H. van Hoogstraten

SAT0180 Onset of Action of Sarilumab in Patients with Rheumatoid Arthritis in 2 Phase 3 Studies

Background The investigational human anti–interleukin 6 receptor monoclonal antibody sarilumab plus methotrexate (MTX) has demonstrated efficacy in patients with rheumatoid arthritis (RA) and inadequate response to MTX (MOBILITY; NCT01061736),1 while sarilumab plus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) demonstrated efficacy in patients with RA and inadequate response or intolerance to tumor necrosis factor (TNF) inhibitors (TARGET; NCT01709578).2 Among the most common treatment-emergent adverse events in both studies were infections, neutropenia, injection site reactions, and increased transaminases. Objectives This analysis of MOBILITY and TARGET study data assessed the time to onset of clinical efficacy of sarilumab and the durability of response over 24 weeks. Methods Adults with active, moderate-to-severe RA were randomized to 1 of 3 groups receiving subcutaneous sarilumab 150 or 200 mg or placebo every 2 weeks (q2w) plus background MTX (MOBILITY) or csDMARDs (TARGET). Clinical efficacy was evaluated in these patients at weeks 2, 4, 8, 12, and 24 in a post hoc analysis. ACR20/50/70 response rates were analyzed using the 2-sided Cochran-Mantel-Haenszel test stratified by prior biologic use and region (MOBILITY) or by region and number of prior TNF inhibitors (TARGET); nonresponder imputation was applied for patients who started rescue medication or discontinued the study. Changes from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI), 28-joint disease activity score by C-reactive protein (DAS28-CRP), and clinical disease activity index (CDAI) were analyzed with a mixed model for repeated measures; no data were imputed. Results Baseline demographic and disease characteristics were similar between treatment groups in both studies.1,2 Improvements in ACR20 responses were observed as early as week 2 in both studies, with nominal P<0.05 observed at week 8 for all sarilumab-treated groups in both studies. Similar trends were observed for ACR50 and ACR70 responses. Greater reductions in DAS28-CRP mean change from baseline vs placebo were observed with both doses of sarilumab by week 2 in both studies (nominal P<0.05). Similarly, numerical improvements in HAQ-DI and CDAI were observed with both doses of sarilumab vs placebo by week 4 in both studies (nominal P<0.05; Table). Improvements in all efficacy parameters were sustained through the end of each study (ie, week 52 for MOBILITY and week 24 for TARGET). The most common treatment-emergent adverse events at week 12 were infection and neutropenia, consistent with the safety profile previously reported for the entire study periods. Conclusions Sarilumab rapidly improved signs and symptoms of RA in patients with inadequate response to MTX (MOBILITY) or TNF inhibitors (TARGET), and improvements were sustained through the end of treatment. References Genovese et al. Arthritis Rheumatol. 2015;67:1424–1437 Fleischmann et al. Presented at: ACR; Nov. 7–11, 2015; San Francisco, CA Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Kristi Porter, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest R. Fleischmann Grant/research support from: AbbVie, Amgen, Ardea Biosciences, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Eli Lilly, Pfizer, Roche, Sanofi, and UCB, Consultant for: AbbVie, Akros Pharma, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Roche, and UCB, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, D. Bauer Shareholder of: Sanofi, Employee of: Sanofi, D. Thompson Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Kivitz Shareholder of: Sanofi and Regeneron Pharmaceuticals, Inc., Consultant for: Sanofi, Pfizer, Roche, and UCB, G. Burmester: None declared

FRI0228 Sarilumab Dose Reduction To Manage Laboratory Abnormalities in An Open-Label Extension Study in RA Patients

