Sarilumab Superior to Adalimumab as Monotherapy in MTX-Intolerant RA

Rheumatoid arthritis in hip
Rheumatoid arthritis in hip
A phase 3 trial examined the superiority of sarilumab monotherapy compared with adalimumab monotherapy in patients who were either intolerant of or inappropriate candidates for methotrexate therapy.

Sarilumab monotherapy was more effective than adalimumab monotherapy for reducing signs and symptoms of rheumatoid arthritis (RA) among patients with intolerance of or an inadequate response to methotrexate (MTX). The results of the SARIL-RA-MONARCH trial were published in the Annals of the Rheumatic Diseases.1

Conventional synthetic disease-modifying antirheumatic drugs (DMARDs) such as MTX are the cornerstone of RA treatment. However, biologic DMARDs (bDMARDs) are used as monotherapy in one-third of patients with RA because of MTX intolerance. Clinical practice data from several countries also show that bDMARDs are commonly used as monotherapy based on physician or patient preference.1

High Yield Data Summary

  • Sarilumab improves functional disability associated with RA, and sarilumab monotherapy is superior compared with TNF-α inhibition for patients with intolerance of or an inadequate response to MTX.

“The widespread use of bDMARD monotherapy calls for more comparative data to support the optimal selection of approved bDMARDs in clinical practice,” the authors, led by Gerd R. Burmester, MD, from the Department of Rheumatology and Clinical Immunology, Charité–University Medicine Berlin, Free University and Humboldt University Berlin, Germany, wrote.1

Sarilumab is a novel interleukin 6 receptor (IL-6R) inhibitor that has been shown to improve disease activity and physical function among patients with RA with an inadequate response to MTX or tumor necrosis factor (TNF) inhibitors.2,3 Adalimumab is a TNF inhibitor that is globally approved for patients with RA for whom treatment failed or who are intolerant to conventional synthetic DMARD therapy.1

In SARIL-RA-MONARCH, Dr Burmester and colleagues compared the safety and efficacy of sarilumab monotherapy vs that of adalimumab monotherapy in patients with RA who had intolerance of or an inadequate response to MTX.1

A total of 369 patients were randomly assigned to sarilumab 200 mg every 2 weeks (n = 184) or adalimumab 40 mg every 2 weeks (n = 185) for a treatment period of 24 weeks. The primary end point was change in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) from baseline at 24 weeks.1

Sarilumab was more effective than adalimumab at improving DAS28-ESR at 24 weeks (DAS28-ESR change from baseline, −3.28 vs −2.20; P <.0001).1

In addition, significantly more patients in the sarilumab group had American College of Rheumatology 20/50/70 response rates than in the adalimumab group (P ≤.0074 for all comparisons). Remission and low disease activity were achieved more frequently among patients receiving sarilumab than among those receiving adalimumab.1

The rates of adverse events were similar for the sarilumab and adalimumab groups (64.1% vs 63.6%). Neutropenia was more common with sarilumab than with adalimumab; however, rates of infection and serious infection were similar in both groups.1

Summary and Clinical Applicability

Although MTX is the mainstay of RA treatment, a substantial number of patients do not tolerate or respond adequately to MTX. As a result, bDMARDs are commonly used as monotherapy to treat RA. Sarilumab is an IL-6R inhibitor that has demonstrated efficacy in patients with RA intolerant to MTX or TNF inhibitors. 

SARIL-RA-MONARCH compared the safety and efficacy of sarilumab vs that of adalimumab in patients with RA with intolerance of or inadequate response to MTX.1

“Collectively, these data demonstrate that sarilumab improves signs and symptoms and functional disability of RA and is an appropriate, effective and superior monotherapy compared with TNF-α inhibition for patients who are unsuitable candidates for continued treatment with MTX due to intolerance or inadequate response,” the authors concluded.

Study Limitations

  • Sarilumab plus MTX was previously shown to improve radiographic outcomes compared with placebo plus MTX; however, radiographic outcomes were not evaluated in SARIL-RA-MONARCH
  • The efficacy of sarilumab as monotherapy was not compared with sarilumab plus MTX combination therapy


This study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals.

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  1.  Burmester GR, Lin Y, Patel R, et al. 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 [published online November 17, 2016]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2016-210310 
  2. Genovese MC, Fleischmann R, Kivitz AJ, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a phase III study. Arthritis Rheumatol. 2015;67:1424-1437. doi: 10.1002/art.39093
  3. Fleischmann R, van Adelsberg J, Lin Y, et al. Sarilumab and non-biologic disease-modifying antirheumatic drugs in patients with active RA and inadequate response or intolerance to TNF inhibitors [published online November 17, 2016]. Arthritis Rheumatol. doi: 10.1002/art.39944  

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