Abstract
BackgroundThe interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors. This analysis investigated the efficacy and safety of sarilumab in patient subgroups.MethodsData were included from phase III studies: two placebo-controlled studies of subcutaneous sarilumab 150/200 mg every 2 weeks (q2w) either + MTX in MTX-IR patients (52 weeks) or + csDMARDs in TNF-IR/INT patients (24 weeks), and a monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w in MTX-IR/INT patients (24 weeks). Prespecified and post hoc subgroups included patient demographics, disease characteristics, and prior treatments. Prespecified and post hoc endpoints included clinical, radiographic, and physical function measures, and p values are considered nominal. Safety was assessed during double-blind treatment.ResultsThe superiority of sarilumab (either as monotherapy vs. adalimumab or in combination with csDMARDs vs. placebo + csDMARDs) across clinical endpoints was generally consistent across subgroups defined by patient demographics, disease characteristics, and prior treatments, demonstrating the benefit of sarilumab treatment for a wide range of patient types. Interaction p values of < 0.05 were consistently observed across studies only for baseline anti-cyclic citrullinated peptide antibody (ACPA) status for American College of Rheumatology 20% response, but not American College of Rheumatology 50% or 70% response. Adverse events and worsening laboratory parameters occurred more frequently in sarilumab-treated vs. placebo-treated patients and were more frequent in the small number of patients ≥ 65 years (n = 289) vs. patients < 65 years (n = 1819). Serious infections occurred in six patients aged ≥ 65 years receiving sarilumab, although the incidence of serious infections was generally higher in patients aged ≥ 65 years regardless of treatment.ConclusionsApart from ACPA status, there were no consistent signals indicating differential effects of sarilumab in any of the subpopulations assessed. Sarilumab demonstrated consistent efficacy and safety across a wide range of patients with RA.Trial registrationClinicalTrials.gov NCT01061736, registered on February 03, 2010; ClinicalTrials.gov NCT01709578, registered on October 18, 2012; ClinicalTrials.gov NCT02332590, registered on January 07, 2015
Highlights
The interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors
The superiority of sarilumab across clinical endpoints was generally consistent across subgroups defined by patient demographics, disease characteristics, and prior treatments, demonstrating the benefit of sarilumab treatment for a wide range of patient types
Serious infections occurred in six patients aged ≥ 65 years receiving sarilumab, the incidence of serious infections was generally higher in patients aged ≥ 65 years regardless of treatment
Summary
The interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors. Glucocorticoid use ACPA anti-cyclic citrullinated peptide antibody, ACR20/50/70 American College of Rheumatology 20%/50%/70% response, bDMARD biological and targeted disease-modifying antirheumatic drug, BMI body mass index, CDAI Clinical Disease Activity Index, CRP C-reactive protein, csDMARD conventional synthetic diseasemodifying antirheumatic drug, DAS28-CRP Disease Activity Score in 28 joints using CRP, DAS28-ESR Disease Activity Score in 28 joints using erythrocyte sedimentation rate, HAQ-DI Health Assessment Questionnaire-Disability Index, INT intolerant, IR inadequate response, NC not calculated, mTSS Modified Total Sharp Score, MTX methotrexate, RA rheumatoid arthritis, RF rheumatoid factor, SDAI Simplified Disease Activity Index, TNF tumour necrosis factor *Assessed at week 16/12/24 in the MTX-IR combination study, TNF-IR/INT combination study, and monotherapy studies, respectively **Assessed at week 52 duration of the studies and small numbers of patients in some subpopulations limit the interpretation of the data. It is likely that treatment responses in patients with RA are influenced by a combination of baseline characteristics rather than isolated characteristics, and additional analyses with larger subpopulations are warranted to investigate this further
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