Background The investigational agent sarilumab is a human monoclonal antibody directed against the interleukin 6 (IL-6) receptor. In the phase 3 MOBILITY (NCT01061736) and TARGET (NCT01709578) studies, sarilumab (150 or 200 mg subcutaneously every 2 weeks [q2w] + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) demonstrated efficacy in adults with active, moderate-to-severe rheumatoid arthritis (RA).1 Among the most common treatment-emergent adverse events in both studies were infections, neutropenia, injection site reactions, and increased transaminases. Laboratory changes were consistent with IL-6 signaling blockade. Objectives This analysis examined laboratory changes and treatment continuation after sarilumab dose reduction in EXTEND (NCT01146652), an open-label, follow-up study that evaluated long-term safety and efficacy of sarilumab with or without concomitant csDMARDs. Methods Adults with RA who previously participated in sarilumab studies were eligible. Patients who entered into EXTEND before dose selection for the phase 3 studies received sarilumab 150 mg every week. After dose selection for the phase 3 studies, patients were switched to or initiated on sarilumab 200 mg q2w. Per protocol, investigators could have reduced the dose of sarilumab to 150 mg q2w for absolute neutrophil count (ANC) ≥0.5 to 1.0 Giga/L, platelet count ≥50 to 100 Giga/L, or alanine aminotransferase (ALT) ≥3 to 5× upper limit of normal. Dose reductions to avoid laboratory changes were also performed at the investigators discretion. Efficacy data from EXTEND were analyzed before and 24 weeks after dose reduction for patients entering from the MOBILITY (n=158) and TARGET (n=42) studies. Results As of the April 2015 interim analysis, dose reduction from sarilumab 200 to 150 mg q2w had occurred in 15% of patients. The most common reasons for dose reduction were decreases in ANC (9.5%) and elevations in ALT (3.3%) (Table). Infection was the most common non-laboratory reason for dose reduction (0.4%). At the time of analysis, 80.1% of patients who dose reduced were continuing treatment, with a mean treatment duration of 1.5 years after dose reduction. Improvements in ANC and ALT were observed over the 6 months after dose reduction. Efficacy of sarilumab was maintained in patients from MOBILITY and TARGET after dose reduction in EXTEND as assessed by ACR20 responses (83.3% and 77.4%, respectively) and HAQ-DI scores (-0.68 and -0.73, respectively). Conclusions In patients whose sarilumab dose was decreased from 200 mg q2w to 150 mg q2w, there was an improvement in laboratory abnormalities and continuation of treatment for the majority of patients. Improvements in signs and symptoms of RA and physical function were maintained after dose reduction. References Genovese et al. Arthritis Rheumatol. 2015;67:1424–1437. Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial support was provided by Kristi Porter, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest M. Genovese Grant/research support from: Roche, Sanofi, GSK, R-Pharma, RuiYi, and Bristol-Myers Squibb, Consultant for: Roche, Sanofi, GSK, R-Pharma, RuiYi, and Bristol-Myers Squibb, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Parrino Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Garg Shareholder of: Sanofi, Employee of: Sanofi, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, A. Boddy Shareholder of: Sanofi, Employee of: Sanofi, R. Martincova Shareholder of: Sanofi, Employee of: Sanofi, N. Graham Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Simon: None declared, G. Burmester Grant/research support from: from AbbVie, Bristol-Myers Squibb, MedImmune, Merck, Pfizer, Roche, and UCB, Consultant for: from AbbVie, Bristol-Myers Squibb, MedImmune, Merck, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and UCB

OP0102 Patient reported benefits of sarilumab monotherapy versus adalimumab monotherapy in adult patients with active rheumatoid arthritis

