Comparing standard versus intensified pneumococcal vaccination regimens in patients with inflammatory bowel disease on biologics: a prospective, multicenter, randomized, open-label study

Abstract Background and aims Pneumococcal vaccination is essential for patients with inflammatory bowel diseases (IBD), but its efficacy is reduced in those on antitumor necrosis factor (TNF) or immunosuppressive therapy. This study compared immune responses to standard versus intensified pneumococcal vaccination strategies in IBD patients receiving anti-TNF (±immunosuppressors) or vedolizumab. Methods In a prospective, multicenter, randomized open-label study across 7 French university hospitals, IBD patients in clinical remission on biologic therapy (anti-TNF ± immunosuppressors, or vedolizumab) were randomized 1:1 to an intensified (PCV13/PCV13/PPSV23) or standard (PCV13/PPSV23) regimen. Vaccine response (ELISA and opsonophagocytic assays [OPA]), side effects, and disease activity were monitored over 36 months. The primary endpoint was vaccine response at month 5 (M5), defined as antibody titers >1 µg/mL for at least 9 of 13 serotypes in ELISA. Results One hundred and four patients (median age, 43 years; 60.6% male; 68.3% Crohn’s disease) were randomized to the standard (n = 51) or intensified (n = 53) regimen. At M5, the vaccine response was significantly higher in the intensified group compared to the standard group, as measured by ELISA (53.2% vs. 27.1%; relative risk [RR[ = 1.96; 95% CI, 1.15–3.36; P = .009) and OPA (90.9% vs. 62.5%; P = .007). OPA responses remained higher in the intensified group at M12, M18, and M36. Reduced responses were associated with anti-TNF therapy, combination therapy, and Crohn’s disease. Both regimens were well tolerated, with no differences in safety profiles or IBD relapse rates. Conclusions Intensified vaccination significantly enhances and sustains immune response over 36 months, particularly benefiting patients with CD on anti-TNF therapy.