Longitudinal trends in immunological biomarkers, and predictors of relapse in pemphigus treated with rituximab: A prospective cohort study

Background Pemphigus relapse after rituximab treatment remains a challenge. Aim To correlate the change trends of immunological biomarkers with timing of pemphigus relapse, and identify its predictors following rituximab treatment Methods This prospective cohort study included 44 patients with pemphigus treated with a rituximab biosimilar (Rheumatoid arthritis protocol). Clinical data were recorded at baseline, and immunological biomarkers (anti-DSG1, anti-DSG3, anti-AChRM3, CD19+ B-cells, CD19+27+ memory B-cells) were estimated at baseline and every three months till 12 months. Patients were clinically followed-up for 2 years or until relapse and grouped as early (<12 months) relapse, relapsing between 12-24 months, and no relapse till 24 months. Results Twenty-four (54.5%) patients relapsed by 2 years, with 18 (75%) relapsing within the first year. Early (3-6 months) rise in CD19+ B-cells, anti-DSG3 and anti-DSG1 levels, and delayed (9-12 months) anti-DSG3 rise distinguished early from late relapse, while patients remaining relapse-free exhibited no significant immunological changes. At month 6, 73.3% of early relapsing patients had anti-DSG3 >120 RU/mL, as compared to 27.3% of patients without early relapse (p=0.008). Early relapse rates were significantly higher in patients with incomplete B-cell depletion at 3 months (100% vs 35%; p=0.02). There was no significant difference in the relapse rates based on B-cell repopulation (p=0.20). Incomplete B-cell depletion at 3 months and/or anti-DSG3 >120 RU/mL at 6 months had a positive and negative predictive value of 64.7% and 87.5% respectively, for early relapse. Limitations Relatively small and heterogeneous sample, including both pemphigus vulgaris and foliaceus, as well as treatment-naïve and relapsed patients Conclusion Patients with incomplete B-cell depletion and/or rising anti-DSG3 are at risk for early relapse and may benefit from closer monitoring or a maintenance rituximab infusion at 6 months.