Background The phase 3 MONARCH superiority study (NCT02332590) compared efficacy and safety of sarilumab (a human anti-IL-6Rα monoclonal antibody [mAb]) 200 mg administered subcutaneously every 2 weeks (q2w), with adalimumab (an anti-TNF-α mAb) 40 mg administered q2w, in patients with active rheumatoid arthritis (RA) who were either intolerant of, or inadequate responders to methotrexate treatment. Sarilumab monotherapy demonstrated superiority to adalimumab monotherapy in reduction of disease activity and improvements in physical function and signs and symptoms of RA, with safety and tolerability consistent with IL-6R or TNF blockade. Objectives To compare patient-reported outcomes (PROs) with sarilumab vs adalimumab from MONARCH. Methods PROs assessed at baseline, weeks 12 and 24 included ACR components (Patient Global Assessment of Disease Activity [PtGA], Pain visual analog scale [VAS], Health Assessment Questionnaire Disability Index [HAQ-DI]), Medical Outcomes Study Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Morning Stiffness VAS, RA Impact of Disease (RAID) and RA-specific Work Productivity Survey (WPS-RA). Least-squares mean (LSM) between-group differences were determined by mixed-model for repeated measures with treatment, visit, treatment-by-visit interaction and region as fixed effects, and the corresponding baseline PRO scores as continuous covariates. A P-value <0.05 was considered statistically significant for PROs in a predefined hierarchy (ACR components, SF-36 physical component summary [PCS], FACIT-F and SF-36 mental component summary [MCS] scores). For PROs not in the hierarchy, significance is not claimed. Changes from baseline were compared with published values for minimum clinically important differences (MCIDs). Results Baseline demographics, disease characteristics and PROs were generally balanced between treatment groups (n=184 sarilumab; n=185 adalimumab). Improvements from baseline to week 24 were greater with sarilumab vs adalimumab across PtGA, Pain VAS, HAQ-DI, SF-36 PCS, Morning Stiffness VAS, RAID and WPS-RA global scores (all P<0.05, statistical significance is claimed only for PROs in the hierarchy; see table). Between-group differences in FACIT-F and SF-36 MCS scores were not significant. Improvements ≥MCID were reported by a greater percentage of patients with sarilumab than adalimumab for HAQ-DI (≥0.22 units), RAID (≥3 units), SF-36 PCS (≥2.5), and Morning Stiffness VAS (≥10) (all nominal P<0.05). Conclusions Sarilumab monotherapy compared with adalimumab monotherapy resulted in greater and clinically meaningful improvements in many PROs, including patient-reported disease activity, pain, physical function, morning stiffness, productivity, health related quality of life and health status. Acknowledgements This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest V. Strand Consultant for: AbbVie, Amgen, AstraZeneca, Biogen, BMS, Celltrion, CORRONA, Crescendo, Genentech/Roche, GSK, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals, Sandoz, Sanofi, and UCB, L. Gossec Grant/research support from: Member of institution that received research funding for the current study, C. Proudfoot Shareholder of: Sanofi, Employee of: Sanofi, C. Chen Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., M. Reaney Shareholder of: Sanofi, Employee of: Sanofi, S. Guillonneau Shareholder of: Sanofi, Employee of: Sanofi, T. Kimura Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Y. Lin Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Pfizer Inc. and Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, G. R. Burmester Grant/research support from: Member of institution that received research funding for the current study

FRI0242 Association between clinical and radiographic responses, and physical function in a phase 3 study of sarilumab plus methotrexate in patients with active, moderate-to-severe rheumatoid arthritis

