≥ 1 swollen peripheral joint and 364 (etanercept 250; SSZ 124) had none at baseline. AS patients treated with etanercept showed significantly greater improvement than those treated with SSZ in all joint assessments regardless of swollen joint involvement.Conclusion.In this analysis, etanercept was significantly more effective than SSZ for management of patients with AS and peripheral joint involvement.

Aim: Rheumatoid arthritis (RA) is an important rheumatologic disease in Asia-Pacific countries, as in other parts of the world. However, limited information is available regarding RA therapy in this region. The Asia-Pacific Study in Patients to be Treated With Etanercept or an Alternative Listed DMARD (APPEAL) compared efficacy and safety of etanercept (ETN) + methotrexate (MTX) versus usual disease-modifying anti-rheumatic drugs (DMARDs) + MTX (reflecting regional practice) in subjects with moderate to severe RA from multiple Asia-Pacific countries. Method: In this open-label, active-comparator, parallel-design, multicenter study, subjects (n = 300) in the Asia-Pacific region were randomized to ETN + MTX (n = 197) or DMARD + MTX (n = 103). The primary efficacy endpoint was the American College of Rheumatology (ACR) response (ACR-N) area under the curve (AUC) over 16 weeks. Results: Baseline characteristics were similar between groups. At Week 16, ACR-N AUC indicated a significantly greater response with ETN + MTX compared with DMARD + MTX (mean difference –145.3; P

Objective Etanercept, a fully human tumor necrosis factor (TNF) receptor, is an effective treatment in patients with ankylosing spondylitis (AS). Sulfasalazine is frequently used for the treatment of both axial symptoms and peripheral symptoms of AS, and it has been the recommended therapy before the use of an anti-TNF agent when peripheral arthritis is present. Until now, no clinical trial has compared the efficacy and safety of a TNF blocker with that of sulfasalazine. This study was undertaken to compare the efficacy and safety of etanercept with that of sulfasalazine after 16 weeks of treatment in patients with axial and peripheral manifestations of AS. Methods In this randomized, double-blind study, patients received etanercept 50 mg once weekly (n = 379) or sulfasalazine titrated to a maximum of 3 gm/day (n = 187) for 16 weeks. The primary end point was the proportion of patients who achieved the Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) at 16 weeks. Last observation carried forward was predefined for imputation of missing values. Results The mean age of the patients was 41 years, 74% were male, and the mean disease duration was 7.6 years. The proportion of ASAS20 responders at week 16 was greater among patients treated with etanercept compared with those treated with sulfasalazine (75.9% versus 52.9%; P < 0.0001). As early as week 2 of treatment, etanercept was found to be more effective than sulfasalazine (P < 0.0001) in ameliorating both the axial symptoms and peripheral manifestations. Serious adverse events rarely occurred, and the rate of serious adverse events did not differ between groups. Conclusion In this population of patients with AS, etanercept was significantly more effective than sulfasalazine in improving the signs and symptoms of AS in the axial skeleton and peripheral joints.

Background: Recent recommendations have established clinical remission ideally or low disease activity (LDA) as therapeutic targets in all patients with rheumatoid arthritis (RA). Controlled studies of biologic agents have primarily assessed treatment effects in patients with severe RA; patients with moderate disease activity, whoconstitute a larger group, have received far less attention. In Period 1 of the PRESERVE trial, the proportion of subjects with moderately active RA achieving LDA or remission were evaluated after treatment with etanercept 50mg once weekly (QW) plus methotrexate for 36 weeks.Methods: Subjects with DAS28 >3.2 and ≤5.1 despite stable doses of oral methotrexate received open-label etanercept 50mg QW plus methotrexate (screening dose permitted to be titrated up to 25 mg/wk through week 28) for 36 weeks.Results: 834 subjects received treatment and were analyzed. Subjects were mostly female (83%), Caucasian (74%), RFþ (73%), and aCCPþ (78%), with a mean age of 48 years and disease duration of 7 years. Mean baseline DAS28 was 4.4; SDAI, 19.1; ESR, 22.2 mm/hr; and CRP, 12.3 mg/L. Efficacy results from Period 1 are shown in the table. The most commonly reported adverse events (AEs) were headache (6.1%), nasopharyngitis (5.4%), and upper respiratory tract infection (4.4%). Twenty-two subjects (2.6%) discontinued due to AEs.Conclusions: Substantial proportions of subjects with moderately active RA who received etanercept 50mg QW plus methotrexate for 36 weeks achieved LDA (85%-86%), DAS28 remission (67%), or SDAI remission (25%). Therefore, these ambitious goals can be achieved realistically in a high percentage of patients with moderate disease activity.

