TOPLINE

Rozanolixizumab, an antibody targeting the neonatal Fc receptor for immunoglobulin G (IgG), showed modest improvement in pain interference and fibromyalgia impact among patients with severe fibromyalgia but did not significantly reduce pain intensity or fatigue. The primary endpoint met the prespecified one-sided statistical threshold but not the standard two-sided significance level.

METHODOLOGY

• This phase 2A, placebo-controlled randomized trial was conducted at seven sites in England (December 2022 to July 2024) and included 63 adults with severe fibromyalgia (87% women; 95% White individuals).
• Participants had a Brief Pain Inventory-Short Form (BPI-SF) interference score, used to assess pain severity and interference due to pain, of 6 or greater and a 10-day mean daily pain numeric rating scale (NRS) score of at least 6 but less than 10.
• Participants were randomly assigned in a 1:1:1 ratio to receive subcutaneous infusion of 560 mg rozanolixizumab once weekly for 24 weeks, placebo for 12 weeks followed by rozanolixizumab for 12 weeks both once weekly, or placebo once weekly for 24 weeks.
• The primary outcome was the mean change in the BPI-SF interference score from baseline at 12 weeks after treatment.
• Secondary endpoints included a change in the Revised Fibromyalgia Impact Questionnaire (FIQR) score from baseline at 10 weeks (evaluating the impact of the condition on health, function, and severity of symptoms) and changes in pain NRS and fatigue NRS scores at 12 weeks based on the prior week.

TAKEAWAY

• The primary endpoint met the prespecified one-sided 10% significance level, with rozanolixizumab showing a greater improvement from baseline than placebo in the mean BPI-SF interference score (least squares mean difference, -0.5; 80% CI, -1.0 to -0.1; P = .065), but this finding was not significant at the two-sided 5% level (least squares mean difference, -0.5; 95% CI, -1.2 to 0.2; P = .13).
• After 10 weeks, rozanolixizumab demonstrated a significant improvement in the FIQR total score compared with placebo (least squares mean change, -8.4; 95% CI, -13.8 to -3.0; P = .0026), with improvements seen across all three FIQR subdomains: activities (P = .0039), symptoms (P = .014), and overall impact (P = .0012).
• No improvement in pain NRS or fatigue NRS scores from baseline to 12 weeks was observed with rozanolixizumab vs placebo.
• Rozanolixizumab was associated with a reduction in total IgG by a median of approximately 60% at 4 weeks after treatment initiation, with the reduction sustained thereafter; serious treatment-emergent adverse events and treatment-emergent adverse events that led to discontinuation of treatment were reported infrequently.

IN PRACTICE

"The small sample size and marked heterogeneity in patient responses limit interpretability of findings. Further work is needed to refine trial endpoints and to better characterise the clinical effects of IgG reduction in fibromyalgia," the authors of the study wrote.

SOURCE

The study was led by Andreas Goebel, Pain Research Institute, University of Liverpool, Liverpool, England. It was published online on September 16 in The Lancet Rheumatology.

LIMITATIONS

The study population was predominantly White, which restricted how these findings may be applicable to more diverse populations. Assessment timepoints for FIQR measurements did not align with other parameters, making it difficult to directly compare effects across endpoints.

DISCLOSURES

The study was funded by UCB. Several authors reported being employees and shareholders of UCB; one of the authors also reported holding shares with other companies. One author reported receiving consultancy fees from Clerkenwell Health and UCB and infrastructure support from the Pain Relief Foundation and serving as a co-inventor on a patent application related to neonatal Fc receptor antagonists for fibromyalgia treatment and another pending patent for a diagnostic serum assay for fibromyalgia, filed by Johns Hopkins University. Another author reported being a former employee of UCB and being a current shareholder.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.