Background In MOBILITY (NCT01061736), SC sarilumab (150 or 200 mg q2w) + MTX demonstrated efficacy in adults with RA and inadequate response to MTX. The most common TEAEs were infections, neutropenia, injection site reactions, and increased transaminases. Objectives To examine association between clinical response and radiographic progression and functional response (HAQ-DI) in MOBILITY. Methods In this post hoc analysis, associations between HAQ-DI and clinical efficacy categories (CDAI, DAS28-CRP, SDAI, and Boolean-based ACR/EULAR remission) were tested at wk 16. Trend for change from baseline (BL) in HAQ-DI across response categories was assessed using the Jonckheere-Terpstra test. Results Regardless of definition, percentage achieving remission (CDAI ≤2.8, DAS28-CRP <2.6, SDAI ≤3.3) or no x-ray progression was higher with sarilumab vs Pbo (P<0.05). Overall, there was a significant trend between magnitude of clinical response at wk 16 and improvement in physical function (Table). This trend was also observed for radiographic progression (mTSS change from BL), regardless of cutoff (≤0.5 and ≤0). In patients achieving remission, there was a numerically greater improvement in HAQ-DI with sarilumab vs placebo (Pbo). Even if patients did not achieve remission or LDA, the sarilumab group had generally greater numerical improvements in HAQ-DI vs Pbo. Conclusions Achieving LDA or remission, or absence of radiographic progression, was associated with overall greater improvement in physical function. Irrespective of whether patients achieved remission or LDA, sarilumab + MTX showed greater improvements in HAQ-DI than Pbo + MTX. Acknowledgements This study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Editorial support was provided by MedThink SciCom and funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Disclosure of Interest M. Genovese Grant/research support from: Roche, Sanofi, GlaxoSmithKline, R-Pharma, RuiYi, and Bristol-Myers Squibb, Consultant for: Roche, Sanofi, GlaxoSmithKline, R-Pharma, RuiYi, and Bristol-Myers Squibb, H. van Hoogstraten Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, W. Kampman Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, S. Jayawardena Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, T. Huizinga Consultant for: Sanofi, Roche, and Abblynx.

SAT0058 Consistency of Radiographic Responses with Sarilumab plus Methotrexate across Subpopulations of Patients with Rheumatoid Arthritis in A Phase 3 Study

Background The investigational drug sarilumab is a human monoclonal antibody directed against the interleukin 6 receptor.1 The phase 3 MOBILITY study (NCT01061736) examined sarilumab + methotrexate (MTX) vs placebo + MTX in a double-blind, 52-week, randomized trial of patients with active, moderate-to-severe rheumatoid arthritis (RA) with inadequate response to MTX.1 Both sarilumab doses (150 and 200 mg subcutaneously every 2 weeks [q2w]) demonstrated statistically significant improvements in signs and symptoms of RA, in physical function, and inhibition of radiographic progression. The most common treatment-emergent adverse events were infections, neutropenia, injection site reactions, and increased transaminases. Objectives In the present study, radiographic efficacy of sarilumab across subpopulations from MOBILITY was assessed. Methods To explore the consistency of radiographic response, treatment-by-subgroup interactions were assessed by rank ANCOVA for change in van der Heijde modified total Sharp score (mTSS) at week 52. A total of 19 subgroups were investigated (listed in Table footnote); those with P≤0.2 for interaction are presented. Radiographic progression was defined as mean change from baseline mTSS. Results Both doses of sarilumab showed less progression relative to placebo across all subgroups. Change in mTSS across subgroups based on rheumatoid factor and anti–cyclic citrullinated peptide status and demographic characteristics such as age, sex, and ethnicity appeared to be consistent with overall study findings. Subgroups with interaction P≤0.2 were prior use of biologics and baseline C-reactive protein (CRP), body mass index (BMI), RA disease duration, median mTSS, and smoking history (Table). In some groups (lower BMI, no prior biologic use, higher baseline CRP, no history of smoking, and high mTSS), the treatment effect increased, because there was greater progression in the placebo group relative to the sarilumab groups. The progression with sarilumab 200 mg q2w was consistently lower compared with sarilumab 150 mg q2w. Progression was substantially greater in placebo patients with baseline mTSS >25 compared with those with baseline mTSS ≤25. These differences were not observed in sarilumab-treated patients. Joint space narrowing and erosion score showed patterns similar to the total score. Overall, sample sizes were limited in some subgroups. Conclusions Sarilumab generally inhibited radiographic progression to a similar extent across a wide spectrum of subgroups. Nonetheless, the treatment effect appeared to be greater in subgroups with poor prognostic markers such as high levels of CRP and more structural damage at baseline, as well as in nonsmokers and patients with low BMI. References Genovese et al. Arthritis Rheumatol. 2015;67:1424–1437. Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Rebecca Slager, PhD, MS, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest D. van der Heijde Consultant for: Sanofi, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, H. van Hoogstraten Shareholder of: Sanofi, Consultant for: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, P. Miranda Grant/research support from: Sanofi, M. Genovese Grant/research support from: Roche, Sanofi, GSK, R-Pharma, RuiYi, and BMS, Consultant for: Roche, Sanofi, GSK, R-Pharma, RuiYi, and BMS

