Search

ObjectiveTo evaluate secukinumab (SEC) 300 mg and 150 mg vs placebo in a United States–only population of biologic-naïve patients with psoriatic arthritis (PsA).MethodsCHOICE was a double-blind, randomized controlled trial conducted in the US. Biologic-naïve patients with PsA and psoriasis (PsO) were randomized 2:2:1 to SEC 300 mg (n = 103), SEC 150 mg (n = 103), or placebo (n = 52). The primary objective was to show superiority of SEC 300 mg vs placebo in American College of Rheumatology 20% (ACR20) response at week 16. Additional objectives included the effect of SEC on dactylitis, enthesitis, PsO, and safety.ResultsACR20 response rates at week 16 were higher with SEC 300 mg than with placebo (51.5% vs 23.1%; odds ratio 3.51 [95% CI 1.65-7.45]; P = 0.001). SEC 300 mg also led to greater ACR50/70 responses and improvements in other variables vs placebo. Responses were generally sustained over time. Patients with inadequate response to SEC 150 mg at weeks 16, 28, or 40 who received dose escalation to 300 mg experienced improved clinical response after uptitration. The most common adverse events were upper respiratory tract infections and diarrhea. No inflammatory bowel disease was reported or new safety signals observed.ConclusionSEC 300 mg led to rapid and significant improvements over placebo in symptoms of PsA in this heavier population of US-only, biologic-naïve patients. Findings were consistent with previous studies and suggest that SEC 300 mg is a safe and efficacious first-line biologic treatment for patients with PsA. [ClinicalTrials.gov: NCT02798211]

Summary Background Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X. Methods COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomly assigned (1:1:1) to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo. Changing background medications or switching to open-label ixekizumab Q2W, or both, was allowed after week 16 at investigator discretion. Primary endpoints were Assessment of SpondyloArthritis international Society-40 (ASAS40) response (defined as an improvement of 40% or more and an absolute improvement from baseline of 2 units or more [range 0–10] in at least three of the four domains [patient global, spinal pain, function, and inflammation] without any worsening in the remaining one domain) at weeks 16 and 52. Patients who switched to open-label ixekizumab were imputed as non-responders in logistic regression analysis. This trial is registered with ClinicalTrials.gov , number NCT02757352 . Findings Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled (105 to placebo, 96 to ixekizumab Q4W, and 102 to ixekizumab Q2W). Both primary endpoints were met: ASAS40 at week 16 (ixekizumab Q4W: 34 [35%] of 96, p=0·0094 vs placebo; ixekizumab Q2W: 41 [40%] of 102, p=0·0016; placebo: 20 [19%] of 105) and ASAS40 at week 52 (ixekizumab Q4W: 29 [30%] of 96, p=0·0045; ixekizumab Q2W: 32 [31%] of 102, p=0·0037; placebo: 14 [13%] of 105). 60 (57%) of 104 patients in the placebo group, 63 (66%) of 96 in the ixekizumab Q4W group, and 79 (77%) of 102 in the ixekizumab Q2W group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events in the ixekizumab groups were nasopharyngitis and injection site reaction. Of the treatment-emergent adverse events of special interest, there was one case of serious infection in the ixekizumab Q4W group. The frequency of serious adverse events was low (four [1%] of 302) and similar across the three groups. There were no malignancies or deaths. No new safety signals were identified. Interpretation Ixekizumab was superior to placebo for improving signs and symptoms in patients with non-radiographic axial spondyloarthritis at weeks 16 and 52. Reports of adverse events were similar to those of previous ixekizumab studies. Ixekizumab offers a potential therapeutic option for patients with non-radiographic axial spondyloarthritis who had an inadequate response or were intolerant to NSAID therapy. Funding Eli Lilly and Company.

