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Objective The target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the efficacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure. Methods A systematic search was performed for randomised controlled trials of ERA using predefined criteria. A random effects model was used to pool the risk ratio (RR) for clinical and radiographic remission at 52–56 weeks of follow-up. Results Seven trials of combination therapy with infliximab, adalimumab, etanercept or abatacept were included. The majority of studies defined clinical remission as a 28-joint disease activity score (DAS28) of 2.6 or less. Radiographic non-progression was primarily defined as a modified total Sharp score change of less than 0.5 units. All trials demonstrated risk estimates in favour of combination therapy: the pooled RR for achieving clinical remission was 1.74 (95% CI 1.54 to 1.98) and for radiographic non-progression was 1.30 (95% CI 1.01 to 1.68). Significant heterogeneity among studies for the latter outcome was detected (p<0.001). Conclusions The efficacy of combination therapy with a biological agent is superior to methotrexate monotherapy for remission. Combination therapy has a greater initial effect on clinical remission than radiographic non-progression. Uniform definitions of remission are needed and the proportion of subjects who achieve the combined endpoint of clinical and radiographic remission should be considered as a meaningful outcome in future studies of ERA. [ABSTRACT FROM PUBLISHER]

Objective: To assess the safety of biological disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA) patients following rituximab. Methods: RA patients who participated in an international rituximab clinical trial programme were included. Patients who had received one or more rituximab courses and entered safety follow-up (SFU) were permitted additional biological DMARD. Serious infection events (SIE) were collected. Results: Of 185 of 2578 patients who entered SFU and received another biological DMARD, 88.6% had peripheral B-cell depletion at the time of initiation of another biological agent. Thirteen SIE (6.99 events/100 patient-years) occurred following rituximab but before another biological DMARD and 10 SIE (5.49 events/100 patient-years) occurred following another biological DMARD. SIE were of typical type and severity for RA patients. 153 had received one or more tumour necrosis factor inhibitor(s). No fatal or opportunistic infections occurred. Conclusions: In this analysis, treatment with biological DMARD after rituximab was not associated with an increased serious infection rate. Sample size with limited follow-up restricts definitive conclusions. [ABSTRACT FROM PUBLISHER]

Objective: To examine the safety and tolerability of a single intra-articular injection of rAAV2-TNFR:Fc, an adenoassociated virus serotype 2 vector containing the cDNA for the human tumour necrosis factor–immunoglobulin Fc fusion gene (tgAAC94), in subjects with inflammatory arthritis. Methods: In a double-blind, placebo-controlled, phase 1, dose-escalation study, 15 subjects with inflammatory arthritis (14 with rheumatoid arthritis and 1 with ankylosing spondylitis) not receiving tumour necrosis factor α (TNFα) inhibitors with persistent moderate (grade 2) or severe (grade 3) swelling in a target joint due to inflammatory arthritis received a single intra-articular injection of rAAV2-TNFR:Fc at 1×10 (n = 5) or 1×10 (n = 6) DNase resistant particles per ml joint volume or placebo (n = 4) into a knee (n = 14) or ankle (n = 1). Safety was assessed through adverse event monitoring. As a secondary objective, changes in injected joint tenderness and swelling scores, each measured on a four-point scale, were evaluated. Results: Intra-articular injections of rAAV2-TNFR:Fc were well tolerated with no major safety issues. One event, mild knee pruritis, was considered probably related. Synovial fluid TNFR:Fc protein was not detected (nor expected) at the doses used. At 12 weeks after injection, a two-point decrease in swelling was noted in 2/11 and 2/4 subjects injected with rAAV2-TNFR:Fc and placebo, respectively. Conclusion: A single dose of intra-articular rAAV2-TNFR:Fc appears to be safe and well tolerated in subjects without concurrent systemic TNFα antagonist use. It is thus feasible to proceed with larger trials to further test the safety and efficacy of local TNFR:Fc gene transfer as a therapeutic modality for patients with inflammatory arthritis. [ABSTRACT FROM PUBLISHER]

