Article Text
Abstract
Objective To evaluate effects of the anti-interleukin-6 receptor monoclonal antibody sarilumab administered with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on patient-reported outcomes (PROs) in the TARGET trial in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitors (TNF-IR).
Methods 546 patients (81.9% female, mean age 52.9 years) were randomised to placebo, sarilumab 150 or 200 mg subcutaneously every 2 weeks + csDMARDs. PROs included patient global assessment (PtGA); pain and morning stiffness visual analogue scales; Health Assessment Questionnaire Disability Index (HAQ-DI); Short Form-36 Health Survey (SF-36); FACIT-Fatigue (FACIT-F); Work Productivity Survey-Rheumatoid Arthritis (WPS-RA) and Rheumatoid Arthritis Impact of Disease (RAID). Changes from baseline at weeks 12 and 24 were analysed using a mixed model for repeated measures; post hoc analyses included percentages of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values.
Results Sarilumab + csDMARDs doses resulted in improvements from baseline at week 12 vs placebo + csDMARDs in PtGA, pain, HAQ-DI, SF-36 and FACIT-F that were maintained at week 24. Sarilumab improved morning stiffness and reduced the impact of RA on work, family, social/leisure activities participation (WPS-RA) and on patients' lives (RAID). Percentages of patients reporting improvements ≥MCID and ≥ normative scores were greater with sarilumab than placebo.
Conclusions In patients with TNF-IR RA, 150 and 200 mg sarilumab + csDMARDs resulted in clinically meaningful patient-reported benefits on pain, fatigue, function, participation and health status at 12 and 24 weeks that exceeded placebo + csDMARDs, and were consistent with the clinical profile previously reported.
Trial registration number NCT01709578; Results.
- Rheumatoid Arthritis
- Outcomes research
- DMARDs (biologic)
- Anti-TNF
- Patient perspective
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Footnotes
Contributors All authors were involved in drafting the article or revising it critically for intellectual content. All authors approved the final version to be submitted for publication. VS had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The study was conceptualised and designed by VS, RF, NMHG, HvH and YL. HvH, YL, CP-T and RF acquired the data. VS, MR, CIC, CWJP, SG, DB, EM, NMHG, HvH, YL, CP-T and RF analysed and interpreted the data. All authors were involved in the study design and/or in the collection, analysis and interpretation of the data, the writing of the manuscript and the decision to submit the manuscript for publication. All authors approved the manuscript for submission.
Funding This study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals. E. Jay Bienen, PhD, provided writing support funded by Sanofi Genzyme and Regeneron Pharmaceuticals.
Competing interests VS has received consulting fees from AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America (CORRONA), Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi and UCB. MR, CWJP, SG, HvH, DB and YL are employees of Sanofi Genzyme and may hold stock and/or stock options in the company. CIC, EM and NMHG are employees of Regeneron Pharmaceuticals, and may hold stock and/or stock options in the company. CP-T has been principal investigator for Roche, Bristol-Myers Squibb, MS, Vertex, Sanofi, AstraZeneca, Johnson & Johnson, Novo Nordisk and AbbVie and has received speaker fees from Roche, Bristol-Myers Squibb, AbbVie, UCB, Janssen and MSD. RF has received research grants from AbbVie, Amgen, Ardea, AstraZeneca, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Pfizer, Roche, Sanofi Aventis and UCB; and has received consulting fees from AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Roche and UCB.
Ethics approval This RCT received approval from the Institutional Review Board/Independent Ethics Committee of the investigational centres.
Provenance and peer review Not commissioned; externally peer reviewed.