Objectives:To compare the effects of etanercept (ETN) 50 mg once weekly plus methotrexate (MTX) versus MTX alone on patient-reported outcomes (PROs) and the relationship between remission and PRO improvement.Methods:In this double-blind, randomised clinical trial (COMET), PROs included: the Health Assessment Questionnaire (HAQ), EuroQoL health status, fatigue and pain visual analogue scales, Hospital Anxiety and Depression Scale, and Medical Outcomes Short-Form-36. Mean changes from baseline were analysed by analysis of covariance using the last observation carried forward method. Results from week 52 are presented.Results:Most PROs demonstrated significantly greater improvements with ETN+MTX than MTX alone, including physical functioning, pain, fatigue and overall health status. A significantly greater improvement in HAQ score was observed in the ETN+MTX than the MTX group (−1.02 vs −0.72; pConclusions:Early treatment with ETN+MTX leads to significantly greater improvements in multiple dimensions of PROs than MTX alone. The close relationship between disease activity and PRO improvement suggests that early treatment, with remission as a goal, should maximise the chance of restoring normal functioning and HRQoL.

Summary Background Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis. The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis (COMET) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept. Methods 542 outpatients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3–24 months were randomly assigned to receive either methotrexate alone titrated up from 7·5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints (DAS28) and radiographic non-progression measured with modified total Sharp score. Treatment was allocated with a computerised randomisation and enrolment system, which masked both participants and carers. Analysis was done by modified intention to treat with last observation carried forward for missing data. This study is registered with ClinicalTrials.gov, number NCT00195494). Findings 274 participants were randomly assigned to receive combined treatment and 268 methotrexate alone. 132 of 265 (50%, 95% CI 44–56%) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 (28%, 23–33%) taking methotrexate alone (effect difference 22·05%, 95%CI 13·96–30·15%, p 5·1). 196 of 246 (80%, 75–85%) and 135 of 230 (59%, 53–65%), respectively, achieved radiographic non-progression (20·98%, 12·97–29·09%, p Interpretation Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate. Funding Wyeth Research.

ObjectivesDisease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) is used instead of erythrocyte sedimentation rate (DAS28-ESR) to assess rheumatoid arthritis disease activity; however, values for remission and low disease activity (LDA) for DAS28-CRP have not been validated. American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) guidelines suggest remission should be calculated by Simplified Disease Activity Index (SDAI) rather than DAS28-ESR. We examined values of remission and LDA of DAS28-CRP that correspond to the respective cut-off points for DAS28-ESR and SDAI from five clinical trials.MethodsDAS28-CRP cut-offs that best correspond to DAS28-ESR remission ResultsPercentage of patients who achieved remission and LDA by DAS28-ESR cut-offs was greater for DAS28-CRP versus DAS28-ESR regardless of patient population or treatment group. Discordance between CRP and ESR cut-offs ranged from 4%–26% and 8%–23% for remission and LDA, respectively, and 19%–40% and 6%–11% for DAS28-CRP versus SDAI, respectively. Estimated (range) remission and LDA thresholds were 2.4 (2.2–2.6) and 2.9 (2.6–3.3), 1.9 (1.6–2.2) and 3.1 (3.1–3.3) and 2.2 (1.1–2.9) and 3.6 (3.4–4.0) for DAS28-CRP versus DAS28-ESR, DAS28-CRP versus SDAI and DAS28-ESR versus SDAI, respectively.ConclusionsDAS28-CRP underestimates disease activity when using cut-off points validated for DAS28-ESR; therefore, DAS28-ESR cut-off values should not be applied to DAS28-CRP. Although DAS28-CRP and DAS28-ESR cut-offs for LDA ≤3.2 correspond to SDAI LDA, neither corresponds well to SDAI remission.