Objective: To evaluate the safety of biological treatments for rheumatoid arthritis (RA) using results from randomised controlled trials (RCT). Methods: The literature was searched to December 2007 for RCT evaluating inhibitors of tumour necrosis factor alpha (anti-TNF) for RA. Safety data were abstracted and risk estimates were calculated using three approaches, meta-analysis with and without adjustment for exposure and simple exposure-adjusted pooling. Results: Eighteen randomised trials involving 8808 RA subjects were included. Treatment with recommended doses of anti-TNF found no increase in the odds of death (odds ratio (OR) 1.39; 95% CI 0.74 to 2.62), serious adverse events (OR 1.11; 95% CI 0.94 to 1.32), serious infection (OR 1.21; 95% CI 0.89 to 1.63), lymphoma (OR 1.26; 95% CI 0.52 to 3.06), non-melanoma skin cancers (OR 1.27; 95% CI 0.67 to 2.42) or the composite endpoint of non-cutaneous cancers plus melanomas (OR 1.31; 95% CI 0.69 to 2.48) when evaluated using the unadjusted meta-analytic method. Risk estimates were similar with the other methods. For subjects who received two to three times the recommended doses of anti-TNF the risk of serious infection was increased with the unadjusted meta-analytic and pooled analysis, (OR 2.07; 95% CI 1.31 to 3.26) and (risk ratio (RR) 1.83; 95% CI 1.18 to 2.85), respectively, but not increased in the exposure-adjusted meta-analysis (RR 1.99; 95% CI 0.90 to 4.37). Meta-regression identified that the risk of serious infection with anti-TNF therapy decreases with increasing trial duration (p = 0.035). Conclusion: Meta-analytic and exposure-adjusted pooled analyses on over 8800 RA subjects in RCT treated over an average of 0.8 years did not identify an increased risk of serious adverse events with recommended doses. High-dose anti-TNF therapy was associated with a twofold increase in the risk of serious infections. [ABSTRACT FROM PUBLISHER]

Objective: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy.Methods: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24.Results: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively.Conclusion: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of radiographic progression and disease activity states in patients with rheumatoid arthritis (RA) treated with methotrexate with or without infliximab. Methods: Patients (n = 1049) with active RA for 3 years or less and no previous methotrexate treatment were randomly assigned (4 : 5 : 5) to receive methotrexate plus placebo or methotrexate plus infliximab 3 or 6 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter to week 46. Disease activity was classified by the simplified disease activity index as remission (⩽3.3), low (>3.3 to ⩽11), moderate (>11 to ⩽26), high (>26). Radiographic progression was measured as a change from baseline to week 54 in total Sharp score. Results: At weeks 14 and 54, more patients receiving methotrexate plus infliximab than methotrexate plus placebo were in remission (10.7% versus 2.8% week 14; 21.3% versus 12.3% week 54; p<0.001 for both). Methotrexate plus placebo halted radiographic progression only if patients achieved remission within 3 months, whereas methotrexate plus infliximab also halted or minimised progression in patients with low or moderate activity, respectively. Patients with persistently high disease activity levels had much less progression of joint damage if treated with methotrexate plus infliximab versus methotrexate monotherapy. Even with infliximab plus methotrexate there was a direct relationship between disease activity and radiographic changes, although the slope was deflected when compared with methotrexate monotherapy. Conclusion: With methotrexate, joint damage progresses even at low and moderate disease activity levels, whereas methotrexate plus infliximab inhibits radiographic progression across all disease activity states. [ABSTRACT FROM PUBLISHER]

Objective: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. Methods: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. Results: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. Conclusion: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function. [ABSTRACT FROM PUBLISHER]

A large number of experts experienced in the treatment of rheumatoid arthritis were involved in formulating a consensus statement on the use of B cell-targeted treatment with rituximab in patients with rheumatoid arthritis. The statement was supported by data from randomised controlled clinical trials and the substantial literature on oncology. The statement underwent three rounds of discussions until its ultimate formulation. It should guide clinicians in the use of this newly approved biological agent in treating patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

TNF blocking agents have proved to be effective DMARDs and they have been a major advance in the treatment of RA. Their use is expanding to other rheumatic diseases. However, rare to uncommon and unexpected toxicities have been found and others may yet be found during their use. Studies in selected areas of efficacy, toxicity, and general use of TNF blocking agents are needed to help further define the most appropriate use of these agents. Use of these drugs will require doctors experienced in the diagnosis, treatment, and assessment of RA and other rheumatic diseases. These doctors will need to make long term observations of efficacy and toxicity. Further considerations which must be made when using TNF blocking agents in this disease include the cost and a recognition that data in subgroups are still being acquired. It is hoped that this statement, which is based upon the best evidence available at the time of its creation, and modified by expert opinion, will facilitate the optimal use of these agents for our patients with RA and other rheumatic diseases. [ABSTRACT FROM AUTHOR]

