Scientific Abstracts Saturday, 15 June 2013 625

life (HRQoL) and ability to perform daily activities. We report here comparative findings from patient reported outcomes (PROs) assessed with subcutaneous abatacept (ABA) or adalimumab (ADA) on background methotrexate (MTX) in the first head-to-head study, AMPLE (Abatacept Versus Adalimumab Comparison in Biologic Naive RA Subjects with Background Methotrexate).Objectives: To compare changes in PROs at 1 year in patients with RA treated with ABA or ADA, both on background MTX.Methods: AMPLE is a phase IIIb, randomized, investigator-blinded study of 2 year duration. Biologic-naïve patients with active RA and inadequate response to MTX were randomized to either 125 mg ABA weekly or 40 mg ADA bi-weekly in combination with MTX. PROs evaluated through Day 365 included: HRQoL assessed using SF-36 (including Physical and Mental Component Summary subscores [PCS and MCS]), activity limitation over the previous 30 days, with the Activity Limitation Questionnaire (ALQ)1, productivity, with the work productivity and activity impairment questionnaire for RA(WPAI:RA)2, physical and psychosocial independence, captured using items from HAQ, SF-36, and ALQ.3 Other PROs previously reported from AMPLE, include: patient pain, patient global assessment, fatigue, and physical function.4 All efficacy analyses were done using the intent-to-treat population. Baseline characteristics were analyzed descriptively and changes in PROs from baseline were assessed using ANCOVA. Results: Baseline demographic and clinical characteristics of the ABA (n=318) and ADA (n=328) treatment arms were similar4. Improvements in all domains of the SF-36, including PCS and MCS observed at Day 169 were maintained at Day 365. At baseline, the number of days (mean ± SD) with limited activity over the previous 30 days was 11.7 ± 10.4 and 12.4 ±10.3, respectively, for ABA and ADA. At Day 169, number of days with limited activity was reduced to 5.5 ± 8.2 and 5.9± 8.1, which remained sustained at Day 365 at 5.1 ± 7.4 and 6.1 ± 8.3 days for ABA and ADA, respectively. Improvements in productivity were seen in both treatment groups; however, numerically greater decreases in work and activity impairment were seen earlier at Day 169, with ABA; at Day 365, improvements were comparable among both treatment groups. At baseline, psychosocial independence was 0.3 ± 0.9 and 0.3 ± 0.8 for ABA and ADA respectively which improved at Day 365 to 1.0±1.0 and 1.0 ± 1.0. Physical independence improved from 0.5 ±1.1 and 0.5 ±1.0 at baseline to 1.4 ± 0.9 and 1.4±1.0 at Day 365 in the two groups.Conclusions: Both SC abatacept and adalimumab, on background MTX, led to comparable improvements in HRQoL, work productivity, activity limitation and physical and psychosocial independence. Improvements in these measures were evident at Day 169 and were sustained through Day 365. References: 1 Wells G et al. J Rheumatol. 2007;34(2):280-289. 2 http://www.reillyassociates.net/WPAI_SHP.html3 Hassett AL et al. Curr Med Res Opin. 2008;24(5):1443-1453.4 Weinblatt et al. Arthritis Rheum. 2013; 65 (1):28-38Disclosure of Interest: R. Fleischmann Grant/research support from: Genentech Inc., Roche, Abbott, Amgen, UCB, Pfizer, Bristol-Myers Squibb, Eli-Lilly, Sanofi-Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, Astra-Zeneca, Jansen, Consultant for: (Roche, Abbott, Amgen, UCB, Pfizer, Bristol-Myers Squibb, Eli-Lilly, Sanofi-Aventis, Lexicon, Novartis, Astellas, Astra-Zeneca, Jansen, HGS, M. Weinblatt Grant/research support from: Bristol-Myers Squibb, Abbott, Consultant for: Bristol-Myers Squibb, Abbott, M. Schiff Consultant for: Bristol-Myers Squibb, Abbott, Speakers bureau: Bristol-Myers Squibb, Abbott, D. Khanna Consultant for: Bristol-Myers Squibb, L. Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Maldonado Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, D. Furst Grant/research support from: Abbott, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: Abbott, Actelion, Amgen, BMS, BiogenIdec, Centocor, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: Abbott, Actelion, UCB (CME ONLY)

