clinical study insights
Clinically Meaningful Improvement in Patient-Reported Outcomes With Interleukin-6 Inhibition
Clinical Study Title:
Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors
Clinical Study 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.
Strand V, Reaney M, Chen CI, et al. Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors. RMD Open. 2017;3(1):e000416.
Professor of Medicine, University of California (emeritus)
“Patients reported benefits in specific domains of importance—including pain, fatigue, physical function, and participation in work within or outside the home. They also reported reductions in the number of days missed of family, social, or leisure activities.”
Sarilumab received US Food and Drug Administration approval in May 2017 and is a human immunoglobulin G1 monoclonal antibody that binds specifically to both soluble and membrane-bound interleukin 6 (IL-6) receptors and inhibits IL-6–mediated signaling through these receptors. IL-6 contributes to inflammation and joint destruction and mediates pain and fatigue in RA, and there is a long track record of success with this target.
PROs are increasingly recognized as critical endpoints that supplement physician-reported data and laboratory values when evaluating treatment responses in RA. Robust collection of patient-reported data has been an important part of the sarilumab program, with the following phase 3, randomized, placebo-controlled trials now reporting PROs: the part B MOBILITY study (NCT01061736), the MONARCH trial (NCT02332590), and the TARGET trial (NCT01709578).
The present analysis is from the TARGET trial, and it complements the clinical efficacy and safety data previously reported with sarilumab. Treatment with sarilumab with csDMARDs resulted in improvements in PROs in patients with TNF-IR in moderate to severely active RA. Patients reported benefits in specific domains of importance—including pain, fatigue, physical function, and participation in work within or outside the home. They also reported reductions in the number of days missed of family, social, or leisure activities.
Such an impact on work within the home and on participation in other activities has infrequently been captured in RA clinical trials and reflects another disease-specific measure that was included in the TARGET study: the WPS-RA.
In conclusion, the TARGET trial demonstrated patient-reported benefits with sarilumab across a range of PROs that were consistent with those in the MOBILITY trial, but in a more difficult-to-treat population.
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.
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, 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.