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Objective To assess whether presence of antiphospholipid antibodies (aPL) in serum at baseline could foreshadow treatment response after 52 weeks of belimumab therapy, based on pooled data from randomised controlled trials (RCTs) in systemic lupus erythematosus (SLE). Methods Data from five RCTs of belimumab in SLE were pooled, i.e., BLISS-52, BLISS-76, BLISS-Northeast Asia, EMBRACE, and BLISS-SC. Patients were divided into six subgroups based on aPL serology at baseline: anti-cardiolipin (aCL) positive, aCL negative, lupus anticoagulant (LAC) positive, LAC negative, positive for any aPL, negative for all aPL. Binary logistic regression models were conducted across four treatment-response constructs every fourth week from baseline, up to and including week 52, i.e., SLE Responder Index (SRI)-4, British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), and Definitions Of Remission In SLE (DORIS) remission. The analyses did not discriminate across different antibody isotypes, and the models were adjusted for trial variance. Participants with insufficient data were excluded from analysis. Results In total, 3086 patients received belimumab at the approved dose of 10 mg/kg monthly intravenously or 200 mg weekly subcutaneously (N=1869) or placebo (N=1217). Of these, 1257 patients had data on LAC at baseline, four of which lacked data on SRI-4. At the 52-week follow-up, belimumab outperformed placebo in inducing treatment response for patients who were LAC negative at baseline (odds ratio 95% confidence interval: SRI-4: 1.58 1.21−2.05, p=0.001; BICLA: 1.35 1.03−1.78, p=0.03; LLDAS: 1.84 1.25−2.71, p=0.002; DORIS: 1.84 1.09−3.13, p=0.023) while there was no significant difference between treatment arms for patients who were LAC positive (SRI-4: 1.54 0.88−2.72, p=0.132; BICLA: 1.45 0.81−2.60, p=0.214; LLDAS: 1.51 0.71−3.23, p=0.289; DORIS: 2.54 0.70−9.18, p=0.154). Belimumab was not shown to benefit aCL positive patients towards attainment of DORIS remission (p=0.187) or aPL negative patients towards BICLA response (p=0.071). In all other subgroups, results in all models favoured belimumab. Conclusion Consistent benefits from belimumab were observed irrespective of aCL or aPL seropositivity, with the exception of LAC positive patients in whom belimumab-induced attainability of SRI-4, BICLA, LLDAS, and DORIS remission was abated. Acknowledgement IP has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia, Bristol Myers Squibb (BMS), Elli Lilly, Gilead, GlaxoSmithKline (GSK), Janssen, Novartis, Otsuka, and Roche. The other authors declare that they have no conflicts of interest related to this work. The funders had no role in the design of the study, the analyses or interpretation of data, or the writing of the manuscript.
Tsoi et al. (Fri,) studied this question.