SAT0130 DEFINING THE OPTIMAL BIOLOGICAL MONOTHERAPY IN RHEUMATOID ARTHRITIS (RA): NETWORK META-ANALYSIS OF RANDOMIZED TRIALS

R. Christensen1, S. Tarp1, D. E. Furst2, M. Østergaard3, T. Lorenzen4, M. S. Hansen5, J. A. Singh6, E. H. Choy7, M. Boers8, M. E. Suarez-Almazor9, B. Ejbjerg10, L. E. Kristensen11, H. Bliddal1. 1Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen University Hospital, Frederiksberg, Denmark, 2David Geffen School of Medicine, UCLA, LA, United States, 3Dept Rheum, Glostrup Hospital, Glostrup, 4Dept Rheum, Silkeborg Hospital, Silkeborg, 5Dept Rheum, Copenhagen University Hospital, Gentofte, Denmark, 6University of Alabama, Birmingham, United States, 7Cardiff School of Medicine, Cardiff, United Kingdom, 8Dept Epi Biostat, VU University Medical Center, Amsterdam, Netherlands, 9University of Texas, Houston, United States, 10Slagelse Hospital, Slagelse, Denmark, 11Lund University, Lund, Sweden

Background: Methotrexate (MTX) is considered the anchor drug in RA, both as monotherapy, as well as for its ability to increase the efficacy of biologic agents when used in combination [1]. Some RA patients have to discontinue DMARD therapy. Thus, it is important to define the optimal biological monotherapy in RA patients.Objectives: To review the evidence for short-term efficacy and safety of biologic monotherapy in RA. The aim was to define the optimal biological monotherapy in RA patients without concomitant use of any DMARD therapy.Methods: Systematic review and Network Meta-Analysis of RCTs with DMARD inadequate responders (IR) and DMARD naïve RA patients,

comparing biologic agents in monotherapy with either placebo (no DMARD) or DMARD, were considered eligible for inclusion. The co-primary outcomes were the number of patients achieving an ACR50 response, and the number discontinuing therapy due to adverse events (AE) [2] preferably after 6 months (3-12 months), respectively. The network meta-analysis was based on mixed-effects logistic regression (GLMM modelled in SAS) [2]; combining statistical inference from both direct and indirect comparisons of the treatment effects between biologics. All dosages applied for all of the nine biologics. Results are reported as odds ratios (OR [95%CI]). For sensitivity, in terms of the included patients, we compared DMARD IR responder trials with DMARD Naïve trials.Results: From the literature search 27 individual studies (7,938 patients) were included: abatacept [Aba:1], adalimumab [Ada:5], anakinra [Ana:2], certolizumab [Cer:2], etanercept [Eta:6], golimumab [Gol:3], infliximab [Inf:1], rituximab [Rit:1] and tocilizumab [Toc:6]. The network only included one ‘closed loop’ with biologics head-to-head: ADACTA (Toc vs. Ada) [3]. Benefit (ACR50): Ana was statistically less likely than Ada, Eta, Gol, and Toc, respectively, to have a clinical response (p<0.05). The odds for responding was statistically higher (p<0.05) for Toc compared to Aba (3.9[1.2;12.4]), Ada (2.1[1.2;3.6]), and Inf (7.7[1.8;32.4]), respectively. Finally, Eta was statistically more likely to result in a response than Inf (5.6[1.3;23.9]). Harm (Withdrawal d/t AEs): Gol seemed less likely to cause withdrawal from side effects (p<0.05) compared to Ada (0.4[0.1;0.9]), Ana (0.3[0.1;0.8]), Cer (0.3[0.1;1.0]), Inf (0.2[0.1;1.0]), and Toc (0.4[0.1;0.8]). For sensitivity, the ACR50 estimates were compared with the direct comparison of Ada vs. Toc [3]; the model apparently did not build on incoherence, as data from the ADACTA study reported a comparable effect size (OR=2.3 [1.5; 3.7]).Conclusions: All biologics are not equal. In RA patients who need biologic therapy without concomitant use of DMARDs, some biologics are better than others with respect to ACR50 responses.References: [1] Smolen J, et al. Ann Rheum Dis. 2010;69(6):964-75. [2] Singh JA, et al. CMAJ. 2009;181(11):787-96.[3] Gabay C, et al. Lancet (Accepted, 2013)Acknowledgedments: Musculoskeletal Statistics Unit, The Parker Institute receives support via research grants from the Oak Foundation.Disclosure of Interest: R. Christensen Grant/research support from: This particular study, including both the protocol and subsequent manuscript, has been supported by a grant from Roche; the grant was provided as an unrestricted grant to Musculoskeletal Statistics Unit, The Parker Institute., Speakers bureau: Abbott, BMS, Pfizer, Roche, MSD, Expanscience, Biogen Idec, Ipsen, Novartis, Bayer, S. Tarp: None Declared, D. Furst: None Declared, M. Østergaard: None Declared, T. Lorenzen: None Declared, M. Hansen: None Declared, J. Singh: None Declared, E. Choy: None Declared, M. Boers: None Declared, M. Suarez-Almazor: None Declared, B. Ejbjerg: None Declared, L. Kristensen: None Declared, H. Bliddal: None Declared

