Sarilumab in relapsing polymyalgia rheumatica: patient-reported outcomes from a phase 3, double-blind, randomised controlled trial.

Background: Sarilumab is approved for adult patients with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. We aimed to evaluate the effect of sarilumab on patient-reported outcomes.

Methods: This phase 3, double-blind, randomised controlled trial was done in 60 centres in 17 countries. Eligible patients were adults aged 50 years or older who had at least one episode of disease flare during a glucocorticoid taper (at a dose of ≥7·5 mg per day or prednisone dose equivalent) within 12 weeks before screening and had a history of at least 8 weeks of glucocorticoid treatment (≥10 mg per day or prednisone dose equivalent). All the patients had symptoms of polymyalgia rheumatica and an erythrocyte sedimentation rate >30 mm/h or a C-reactive protein concentration of at least 10 mg/L within 12 weeks before screening. Patients were randomly assigned (1:1) to receive either subcutaneous sarilumab 200 mg once every 2 weeks with a 14-week glucocorticoid taper or matching placebo with a 52-week glucocorticoid taper. Patients and investigators were masked to treatment allocation. The patient-reported outcomes measured were Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Global Assessment of Health Visual Analog Scale (VAS), Pain VAS, Short Form Health Survey (SF-36 v2), EuroQoL 5-Dimensions 3-Levels (EQ-5D including the descriptive system and the VAS), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Patient-reported outcomes were analysed until week 52 as changes from baseline. Post-hoc analyses included proportions of patients reporting improvements of at least minimum clinically important difference and scores of at least normative values. p values were nominal. Analyses were done in the intention-to-treat population. There was no involvement of people with lived experience at any stage of the study. This trial is registered with ClinicalTrials.gov, NCT03600818.

Findings: Between Oct 9, 2018, and July 15, 2020, 118 patients were enrolled and randomly assigned to receive sarilumab (n=60) or placebo (n=58). Of these, 117 patients received treatment (59 in the sarilumab group and 58 in the placebo group). One patient assigned to the sarilumab group did not receive treatment. Mean age was 68·9 years (SD 8·1). 82 (69%) of 118 patients were female and 36 (31%) were male, and 98 (83%) were White. At baseline, moderate-to-severe fatigue was reported by 43 (73%) of 59 patients in the sarilumab group and 43 (74%) of 58 patients in the placebo group. At week 52, patients in the sarilumab group reported greater improvements than patients in the placebo group in SF-36 Physical Component Summary (PCS; least-squares mean [LSM] change 7·65 vs 2·87, p=0·020) and Mental Component Summary (MCS; 3·04 vs -1·71, p=0·030) scores, and in five of eight domains. Sarilumab showed greater improvements in EQ-5D utility index (0·11 vs -0·02, p=0·034) and VAS scores (8·37 vs -0·46, p=0·084), FACIT-F (7·91 vs 4·17, p=0·060), HAQ-DI (-0·39 vs -0·15, p=0·054), Pain VAS (-20·57 vs -12·04, p=0·20), and Patient Global Assessment VAS (-15·01 vs -6·08, p=0·13). More patients in the sarilumab group than in the placebo group reported improvements of minimum clinically important difference or greater in SF-36 PCS scores (odds ratio 3·46 [95% CI 1·16-10·62], p=0·020). More than 50% of patients in the sarilumab group reported scores of at least normative values for SF-36 MCS and four domain scores, whereas this was not the case for any domain in the placebo group.

Interpretation: Patients with relapsing polymyalgia rheumatica have impaired health-related quality of life. The use of sarilumab 200 mg once every 2 weeks with a 14-week glucocorticoid taper led to clinically important improvements in health-related quality of life and patient-reported outcomes versus placebo with a 52-week glucocorticoid taper. Improvements were highest in patients with most severe disease. These findings provide support for the use of sarilumab in patients with polymyalgia rheumatica whose disease activity and health-related quality of life is not adequately managed by glucocorticoid monotherapy according to treat-to-target principles.

Funding: Sanofi and Regeneron Pharmaceuticals.