Background/Purpose: Abnormalities of B cell function are part of the pathogenesis of systemic sclerosis (SSc), and B-lymphocyte stimulator (BLyS) is increased in the serum and skin of patients with SSc. Belimumab, a human monoclonal antibody, is a BLyS-specific inhibitor indicated for the treatment of some patients with systemic lupus erythematosus. It is not known whether there may be a role for the use of belimumab in the treatment of SSc.

Methods: This was an investigator-initiated, industry-sponsored, single-center, randomized, double-blind, placebo-controlled, pilot study. Adults with diffuse cutaneous (dc)SSc of ≤3 years duration from first non-Raynaud’s symptom were randomly assigned 1:1 to belimumab IV (10 mg/kg) or placebo after starting on background mycophenolate mofetil (MMF) 1000 mg po bid. The primary objectives were to assess the safety and tolerability of belimumab in patients with early dcSSc on background MMF as assessed by the number of adverse events (AE) and serious (S)AE and to assess efficacy as measured by change in Modified Rodnan Skin Score (MRSS) after 52 weeks.

Results: Baseline demographic information is shown below and was balanced between groups. After a MMF wash-in period, 20 patients were randomized: 10 to belimumab and 10 to placebo. One patient in each group was withdrawn by the investigators soon after randomization due to disease progression. A modified intent-to-treat analysis was performed including all patients who had at least one MRSS assessment after randomization. All randomized patients were included in the safety analysis. In the belimumab+MMF group, the MRSS decreased from a mean (SD) of 26.7 (5.4) to 19.1 (10.3), p = 0.039. In the placebo+MMF group, the mean MRSS decreased from 26.4 (5.4) to 19.9 (8.8), p= 0.023. The mean change in MRSS at 52 weeks was –8.6 (7.7) in the belimumab group and –6.6 (7.7) in the placebo group, p=0.40. In the belimumab group 7/9 patients achieved an MRSS improvement of ≥ 20% versus 3/9 patients in the placebo group, p=0.08. Patients in the belimumab group had a greater improvement in health assessment questionnaire – disability index (HAQ-DI). There were no significant differences in AE with 56 AE, 16 of which were infections, in the placebo group and 53 AE, 18 of which were infections, in the belimumab group. Three SAEs occurred after randomization, all in the placebo group and not deemed related to study medication.

Conclusion: Patients in both the belimumab+MMF and the placebo+MMF groups experienced clinically and statistically significant improvement in MRSS although the difference in the mean change in MRSS between the groups was not significant in this small pilot study. A higher proportion of patients in the belimumab group achieved an improvement in MRSS ≥ 20% although this missed statistical significance. Adverse events and rates of infection were similar in the groups. Additional study is needed to determine the role of belimumab in the treatment of dcSSc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-belimumab-with-background-mycophenolate-for-early-diffuse-cutaneous-systemic-sclerosis-a-randomized-placebo-controlled-pilot-trial/