The articular manifestations of progressive systemic sclerosis (PSS) were studied in 38 patients. Of these, 66% experienced joint pain and 61% had signs of joint inflammation. Limitation of joint movement was seen in 45%. Radiological abnormalities included periarticular osteoporosis (42%), joint space narrowing (34%), and erosions (40%). Erosive disease did not correlate with disease duration, presence of rheumatoid factor, antinuclear antibodies, distal tuft resorption, or the extent of the scleroderma skin changes. Calcinosis was seen more frequently in those patients with articular erosions (67%). Erosive osteoarthritis of the distal interphalangeal joints (7 patients) was associated with impaired finger flexion. Joint involvement in PSS occurs frequently and may resemble rheumatoid arthritis in the early stages but is less destructive. The occurrence of unrelated arthropathy, such as primary osteoarthritis, is not uncommon, and its differentiation from true PSS joint disease can be difficult. [ABSTRACT FROM AUTHOR]

A case of destructive polyarthritis due to infection by Mycobacterium kansasii is described in a 68-year-old patient with long-standing rheumatoid arthritis (RA) receiving prednisone and azathioprine therapy. Superimposed infection was suggested by positive Ziehl-Neelsen stains of synovial fluid from the patient's right shoulder and wrists, with confirmation on culture. Histological examination of synovium revealed abundant noncaseating granulomata within subsynovial cellular infiltrates. Treatment with triple antituberculous chemotherapy resulted in substantial extra-articular improvement within 3 months. However, articular destruction progressed unabated. A high index of suspicion is needed to diagnose joint infections in patients with underlying polyarthritis who are receiving immunosuppressive therapy. The progressive joint damage, despite periarticular resolution, may suggest the need for a combination of surgical synovectomy and antituberculous chemotherapy. [ABSTRACT FROM AUTHOR]

Two patients with severe seropositive rheumatoid arthritis previously unresponsive to conventional therapy have been treated with leucapheresis. This technique involves continuous cell separation daily to remove primarily lymphocytes. Clinical improvement was recorded with the use of standard rheumatological measures of inflammation. It is concluded that leucapheresis may help in the management of severely active rheumatoid arthritis when conventional therapy has been unsuccessful. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented concerning the use of the determination of serum myosin light chain (MLC) in the assessment of disease activity in inflammatory myopathies and comments that MLC has been used to diagnose myocardial infarction and determine the extent of myocardial damage.