Objective: To evaluate the safety and efficacy of golimumab through 5 years in adults with active rheumatoid arthritis (RA) who had not previously received methotrexate (MTX). Methods: In the GO-BEFORE study, 637 MTX-naive adult patients with active RA were randomized (1:1:1:1) to placebo + MTX (group 1), golimumab 100 mg + placebo (group 2), golimumab 50 mg + MTX (group 3), or golimumab 100 mg + MTX (group 4). Inadequate responders in groups 1, 2, and 3 entered early escape at week 28 to golimumab 50 mg + MTX, golimumab 100 mg + MTX, or golimumab 100 mg + MTX, respectively; remaining patients in group 1 could cross over to golimumab 50 mg + MTX at week 52. Assessments included the American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) response, the Disease Activity Score in 28 joints (DAS28) using C-reactive protein (CRP) level, and the modified Sharp/van der Heijde score (SHS). Efficacy was analyzed using an intent-to-treat (ITT) analysis. Pharmacokinetics and immunogenicity were evaluated at selected visits. Results: A total of 422 patients completed golimumab treatment through week 256. At week 256, 72.8%, 54.6%, and 38.0% of all patients in the full ITT population (n = 637) had an ACR20/50/70 response, respectively; 84.1% had a good or moderate DAS28-CRP response; and 72.7% had a clinically meaningful improvement in physical function. Radiographic progression was minimal in all treatment groups through week 256, and the overall mean change from baseline in SHS was 1.36. Serum trough golimumab concentrations were approximately dose proportional and maintained through week 256. Antibodies to golimumab occurred in 9.6% of patients through week 256. Infections were the most common type of adverse event (AE); 204 of 616 patients (33.1%) had ≥1 serious AE. Conclusions: Clinical efficacy with golimumab treatment was maintained through week 256 of the GO-BEFORE trial of MTX-naive RA patients. No unexpected AEs occurred; safety results through 5 years are consistent with earlier reports.

Objective The aim of the Patient/Physician Reported Efficacy Determination In Clinical Practice Trial (PREDICT; ClinicalTrials identifier NCT01255761) was to compare the patient-reported Routine Assessment of Patient Index Data 3 (RAPID-3) instrument with the investigator-based Clinical Disease Activity Index (CDAI) for assessing certolizumab pegol (CZP) treatment response in rheumatoid arthritis patients at 12 weeks and to predict the treatment response at week 52 using the data from week 12 (coprimary end points). Methods Patients received 400 mg of CZP at weeks 0, 2, and 4 (loading dose), followed by 200 mg every 2 weeks thereafter. Patients were randomized 1:1 to assessment with the RAPID-3 or the CDAI. Responder classification was performed at week 12; treatment response was defined as a score of ≤6 or a 20% improvement over baseline on the RAPID-3 or a score of ≤10 or a 20% improvement over baseline on the CDAI. Long-term treatment success was defined as a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) of ≤3.2 at week 52. Comparisons were made for the coprimary end points using noninferiority methods. Patients with improvement of 22 or RAPID-3 score >12) at 2 consecutive visits were withdrawn from the study. Results Patients had longstanding disease (mean 8.9 years) and high levels of disease activity (mean scores of 6.3 on the DAS28-ESR, 16.1 on the RAPID-3, and 40.2 on the CDAI). Previous anti–tumor necrosis factor therapy had failed in 55.5% of them. At week 12, a total of 64.7% (by RAPID-3) and 76.4% (by CDAI) of the patients were classified as responders (difference of −11.9% [95% confidence interval −18.4%, −5.3%]). At week 52, a total of 31.5% (by RAPID-3) and 32.3% (by CDAI) of the responders achieved a low level of disease activity on the DAS28-ESR (difference of −1.3% [95% confidence interval −9.3%, 6.6%]). Conclusion The CDAI classified more patients as CZP responders at week 12 than did the RAPID-3. Although these outcome measures were not statistically comparable, the positive predictive value for low disease activity at week 52 was similar. As these tools cover differing domains of therapy response, further evaluation for clinical disease activity assessments and treatment decisions is needed.

To assess 2-year golimumab efficacy/safety in patients with active rheumatoid arthritis (RA) who had never taken methotrexate (MTX).RA patients who had never taken MTX (n = 637) were randomized (1:1:1:1) to placebo + MTX (group 1), golimumab 100 mg + placebo (group 2), golimumab 50 mg + MTX (group 3), or golimumab 100 mg + MTX (group 4) every 4 weeks. Nonresponders based on week 28 swollen/tender joint counts changed treatment as follows: group 1 added golimumab 50 mg, group 2 added MTX, group 3 increased golimumab to 100 mg, and group 4 had no change. Most group 1 patients (85%) initiated golimumab 50 mg + MTX at week 28 or subsequently at week 52. After the last patient completed week 52 and blinding was broken, the investigator could escalate golimumab to 100 mg and/or adjust MTX. The co–primary end points (week 24 American College of Rheumatology criteria for 50% improvement [ACR50] response and week 52 change in Sharp/van der Heijde score [SHS]) have been published previously. We now detail week 52 major secondary end points (Health Assessment Questionnaire [HAQ] disability index [DI] scores and SHS among patients with a baseline C-reactive protein [CRP] level1.0 mg/dl) and week 104 findings.At week 52 for combined groups 3 and 4 versus group 1, the respective proportions of patients achieving ACR20 and ACR50 responses were 63.2% versus 51.9% (P = 0.017) and 45.3% versus 35.6% (P = 0.044). Respective week 52 mean HAQ DI improvements were 0.70 versus 0.58 (P = 0.053); mean SHS changes were 0.41 versus 1.37 (P = 0.006) among all patients and 0.74 versus 2.16 (P = 0.003) in patients with a CRP level1.0 mg/dl. Improvements were maintained through week 104. Golimumab + MTX for 2 years yielded statistically less radiographic progression than initial MTX or golimumab 100 mg monotherapy. Golimumab safety profiles through weeks 24, 52, and 104 were generally consistent with those observed in other golimumab studies.In RA patients who had never taken MTX, up to 2 years of golimumab + MTX yielded sustained improvements in clinical signs/symptoms, physical function, and radiographic progression.

