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, 1000 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.