ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1632

Efficacy and Safety of Sarilumab in Subgroups of Patients with Rheumatoid Arthritis from 2 Phase 3 Studies

Mark C. Genovese1, Roy Fleischmann2, Erin Mangan3, Janet van Adelsberg4, Melitza Iglesias-Rodriguez5, Deborah Dukovic6, Chunpeng Fan7 and Tom WJ Huizinga8, 1Stanford University Medical Center, Palo Alto, CA, 2Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 3Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 4Clinical Science, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, 5Sanofi Genzyme, Cambridge, MA, 6Sanofi Genzyme, Bridgewater, NJ, 7Biostatistics, Sanofi Genzyme, Bridgewater, NJ, 8Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , ,

Session Information

Date: Monday, November 14, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy - Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Sarilumab is a human mAb blocking the IL-6Rα. Efficacy of sarilumab + MTX was demonstrated in patients with RA and inadequate response to MTX (MOBILITY; NCT01061736).1 Sarilumab + conventional synthetic DMARDs demonstrated efficacy in patients with RA and inadequate response or intolerance to TNF inhibitors (TARGET; NCT01709578).2 Efficacy and safety of sarilumab across prespecified subpopulations were assessed in a pooled analysis of patients from MOBILITY and TARGET.

Methods: Adult patients from MOBILITY and TARGET were included in this analysis (N=1743). Incidence of ACR20 response at week 24, change from baseline in HAQ–Disability Index (HAQ-DI) at week 12, and change from baseline in DAS28-CRP at week 24 were evaluated for placebo (n=579), sarilumab 150 mg every 2 weeks (q2w) (n=581), and sarilumab 200 mg q2w (n=583) in prespecified subpopulations. Post hoc analysis of clinical disease activity index (CDAI) at week 24 was performed. Treatment-by-subgroup interactions were assessed by a logistic regression model (ACR20: week 24) or mixed-effect model for repeated measures (HAQ-DI: week 12; DAS28-CRP, CDAI: week 24).

Results: Superiority of both sarilumab doses vs placebo was observed across all subgroups except baseline RF status, anti-CCP autoantibody status, and weight (Table; Figure). A smaller treatment effect for sarilumab 150 mg q2w was observed in RF and anti-CCP seronegative patients and those weighing ≥100 kg for ACR20 and DAS28-CRP (Table). Treatment-emergent AEs and serious AEs were more frequent with sarilumab vs placebo. Infections, neutropenia, injection site reactions, and increased transaminases were among the most common TEAEs and occurred more frequently with sarilumab. As previously reported in the individual trials, no serious infections were associated with neutrophil reductions.

Conclusion: Superiority of sarilumab vs placebo, measured by ACR20 response and changes in HAQ-DI, DAS28-CRP, and CDAI, was generally consistent across patient subgroups. The magnitude of the treatment effect was smaller, particularly for sarilumab 150 mg q2w, in patients with baseline seronegativity for RF or anti-CCP autoantibody or with baseline weight ≥100 kg, although there were few patients in these subgroups.

References: 1. Genovese et al. Arthritis Rheumatol. 2015;67:1424-1437.

2. Fleischmann et al. Presented at: ACR; November 7-11, 2015; San Francisco, CA.  

Table. Incidence of ACR20 Response at Week 24, LS Mean Change From Baseline in HAQ-DI at Week 12, LS Mean Change From Baseline in DAS28-CRP at Week 24, and LS Mean Change From Baseline in CDAI at Week 24 in MOBILITY and TARGET Subgroups: Treatment-by-Subgroup Interactions
 

P value (interaction)

Subgroup

ACR20 at week 24a

LS mean change from baseline in HAQ-DI at week 12b

LS mean change from baseline in DAS28-CRP at week 24b,c

LS mean change from baseline in CDAI at week 24b

Baseline demographics

 

 

 

 

Sex (male, female)

0.699

0.190

0.768

0.348

Race (white vs all other races)

0.531

0.770

0.772

0.506

Ethnicity (Hispanic vs non-Hispanic)