SAT0174 Efficacy of Sarilumab plus csDMARDs in Rheumatoid Arthritis Patients Who Had An Inadequate Response To One or More than One Prior TNF Inhibitor

Background In the phase 3 TARGET study (NCT01709578), sarilumab (150 or 200 mg subcutaneously [SC] every 2 weeks [q2w] plus conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) demonstrated efficacy in adults with active, moderate-to-severe rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor inhibitors (TNFis).1 Consistent with IL-6 inhibition and the safety profile of SC sarilumab, infections, neutropenia, injection site reactions, increased lipids, and increased transaminases were among the most common treatment-emergent adverse events. Objectives This prespecified analysis examined whether the efficacy of sarilumab plus csDMARDs was affected by the number of prior TNFis. Methods Adults with active, moderate-to-severe RA with inadequate response or intolerance to ≥1 TNFi were randomized to receive placebo (n=181), sarilumab 150 mg q2w (n=181), or sarilumab 200 mg q2w (n=184) SC plus csDMARD(s) for 24 weeks.1 Efficacy by number of prior TNFis (1 vs >1) was analyzed for the coprimary endpoints of ACR20 response at week 24 and mean change from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI) at week 12. Additional post hoc analyses evaluated the secondary endpoints of ACR50/70. Treatment-by-subgroup interactions were analyzed using a logistic regression model for ACR20 at week 24 and a mixed-effect model for repeated measures for HAQ-DI at week 12; treatment-by-subgroup interaction with P<0.05 was considered significant. Results A majority of patients (76.8%) reported prior use of only 1 TNFi; 23.2% of patients used >1 TNFi. Most patients discontinued TNFi treatment because of inadequate response (92.3%). ACR20 responses were numerically greater in patients receiving either dose of sarilumab in both the 1 and the >1 prior TNFi groups at week 24 relative to placebo patients (Table). Responses in placebo and sarilumab groups were numerically higher in the group that failed 1 TNFi. Similar results were observed with ACR50/70 responses. The mean change from baseline in HAQ-DI at week 12 was greater in sarilumab patients than in placebo patients in both prior TNFi exposure groups. Interaction test analyses indicated no significant treatment-by-subgroup effect in the proportion of patients with 1 or >1 prior TNFi who achieved ACR20 at week 24 (P=0.1215) or in mean change from baseline in HAQ-DI at week 12 (P=0.1767). Conclusions Efficacy of sarilumab was observed in patients with inadequate response to TNFis, irrespective of the number of prior TNFi therapies. In harder to treat patients (ie, patients with prior exposure to >1 TNFi), sarilumab 200 mg was associated with a greater numerical trend in ACR20/50 when compared with sarilumab 150 mg. References Fleischmann et al. Presented at: ACR; Nov. 7–11, 2015; San Francisco, CA. Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial support was provided by Kristi Porter, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest M. Genovese Grant/research support from: BMS, GSK, R-Pharma, Roche, RuiYi, and Sanofi, Consultant for: BMS, GSK, R-Pharma, Roche, RuiYi, and Sanofi, G. da R.C. Pinheiro Consultant for: AbbVie, AstraZeneca, GlaxoSmithKline, Hospira, Janssen, Pfizer, Roche, RuiYi, and Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Y. Lin Shareholder of: Sanofi, Employee of: Sanofi, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, D. Thompson Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, R. Fleischmann Grant/research support from: AbbVie, Amgen, Ardea, AstraZeneca, BMS, Celgene, Eli Lilly, GSK, Janssen, Merck, Pfizer, Roche, Sanofi, and UCB, Consultant for: AbbVie, Akros, Amgen, AstraZeneca, BMS, Eli Lilly, Janssen, Pfizer, Roche, and UCB

