Optimizing Pemphigus Management With Rituximab and Short-Term Relapse Predictors

Importance: Rituximab is approved for the treatment of moderate to severe pemphigus. However, 20% of patients in the RITUX 3 trial relapsed within the first year of treatment. Objective: To assess the outcome of an additional rituximab infusion at month 6 in patients with pemphigus who were in complete remission (CR) after rituximab regimen but had 1 or more predictors of relapse at month 3. Design, Settings, and Participants: This multicenter cohort study was conducted in France from September 2018 to June 2023 to assess patients with newly diagnosed pemphigus who were in CR after treatment with the RITUX 3 regimen but had predictors of relapse at month 3. Relapse factors were a Pemphigus Disease Area Index (PDAI) score of 45 or higher, desmoglein 1 (DSG1) antibodies greater than 20 IU/mL, and/or DSG3 antibodies greater than 130 IU/mL. Exposure: Patients in CR at month 6 with at least 1 predictor of relapse were treated with an additional rituximab infusion at month 6. Main Outcomes and Measures: Primary end point was the rate of CR without corticosteroid therapy for 2 months at month 12. Secondary end points were the rate of relapse, number of patients needing to be re-treated (NNT) with rituximab to avoid a relapse, and safety. Results: The study population comprised 87 patients (44 females [50.6%] and 43 [49.4%] males), with a mean (SD [range]) age of 55.3 (15.2 [24-92]) years at pemphigus diagnosis. Of these, 64 patients (73.6%) had pemphigus vulgaris and 23 (26.4%) had pemphigus foliaceus. At month 6, CR had been achieved by 77 patients (88.5%), and 10 (11.5%) had persistent disease activity. Of the 77 patients in CR, 30 (39.0%) had at least 1 predictor of relapse and received an additional infusion of rituximab; 47 patients (61.0%) without a predictor did not. Two patients without a predictor and no patients with a predictor experienced relapse-an overall relapse rate of 2.6% and an NNT of 3.6 (95% CI, 1.6-46.5). The 10 patients (11.5%) with persistent disease activity at month 6 were re-treated with rituximab, 2000 mg. At month 12, the rate of CR without corticosteroid therapy for a minimum of 2 months was 72 of 77 (93.5%) among patients who had achieved CR at month 6, and 72 of 87 (82.7%) for the whole study population. Eight serious adverse effects were reported among 5 patients; there were no deaths. Conclusion and Relevance: This multicenter cohort study indicates that using predictors such as baseline PDAI score, anti-DSG1 antibodies, and/or anti-DSG3 antibodies to initiate preemptive treatment with additional rituximab may reduce the rate of short-term relapse.