0.300

0.322

0.907

0.870

Region (regions 1, 2, 3)d,e

0.297

0.308

0.308

0.247

Age group (<65, ≥65 y)

0.269

0.982

0.687

0.800

Baseline weight (<60, ≥60 to <100, ≥100 kg)

0.013

0.189

0.006

0.199

BMI (<25, ≥25 to <30, ≥30 kg/m2)

0.081

0.463

0.002

0.051

Number of prior DMARDs (none, 1, ≥2)

0.941

0.946

0.435

0.225

Smoking history (yes, no)

0.592

0.320

0.076

0.205

Baseline disease characteristics

 

Rheumatoid factor (positive, negative)

0.006

0.001

0.011

0.360

Anti-CCP autoantibody (positive, negative)

0.001

0.010

0.001

0.0002

Baseline CRP (≤15, >15 mg/L)c

0.644

0.317

0.142

0.373

Baseline DAS28-CRP (≤5.1, >5.1)c

0.379

0.379

0.096

0.074

Duration of RA (≤3, >3 to ≤10, >10 y)

0.495

0.814

0.506

0.387

CDAI, clinical disease activity index; HAQ-DI, HAQ–Disability Index; LS, least squares; MMRM, mixed-effect model for repeated measures. aLogistic regression model with terms of treatment, region, subgroup, treatment-by-subgroup, and study indicator. bMMRM assuming an unstructured covariance structure with covariate baseline and terms of treatment, region, subgroup, treatment-by-subgroup, visit, treatment-by-visit, treatment-by-visit-by-subgroup, study indicator, and study indicator-by-visit. cCRP was measured via high-sensitivity assay. dRegion 1: Austria, Australia, Belgium, Canada, Czech Republic, Finland, Germany, Greece, Hungary, Israel, Italy, New Zealand, Norway, Portugal, Spain, Switzerland, USA. Region 2: Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Peru. Region 3: Belarus, Estonia, Hong Kong, India, Lithuania, Malaysia, Philippines, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Taiwan, Thailand, Turkey, Ukraine. eFor ACR20 at week 24, a logistic regression model with terms of treatment, region, treatment-by-region, and study indicator was used. For LS mean change from baseline in HAQ-DI at week 12 and DAS28-CRP and CDAI at week 24, MMRM model with terms of treatment, region, treatment-by-region, visit, treatment-by-visit, treatment-by-visit-by-region, study indicator, and study indicator-by-visit was used.

Figure. Odds ratio for ACR20 response for sarilumab vs placebo at week 24 by subgroup.      

Disclosure: M. C. Genovese, Bristol-Myers Squibb, GlaxoSmithKline, R-Pharma, Roche, RuiYi, and Sanofi, 2,Bristol-Myers Squibb, GlaxoSmithKline, R-Pharma, Roche, RuiYi, and Sanofi, 5; R. Fleischmann, AbbVie, Amgen, Ardea, AstraZeneca, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Pfizer, Roche, Sanofi, and UCB, 2,AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Roche, and UCB, 5; E. Mangan, Regeneron Pharmaceuticals, Inc., 1,Regeneron Pharmaceuticals, Inc., 3; J. van Adelsberg, Regeneron Pharmaceuticals, Inc., 1,Regeneron Pharmaceuticals, Inc., 3; M. Iglesias-Rodriguez, Sanofi Genzyme, 1,Sanofi Genzyme, 3; D. Dukovic, Sanofi Genzyme, 1,Sanofi Genzyme, 3; C. Fan, Sanofi Genzyme, 1,Sanofi Genzyme, 3; T. W. Huizinga, Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, GSK, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, Zydus, Epirus and Eli Lilly, 5.

To cite this abstract in AMA style:

Genovese MC, Fleischmann R, Mangan E, van Adelsberg J, Iglesias-Rodriguez M, Dukovic D, Fan C, Huizinga TW. Efficacy and Safety of Sarilumab in Subgroups of Patients with Rheumatoid Arthritis from 2 Phase 3 Studies [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/efficacy-and-safety-of-sarilumab-in-subgroups-of-patients-with-rheumatoid-arthritis-from-2-phase-3-studies/. Accessed .

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