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Original Investigation
October 23, 2019

Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus

Author Affiliations
  • 1Department of Dermatology, University of Pennsylvania, Philadelphia
  • 2Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania
  • 3Division of Dermatology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand
  • 4Division of Hematology Oncology, Department of Internal Medicine, University of Pennsylvania, Philadelphia
JAMA Dermatol. 2019;155(12):1404-1409. doi:10.1001/jamadermatol.2019.3236
Key Points

Question  What are the rates of improvement, safety profile, and prognostic factors for rituximab use in a large cohort of patients with pemphigus at a tertiary care center?

Findings  In this cohort study of 112 patients with pemphigus, 48.2% of the patients achieved complete remission off therapy with oral systemic agents after the first cycle of rituximab therapy, 70.5% achieved remission following multiple cycles at a median follow-up time of 10.5 months, and 50.0% of patients experienced relapse after a median of 23.3 months. Lymphoma dose regimen, age greater than 65 years, and body mass index greater than or equal to 35 were significantly associated with rate of complete remission off therapy.

Meaning  Long-term outcomes and prognostic factors for complete remission when not receiving oral systemic therapy may inform patient and clinician expectations for rituximab therapy for pemphigus during routine clinical practice.

Abstract

Importance  Rituximab has emerged as a front-line therapy for pemphigus, but prognostic factors for achieving complete remission off therapy (CROT) with oral systemic agents remain unknown.

Objectives  To describe rates of CROT and relapse and identify prognostic factors for achieving CROT after rituximab therapy for pemphigus.

Design, Setting, and Participants  A single-center, retrospective, cohort study was conducted at the University of Pennsylvania including 112 patients with pemphigus treated with rituximab with at least 12 months’ clinical follow-up after the start of rituximab therapy. Multivariate regression analysis of factors predictive of CROT and Kaplan-Meier analysis of disease relapse were conducted. The study included patients treated with rituximab from March 15, 2005, until December 19, 2016. Data analysis was performed from December 2017 to June 2018.

Main Outcomes and Measures  The primary study outcome was CROT after 1 cycle. Secondary study outcomes included rate of CROT or the composite end point of CROT or complete remission on minimal therapy after 1 or more cycle, and median time to relapse. Multivariate regression analysis for prognostic variables for CROT, including age, sex, pemphigus subtype, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), disease duration, and dosing regimen, was performed.

Results  A total of 112 patients with pemphigus with median 37.8 months (range, 12.1-130.7) follow-up after rituximab therapy were identified. Of these, 65 were women (58.0%). At the time of first rituximab infusion, median age was 52.3 years (range, 20.0-89.3). Including patients who received multiple cycles of rituximab, 79 patients (70.5%) achieved CROT after a median time of 10.5 months (range, 2.0-49.8), and 36 of 72 patients (50.0%) subsequently experienced relapse after a median of 23.3 months (interquartile range, 10.8-50.4 months). Considering only the first cycle of rituximab, 54 patients (48.2%) achieved CROT. Controlling for age, sex, pemphigus subtype, BMI, and disease duration, patients who received lymphoma vs rheumatoid arthritis dosing were 2.70-fold more likely to achieve CROT (odds ratio [OR], 2.70; 95% CI, 1.03-7.12; P = .04). Increasing age was associated with significant increases in achieving CROT (Wald test for trend, P = .01), whereas BMI greater than or equal to 35 was associated with a 0.14 OR (95% CI, 0.03-0.63; P = .01) for achieving CROT, regardless of the dosing regimen. In multivariate analysis, there was no significant difference in CROT rates with sex (OR, 1.01; 95% CI, 0.42-2.50; P = .97), pemphigus subtype (OR, 0.37; 95% CI, 0.09-1.51; P = .17), or disease duration (OR, 0.99; 95% CI, 0.98-1.00; P = .09).

Conclusions and Relevance  Lymphoma dosing and older age may be associated with CROT and BMI greater than or equal to 35 may be a negative prognostic factor for CROT after rituximab therapy for pemphigus. These findings help inform clinical expectations and merit evaluation in future prospective clinical trials.

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