Sequential rituximab after belimumab does not improve disease control in SLE

A single cycle of rituximab after therapy with belimumab did not improve disease control or remission in patients with active systemic lupus erythematosus (SLE). This was the disappointing main result of the BLISS-BELIEVE study.

“Given a potential synergistic mode of action, belimumab and rituximab combination therapy may enhance clinical benefit in SLE patients,” Prof. Cynthia Aranow (Feinstein Institutes for Medical Research, NY, USA) explained [1]. This could be of importance since disease control remains an unmet need in SLE. The objective of the double-blind, placebo-controlled, 104-week, phase 3 study BLISS-BELIEVE (NCT03312907) was to assess the efficacy and safety of sequential therapy with belimumab followed by a single rituximab cycle in patients with SLE.

Thus, patients with active SLE received subcutaneous belimumab once weekly for 52 weeks and were randomised 1:2:1 to receive additionally: placebo at weeks 4 and 6 (group A), rituximab in a dose of 1,000 mg intravenous at weeks 4 and 6 (group B), or standard therapy for 104 weeks (group C). Group A and B discontinued immunosuppressants by week 4. A 52-week observation therapy followed the 52-week treatment phase in groups A and B. The primary study endpoint was the percentage of patients with disease control (assessed as SLE Disease Activity Index score 2,000 [SLEDAI-2K] without other immunosuppressants and prednisone-equivalent dose of ≤5 mg/day) at week 52. As Prof. Aranow pointed out, the primary comparison was between groups A and B, group C was included for reference comparison only.

Overall, 19.4% of patients in group A, 18.8% in group B, and 19.7% in group C discontinued belimumab treatment by week 52 mainly due to adverse events. No statistically significant differences were detected between group A and B in the proportions of patients with disease control at week 52, clinical remission at week 64, and disease control at week 104. Duration of disease control was significantly higher in group B than group A at week 52. At this time, anti-dsDNA positive patients at baseline achieved a significant decrease from baseline in anti-dsDNA when treated with belimumab followed by rituximab than with belimumab followed by placebo.

Regarding safety, more serious infections were reported in group B. “In conclusion, compared with belimumab alone, sequential therapy did not improve disease control or remission, although the duration of disease control at week 52 and SLEDAI-2K reductions at weeks 1 and 4 were greater,” Prof. Aranow said. In addition, more serious infections were seen in patients using belimumab rituximab sequential therapy. “Using new clinical endpoints underscores the efficacy of belimumab for disease control,” Prof. Aranow concluded.

1. Aranow C, et al. Efficacy and safety of subcutaneous belimumab (BEL) and rituximab (RTX) sequential therapy in patients with systemic lupus erythematosus: the phase 3, randomized, placebo-controlled BLISS-BELIEVE Study. Abstract L13, ACR Convergence 2021, 3–10 November.

 

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Posted on 14 January 202217 May 2024