Cardiometabolic, clinical and quality-of-life (QoL) measures were assessed before and after etanercept treatment in patients who had moderate-to-severe plaque psoriasis with and without psoriatic arthritis (PsA) in the PRISTINE trial. Adult patients were randomized to receive etanercept 50 mg once weekly or twice weekly double-blind for 12 weeks; all patients subsequently received etanercept 50 mg once weekly open-label through week 24. Metabolic syndrome was identified in 44 and 41% of patients with and without PsA, elevated blood pressure in 73 and 56% (p

Objective To assess the efficacy of etanercept in the treatment of early active nonsteroidal antiinflammatory drug (NSAID)–refractory nonradiographic axial spondyloarthritis (SpA). Methods The study population consisted of patients who met the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA but not the modified New York radiographic criteria for ankylosing spondylitis (as assessed by a radiologist at the central trial site), had a symptom duration of >3 months but

We would like to thank Dr Feldtkeller1 for his remarks regarding our manuscript.1 We do agree that in ankylosing spondylitis onset is more accurately described by onset of symptoms as opposed to age at diagnosis. Unfortunately, we did not collect the time-of-symptom-onset data in three of the four studies in this analysis. Thus, we used the age at diagnosis as proxy for disease onset. In the ASCEND study (women n=147; men n=419) we reviewed the onset of symptom data that was similar between women (mean 13.0 years) and men (mean 13.4 years), which supports Dr Feldtkeller's statement, “the average age of disease onset (first symptoms of AS) does not differ significantly between male and female patients with AS”.2–4 In addition, the mean age of diagnosis in the …

Objective: To assess cardiometabolic biomarkers in patients with psoriasis before and after etanercept treatment. Methods: Patients with moderate-to-severe plaque psoriasis were randomized to etanercept 50 mg once or twice weekly, double-blinded. Cardiometabolic biomarkers were assessed at baseline and after 12 weeks of treatment (n = 273). Results: At baseline, 42% of patients had metabolic syndrome. Etanercept was not associated with any clinically relevant adverse effects on cardiometabolic biomarkers. In the once-weekly subgroup, significant mean percentage changes from baseline (p < 0.05) were observed for the quantitative insulin-sensitivity check index (QUICKI; -2.2%), apolipoprotein (Apo) A1 (3.2%), Apo B: Apo A1 ratio (-3.5%), leptin (8.6%) and high-sensitivity C-reactive protein (hsCRP) (-65.5%); and in the twice-weekly subgroup for plasma insulin (15.9%), QUICKI (-2.7%), high-density lipoprotein cholesterol (HDL-C; 2.9%), apolipoprotein (Apo) A1 (2.8%), Apo B: Apo A1 (-4.6%) and hsCRP (-74.4%). Conclusion: Metabolic syndrome was common in these patients with moderate-to-severe psoriasis. Etanercept treatment may provide some potentially favorable modulation of insulin sensitivity, HDL-C, Apo A1 and Apo B: Apo A1 ratio.

BACKGROUND Previous global studies examined etanercept (ETN) + methotrexate (MTX) for treatment of rheumatoid arthritis (RA), but included few subjects from Latin America. OBJECTIVE The objective of this study was to compare the safety and efficacy of ETN + MTX versus a standard-of-care disease-modifying antirheumatic drug (DMARD) + MTX in Latin American subjects with moderate to severe active RA despite MTX therapy. METHODS This open-label, active-comparator study (NCT00848354) randomized subjects 2:1 to ETN 50 mg/wk + MTX or investigator-selected DMARD (sulfasalazine or hydroxychloroquine) + MTX (ETN + MTX, n = 281; DMARD + MTX, n = 142). The primary end point was the proportion achieving American College of Rheumatology (ACR) 50 at week 24. Secondary end points included ACR20/70, disease activity score (DAS) 28 measures, and mean change in modified total Sharp score. Patient-reported outcomes were the Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment: RA (WPAI:RA), and Caregiver Burden and Resource Utilization. Statistical analyses were stratified by country; χ test and analysis of covariance were used. Adverse events were monitored. RESULTS More subjects achieved ACR50 at week 24 with ETN + MTX versus DMARD + MTX (62% vs 23%, respectively), in addition to secondary end points (P < 0.0001 for all); mean change in modified total Sharp score was lower for the ETN + MTX group (0.4 vs 1.4, respectively; P = 0.0270). Improvements in patient-reported outcomes favored ETN + MTX for Health Assessment Questionnaire, 36-item Short-Form, Hospital Anxiety and Depression Scale for depression, WPAI:RA, and Caregiver Burden and Resource Utilization emergency department visits for RA (P < 0.01). Overall, adverse events were similar between the groups (69% vs 68%,); serious adverse events were also similar (4% vs 1%). The rate of overall infections was higher with ETN + MTX (38%) than DMARD + MTX (22%, P ≤ 0.001). CONCLUSIONS Consistent with published global data among RA patients with inadequate response to MTX, adding ETN to MTX demonstrated better efficacy than adding one other conventional DMARD to MTX. No new safety issues were observed. ETN + MTX provided favorable benefit-risk profile among RA patients from LA region.

