Rheumatology (Oxford). 2023 Jun 16:kead281. doi: 10.1093/rheumatology/kead281. Online ahead of print.
ABSTRACT
OBJECTIVE: To evaluate belimumab addition to standard of care (SoC) in patents with refractory Idiopathic Inflammatory Myopathy (IIM).
METHODS: We conducted a 40-week multicentre randomized, double-blind, placebo-controlled trial with 1:1 IV belimumab 10 mg/kg or placebo randomization and a 24-week open-label extension. Clinical responses were measured by the Definition of Improvement (DOI) and Total Improvement Score (TIS). Flow cytometry analyses were performed on available samples before randomization, at 24 and 60-64wk. Descriptive statistics, t test, Fisher’s exact test and ANOVA tests were used.
RESULTS: 17 patients were randomized, 15 received ≥ 5 doses of belimumab or placebo and were included in the intention -to-treat analysis. More belimumab patients vs placebo attained TIS ≥ 40 (55.5% vs 33.3%; p=NS) and achieved DOI (33.3% vs 16.7%; p = NS) at Wk40 and Wk64; mean TIS was similar among groups. Two patients achieved major responses (TIS= 72.5) after Wk40 in the belimumab arm, none in the placebo arm. No improvement in placebo arm after switching to the open label phase was observed. There was no steroid-sparing effect. No new safety signals were detected.Although total B-cells were not reduced, belimumab induced naïve B-cells depletion while enhancing memory B cells number and frequency.
CONCLUSION: The study did not meet the primary end point and no statistically significant differences were observed in clinical responses between arms. More patients achieved sustained TIS ≥ 40 and reached DOI. Most patients who received belimumab longer than 40 weeks had clinical improvement. Phenotypic changes in B cell populations were not associated with clinical responses.
CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, https://clinicaltrials.gov/, NCT02347891.
PMID:37326854 | DOI:10.1093/rheumatology/kead281
