Role of Trimethoprim-Sulfamethoxazole Prophylaxis Against the Infectious Complications of Rituximab Treatment in Autoimmune Blistering Diseases – a Retrospective Descriptive Study

Abstract

Background: Rituximab has emerged as a highly successful treatment in patients with severe-refractory autoimmune blistering diseases (AIBD) including pemphigus vulgaris. Marked clinical responses have been documented within just a few weeks of therapy and response rates as high as 97% have been reported. The B cell depleting action of rituximab occurs within 2 weeks of the first infusion and persists for an average of 11 months. Patients with AIBD on rituximab, often receive concurrent therapy with steroids and immunosuppressive agents. Thus, the B cell depleting action of rituximab occurs in the setting of glucocorticoid-mediated T cell suppression. Severe infection after rituximab treatment has been reported in up to 10% of patients, some fatal. This study investigates the rate and spectrum of infectious complications of rituximab in AIBD and potential role of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. Methods: We performed a retrospective cohort study of 30 patients with AIBD treated with rituximab. Patients received varying protocols of rituximab treatment. All patients received concurrent systemic corticosteroids and/ or immunosuppressive agents. We analyzed the incidence and spectrum of infectious complications as well as the use of antibiotic prophylaxis in the cohort. Results: Seventy-seven percent of patients received antibiotic prophylaxis. Thirty-three percent of patients developed at least one infectious complication of rituximab, 7% of infections were fatal. TMP-SMX was the agent of choice. The mean duration of antibiotic prophylaxis was 9 months. No adverse effects of TMP-SMX were observed. There was a decreased rate of infectious complications in patients who received antibiotic prophylaxis (RR 0.4; p 0.05), however this trend was not statistically significant. Conclusion: Even in the absence of published guidelines, physicians frequently administer TMP-SMX as prophylaxis for infections in patients with AIBD on rituximab, during treatment and in subsequent periods of B cell depletion. Based on our findings and existing guidelines for patients long term prednisone, we advocate for the use of TMP-SMX prophylaxis in patients with AIBD on rituximab and concurrent steroid-immunosuppressive therapy.