Therapies involving anti-tumour necrosis factor are associated with increased risk of serious infections, opportunistic infections, and some types of malignancies in subjects with rheumatic diseases. However, limited data have been collected for subjects with ankylosing spondylitis (AS). The aim of this retrospective analysis of all sponsor-conducted trials was to examine the rates of serious infections, inflammatory bowel disease (IBD), malignancies, and non-malignant skin cancers during treatment in subjects with AS.Data from five randomized controlled trials (one sulfasalazine-controlled, four placebo-controlled) and four open-label studies evaluating etanercept were pooled for analyses. All randomized subjects who received at least one dose of treatment were included in the study.Analyses included 1323 subjects (1500 subject-years of treatment). Rate ratios of serious infections and IBD events for etanercept vs. placebo/sulfasalazine during the double-blind studies were 2.19 [95% confidence interval (CI) 0.22-107.79] and 1.09 (95% CI 0.06-64.56), respectively. There were no reports of opportunistic infections. Using the Surveillance, Epidemiology and End Results database, the standardized incidence ratio for malignancies was 1.47 (95% CI 0.54-3.21).These data suggest that etanercept is well tolerated in subjects with AS. Despite the large number of patients, the 95% CI data all cross 1.0, limiting possible conclusions. No new safety signals were observed.

Background: In rheumatoid arthritis (RA), there is discordance between patient and physician assessments of disease severity and treatment response. Objective: This retrospective analysis of the RADIUS (RA DiseaseModifying Anti-Rheumatic Drug Intervention and Utilization Study) 1 cohort examined specific factors that influence differences in global assessments for therapeutic effectiveness of disease-modifying antirheumatic drugs made by physicians (physician global assessment [PhGA]) and patients (patient global assessment [PtGA]). Methods: The RADIUS 1 cohort consisted of primarily communitybased private practice patients with RA requiring either the addition of or a switch to a new biologic or nonbiologic disease-modifying antirheumatic drug and who were followed for up to 5 years by their rheumatologists. Periodic assessments included PhGA, PtGA, Health Assessment QuestionnaireYDisability Index (HAQ-DI), 28-item tender/ painful joint count (TJC28), swollen joint count (SJC28), pain Visual Analog Scale (VAS), and acute-phase reactants. Results: Among 4359 patients (mean disease duration, 7.3 years), PhGA most highly correlated with TJC28 (0.6956; 95% confidence interval [CI], 0.6881Y0.7030) and SJC28 (0.6757; 95% CI, 0.6678Y 0.6834). Moderate overall correlations were observed for PtGA with TJC28 (0.5000; 95% CI, 0.4890Y0.5108) and less 50 with SJC28 (0.3754; 95% CI, 0.3628Y0.3878). Patient global assessment most strongly correlated with pain VAS (0.8349; 95% CI, 0.8305Y0.8392) and moderately correlated with HAQ-DI (0.5979; 95% CI, 0.5886Y0.6071). Acute-phase reactants poorly correlated with PhGA and PtGA. Conclusions: Low correlations between PhGA and acute-phase reactants suggest that these measurements have a limited contribution compared with the physical examination when physicians make global assessments. These results also suggest that physicians should consider patients’ assessments of their disease activity (HAQ, pain VAS, and PtGA) and put joint counts into proper context.

