J. van Adelsberg

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 Ugt1a1 genetic variants are associated with increases in bilirubin levels in rheumatoid arthritis patients treated with sarilumab

Background Sarilumab is a human mAb that blocks IL-6 from binding to both membrane-bound and soluble IL-6Rα. Variants in the UGT1A1 gene have been shown to be strongly associated with increased unconjugated bilirubin levels in patients treated with tocilizumab, another IL-6Rα inhibitor.1,2 UGT1A1 encodes the enzyme responsible for the glucuronidation of bilirubin and variation in this gene is also responsible for Gilberts syndrome, a mild benign condition characterized by elevations in unconjugated bilirubin and jaundice. The underlying main genetic variation responsible for Gilberts syndrome has been identified as a TA repeat located in the promoter of UGT1A1 (UGT1A1*28 allele), which is in linkage disequilibrium with a single nucleotide polymorphism, rs6742078, previously associated with higher bilirubin levels after tocilizumab treatment.1 Objectives To test for an association between rs6742078 and bilirubin levels in RA patients treated with sarilumab. Methods DNA was collected from patients enrolled in MOBILITY (NCT01061736), which evaluated the efficacy and safety of sarilumab + methotrexate (MTX) in RA patients with inadequate response to MTX. The pharmacogenetic analysis was conducted in 599 Caucasian patients treated with MTX + sarilumab (150 or 200 mg q2w) or placebo. Log-transformed unconjugated and total bilirubin levels were analyzed at baseline and over the treatment period (using maximum bilirubin). Results There was a strong association between the rs6742078 TT genotype and higher unconjugated bilirubin levels. The least squares mean (SE) for patients at baseline with the TT genotype was 0.48 (0.02) mg/dL vs 0.25 (0.009) and 0.21 (0.009) mg/dL for those with GT and GG genotypes, respectively (p=1.02×10-21). After sarilumab treatment, the difference between genotype groups increased over the course of the study (p=4.3×10-10; Figure). In the binary analysis of maximum total bilirubin in sarilumab-treated patients, the TT genotype was significantly associated with mild bilirubin elevations (OR =34.7; p=1.2×10-8; Table).Table 1. Maximum Total Bilirubin in Sarilumab-Treated Patients by rs6742078 Genotype Maximum total bilirubin, n (%) Genotype, n (%) ≤1.5×ULN >1.5×ULN Total GG/GT 352 (92) 4 (27) 356 (90) TT 29 (8) 11 (73)a 40 (10) 381 15 396 OR=34.7b; p=1.2×10-8. aElevations remained ≤2×ULN. bLogistic regression with recessive genetic model, adjusting for ancestry covariates. Conclusions The association observed between the rs6742078 TT genotype in UGT1A1 and unconjugated bilirubin elevations in sarilumab-treated patients is consistent with previous observations in tocilizumab-treated patients. These findings suggest that sarilumab-related increases in bilirubin levels are likely benign and caused by common genetic variation in UGT1A1 and are not due to underlying liver injury. References Mori et al. Mod Rheumatol. 2012;22:515–523. Lee et al. Pharmacogenet Genomics. 2011;21:365–374. 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 A. Damask Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Boyapati Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Hamilton Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, S. Hamon Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, C. Paccard Shareholder of: Sanofi R&D, Employee of: Sanofi R&D, J. Parrino Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, N. Graham Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Penn Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Lopez Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Reid Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Overton Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Baras Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, A. Shuldiner Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, C. Paulding 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

THU0275 IL-6 Receptor (IL-6R) Blockade with Sarilumab Reduced Circulating Markers Related to Synovial Inflammation and Structural Damage in Patients with Rheumatoid Arthritis (RA) in A Phase 2 Study

Background Sarilumab is the first fully-human monoclonal antibody directed against the IL-6R and is being investigated for the treatment of RA. Patients with RA have elevated tissue turnover at sites of inflammation, resulting from increased activity of proteases, including matrix metalloproteinase (MMP). MMP-cleaved fragments of collagen type 1 (C1M), collagen type 2 (C2M), collagen type 3 (C3M), and C-reactive protein (CRPM) are elevated in sera from patients with RA and reductions may be associated with treatment response. Indeed, the C1M neo-epitope has been recently identified as a potentially prognostic biomarker of bone erosion. Objectives The objective of this study was to determine whether sarilumab reduces the levels of serum biomarkers related to synovial inflammation and joint damage in patients with RA. Methods MOBILITY part A was the dose-ranging phase 2 portion of the MOBILITY trial of subcutaneous sarilumab in patients with active RA treated with concomitant methotrexate (MTX). Sera were collected at baseline, 2 weeks, and 12 weeks from patients randomized to treatment with MTX+placebo (Pbo), MTX+sarilumab 150 mg q2w, or MTX+sarilumab 200 mg q2w. C1M, C2M, C3M and CRPM were analyzed by ELISA. Results Baseline levels of each biomarker were similar among treatment groups. Sarilumab treatment at both doses resulted in marked reduction in levels of C1M, C2M, C3M and CRPM from baseline at 2 weeks (Table, percent change from baseline ± SE) and suppression of each marker was maintained at 12 weeks (data not shown). In contrast, in the MTX+Pbo group there was no significant decrease in these biomarkers at both 2 and 12 weeks. Observed AEs were similar to those reported with other IL-6 inhibitors. Conclusions Sarilumab treatment in patients with RA resulted in significant dose-dependent reduction in MMP-generated neo-epitope biomarkers related to joint and tissue turnover. The most dramatic reduction associated with sarilumab treatment was observed with the C1M neo-epitope, a potentially prognostic biomarker of structural damage (ref). Additional studies are needed to determine if reduction of MMP-cleaved fragments, such as C1M or CRPM, predict clinical and/or radiographic responses (bone erosion and/or joint space narrowing) in patients treated with sarilumab. References AS Siebuhr et al. Serological identification of fast progressors of structural damage with rheumatoid arthritis. Arthritis Research & Therapy 2013, 15:R86 doi:10.1186/ar4266. Acknowledgements Sponsored by Sanofi and Regeneron Pharmaceuticals Inc. (NCT01061736). Disclosure of Interest : S. Fiore Shareholder of: Sanofi US, Employee of: Sanofi US, A. Boyapati Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., S. Hamon Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., M. Liu Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., J. Hamilton Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc. DOI 10.1136/annrheumdis-2014-eular.3852