SAT0131 LONG-TERM SAFETY OF RITUXIMAB: POOLED ANALYSIS OF THE RHEUMATOID ARTHRITIS GLOBAL CLINICAL TRIAL PROGRAMME OVER 11 YEARS

R. F. van Vollenhoven1, P. Emery2, C. O. Bingham3, E. Keystone4, R. M. Fleischmann5, D. Furst6, E. W. Hessey7, A. Vashishtha8, A. Mehbob7, P. B. Lehane7. 1Department of Medicine, Karolinska Institute, Stockholm, Sweden, 2Division of Rheumatic & Musculoskeletal Disease, University of Leeds and Leeds Teaching Hospitals Trust, Leeds, United Kingdom, 3Department of Medicine, The Johns Hopkins University, Baltimore, United States, 4The Rebecca MacDonald Centre for Arthritis and Autoimmunity, Mount Sinai Hospital, Toronto, Canada, 5Southwestern Medical Center at Dallas, University of Texas, Dallas, 6Department of Rheumatology, UCLA, Los Angeles, United States, 7Roche Products Limited, Welwyn Garden City, United Kingdom, 8Genentech Inc., South San Francisco, United States

Objectives: To conduct an updated overall safety analysis of rituximab (RTX) in RA patients in the global clinical trial programme.Methods: Pooled observed case analysis of safety data from patients with moderate to severe active RA treated with RTX+MTX. Patients were retreated based on physician’s determination of clinical need and evidence of active disease (defined as either SJC and TJC ≥8 or DAS28 ≥2.6). Pooled data from patients who received placebo during placebo-controlled study periods were also analysed.Results: As of Sep 2012, 3595 patients (All-Exposure population) had received up to 20 courses of RTX over the 11-yr observation period (14 816 pt-yrs). Of these patients, 1246 had >5yrs follow-up. The placebo population comprised 818 patients (1107 pt-yrs) with a mean follow-up of 1–1.5 yrs. In the All-Exposure population, infusion-related reaction (IRR) was the most frequent adverse event (AE); most were grade 1 or 2, were rarely serious (0.5%), and primarily occurred following the 1st infusion of the 1st course (799/3595 patients; 22%). Rates per 100 pt-yrs for AEs, serious AEs (SAEs), and infections were not increased when compared to placebo (Table). Overall the serious infection rate in RTX-treated patients was comparable to that observed in placebo patients. Pneumonia was the most frequently reported serious infection (2% of RTX patients). There were no cases of hepatitis B reactivation. Serious opportunistic infections were rare (0.05/100 pt-yrs in RTX patients vs 0.09/100 pt-yrs in placebo). One confirmed case of PML in the RA clinical trial programme has been reported, as previously described.1 Following RTX treatment low immunoglobulin (Ig) concentrations (particularly IgM, less often IgG) were observed. For both Ig classes, serious infection rates were similar before and during/after development of low Ig. No increased risk of malignancy

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Network Meta-Analysis of Randomized TrialsMonotherapy in Rheumatoid Arthritis (RA):

Defining the Optimal Biological SAT0130

Ejbjerg, L. E. Kristensen and H. BliddalHansen, J. A. Singh, E. H. Choy, M. Boers, M. E. Suarez-Almazor, B. R. Christensen, S. Tarp, D. E. Furst, M. Østergaard, T. Lorenzen, M. S.

doi: 10.1136/annrheumdis-2013-eular.18562013 72: A625 Ann Rheum Dis 

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