Objective. To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis (RA). Methods. MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1). Results. An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P = 0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P = 0.049) and between group 3 (40.5%; P = 0.038) but not group 4 (36.5%; P = 0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound -5.2%; predefined delta value for noninferiority -10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively. Conclusion. Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns.

OBJECTIVE: The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis. METHODS: This was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1∶1∶1∶1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control (saline). The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs). RESULTS: A total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control (-0.93 vs -0.72; estimated difference from control: -0.25, p = 0.004); an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was -0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%). CONCLUSIONS: This clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee. TRIAL REGISTRATION: ClinicalTrials.gov NCT01839331.

Objective. Rheumatoid arthritis (RA) causes substantial morbidity and mortality, and current treatments are suboptimal. Recent studies have demonstrated the short-term efficacy of minocycline in the treatment of patients with early RA. This study was undertaken to compare patients treated with conventional therapy in the early phase of their RA and those treated with minocycline, after 4 years of followup. Methods. Forty-six patients with seropositive RA of <

Objective To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). Methods RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. Results Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. Conclusion The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ.

Background Guidelines support regular quantitative disease activity monitoring and early intervention in rheumatoid arthritis (RA), but there is no uniform agreement on the best measurement tool. 1,2 While physician-based tools like the Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI) are commonly used, 3 the patient-based Routine Assessment of Patient Index Data (RAPID3) tool has also been shown to be able to distinguish active from control treatments in clinical trials. 4 Objectives To compare the CDAI to the RAPID3 tool in RA patients (pts) 12 weeks (wks) after starting certolizumab pegol (CZP) and assess their ability to predict treatment success at Wk52 and to report patient-reported outcomes (PROs) from the PREDICT trial. Methods In this 52-wk study (NCT01255761), pts received CZP standard dosing regimen (400mg at Wks 0, 2, 4 [loading dose], then 200mg Q2W). Pts were randomized 1:1 to RAPID3 or CDAI for classification as Responder/Non-Responder at Wk12. Treatment decision at Wk12 was based upon randomization arm (RAPID3 Responder, ≤6 or 20% improvement from Baseline [BL]; CDAI Responder, ≤10 or 20% improvement from BL). Treatment success at Wk52 was defined as DAS28(ESR) ≤3.2. PRO endpoints included assessment of physical function, pain, disease activity and symptomatic state. The results are presented for the full analysis set (FAS); for efficacy results, both arms were adjusted for BL covariates, including DAS28(ESR) scores. Results At Wk12, 64.7% and 76.4% of pts randomized to RAPID3 and CDAI, respectively, were classified as Responders (Table). At Wk52, 31.5% of Wk12 RAPID3 Responders and 32.3% of Wk12 CDAI Responders achieved DAS28(ESR) low disease activity (LDA), and 21.8% and 23.2% achieved remission, respectively, demonstrating similar positive predictive values of these measures (Table). Pts reported improvements for physical function (MDHAQ-FN), pain (PtAAP), disease activity (PtGADA) and symptomatic state (PASS) as early as Wk2, which continued to Wk12 and were maintained to Wk52. Similar changes were observed in PRO measures of both groups. Conclusions The physician-based assessment detected greater CZP response at Wk12, compared with the patient-reported tool. The positive predictive value for LDA at Wk52 for both assessments was similar. Further analysis is needed to evaluate the sensitivity and specificity of these measures for disease activity assessments and treatment decisions in RA. Improvements in PROs were observed in both groups as early as Wk2 and were maintained to Wk52. References Saag K.G. Arthritis Rheum 2008; 59(6):762-784; 2. Smolen J.S. Curr Med Res Opin 2011; 27(2):315-325; 3. Anderson J. Arthritis Care Res 2012; 64:640-647; 4. Castrejόn I. Clin Exp Rheumatol 2012; 30:S50-55 Acknowledgements The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. Disclosure of Interest J. Curtis Grant/research support: Roche, Genentech, UCB Pharma, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, Consultant for: Roche, Genentech, UCB Pharma, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, AbbVie, M. Churchill: None declared, A. Kivitz Grant/research support: Abbott, Pfizer, Merck, Janssen, Novartis, Celgene, UCB Pharma, Consultant for: Abbott, Pfizer, Janssen, Celgene, UCB Pharma, A. Samad Employee of: Ardea Biosciences, L. Gauer Employee of: UCB Pharma, G. Coteur Employee of: UCB Pharma, L. Gervitz Employee of: UCB Pharma, W. Koetse Shareholder of: UCB Pharma, Employee of: UCB Pharma, J. Melin Employee of: UCB Pharma, Y. Yazici Grant/research support: BMS, Genentech, Celgene, Consultant for: Abbvie, BMS, Celgene, Genentech, Pfizer, Samumed, UCB Pharma DOI 10.1136/annrheumdis-2014-eular.1674

