Efficacy, safety, and B-cell depletion capacity of 3 rituximab dosing regimens in the treatment of moderate-to-severe pemphigus vulgaris and pemphigus foliaceus: A 52-week clinical trial

Abstract

Background: Rituximab (RTX) is effective for pemphigus, but optimal dosing remains uncertain.

Objective: Compare efficacy, safety, and B-cell depletion of 3 RTX regimens over 52 weeks.

Methods: In an open-label trial (May 2023-October 2024), 52 pemphigus vulgaris and pemphigus foliaceus patients received ultralow-dose rituximab (ULRTX) (100 mg), low-dose rituximab (LRTX) (500 mg), and standard-dose rituximab (SDRTX) (1000 mg) at weeks 0 and 2, with supplemental doses guided by CD20⁺ B-cell reconstitution. All received concomitant glucocorticoids.

Primary outcomes: time to disease control, complete remission, complete remission off therapy, and complete remission on minimal therapy.

Secondary outcomes: pemphigus disease area index changes, glucocorticoid use, relapse rates, and autoantibody seroconversion.

Results: All achieved disease control (median days: ULRTX = 15.5, LRTX = 14.0, SDRTX = 13.0; P = .02). CD20⁺ B-cell depletion occurred universally by week 2, with faster reconstitution in ULRTX by 26 weeks. Complete remission rates: 92.3% (ULRTX) versus 100% (LRTX/SDRTX); complete remission off therapy/complete remission on minimal therapy showed no intergroup differences. Median pemphigus disease area index reduction, cumulative glucocorticoid doses, relapse rates, and autoantibody seroconversion were comparable. No significant difference was found in adverse events. ULRTX demonstrated cost advantages.

Limitations: Single-center, nonrandomized design, small sample.

Conclusion: All regimens demonstrated comparable efficacy and B-cell depletion. ULRTX, despite a marginally longer time to disease, had the lowest adverse events and cost, supporting its utility in pemphigus management.

Keywords: B-cell depletion; efficacy; pemphigus; rituximab; safety.