Objectives: To demonstrate efficacy equivalence of CT-P47 and EU-approved reference tocilizumab (r-TCZ) in patients with rheumatoid arthritis (RA)., Methods: This double-blind, phase III study randomised (1:1) patients to receive CT-P47 or r-TCZ (8 mg/kg) every 4 weeks until week 20 during treatment period (TP) 1. Prior to week 24 dosing, patients receiving r-TCZ were randomised (1:1) to continue r-TCZ or switch to CT-P47; patients receiving CT-P47 continued CT-P47 (TP2, 8 mg/kg every 4 weeks until week 48). The dual primary endpoints (for different regulatory requirements) were mean changes from baseline in Disease Activity Score in 28 joints (DAS28; erythrocyte sedimentation rate (ESR)) at week 12 and week 24. Efficacy equivalence was determined if CIs for the treatment difference were within predefined equivalence margins: (95% CI -0.6, 0.6 (analysis of covariance (ANCOVA)) at week 12 or 90% CI -0.6, 0.5 (ANCOVA with multiple imputation) at week 24). Additional efficacy, pharmacokinetic (PK) and safety endpoints, including immunogenicity, were investigated. Findings up to week 32 are presented., Results: In TP1, 471 patients were randomised (234 CT-P47; 237 r-TCZ). The 95% and 90% CIs for the estimated treatment differences were contained within the predefined equivalence margins; the estimated difference in DAS28-ESR at week 12 was -0.01 (95% CI -0.26, 0.24) and at week 24 was -0.10 (90% CI -0.30, 0.10). Secondary efficacy endpoints, PKs and overall safety were comparable between groups up to week 32., Conclusions: Efficacy equivalence, alongside comparable PK, safety and immunogenicity profiles, was determined between CT-P47 and r-TCZ in adults with RA, including after switching from r-TCZ to CT-P47., Competing Interests: Competing interests: JSS has received payments to institution from AbbVie, AstraZeneca, Eli Lilly, Novartis, Galapagos, and Roche; personal fees from AbbVie, Amgen, Ananda, Astro, BMS, Celltrion, Inc., Chugai, Eli Lilly, Gilead, Immunovant, MSD, Novartis, Pfizer, Roche, R-Pharma, Samsung, Sanofi, and UCB; payments or honoraria from Eli Lilly; and support for meeting attendance from Eli Lilly. MK has received support for meeting attendance from Accord, Egis, Medac, and Sandoz. SJ has received consulting fees from AbbVie, Celltrion, Inc., Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB; and payments or honoraria from AbbVie, Celltrion, Inc., Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB. RW has received speaker fees from Eli Lilly, Janssen, Novartis, SOBI, and UCB; support for meeting attendance from AbbVie; and is involved in the leadership of the Polish Rheumatology Society. MKW has received payments or honoraria from AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Medac, MSD, Novartis, Pfizer, Sandoz, SOBI and UCB; and support for meeting attendance from AbbVie, Medac, Novartis, Pfizer, and SOBI. PH has received research grants from Celltrion, Inc. GB has received honoraria for consulting and lectures from Celltrion, Inc., Chugai, Fresenius, and Sanofi. EK has received consulting fees/served on advisory boards for AbbVie, Celltrion, Inc., Eli Lilly, GSK, Pfizer, Sandoz, and Samsung Bioepsis; and has received speaker fees from AbbVie, Celltrion, Inc., GSK, Eli Lilly, Pfizer, and Sandoz. SHK is an employee of Celltrion, Inc. YJB, YBJ, GEY, and JWH are employees of Celltrion, Inc., and hold stocks in Celltrion, Inc. JT, AR, JJ, AZ, AD, KK, and PAK report no disclosures., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the relationship between disease activity and radiographic progression in rheumatoid arthritis, three phase III studies of SB4, SB2 and SB5 (biosimilars of etanercept, infliximab and adalimumab) were pooled to assess radiographic progression by disease activity status., Methods: Patients from each study with radiographic data were pooled and grouped based on disease activity state (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)), determined by disease activity score based on 28-joint count (DAS28) per erythrocyte sedimentation rate, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) at different time points. Mean change in modified Total Sharp Score (mTSS) and the proportion of radiographic non-progressors of higher disease activity groups (LDA, MDA and HDA) in reference to remission were summarised descriptively, with comparison of ORs using logistic models., Results: 1265 patients were included. In all treatments combined, the 1 year mean change in mTSS was 0.03, 0.4, 0.3 and 1.3 and proportion of radiographic non-progressors was 79.8%, 78.1%, 74.1% and 58.4% in the week 24/30 DAS28-determined remission, LDA, MDA and HDA groups, respectively. ORs (95% CIs) of the proportion of non-progressors were lowest in the HDA group in reference to remission (0.35 (0.23 to 0.54)), followed by MDA (0.72 (0.50 to 1.05)) and LDA (0.90 (0.55 to 1.48)) groups. Similar trends were observed when disease activity was assessed using SDAI or CDAI., Conclusion: A pooled analysis of radiographic assessment data from three biosimilar studies showed that radiographic progression is small overall but increases with worse disease activity., Trial Registration Numbers: NCT01895309, NCT01936181 and NCT02167139., Competing Interests: Competing interests: JSS has received personal remuneration from AbbVie, Amgen, Astra-Zeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Novo-Nordisk, Pfizer, Roche, Samsung, Sanofi and UCB and research funding from AbbVie, Janssen, Lilly, Novartis-Sandoz, Pfizer and Roche. MEW has received research funding from Bristol-Myers Squibb, Crescendo Bioscience and Sanofi/Regeneron; has served as a consultant and/or advisory board member for AbbVie, Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Corrona, GSK, Gilead, Lilly, Lycera, Merck, Novartis, Pfizer, Roche, Samsung Bioepis and Set Point; and has financial interests/stock ownership in Lycera, Canfite, Scipher and Vorso. PE has been a clinical trials investigator and advisor to Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly and has received consulting fees from Bristol-Myers Squibb, AbbVie, Gilead, Pfizer, MSD, Novartis, Roche and UCB; his employer has received research grants from