Efficacy and safety of rozanolixizumab in severe fibromyalgia: a phase 2A randomised, double-blind, placebo-controlled, multicentre trial.

Abstract

Fibromyalgia is a chronic disorder characterised by widespread pain, fatigue, sleep disturbances, and cognitive dysfunction. Evidence suggests pathogenic IgG autoantibodies might contribute to severe symptoms. Rozanolixizumab reduces IgG concentration by targeting the neonatal Fc receptor. This study evaluated its efficacy and safety in patients with severe fibromyalgia. This phase 2A, multicentre, randomised, double-blind, placebo-controlled study, included adults (aged 18-70 years) at seven sites in north west England with severe fibromyalgia (Brief Pain Inventory-Short Form [BPI-SF] interference score of ≥6; 10-day mean daily Pain Numeric Rating Scale score of ≥6 to <10). The study consisted of a screening period; a 2-week single-blind placebo run-in period; two subsequent 12-week, double-blind treatment periods; a 2-week single-blind placebo run-out period; and a 5-week safety follow-up. Participants were randomly assigned 1:1:1 to once a week rozanolixizumab 560 mg for 24 weeks (rozanolixizumab-rozanolixizumab); placebo for 12 weeks then rozanolixizumab for 12 weeks (placebo-rozanolixizumab); or placebo for 24 weeks (placebo-placebo); all administered by subcutaneous infusion. The primary endpoint was BPI-SF interference score mean change from baseline after 12 weeks. Treatment-emergent adverse events were assessed. People with lived experience of fibromyalgia consulted on the study and reviewed study materials. This trial is registered with ClinicalTrials.gov, NCT05643794. Between Dec 21, 2022, and July 9, 2024, 165 participants were screened, of whom 63 (eight [13%] male and 55 [87%] female, median age 47 years [IQR 38-55], 60 [95%] White) were randomly assigned: 22 to rozanolixizumab-rozanolixizumab, 20 to placebo-rozanolixizumab, and 21 to placebo-placebo. 55 (87%) of 63 participants completed all phases of the study. The primary endpoint met the pre-specified one-sided 10% α level, with greater improvement from baseline observed for rozanolixizumab versus placebo (least squares mean difference -0·5, 80% CI -1·0 to -0·1; p=0·065), but without significance at a two-sided 5% α level (95% CI -1·2 to 0·2; p=0·13). During treatment, no serious treatment-emergent adverse events were reported by study participants receiving rozanolixizumab. The most common treatment-emergent adverse event across the study was headache, reported by nine (41%) of 22 and 11 (30%) of 37 participants receiving rozanolixizumab versus 17 (41%) of 41 and three (15%) of 20 participants receiving placebo, in the first 12 weeks and second 12 weeks of double-blind treatment, respectively. Rozanolixizumab did not demonstrate broad efficacy in this severe fibromyalgia population. While there was an improvement in BPI-SF, this was not meaningful at a group level. Inability to select for patients with pathogenic autoantibodies might have contributed to between-patient heterogeneity. Response-predictors are required to determine whether IgG reduction benefits subsets of patients with severe fibromyalgia. UCB.