Objective.To determine whether disease activity and disability independently correlate with serious infection event (SIE) risk in a large rheumatoid arthritis (RA) cohort.Methods.The associations between SIE and Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in the Rheumatoid Arthritis Disease-Modifying Antirheumatic Drug Intervention and Utilization Study (RADIUS 1) cohort were evaluated using the Andersen-Gill model (a proportional HR model allowing > 1 event per patient).Results.Of 4084 patients with 347 SIE, 271 patients experienced ≥ 1 SIE. A 5-unit CDAI increase and 0.4-unit HAQ-DI increase corresponded to an increase in SIE risk with and without covariate adjustments. A 5-unit CDAI increase corresponded with a 7.7% increased SIE risk (adjusted HR 1.077, 95% CI 1.044–1.112, p < 0.0001) and a 0.4-unit HAQ-DI increase with a 30.1% increased risk (adjusted HR 1.301, 95% CI 1.225–1.381, p < 0.0001). Categorical analysis showed that more severe RA activity (even after controlling for disability) and disability were associated with an increased SIE risk.Conclusion.Increased RA disease activity and disability were each associated with a significantly increased SIE risk in the RADIUS 1 cohort, which could not be completely accounted for by disability.

Clinical remission and low disease activity are essential treatment targets in patients with rheumatoid arthritis. Although moderately active rheumatoid arthritis is common, treatment effects in moderate disease have not been well studied. Additionally, optimum use of biologics needs further investigation, including the use of induction, maintenance, and withdrawal treatment strategies. The aim of the PRESERVE trial was to assess whether low disease activity would be sustained with reduced doses or withdrawal of etanercept in patients with moderately active disease.In a randomised controlled trial, patients aged between 18 and 70 years with moderately active rheumatoid arthritis (disease activity score in 28 joints [DAS28]3.2 and ≤5.1) despite treatment with methotrexate were enrolled at 80 centres in Europe, Latin America, Asia, and Australia between March 6, 2008, and Sept 9, 2009. To be eligible, patients had to have been receiving 15-25 mg of methotrexate every week for at least 8 weeks. In an open-label period of 36 weeks, all patients were given 50 mg etanercept plus methotrexate every week. To be eligible for a subsequent double-blind period of 52 weeks, participants had to have achieved sustained low disease activity. These patients were randomly assigned (1:1:1) by an interactive voice-response system to one of three treatment groups: 50 mg etanercept plus methotrexate, 25 mg etanercept plus methotrexate, or placebo plus methotrexate. Patients were stratified in blocks of three by DAS28 response (low disease activity or remission) at week 36. Patients, investigators, data analysts, and study staff were all masked to treatment allocation. The primary endpoint was the proportion of patients with low disease activity at week 88 in the groups given 50 mg etanercept or placebo in the double-blind period. A conditional primary endpoint was the proportion of patients receiving 25 mg etanercept who achieved low disease activity. Modified intention-to-treat populations were used for analyses. This trial is registered with ClinicalTrials.gov, number NCT00565409.604 (72.4%) of 834 enrolled patients were eligible for the double-blind period, of whom 202 were assigned to 50 mg etanercept plus methotrexate, 202 to 25 mg etanercept plus methotrexate, and 200 to placebo plus methotrexate. At week 88, 166 (82.6%) of 201 patients who had received at least one dose of 50 mg etanercept and one or more DAS28 evaluations had low disease activity, compared with 84 (42.6%) of 197 who had received placebo (mean difference 40.8%, 95% CI 32.5-49.1%; p0.0001). Additionally, 159 (79.1%) of 201 patients given 25 mg etanercept had low disease activity at week 88 (mean difference from placebo 35.9%, 27.0-44.8%; p0.0001).Conventional or reduced doses of etanercept with methotrexate in patients with moderately active rheumatoid arthritis more effectively maintain low disease activity than does methotrexate alone after withdrawal of etanercept.Pfizer.

Background Patient reported outcomes (PROs) are especially useful in assessing treatments for rheumatoid arthritis (RA) since they measure dimensions of health-related quality of life that cannot be captured using strictly objective physiological measures. The aim of this study was to compare the effects of combination etanercept and methotrexate (ETN + MTX) versus combination synthetic disease modifying antirheumatic drugs (DMARDs) and methotrexate (DMARD + MTX) on PRO measures among RA patients from the Asia-Pacific region, a population not widely studied to date. Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied. Methods Patients were randomized to either ETN + MTX (N = 197) or DMARD + MTX (N = 103) in an open-label, active-comparator, multicenter study, with PRO measures designed as prospective secondary endpoints. The Health Assessment Questionnaire (HAQ), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue), Medical Outcomes Short Form-36 Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS) and the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI:GH) were used. Results Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5, compared to patients in the DMARD + MTX group. SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms. Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue, HADS, and WPAI:GH mean scores. Conclusion Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures, compared to combination therapy with usual standard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region. Trial registration clintrials.gov # NCT00422227