AbbVie, Bristol-Myers Squibb, Pfizer, MSD and Roche. EK has received research funding from AbbVie, Amgen, Lilly, Gilead, Pfizer, PuraPharm, Sanofi and Merck; has served as a consultant and/or advisory board member for AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celltrion, Crescendo Bioscience, Roche, Genentech, Gilead, Janssen, Lilly, Merck, Pfizer, Sandoz, Sanofi and Samsung Bioepis; and has received speaker honoraria for Amgen, AbbVie, Bristol-Myers Squibb, Roche, Janssen, Merck, Pfizer, Sanofi and UCB. MCG has received research funding from AbbVie; has received consulting fees from Samsung Bioepis, Merck, Abbvie, Amgen and FKB. GM, EH, IB and JG are employees of Samsung Bioepis., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Early rheumatoid arthritis (RA) treatment requires timely recognition. This large, multicentre study compared patient-reported vs physician-reported onset of early RA., Methods: Patients from the Canadian Early ArThritis CoHort with early/suspected RA (persistent synovitis <1 year) completed questionnaires asking about the date of symptom onset; and rheumatologists date of onset for persistent synovitis. Groups with similar reported timing (patient and physician) versus differing timing of 30 days or more were compared., Results: In 2683 patients, the median patient symptom duration (IQR) was 178 days (163) and physician-reported duration was 166 (138). 1940 (72%) patients had similar patient-reported and physician-reported onset (<30 days), whereas 497 (18%) reported onset 30 or more days preceding physicians, and 246 (9%) 30 or more days after physicians. Patients reporting onset preceding physicians had lower baseline Disease Activity Score based on 28 joint count, swollen joint counts and erythrocyte sedimentation rate (p<0.05). Patients reporting onset after physicians were more likely to be rheumatoid factor positive (p<0.001) and had higher anticitrullinated protein antibody titres (p<0.009). Regression showed low income, smoking, fibromyalgia, osteoarthritis and baseline non-methotrexate non-biological disease-modifying antirheumatic drug use were predictors for longer patient-reported symptoms. At 12 months, patients reporting longer symptom duration than physicians had lower rates of Simplified Disease Activity Index remission and higher physician global assessments., Conclusion: Over one-fourth of patients reported differences of >1 month in symptom onset from their rheumatologist. Patients with longer symptom durations had less improvement at 1 year, which may be reflective of comorbid musculoskeletal conditions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study evaluated the interaction of anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in predicting sustained clinical response in an observational registry of patients with rheumatoid arthritis (RA) followed in routine practice., Methods: Patients with RA enrolled in the Ontario Best Practices Research Initiative registry, with ≥1 swollen joint, autoantibody information and ≥1 follow-up assessment were included. Sustained clinical remission was defined as Clinical Disease Activity Index (CDAI) ≤2.8 in at least two sequential visits separated by 3-12 months. Time to sustained remission was assessed using cumulative incidence curves and multivariate cox regression., Results: Among 3251 patients in the registry, 970 were included, of whom 262 (27%) were ACPA neg /RF neg , 60 (6.2%) ACPA pos /RF neg , 117 (12.1%) ACPA neg /RF pos and 531 (54.7%) ACPA pos /RF pos at baseline. Significant between group differences were observed in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02) and Health Assessment Questionnaire (p=0.002), with ACPA pos patients being youngest with lowest disease activity and disability. No difference in biologic use was found between groups (20.2% of patients).Over a mean follow-up of 3 years, sustained remission was achieved by 43.5% of ACPA pos /RF pos patients, 43.3% of ACPA pos /RF neg patients, 31.6 % of ACPA neg /RF pos patients and 32.4% of ACPA neg /RF neg patients (p=0.01). Significant differences were observed in CDAI improvement based on ACPA and RF status where ACPA pos /RF pos had a shorter time to achieving sustained remission (HR 1.30; 95% CI 1.01 to 1.67) and experienced significantly higher improvements compared with ACPA neg /RF neg patients., Conclusions: Combined ACPA and RF positivity were associated with improved and faster response to antirheumatic medications in patients with RA., Competing Interests: Competing interests: No funding has been provided for this manuscript. JP has done research studies and/or consulting for AbbVie, Amgen, BMS, GSK, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB. ER and JSS: none relevant to this project; employees at JSS Medical Research, a Contract Research Organization. EK has received sources of funding for research from Abbott Laboratories, Amgen, Bristol-Myers Squibb, F. Hoffmann-La Roche, Gilead, Janssen, Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis; has a consulting agreement and is a member of an advisory board for Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche, Genentech, Gilead, Janssen, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, UCB, Sandoz and received speaker honoraria agreements for Amgen, Abbott Laboratories, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche, Janssen, Merck, Pfizer Pharmaceuticals, Sanofi Genzyme UCB. CT has served in advisory boards for AbbVie, Amgen, Celgene, Lilly, Medexus/Medac, Merck, Novartis, Pfizer and Sanofi; has been a consultant for AbbVie, Centocor, Janssen, Lilly, Medexus/Medac and Pfizer; has been a speaker for Medexus/Medac; has participated in investigator-initiator studies supported by Amgen and Pfizer and has participated in randomised controlled trials supported by AbbVie, Celgene, CaREBiodam, Novartis and Pfizer. MM, AC, and CB are employees at OBRI. OBRI was funded by peer reviewed grants from Canadian Institute for Health Research (CIHR), Ontario Ministry of Health and Long-Term Care (MOHLTC), Canadian Arthritis Network (CAN) and unrestricted grants from Abbvie, Amgen, Celgene, Hospira, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sanofi and UCB.