E.K. Mangan

Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial

Objectives To compare efficacy and safety of sarilumab monotherapy with adalimumab monotherapy in patients with active rheumatoid arthritis (RA) who should not continue treatment with methotrexate (MTX) due to intolerance or inadequate response. Methods MONARCH was a randomised, active-controlled, double-blind, double-dummy, phase III superiority trial. Patients received sarilumab (200 mg every 2 weeks (q2w)) or adalimumab (40 mg q2w) monotherapy for 24 weeks. The primary end point was change from baseline in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) at week 24. Results Sarilumab was superior to adalimumab in the primary end point of change from baseline in DAS28-ESR (−3.28 vs −2.20; p<0.0001). Sarilumab-treated patients achieved significantly higher American College of Rheumatology 20/50/70 response rates (sarilumab: 71.7%/45.7%/23.4%; adalimumab: 58.4%/29.7%/11.9%; all p≤0.0074) and had significantly greater improvement in Health Assessment Questionnaire-Disability Index (p=0.0037). Importantly, at week 24, more patients receiving sarilumab compared with adalimumab achieved Clinical Disease Activity Index remission (7.1% vs 2.7%; nominal p=0.0468) and low disease activity (41.8% vs 24.9%; nominal p=0.0005, supplemental analysis). Adverse events occurred in 63.6% (adalimumab) and 64.1% (sarilumab) of patients, the most common being neutropenia and injection site reactions (sarilumab) and headache and worsening RA (adalimumab). Incidences of infections (sarilumab: 28.8%; adalimumab: 27.7%) and serious infections (1.1%, both groups) were similar, despite neutropenia differences. Conclusions Sarilumab monotherapy demonstrated superiority to adalimumab monotherapy by improving the signs and symptoms and physical functions in patients with RA who were unable to continue MTX treatment. The safety profiles of both therapies were consistent with anticipated class effects. Trial registration number NCT02332590.

Two years of sarilumab in patients with rheumatoid arthritis and an inadequate response to MTX: safety, efficacy and radiographic outcomes

Abstract Objectives To examine 2-year safety, efficacy and radiographic outcomes of sarilumab in adults with RA and inadequate response to MTX (MTX-IR). Methods In the randomized, placebo-controlled MOBILITY trial, MTX-IR patients received subcutaneous sarilumab (150 or 200 mg) or placebo every 2 weeks (q2w) plus MTX for up to 1 year. Upon study completion, patients could enrol in the open-label, long-term extension study (EXTEND, NCT011046652), in which all patients received sarilumab 200 mg q2w plus MTX. Dose reduction to 150 mg q2w was allowed for abnormal laboratory findings and per investigator’s discretion. Results Of 1197 patients participating in MOBILITY, 901 entered EXTEND. Over the 2-year period, treatment-emergent adverse events (TEAEs) and serious AEs occurred at rates of 279.6 events per 100 patient-years and 16.6 events per 100 patient-years, respectively. The most common TEAEs were neutropenia, injection site erythema, increased alanine aminotransferase and upper respiratory tract infections. After 1 year in the open-label, long-term extension, disease activity reached similar levels regardless of initial treatment. Modified total Sharp scores at year 1 were maintained through year 2. Best radiographic outcomes were observed in patients initially randomized to sarilumab 200 mg q2w. After dose reduction, 89.4% of patients continued the study through 2 years. Conclusion Sarilumab safety through year 2 was consistent with IL-6 receptor blockade. Clinical response was similar irrespective of initial treatment, and radiographic progression stabilized. Patients initiated on sarilumab 200 mg q2w had the best radiographic outcomes. Dose reduction allowed most patients to continue with the study.

Fesoterodine for the Treatment of Nocturnal Urgency in Patients with Overactive Bladder Syndrome: An Analysis of Responders and Nonresponders

Purpose: A recent study demonstrated improvement in nocturnal urgency in patients with overactive bladder when treated with fesoterodine. In the current study we aimed to determine which bladder diary parameters predict the response to fesoterodine in these patients. Materials and Methods: Patients with nocturnal urgency completed a 2‐week, single‐blind placebo run‐in followed by 1:1 double‐blind randomization to 12 weeks of fesoterodine or placebo. We analyzed bladder diary parameter changes from baseline to week 12, including the actual number of night voids (total number of nocturia episodes), maximum voided volume, nocturnal bladder capacity, Nocturnal Bladder Capacity Index (NBCi) (actual number of night voids ‐ nocturnal urine volume/maximum voided volume ‐ 1), nocturnal urine volume, the nocturia index (nocturnal urine volume/maximum voided volume) and the nocturnal polyuria index (nocturnal urine volume/24‐hour volume). Additionally, we analyzed OAB‐q (Overactive Bladder Questionnaire) changes. Results: There was a linear relationship between the likelihood of being a responder for NBCi and the nocturia index. Responders had a significant decrease in nocturnal urine volume relative to baseline (‐181.7 ml, p <0.01). Neither group showed a significant change in maximum voided volume relative to baseline. There was a significant decrease in NBCi and the nocturia index in responders (‐0.82 and ‐0.61, respectively, each p <0.01). Responders demonstrated improvement in the OAB‐q concern, coping, sleep, bother and total score metrics. Conclusions: Patients with nocturnal urgency secondary to overactive bladder syndrome and low nocturnal bladder capacity with a mismatch between nocturnal urine production and bladder capacity may benefit from fesoterodine. Symptom improvement appears to be mediated by increases in typical rather than maximum nocturnal voided volumes. Symptom improvement was associated with improved quality of life.