randomized controlled trial (RCT)—the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial—to examine whether responses to intensive combination treatments in early RA differ by ACPA status. Methods: The CARDERA trial randomized 467 patients with early active RA to receive: (i) MTX (ii) MTX/ciclosporin (iii) MTX/prednisolone or (4) MTX/ciclosporin/prednisolone in a factorial-design. Patients were assessed 6 monthly for 2 years. In this analysis we evaluated 431 patients with archived serum available for ACPA status determination (using the anti-CCP2 ELISA assay). To minimize multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline for each outcome (Larsen, DAS28, HAQ, EuroQol, PCS and MCS scores). When a significant interaction was present, mean changes in outcomes were compared by treatment group at each time point stratified by ACPA status using t-tests. Odds ratios (ORs) for the onset of new erosions with treatment were calculated stratified by ACPA. Results: Of the 431 RA cases, 310 (72%) were ACPA-positive; 121 (28%) were ACPA-negative. ACPA status influenced the effect of treatment on radiological progression, with a significant ACPA*treatment interactive effect on Larsen score changes seen in the ANOVA model (P< 0.001). ACPA-positive patients had significant reductions in Larsen score progression with all treatments; no effect was seen in ACPAnegative RA. ACPA-positive patients receiving triple therapy had the greatest benefits: mean Larsen score increases over 2 years were 3.66 (95% CI 2.27, 5.05) with triple therapy and 9.58 (95% CI 6.76, 12.39) with monotherapy; OR for new erosions with triple therapy vs monotherapy was 0.32 (95% CI 0.14, 0.72; P1⁄40.003). ACPA-negative patients had minimal radiological progression irrespective of treatment strategy: mean Larsen score increases over 2 years comprised 1.70 (95% CI 0.29, 3.10) with triple therapy and 2.72 (95% CI 1.15, 4.29) with monotherapy; only 7% developed new erosions. The beneficial effects of high-dose corticosteroids on reducing disease activity and improving physical health were confined to ACPA-positive RA. Conclusion: ACPA status influences the need for, and response to, combination DMARDs and high-dose tapering corticosteroids in early RA. Combination DMARDs and corticosteroids only provided radiological, disease activity and physical health benefits in ACPA-positive patients. This suggests that current UK guidelines advocating combination DMARDs and corticosteroids in all early active RA patients require reconsideration. Funding: This research was supported Arthritis Research UK [Grant Number 19739 to ICS], the National Institute for Health Research (NIHR) and the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. Disclosure statement: The authors have declared no conflicts of interest.

Objective. To determine if minocycline is an effective therapy for seropositive rheumatoid arthritis (RA) when used within the first year of disease. Methods. The Rheumatoid Arthritis Investigational Network enrolled 46 patients with RA of

