B-cell-depleting therapy in systemic lupus erythematosus

Abstract

The emergence of a new class of agents (B-cell-depleting therapies) has opened a new era in the therapeutic approach to systemic lupus erythematosus, with belimumab being the first drug licensed for use in systemic lupus erythematosus in more than 50 years. Four agents deserve specific mention: rituximab, ocrelizumab, epratuzumab, and belimumab. Controlled trials have shown negative results for rituximab, promising results for epratuzumab, and positive results for belimumab. Despite these negative results, rituximab is the most-used agent in patients who do not respond or are intolerant to standard therapy and those with life-threatening presentations. B-cell-depleting agents should not be used in patients with mild disease and should be tailored according to individual patient characteristics, including ethnicity, organ involvement, and the immunological profile. Forthcoming studies of B-cell-directed strategies, particularly data from investigations of off-label rituximab use and postmarketing studies of belimumab, will provide new insights into the utility of these treatments in the routine management of patients with systemic lupus erythematosus.

Figure

Summary of the main randomized controlled trials in systemic lupus erythematosus (SLE). % of benefit over placebo: low dose (light brown) and high dose (dark brown). % of severe infection: low dose (light brown), high dose (dark brown), and placebo (white). *Statistical significance difference vs placebo. ^aOverall response; BILAG = British Isles Lupus Assessment Group disease activity index; SELENA = Safety of Estrogen in Lupus Erythematosus National Assessment; SLEDAI = Systemic Lupus Erythematosus Disease Activity Index; SRI = Systemic Lupus Erythematosus Responder Index; CRI = Combined Responder Index; LN = lupus nephritis; SLE: systemic lupus erythematosus.