Rheumatology

Rheumatoid Arthritis

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Comparative Data Favor Interleukin-6 Receptor Inhibitor Monotherapy

clinical study insights by Daniel E. Furst, MD

Overview

Clinical Study Title:
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

Clinical Study 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.

Reference:
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. Ann Rheum Dis. 2017;76(5):840-847.

Expert Commentary

Daniel E. Furst, MD

Professor of Medicine, University of California (emeritus)
UCLA Medical Center, Department of Medicine
Division of Rheumatology
UCLA Medical Center
Los Angeles, CA

“Interestingly, patients receiving sarilumab reported greater improvement in their health status, as reflected by differences in Short Form-36 Physical Component Summary, Health Assessment Questionnaire-Disability Index, and pain visual analogue scale scores, along with a trend toward greater improvement in fatigue.”

Daniel E. Furst, MD

For patients with RA, biologic monotherapy is an important option when the use of a biologic in combination with MTX or other conventional synthetic disease-modifying antirheumatic drugs would be inappropriate or is poorly tolerated.

Sarilumab is a human immunoglobulin G1 monoclonal antibody that binds specifically to both soluble and membrane-bound interleukin 6 (IL-6) receptors; it has been shown to inhibit IL-6–mediated signaling through these receptors. In the MONARCH trial (NCT02332590), as reported by Burmester and colleagues, sarilumab demonstrated superiority to adalimumab in the reduction of disease activity and the improvement in the signs and symptoms of RA, as shown by the greater reduction in DAS28-ESR. Greater efficacy with sarilumab versus adalimumab was also observed with the Clinical Disease Activity Index, with researchers reporting that the benefits of sarilumab monotherapy extended beyond the pharmacodynamic effects on acute-phase reactants.

Interestingly, patients receiving sarilumab reported greater improvement in their health status, as reflected by differences in Short Form-36 Physical Component Summary, Health Assessment Questionnaire-Disability Index, and pain visual analogue scale scores, along with a trend toward greater improvement in fatigue. The safety profiles of sarilumab and adalimumab monotherapy observed in the MONARCH trial were generally comparable.

Whether IL-6 inhibition improves patient-reported outcomes through anti-inflammatory effects or directly by blocking IL-6 signaling remains to be seen. We are fortunate, however, to have both sarilumab and tocilizumab available for clinical use, and both IL-6 inhibitors have demonstrated efficacy as monotherapy and concomitantly with MTX.

References

Emery P, Sebba A, Huizinga TW. Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis. Ann Rheum Dis. 2013;72(12):1897-1904.

Fleischmann R, van Adelsberg J, Lin Y, et al. Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2017;69(2):277-290.

Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26.

Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001.

Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-977.

Strand V, Kosinski M, Chen CI, et al. Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial. Arthritis Res Ther. 2016;18:198.

Daniel E. Furst, MD

Professor of Medicine, University of California (emeritus)
UCLA Medical Center, Department of Medicine
Division of Rheumatology
UCLA Medical Center
Los Angeles, CA

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