SAT0168 Clinical Remission Outcomes with Sarilumab plus Csdmards in Active, Moderate-To-Severe RA Patients with Inadequate Response To Tumor Necrosis Factor Inhibitors

Background Clinical remission is an important treatment goal in rheumatoid arthritis (RA) and is associated with improved physical function and quality of life.1,2 In the phase 3 TARGET study (NCT01709578), sarilumab (150 or 200 mg subcutaneously every 2 weeks + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) demonstrated efficacy in adults with active, moderate-to-severe RA and inadequate response to tumor necrosis factor (TNF) inhibitors.3 Infections, neutropenia, injection site reactions, and increased transaminases were among the most common treatment-emergent adverse events.3 Objectives This analysis assessed the proportions of patients achieving clinical remission measured by 4 different disease activity measures in a difficult-to-treat patient population with active RA and inadequate response or intolerance to ≥1 prior TNF inhibitor(s). Methods Four definitions of remission were used: 28-joint disease activity score by C-reactive protein (DAS28-CRP) <2.6, clinical disease activity index (CDAI) ≤2.8, simplified disease activity index (SDAI) ≤3.3, and Boolean-based ACR/EULAR remission (tender and swollen joint counts [28 joints] ≤1, CRP ≤10 mg/L, and patient global visual analog scale ≤10 mm/100 mm). Differences in incidence of these benchmarks between the active treatment groups and placebo were assessed using 2-sided Cochran-Mantel-Haenszel tests stratified by geographic region and number of prior TNF inhibitors. Patients who started rescue medication or discontinued the study were considered not to be in remission (nonresponder imputation). Results Baseline demographic and disease characteristics were balanced among the 3 treatment groups. At week (wk) 12 and wk 24, the proportion of patients achieving DAS28-CRP <2.6, CDAI, SDAI, and Boolean-based remission was higher in the sarilumab-treated groups than in the placebo group (Table). At wk 24, a significantly greater proportion of sarilumab patients achieved DAS28-CRP <2.6 compared with placebo. In comparison with placebo patients, a greater proportion of sarilumab patients who achieved DAS28-CRP <2.6 or Boolean-based remission also had clinically meaningful improvements in Health Assessment Questionnaire–Disability Index (HAQ-DI) and Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) at wk 24 (Table). Conclusions Sarilumab induced remission (using a broad range of definitions) as early as 12 weeks after initiation of therapy in patients with an inadequate response to TNF inhibitors. Patients with remission generally had improvements in physical function and fatigue as well. References Smolen et al. Ann Rheum Dis. 2014;73:492–509. Radner et al. Arthritis Res Ther. 2014;16:R56. Fleischmann et al. Presented at: ACR; November 7–11, 2015; San Francisco, CA. Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Kristi Porter, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest G. Burmester Grant/research support from: AbbVie, Pfizer, Roche, and UCB, Consultant for: AbbVie, BMS, Pfizer, Merck, MedImmune, UCB, and Roche, Speakers bureau: AbbVie, BMS, Pfizer, Merck, UCB, and Roche, P. Hrycaj: None declared, C. Pacheco-Tena Consultant for: BMS, Janssen, Pfizer, Roche, and UCB, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Y. Lin Shareholder of: Sanofi, Employee of: Sanofi, D. Bauer Shareholder of: Sanofi, Employee of: Sanofi, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Parrino Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Kivitz Shareholder of: Sanofi and Regeneron Pharmaceuticals, Inc., Consultant for: Sanofi, Pfizer, Roche, and UCB

AB0321 Predicting the Need for Rescue Medication Using Baseline Variables: Evidence from Rheumatoid Arthritis (RA) Patients in the Sarilumab Mobility Phase 3 Trial

