Combination Therapy With Ensitrelvir and Remdesivir Versus Antiviral Monotherapy in Patients Receiving Anti-CD20 Monoclonal Antibody Therapy: A Retrospective Cohort Study.

Background We aimed to evaluate the effectiveness of combination therapy with ensitrelvir and remdesivir compared to antiviral monotherapy in patients with a history of anti-CD20 monoclonal antibody therapy who were hospitalized with COVID-19. Methods This retrospective cohort study was conducted at St. Marianna University Hospital (a tertiary care hospital) in Kawasaki, Kanagawa, Japan. Among 1,549 patients hospitalized with COVID-19 between April 2022 and December 2024, 17 patients with a history of anti-CD20 monoclonal antibody therapy were included in the study. Among them, seven patients received combination therapy (ensitrelvir and remdesivir), and 10 received antiviral monotherapy. Ensitrelvir and remdesivir were administered for five and five to 10 days, respectively. Results No deaths occurred within 30 days. The one-year mortality rate was significantly lower in the combination group (1/7, 14.3%) than in the monotherapy group (7/9, 77.8%; p = 0.041). Case 8 was excluded from this analysis due to insufficient follow-up duration. At baseline, the combination therapy group had a higher proportion of patients with severe or critical COVID-19 (6/7, 85.7% vs. 2/10, 20.0%), a lower median serum IgG level (526 vs. 908.5 mg/dL), and a higher prevalence of pneumonia (6/7, 85.7% vs. 2/10, 40.0%). Despite these more severe baseline characteristics, the combination therapy group showed significantly lower post-treatment antigen levels (median (IQR): 11.24 pg/mL (1.76-49.39 pg/mL) vs. 2792.41 pg/mL (186.9-5000 pg/mL), p = 0.0303). Conclusions Combination therapy with ensitrelvir and remdesivir was associated with lower long-term mortality and viral burden in patients with COVID-19 who had received anti-CD20 monoclonal antibody therapy. However, these results are based on a small retrospective cohort and should be interpreted as hypothesis-generating; larger prospective studies are needed to determine whether this association reflects a true therapeutic effect.