Treatment with the type II anti-CD20 monoclonal antibody obinutuzumab significantly improved disease activity and reduced glucocorticoid use in patients with active systemic lupus erythematosus (SLE), a phase 3 trial has found.
More than three quarters of patients receiving obinutuzumab achieved a clinical response after 52 weeks, compared with just over half of those receiving placebo, according to the study published in the New England Journal of Medicine [link here].
The trial, which was funded and designed by F. Hoffmann–La Roche, enrolled 303 patients with active SLE (SLEDAI-2K score ≥8) receiving standard therapy but without proliferative or membranous lupus nephritis. Participants were randomly assigned to receive obinutuzumab 1000 mg (n=151) or placebo (n=152) on day 1 and at weeks 2, 24, and 26.
At 52 weeks, 77% of patients in the obinutuzumab group achieved an SLE Responder Index-4 (SRI-4) response, compared with 54% in the placebo group (p<0.001). When non-fatal intercurrent events were excluded, response rates were 85% and 69%, respectively (p<0.001).
Patients receiving obinutuzumab were also more likely to achieve a BILAG-based Composite Lupus Assessment (BICLA) response (62% vs 40%, p<0.001) and less likely to experience a BILAG-defined flare (33.8% vs 48.7%; hazard ratio 0.58, p=0.002).
Among patients taking at least 10 mg of prednisone daily at baseline, 80% of those receiving obinutuzumab reduced their dose to 7.5 mg/day or less between weeks 40 and 52, compared with 54% in the placebo group (p<0.001).
Professor Richard Furie
“The glucocorticoid-sparing effect among patients receiving at least 10 mg daily of prednisone (or equivalent) at baseline (a subgroup of the intention-to-treat population) and the markedly reduced incidence of flares together address two of the most critical unmet needs in long-term care of patients with SLE,” wrote the authors, led by Professor Richard Furie of Northwell, New York, USA and including representatives from F. Hoffmann–La Roche and Genentech.
Rates of remission and low disease activity were also higher with obinutuzumab at week 52, with 35% meeting the Definition Of Remission In SLE (DORIS) criteria compared with 14% in the placebo group. Lupus Low Disease Activity State (LLDAS) was achieved by 58% of patients receiving obinutuzumab and 26% of those receiving placebo.
“Although the analyses were not controlled for type I error, DORIS response and LLDAS scores (measures of remission and low disease activity, respectively) also appeared to be improved with obinutuzumab; these findings are relevant given that guidelines emphasise treat-to-target approaches aiming for remission with low doses of glucocorticoids,” the authors wrote.
Adverse events occurred in 89% of patients receiving obinutuzumab and 82% receiving placebo. Grade 3 or higher adverse events occurred in 17% and 14%, respectively, and serious adverse events in 16% and 12%.
Infections were more common in the obinutuzumab group, although investigators said the safety findings were consistent with the known profile of the drug and the underlying disease.