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Rheumatoid arthritis
Original article
Evaluation of the efficacy and safety of sarilumab combination therapy in patients with rheumatoid arthritis with inadequate response to conventional disease-modifying antirheumatic drugs or tumour necrosis factor α inhibitors: systematic literature review and network meta-analyses
  1. Ernest Choy1,
  2. Nick Freemantle2,
  3. Clare Proudfoot3,
  4. Chieh-I Chen4,
  5. Laurence Pollissard5,
  6. Andreas Kuznik4,
  7. Hubert Van Hoogstraten6,
  8. Erin Mangan7,
  9. Paulo Carita5 and
  10. Thi-Minh-Thao Huynh8
  1. 1 Division of Infection and Immunity, Cardiff University, Cardiff, UK
  2. 2 Institute for Clinical Trials and Methodology, University College London, London, UK
  3. 3 Formerly, Health Economics and Outcomes Research, Sanofi, Guildford, UK
  4. 4 Health Economics and Outcomes Research, Regeneron Pharmaceuticals, Inc, New York City, New York, USA
  5. 5 Global Health Economics & Value Assessment, Sanofi France, Chilly-Mazarin, France
  6. 6 Global Medical Affairs, I&I, Sanofi, Bridgewater, New Jersey, USA
  7. 7 Medical Affairs, Regeneron Pharmaceuticals, Inc, New York City, New York, USA
  8. 8 Real World Evidence & Clinical Outcome Generation, Sanofi France, Chilly-Mazarin, France
  1. Correspondence to Dr Thi-Minh-Thao Huynh; thi-minh-thao.huynh{at}sanofi.com

Abstract

Objective To compare efficacy and safety of subcutaneous sarilumab 200 mg and 150 mg every 2 weeks plus conventional synthetic disease-modifying antirheumatic drugs (+csDMARDs) versus other targeted DMARDs+csDMARDs and placebo+csDMARDs, in inadequate responders to csDMARDs (csDMARD-IR) or tumour necrosis factor α inhibitors (TNFi-IR).

Methods Systematic literature review and network meta-analyses (NMA) conducted on 24 week efficacy and safety outcomes: Health Assessment Questionnaire Disability Index, modified total sharp score (mTSS, including 52 weeks), American College of Rheumatology (ACR) 20/50/70, European League Against Rheumatism Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28)<2.6; serious infections/serious adverse events (including 52 weeks).

Results 53 trials were selected for NMA. csDMARD-IR: Sarilumab 200 mg+csDMARDs and 150 mg+csDMARDs were superior versus placebo+csDMARDs on all outcomes. Against most targeted DMARDs, sarilumab 200 mg showed no statistically significant differences, except superiority to baricitinib 2 mg, tofacitinib and certolizumab on 24 week mTSS. Sarilumab 150 mg was similar to all targeted DMARDs. TNFi-IR: Sarilumab 200 mg was similar to abatacept, golimumab, tocilizumab 4 mg and 8 mg/kg intravenously and rituximab on ACR20/50/70, superior to baricitinib 2 mg on ACR50 and DAS28<2.6 and to abatacept, golimumab, tocilizumab 4 mg/kg intravenously and rituximab on DAS28<2.6. Sarilumab 150 mg was similar to targeted DMARDs but superior to baricitinib 2 mg and rituximab on DAS28<2.6 and inferior to tocilizumab 8 mg on ACR20 and DAS28<2.6. Serious adverse events, including serious infections, appeared similar for sarilumab versus comparators.

Conclusions Results suggest that in csDMARD-IR and TNFi-IR (a smaller network), sarilumab+csDMARD had superior efficacy and similar safety versus placebo+csDMARDs and at least similar efficacy and safety versus other targeted DMARDs+csDMARDs.

  • sarilumab
  • biologic disease-modifying antirheumatic drugs
  • rheumatoid arthritis
  • network meta-analysis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/rmdopen-2018-000798

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    Footnotes

    • Funding This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.

    • Competing interests EC has received research grants, consultancy and speaker fees from Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai Pharma, Eli Lilly, Janssen, Novimmune, Novartis, Pfizer, Regeneron, Roche, R-Pharm, Sanofi, Tonix and UCB. T-M-TH, LP, HvH and PC are employees of Sanofi and hold stock and/or stock options in the company. CP is a former employee of and current shareholder in Sanofi and current employee of Novartis. C-IC, AK and EM are employees of Regeneron Pharmaceuticals, Inc. and hold stock and/or stock options in the company. NF has received consulting fees from Sanofi, Novo Nordisk, Ipsen, Allergan, Takeda, Biogen, Abbvie, Lifecell.

    • Patient consent Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No associated data will be shared.