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Clinical Trial
. 2017 May;76(5):840-847.
doi: 10.1136/annrheumdis-2016-210310. Epub 2016 Nov 17.

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

Gerd R Burmester  1 , Yong Lin  2 , Rahul Patel  2 , Janet van Adelsberg  3 , Erin K Mangan  3 , Neil M H Graham  3 , Hubert van Hoogstraten  2 , Deborah Bauer  2 , Juan Ignacio Vargas  4 , Eun Bong Lee  5
Affiliations
Clinical Trial

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

Gerd R Burmester et al. Ann Rheum Dis. 2017 May.

Abstract

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.

Keywords: DMARDs (biologic); Rheumatoid Arthritis; Treatment.

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Conflict of interest statement

Competing interests: GRB has received research grants or consulting fees from AbbVie, Bristol-Myers Squibb, MedImmune, Merck, Pfizer, Roche and UCB and has participated in speakers' bureaus for AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche and UCB. EBL has acted as a consultant to Pfizer. JIV has received speaker fees from Roche, Bristol-Myers Squibb and Pfizer and has participated in speakers' bureaus for Bristol-Myers Squibb. YL, RP, HvH and DB are employees of Sanofi Genzyme and may hold stock and/or stock options in the company. JvA, EKM and NMHG are employees of Regeneron Pharmaceuticals and may hold stock and/or stock options in the company.

Figures

Figure 1
Figure 1
Flow diagram showing patient disposition. *Primary reasons for patient ineligibility were meeting the exclusion criteria related to tuberculosis (12.0%) or failure to meet the inclusion criterion for severity of disease (8.1%). †One patient was randomised but not treated in the adalimumab group. ‡The actual number of patients who received a dose-escalation kit on the basis of meeting protocol criteria were 6 (3.2%) in the adalimumab group and 5 (2.7%) in the sarilumab group. q2w, every 2 weeks.
Figure 2
Figure 2
Change from baseline in (A) DAS28-ESR and (B) DAS28-CRP in patients receiving adalimumab 40 mg q2w or sarilumab 200 mg q2w. **p<0.001 versus adalimumab (DAS28-CRP are nominal p values). CRP, C reactive protein; DAS28-ESR, 28-joint disease activity score using erythrocyte sedimentation rate; LS, least squares; q2w, every 2 weeks.
Figure 3
Figure 3
Incidence of (A) DAS28-ESR remission or LDA, (B) ACR20, ACR50 and ACR70 response from weeks 4 to 24, (C) CDAI remission or LDA and (D) HAQ-DI responders achieving ≥0.22 or ≥0.3 units of improvement in patients receiving adalimumab 40 mg q2w or sarilumab 200 mg q2w. *p<0.05 versus adalimumab; **p<0.01 versus adalimumab (CDAI and HAQ-DI responders at week 24 are nominal p values); †p<0.0001 versus adalimumab. ACR, American College of Rheumatology; CDAI, Clinical Disease Activity Index; DAS28-ESR, 28-joint disease activity score using erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; LDA, low disease activity; q2w, every 2 weeks.
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