Background RA patients may require additional medication or increased doses to successfully manage active disease. The ability to identify variables that predict this need could result in more effective treatment. Objectives To identify baseline predictors for rescue medication in the intent-to-treat population (N=1,197) enrolled in MOBILITY. Methods Patients were randomized 1:1:1 to receive placebo+MTX, sarilumab 150mg every 2 wks (q2wk)+MTX or 200mg q2wk+MTX. Outcomes were assessed at baseline, every 4 wk from wk 2 –28; every 8 thereafter to wk 52. On or after wk 16, patients with <20% improvement in either SJC or TJC for 2 consecutive visits were rescued with sarilumab 200mg q2wk. Patients were classified as: 1) no rescue; 2) early rescue - wk 16; 3) late rescue - wks 20 to 52. A multinomial logistic model (MLM) was used to estimate the impact of treatment on rescue medication status (none/early/late), then to examine the ability of each baseline variable to predict rescue independent of treatment. Models used baseline variables: (n=27) demographic and disease characteristics, clinical measures and patient-reported outcomes (PROs); treatment arm and interactions between baseline variables and treatments as predictors of rescue status. Variables significant at P<0.05 were included in multivariate MLMs. Results 940 patients never received rescue medication, 153 were rescued early and 104 between wks 20 – 52. The percentages of no, early and late rescued patients were 61%, 15% and 24% for placebo; sarilumab 150mg: 86%, 6% and 8% and 200mg: 89%, 4% and 7%, respectively. Baseline SJC, TJC, DAS28, SDAI, CDAI, SF-36 Vitality (VT) domain and FACIT-Fatigue (FACIT-F) scores independently predicted the need for rescue medication. In MLMs, treatment group, DAS28, SF-36 VT and FACIT scores were most strongly associated with rescue. Estimated odds ratios (OR) for early rescue vs no rescue for placebo patients were 4.6/5.2 times higher than for sarilumab 150mg/200mg. 2 and 4 point higher baseline DAS28 scores were associated with 78%/218% increases in OR for “early rescue”; 5 and 10 point lower SF-36 VT scores with 5% and 10% increased OR. 5 and 10 lower scores in FACIT increased the OR for early rescue by 7% and 13%. Conclusions Sarilumab treatment lowered the odds for requiring early and late rescue. DAS28 scores and PROs of pep, energy and fatigue predicted the need for rescue among MOBILITY patients across all treatment arms, highest in placebo. These results may help clinicians to better target RA therapy. Acknowledgements The study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Editorial support was provided by Jennifer Dunphy of Optum and was funded by Sanofi and Regeneron Pharmaceuticals Inc. Disclosure of Interest V. Strand Consultant for: AbbVie, Afferent, Amgen, Biogen Idec, Bioventus, BMS, Carbylan, Celgene, Celltrion, Consortium of Rheumatology Researchers of North America (CORRONA), Crescendo, Genentech/Roche, GSK, Hospira, Iroko, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, SKK, Takeda, UCB, Vertex, R. Rendas-Baum Consultant for: Sanofi, Regeneron Pharmaceuticals, C. Chen Employee of: Regeneron Pharmaceuticals, G. Joseph Shareholder of: Amgen Inc., Pfizer Inc., Employee of: Sanofi, N. Graham Shareholder of: Regeneron Pharmaceuticals, Employee of: Regeneron Pharmaceuticals, H. Van Hoogstraten Employee of: Sanofi, M. Genovese Grant/research support from: Sanofi, Regeneron Pharmaceuticals, Eli Lilly, Consultant for: Sanofi, Regeneron Pharmaceuticals, Eli Lilly, T. Huizenga Consultant for: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, Zydus, and Eli Lilly, Speakers bureau: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, Zydus, and Eli Lilly

FRI0058 Improvements in Health Related Quality of Life (HRQOL) Reported by Rheumatoid Arthritis (RA) Patients in a Randomized Controlled Trial [RCT] of Sarilumab [Mobility] that Met or Exceeded the Patient Acceptable Symptom State [Pass] And Normative Values