Biologics have mainly been assessed in patients with severe rheumatoid arthritis (RA) globally. Less attention has been paid to moderately active disease, especially in Central and Eastern Europe (CEE). Access to biologics and the disease features of RA patients may differ in CEE, relative to other regions. We assessed the clinical and patient-reported outcomes (PROs) of treatment from CEE patients in the multinational PRESERVE study ( NCT00565409 ). Patients with moderate RA 28-joint disease activity score ((DAS28) erythrocyte sedimentation rate (ESR) >3.2 and ≤5.1) despite methotrexate (MTX) treatment received open-label etanercept (ETN) 50 mg QW + MTX for 36 weeks. Low disease activity (DAS28 low disease activity (LDA) ≤3.2) and remission (DAS28 ESR

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. Limited real-world data exist comparing tofacitinib with biologic DMARDs (bDMARDs) in biologic-experienced (BE) RA patients (pts). Objectives To compare pt characteristics, treatment patterns and costs in BE RA pts receiving tofacitinib vs ADA, ETN and ABA using US claims data. Methods This retrospective cohort study included pts aged ≥18 years with RA (ICD9: 714.0x–714.4x; 714.81) and ≥1 tofacitinib (identified first) or bDMARD claim in the Truven MarketScan® Commercial and Medicare Supplemental healthcare claims database (01/11/2012–31/10/2014). Pts were continuously enrolled for ≥12 months (mos) pre- /post-index and had 1 bDMARD pre-index (due to greater imbalance in number of tofacitinib/bDMARD pts with ≥2 prior bDMARDs). Monotherapy was defined as absence of select conventional synthetic DMARDs within 90 days post-index. Outcomes were treatment persistence (index refills without a 60-day gap after prescription/administration days9 supply expiration), adherence (proportion of days covered [PDC]), and 12-mo pre-/post-index RA-related costs. Adjusted analyses were performed using generalized linear models, which included demography, disease status/duration and pre-index therapy variables; 12-mo pre-index costs were included for cost-related dependent variables. Results 392 tofacitinib, 178 ADA, 118 ETN and 191 ABA pts met selection criteria. 12-mo pre-index bDMARD use was most common for tofacitinib (78%) vs ADA (60%), ETN (49%) and ABA (48%) pts (all p Conclusions More BE pts started tofacitinib vs ADA, ETN and ABA after recent (prior 12 mos) bDMARD use; BE tofacitinib pts had the highest proportion of monotherapy use. Persistence and adherence were at least similar for tofacitinib and bDMARD pts. Tofacitinib pts had lower adjusted RA-related total costs post-index vs bDMARD pts. Acknowledgement Study sponsored by Pfizer Inc. Editorial support provided by K Munn of Complete Medical Communications and funded by Pfizer Inc. Disclosure of Interest J. Harnett Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Gerber Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Koenig Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Chen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

The objective of this post hoc analysis was to test the benefits of treating very early rheumatoid arthritis (VERA; ≤4 months) using COMET trial data. Treatment response in VERA and early rheumatoid arthritis (ERA;4 months to 2 years) with combination etanercept+methotrexate (ETN+MTX) or MTX monotherapy was compared.Data assessed at week 52 for baseline disease duration effect included remission (disease activity score (DAS)282.6, SDAI ≤3.3, Boolean), low disease activity (LDA; DAS283.2), Boolean components of remission and radiographic non-progression. Subjects who discontinued because of lack of efficacy were included as non-responders.Higher proportions of VERA subjects achieved LDA (79%) and DAS28 remission (70%) than ERA (62%, 48%, respectively, p0.05) with ETN+MTX. Such high responses with MTX monotherapy were not observed (VERA, LDA=47%, DAS28 remission=35%; ERA, 47% and 32% respectively, p0.70 for each). Regardless of disease duration, no radiographic progression was seen in 80% of subjects with ETN+MTX. In contrast, a higher proportion of VERA subjects showed no radiographic progression compared with ERA subjects treated with MTX (73.9% vs 50%, p=0.01).Treatment of VERA with ETN+MTX provides qualitatively improved clinical outcomes not seen with MTX monotherapy, supporting the pivotal role of TNF inhibition in early disease.