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

SAT0207 Depressive symptoms in patients with rheumatoid arthritis in sarilumab target and mobility trials and impact of treatment

Background: In patients with clinical depression, elevated interleukin-6 (IL-6) levels have been associated with higher symptom severity and greater resistance to standard antidepressant treatments. Depression and IL-6 elevation are highly prevalent in patients with rheumatoid arthritis (RA), and their co-occurrence may have an impact on health-related quality of life (HRQoL). Sarilumab is a human immunoglobulin G1 anti IL-6 receptor α (anti-IL-6Rα) monoclonal antibody for treatment of moderately-to-severely active RA. Objectives: To explore the effect of sarilumab on HRQoL in patients with moderate-to-severely active RA with co-existing symptoms of depression. Methods: Post-hoc statistical analyses were performed on the Medical Outcomes Study Short Form 36 (SF-36) in 2 randomized controlled trials, MOBILITY (NCT01061736) and TARGET (NCT01709578), of sarilumab subcutaneous 150 mg or 200 mg every 2 weeks vs placebo, each combined with conventional synthetic disease modifying anti-rheumatic drugs. Patients were classified at baseline for probable major depressive disorder1 (PMDD; SF-36 mental health (MH) domain score ≤56) or probable depressed mood and anhedonia2 (PDMA; score ≤10 on both items of the MH domain: “Have You Felt Downhearted and Depressed” and “Have You Felt So down in the Dumps that nothing could cheer you up”). Analyses of least squares mean differences in changes from baseline in SF-36 domain scores for sarilumab versus placebo in the PMDD and PDMA subgroups were performed at Weeks 4, 12 and 24 for TARGET and Weeks 24 and 52 for MOBILITY. Sensitivity analysis adjusted for baseline Disease Activity Score 28 C-reactive protein (DAS28-CRP). Results: Of the 546 patients from TARGET and 1197 from MOBILITY, 59.5% and 60.2% were classified as PMDD respectively, and 50.4% and 51.6% as PDMA. In both RCTs disease duration and baseline DAS-28 CRP, tender and swollen joint count (table 1) and SF-36 domain scores (figure 1) were similar between sarilumab and placebo within the PMDD and PMDA subpopulations. TARGET: MH scores for PMDD and PDMA subgroups were nominally higher (p<0.05) for sarilumab 200 mg versus placebo at all assessments. Both subgroups also scored nominally higher (p<0.05) in the domains of physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT) and social functioning (SF) but not role-emotional (RE) in the PMDD subgroup at Week 24 (figure 1). MOBILITY: all scores except PF and RE were nominally higher (p<0.05) for sarilumab 200 mg versus placebo for Weeks 24 (figure 1). Sensitivity analysis provided similar results. Exploratory results also suggested reduced prevalence of depressive symptoms over the course of the trial.Figure 1 PMDD: SF-36 MH domain score ≤56; PDMA: ≤10 on both items of SF-36 MH domain Conclusions: In patients with RA and depressive symptoms, sarilumab provided clinically meaningful improvements in most domains of health status/HRQoL compared with placebo, which may be a function of targeting the IL-6Rα and subsequent reduction in disease activity. References [1]Matcham, et al. BMC Musculoskeletal Disorders2016;17:224. [2]Sun Y, et al. EULAR Congress2017June 14–17; Madrid, Spain. Acknowledgements: Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interest: V. Strand Consultant for: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi and UCB, O. Hagino Shareholder of: Sanofi, Employee of: Sanofi, S. Guillonneau Shareholder of: Sanofi, Employee of: Sanofi, S. Boklage Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., M. Reaney Shareholder of: Sanofi, Employee of: Sanofi, J. Sadeh Shareholder of: Sanofi, Employee of: Sanofi, N. Narcisse Consultant for: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., T. Kirmura Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc.

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

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