Belimumab

Belimumab (anti-BAFF/BLyS monoclonal antibody) has been tested in IIM largely as a proof-of-concept B-cell–pathway intervention, based on observations that BAFF is upregulated in dermatomyositis/polymyositis and correlates with disease activity. The key trial is a multicenter, randomized, double-blind, placebo-controlled study in refractory adult idiopathic inflammatory myopathy (polymyositis/dermatomyositis and related IIM phenotypes), using IV belimumab 10 mg/kg monthly added to background standard of care for 40 weeks, followed by a 24-week open-label extension in which all participants received belimumab. Clinical response was assessed with ACR/EULAR myositis response criteria (Definition of Improvement and Total Improvement Score). Established peer-reviewed data now come from the full report of this trial, whereas earlier “preliminary” reporting appeared in meeting abstracts from the same study. [1,2]

17 patients were randomized and 15 were included in the intention-to-treat analysis (≥5 infusions). The trial did not meet its primary endpoint and between-arm differences were not statistically significant. Numerically, more belimumab-treated patients achieved TIS ≥40 at week 40 (55.5% [5/9] vs 33.3% [2/6]) and met the Definition of Improvement (33.3% [3/9] vs 16.7% [1/6]) at week 40, but without significant separation; mean TIS over time was similar. Two belimumab-arm participants achieved major improvement (reported as TIS 72.5) after week 40, while none in placebo did. Importantly for inpatient “steroid momentum,” the study found no steroid-sparing effect, and the placebo group showed no additional improvement after crossover to open-label belimumab. [1] These same themes—signal without statistical separation in a small sample—were already apparent in preliminary meeting reports from the trial. [2]

Safety in this IIM dataset was generally reassuring but necessarily limited by size. Across phases, 45 adverse events were recorded; during the randomized phase, event counts were similar (17 in belimumab vs 15 in placebo), with 11 infections observed overall (mostly mild respiratory infections; infections were not clearly increased in belimumab vs placebo). One serious adverse event occurred in the belimumab arm (a perforated appendix leading to discontinuation), and no new safety signals were detected; biologically, belimumab shifted B-cell subsets (naïve B-cell depletion with relative increases in memory subsets) without a clear correlation to clinical response. Taken together, current evidence supports belimumab as biologically active but not yet proven effective for refractory IIM in controlled data; if pursued further, it likely requires larger, phenotype-enriched trials (the investigators note the placebo response and small n as major constraints). [1–3]

References (with links)

Marder G, Quach T, Chadha P, et al. Belimumab treatment of adult idiopathic inflammatory myopathy. Rheumatology (Oxford). 2024 (collection);63(3):742-750. doi:10.1093/rheumatology/kead281.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10907809/

(Meeting abstract) Safety and efficacy of belimumab in the treatment of adult idiopathic inflammatory myositis (polymyositis and dermatomyositis). ACR Meeting Abstracts (reported results from the same randomized trial).

https://acrabstracts.org/abstract/safety-and-efficacy-of-belimumab-in-the-treatment-of-adult-idiopathic-inflammatory-myositis-polymyositis-and-dermatomyositis/

Belimumab for Maintenance Therapy in Idiopathic Inflammatory Myositis (protocol/SAP; NCT02347891). ClinicalTrials.gov document (protocol).

https://cdn.clinicaltrials.gov/large-docs/91/NCT02347891/Prot_SAP_000.pdf