Objectives To compare health-related quality of life (HRQoL) before and after treatment with etanercept in patients with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis using spydergram representations. Methods Data from randomised, controlled trials of etanercept in patients with RA, PsA and psoriasis were analysed. HRQoL was assessed by the medical outcomes survey short form 36 (SF-36) physical (PCS) and mental (MCS) component summary and domain scores. Baseline comparisons with age and gender-matched norms and treatment-associated changes in domain scores were quantified using spydergrams and the health utility SF-6D measure. Results Mean baseline PCS scores were lower than age and gender-matched norms in patients with RA and PsA, but near normative values in patients with psoriasis; MCS scores at baseline were near normal in PsA and psoriasis but low in RA. Treatment with etanercept resulted in improvements in PCS and MCS scores as well as individual SF-36 domains across all indications. Mean baseline SF-6D scores were higher in psoriasis than in RA or PsA; clinically meaningful improvements in SF-6D were observed in all three patient populations following treatment with etanercept. Conclusions Patients with RA, PsA and psoriasis demonstrated unique HRQoL profiles at baseline. Treatment with etanercept was associated with improvements in PCS and MCS scores as well as individual domain scores in patients with RA, PsA and psoriasis.

Objective To evaluate how continuation of and alterations to initial year 1 combination etanercept–methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and radiographic progression in early, active rheumatoid arthritis. Methods Subjects were randomized at baseline for the entire 2-year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n = 111) or received etanercept monotherapy (the EM/E group; n = 111) in year 2; the original MTX monotherapy group either received combination therapy (the M/EM group; n = 90) or continued monotherapy (the M/M group; n = 99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28]

Objective:To assess uveitis (including iritis and iridocyclitis) incidence from clinical trials of etanercept in patients with ankylosing spondylitis (AS).Methods:Clinical trials of etanercept in AS (four placebo-controlled; one active-controlled; three open-label) were examined for reports of uveitis. Between-group differences with confidence intervals (CIs) in the uveitis rates were calculated for the double-blind, active-controlled and long-term studies.Results:In placebo-controlled trials, the uveitis rate per 100 subject years (95% CI) for etanercept (8.6 (4.5 to 14.2)) was lower than that for placebo (19.3 (11.0 to 29.8), p = 0.03). In the active comparator trial, rates for etanercept and sulfasalazine were similar (10.7 (5.5 to 17.6) and 14.7 (6.4 to 26.5), respectively; p = 0.49). The long-term rate for etanercept, estimated from both placebo-controlled and open-label extension studies was 12.0 (10.0 to 14.1).Conclusions:In subjects with AS, rates of uveitis events with etanercept were lower than with placebo in placebo-controlled trials and similar to sulfasalazine in an active comparator trial.

Background High baseline C-reactive protein (CRP) levels have been shown to be indicative of treatment response in patients with ankylosing spondylitis (AS). 1,2 A range of other baseline AS-specific demographics and characteristics have also been associated with treatment response. 1,2 Objectives The objective of this post hoc analysis was to determine if CRP levels correlate with demographics and disease characteristics and to compare CRP to other AS-specific measures as predictors of treatment response in patients with active AS. Methods Responses to etanercept (ETN), sulfasalazine (SSZ), or placebo plus non-steroidal anti-inflammatory drugs (PBO) were analyzed from four pooled large randomized controlled AS studies. Baseline CRP ≤upper limit of normal (ULN) versus CRP >ULN was compared across a number of AS-specific baseline measures. Baseline predictors, including CRP (≤ULN versus >ULN), were analyzed using odds ratios (ORs) in logistic models with treatment response defined as ASAS20 at Week 12 (Assessment of SpondyloArthritis International Society 20 criteria). Results In total, data from 1283 patients were used for this analysis: ETN n=867, SSZ n=187, and PBO n=229. Across all treatment groups, baseline CRP >ULN was significantly associated with lower age at diagnosis, higher Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) score, more males, and a higher proportion with positive Human Leukocyte Antigen B27 (HLA-B27) status (P ULN (1.7, 1.3–2.3), ASDAS-CRP >3.5 (1.7, 1.3–2.3), age of diagnosis ≤40 (1.8, 1.3–2.5), positive HLA-B27 (2.0, 1.4–3.0), and higher nocturnal back pain based on quartiles (1.2, 1.1–1.4), with all predictors appearing to have similar effects on ASAS20 based on similar odds ratios. A Bath Ankylosing Spondylitis Disease Activity Index score of ≤40 was significantly predictive of response to SSZ (OR 3.0, 95% CI 1.1–8.0), as was ASDAS-CRP >3.5 (OR 0.51, 95% CI 0.28–0.92) for PBO. Conclusions Baseline CRP was significantly associated with typical parameters of the disease (age of diagnosis, ASDAS-CRP, gender, HLA-B27) and significantly predicted short-term treatment response in patients receiving ETN but not other active compounds such as SSZ or NSAIDs. References Arends S et al. Arthritis Res Ther 2011;13:R94. Vastesaeger N et al. Ann Rheum Dis 2011;70:973-81 Acknowledgements We wish to thank all patients who participated in the trials and medical staff of all participating centres. Medical writing support was provided by John Bilbruck of Engage and was funded by Pfizer Inc. Disclosure of Interest X. Baraliakos Grant/research support from: MSD, Janssen, Pfizer, Abbott, Novartis, Chugai, UCB, Celgene, Consultant for: MSD, Janssen, Pfizer, Abbott, Novartis, Chugai, UCB, Celgene, Speakers bureau: MSD, Janssen, Pfizer, Abbott, Novartis, Chugai, UCB, Celgene, A. Szumski Consultant for: Employee of inVentiv Health and was contracted by Pfizer Inc. to provide statistical support, A. Koenig Employee of: Employee of Pfizer Inc., H. Jones Employee of: Employee of Pfizer Inc.