Background Clinical and patient reported outcomes provide complimentary information about the efficacy of treatment in RCTs in RA. Linking these two may improve our understanding of treatment benefit. The MOBILITY intent-to-treat population included 1,197 patients randomized 1:1:1 to placebo+MTX, sarilumab 150mg every two weeks (q2w) +MTX or 200mg q2w+MTX. Most common TEAEs included infections and injection site reactions. A higher incidence of serious infections was observed with sarilumab1. Objectives To evaluate reported improvements in HRQoL by ACR20 responders in this phase 3 RCT. Methods HRQoL was measured using the SF-36v2; fatigue by FACIT-Fatigue. Only ACR20 responders were included, since there were few ACR50 responders in the placebo group and no differences in baseline characteristics of responders between treatment groups. At wk 24, we calculated the percentage of ACR20 responders that met or exceeded: 1) PASS2,3, a state of well-being which patients consider to be satisfactory, in 6 SF-36v2 domains; 2) general population normative values for SF-36v2 and FACIT-Fatigue scores. Differences from placebo were tested for statistical significance (p<0.05) by Chi-square. Results ACR20 responses were 33.5% in placebo, 58.4% in 150mg and 66.4% in 200mg sarilumab groups. The percentages of responders in both 150mg and 200mg sarilumab groups with scores ≥PASS at wk 24 exceeded placebo across all 6 SF-36 domains; statistically significant for physical functioning, vitality, social functioning and mental health domains. For example, 82.7% (150mg) and 87.6% (200mg) sarilumab patients reported improvements ≥PASS in SF-36v2 vitality domain vs 72.7% placebo. The percentages of responders receiving 150mg and 200mg sarilumab with scores ≥normative values at wk 24 exceeded placebo across all SF-36v2 domains and FACIT; statistically significant for SF-36v2 bodily pain, vitality, mental health domains; mental component summary score and FACIT. For example, 46.3% (150mg) and 54% (200mg) of sarilumab patients reported scores ≥normative values in SF-36v2 vitality domain vs 38.6% placebo. Similar findings were observed at wk 52. Conclusions Among ACR20 responders, those receiving sarilumab+MTX reported better HRQoL than with placebo+MTX, particularly in measures of bodily pain, vitality, and fatigue by SF-36 and FACIT. Largest percentage differences vs placebo were observed based on scores attaining normative values, which were more discriminative for the Sarilumab 200mg dose than PASS. Observed differences may be driven in part by more high level responders in the active treatment groups. References Genovese M et al. Abstr. EULAR14-SCIE-3001, EULAR 2014 Heiberg T et al. Ann Rheum Dis 2008;67:967-971 Strand V et al. J Rheumatol. 2011;38(8):1720-1727 Acknowledgements The study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Editorial support was provided by Jennifer Dunphy of Optum and was funded by Sanofi and Regeneron Pharmaceuticals Inc. Disclosure of Interest V. Strand Consultant for: AbbVie, Afferent, Amgen, Biogen Idec, Bioventus, BMS, Carbylan, Celgene, Celltrion, Consortium of Rheumatology Researchers of North America (CORRONA), Crescendo, Genentech/Roche, GSK, Hospira, Iroko, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, SKK, Takeda, UCB, Vertex, M. Kosinski Consultant for: Sanofi, Regeneron, G. Joseph Shareholder of: Amgen Inc, Pfizer Inc., Employee of: Sanofi, C. Chen Employee of: Regeneron Pharmaceuticals, H. Van Hoogstraten Employee of: Sanofi, N. Graham Shareholder of: Regeneron Pharmaceuticals, Employee of: Regeneron Pharmaceuticals, T. Huizenga Consultant for: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, Zydus, and Eli Lilly, Speakers bureau: Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, Zydus, and Eli Lilly, M. Genovese Grant/research support from: Sanofi, Regeneron Pharmaceuticals, Eli Lilly, Consultant for: Sanofi, Regeneron Pharmaceuticals, Eli Lilly