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- Title
Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus : A Randomized Controlled Trial.
- Authors
Shipa, Muhammad; Embleton-Thirsk, Andrew; Parvaz, Mariea; Santos, Liliana Ribeiro; Muller, Patrick; Chowdhury, Kashfia; Isenberg, David A.; Doré, Caroline J.; Gordon, Caroline; Ehrenstein, Michael R.; Isenberg, David; D'Cruz, David P.; Jordan, Natasha; Parker, Benjamin; Lightstone, Liz; Salama, Alan; Pyne, Debasish; Edwards, Christopher J.; Griffiths, Bridget; Vital, Edward M.
- Abstract
<bold>Background: </bold>B-cell depletion with rituximab is commonly used for patients with systemic lupus erythematosus (SLE) that is refractory to conventional therapy, but it yields variable responses. We hypothesized that high B-cell activating factor (BAFF) levels after rituximab can cause disease flares, thereby limiting its effectiveness.<bold>Objective: </bold>To obtain preliminary evidence for efficacy of the anti-BAFF therapeutic belimumab after rituximab in SLE.<bold>Design: </bold>Phase 2, randomized, double-blind (patients, assessors, researchers, care providers), placebo-controlled, parallel-group, superiority trial. (ISRCTN: 47873003).<bold>Setting: </bold>England.<bold>Participants: </bold>Fifty-two patients who had SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy were recruited between 2 February 2017 and 28 March 2019.<bold>Intervention: </bold>Participants were treated with rituximab and 4 to 8 weeks later were randomly assigned (1:1) to receive intravenous belimumab or placebo for 52 weeks.<bold>Measurements: </bold>The prespecified primary end point was serum IgG anti-double-stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes included incidence of disease flares and adverse events.<bold>Results: </bold>At 52 weeks, IgG anti-dsDNA antibody levels were lower in patients treated with belimumab compared with placebo (geometric mean, 47 [95% CI, 25 to 88] vs. 103 [CI, 49 to 213] IU/mL; 70% greater reduction from baseline [CI, 46% to 84%]; P < 0.001). Belimumab reduced risk for severe flare (BILAG-2004 grade A) compared with placebo (hazard ratio, 0.27 [CI, 0.07 to 0.98]; log-rank P = 0.033), with 10 severe flares in the placebo group and 3 in the belimumab group. Belimumab did not increase incidence of serious adverse events. Belimumab significantly suppressed B-cell repopulation compared with placebo (geometric mean, 0.012 [CI, 0.006 to 0.014] vs. 0.037 [CI, 0.021 to 0.081] × 109/L) at 52 weeks in a subset of patients (n = 25) with available data.<bold>Limitations: </bold>Small sample size; biomarker primary end point.<bold>Conclusion: </bold>Belimumab after rituximab significantly reduced serum IgG anti-dsDNA antibody levels and reduced risk for severe flare in patients with SLE that was refractory to conventional therapy. The results suggest that this combination could be developed as a therapeutic strategy.<bold>Primary Funding Source: </bold>Versus Arthritis.
- Subjects
ENGLAND; SYSTEMIC lupus erythematosus; TALL-1 (Protein); BELIMUMAB; RANDOMIZED controlled trials; RITUXIMAB; THERAPEUTIC use of monoclonal antibodies; AUTOANTIBODIES; RESEARCH; RESEARCH methodology; ARTHRITIS Impact Measurement Scales; EVALUATION research; COMPARATIVE studies; BLIND experiment; RESEARCH funding; IMMUNOSUPPRESSIVE agents; STATISTICAL sampling
- Publication
Annals of Internal Medicine, 2021, Vol 174, Issue 12, p1647
- ISSN
0003-4819
- Publication type
journal article
- DOI
10.7326/M21-2078