Background Biologic DMARDs (bDMARDs) are used to treat patients (pts) with moderate to severe rheumatoid arthritis (RA). Pts may experience clinical benefits from treatment with bDMARDs alone or with a conventional synthetic DMARD (csDMARD). Objectives To assess treatment patterns and healthcare resource use (HCRU) after prescription/administration of a bDMARD alone or with a csDMARD. Methods In this retrospective cohort analysis, pts aged ≥18 years (yrs) with an RA diagnosis (ICD9: 714.xx) who were prescribed/administered a DMARD (2007–2011) were selected from de-identified US electronic health records (EHR; Humedica). Index date was date of first prescription/administration for a bDMARD (adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, anakinra, tocilizumab). Pts did not receive bDMARDs for ≥6 months pre-index and were followed for ≥1 yr post-index. Pts were classified by index biologic monotherapy (Bmono) or combination therapy with bDMARD and csDMARD (B+CScombo; based on methotrexate, leflunomide, sulfasalazine, hydroxychloroquine at index). Regression analyses for switch (new bDMARD/csDMARD prescription/administration and no index drug for ≥120 days) and RA-related costs were assessed controlling for differences in pt demographics/characteristics. RA-related costs were derived from a pt subset with linked Optum claims data and applied to RA visits and pharmacy use in EHR. Results Of 2119 pts initiating a bDMARD, 70.6% received Bmono and 29.1% received B+CScombo; 0.2% had ≥2 biologics. Pt characteristics and treatment patterns are presented in Table 1. Mean age and percentage of females were similar for Bmono and B+CScombo pts. Compared with B+CScombo pts, Bmono pts were more likely to be treated by a rheumatologist, had a higher Deyo-Charlson Co-morbidity Index score and were more likely to have cardiovascular disease, hyperlipidaemia, hypertension and renal disease. Most Bmono and B+CScombo pts were prescribed a TNF inhibitor (TNFi). During 1-yr follow-up (FU), B+CScombo pts were less likely to switch index regimen vs Bmono pts (OR 0.37; 95% CI 0.27, 0.51; p Conclusions In this analysis of EHR data characterising bDMARD prescriptions/administrations in pts with RA, 70.6% received Bmono, and had a greater prevalence of co-morbidities and were more likely to be treated by a rheumatologist vs B+CScombo pts. B+CScombo pts were less likely to switch index regimen in 1-yr of FU and had lower RA-related medical HCRU but greater total costs vs Bmono pts. High prevalence of Bmono use may be due to a stricter concomitant csDMARD definition or the data source, which included specialties other than rheumatology. Acknowledgements This study was sponsored by Pfizer Inc. Editorial Support was provided by Karen Irving at Complete Medical Communications and funded by Pfizer Inc. Disclosure of Interest J. Harnett Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., R. Gerber Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., D. Gruben Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., D. Wiederkehr Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., E. Mahgoub Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., G. Wallenstein Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., A. Koenig Shareholder of: Pfizer Inc., Employee of: Pfizer Inc.