Objectives Final 5yr safety and efficacy results of subcutaneous golimumab (GLM)+/-MTX evaluated in a phase 3 trial (GO-BEFORE) of MTX-naive pts with rheumatoid arthritis (RA) are reported. Methods Pts were randomized to PBO+MTX, GLM 100mg+PBO, GLM 50mg+MTX, or GLM 100mg+MTX q4w. PBO+MTX pts crossed over to GLM+MTX at wks 28 (blinded early escape) or 52 (pts with ≥1 swollen/tender joint). Pts continued treatment at wk52 (start of long-term extension). After the last pt completed wk52 and unblinding occurred, PBO+MTX pts could switch to GLM 50mg+MTX, MTX and corticosteroid use could be adjusted, and a one-time GLM dose change (50 → 100mg or 100 → 50mg) was permitted at investigator’s discretion. The last GLM injection was at wk252. Observed efficacy results (ACR20/50/70, DAS28-CRP, HAQ-DI, radiographic) by randomized treatment group and cumulative safety data are reported through wks 256 and 268, respectively. Results Of 637 randomized pts, 3 were never treated; 419 continued treatment through wk252, and 215 withdrew (111 for AE, 23 for lack of efficacy, 20 lost to follow-up, 53 for other reasons, 8 deaths). 402 completed the safety follow-up through wk268. Efficacy results are presented in the table. At wk 256, 84.3% of all pts had an ACR20, 93.9% had DAS28-CRP EULAR response, and 80.6% had improvement in HAQ-DI ≥0.25. Mean changes from baseline in total vdH-S score were small and 64% of pts randomized to GLM+MTX had no radiographic progression (ΔvdH-S≤0). The most common AEs were upper respiratory tract infection(29.4%), nausea(19.6%), bronchitis(16.6%), and increased alanine aminotransferase(16.1%); 11.9% of pts had an injection-site reaction. Through wk268, 204/616(33.1%) pts had an SAE; 17.5% of pts discontinued study agent due to AEs. Overall rates of serious infections, malignancies, and death were 12.2%, 3.4%, and 1.9%, resp. Of 595 pts with available samples, 58(9.7%) were positive for antibodies to GLM. Image/graph Conclusions The retention rate was high(66.1%) through 5yrs. GLM+MTX therapy resulted in maintained improvements in signs/symptoms of RA and in physical function, and inhibited structural damage progression long-term. No new safety signals were detected through 5years in MTX-naive RA pts. Disclosure of Interest P. Emery Grant/research support from: Janssen R&D, LLC, R. Fleischmann Grant/research support from: Janssen R&D, LLC, I. Strusberg Grant/research support from: Janssen R&D, LLC, P. Durez Grant/research support from: Janssen R&D, LLC, P. Nash Grant/research support from: Janssen R&D, LLC, E. Amante Grant/research support from: Janssen R&D, LLC, M. Churchill Grant/research support from: Janssen R&D, LLC, W. Park Grant/research support from: Janssen R&D, LLC, B. Pons-Estel Grant/research support from: Janssen R&D, LLC, C. Han Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, T. Gathany Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Y. Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, S. Xu Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC, E. Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen R&D, LLC

Introduction The aim of this study was to evaluate the safety, pharmacokinetics, and clinical response of brodalumab (AMG 827), a human, anti-IL-17 receptor A (IL-17RA) monoclonal antibody in subjects with moderate-to-severe rheumatoid arthritis (RA). Methods This phase Ib, randomized, placebo-controlled, double-blind multiple ascending dose study enrolled subjects with moderate to severe RA (≥6/66 swollen and ≥8/68 tender joints). Subjects were randomized 3:1 to receive brodalumab (50 mg, 140 mg, or 210 mg subcutaneously every two weeks for 6 doses per group; or 420 mg or 700 mg intravenously every 4 weeks for two doses per group) or placebo. Endpoints included incidence of adverse events (AEs) and pharmacokinetics. Exploratory endpoints included pharmacodynamics, and improvements in RA clinical metrics. Results Forty subjects were randomized to investigational product; one subject discontinued due to worsening of RA (placebo). The study was not designed to assess efficacy. AEs were reported by 70% (7/10) of placebo subjects and 77% (22/30) of brodalumab subjects. Three serious AEs were reported in two subjects; there were no opportunistic infections. Brodalumab treatment resulted in inhibition of IL-17 receptor signaling and receptor occupancy on circulating leukocytes. No treatment effects were observed with individual measures of RA disease activity. On day 85 (week 13) 37% (11/30) of brodalumab subjects and 22% (2/9) of placebo subjects achieved ACR20; 7% (2/30) brodalumab subjects and 11% (1/9) of placebo subjects achieved ACR50; and 0% (0/30) brodalumab subjects and 0% (0/9) of placebo subjects achieved ACR70. Conclusions Multiple dose administration of brodalumab was tolerated in subjects with active RA. There was no evidence of a clinical response to brodalumab in subjects with RA. Trial registration ClinicalTrials.gov, NCT00771030