Introduction

Pneumococcal vaccination is essential in IBD patients. However, its efficacy in patients on immunosuppressive or anti-TNF therapy is much lower than in the normal population (45% vs 80%). Vaccine regimen recommendations vary according to the degree of immunodepression. The aim of our study was to identify an optimal vaccination strategy for immunocompromised IBD patients treated with anti-TNF, vedolizumab and/or IS.

Aims & Methods

This is a prospective, multicenter, randomized study comparing two vaccine regimens: intensified vaccine strategy (Prevenar13®/Prevenar13®/PSV-23® (or Pneumovax as a replacement for PSV-23) vs. normal strategy (Prevenar13®/PSV-23® (or Pneumovax as a replacement for PSV-23), (randomization 1: 1) on vaccine immunogenicity measured by antibody titer against at least 9 of the 13 pneumococcal serotypes contained in Prevenar13®. Any patient with confirmed IBD under biotherapy (anti TNF with or without immunosuppressive drugs or Vedolizumab) and in clinical remission (HBI <4 for CD and partial Mayo Score <3 for UC) was included. Vaccination and vaccine monitoring were carried out by the vaccination center of each center, with adverse events reported at each visit (8 for 36 months of follow-up), and ELISA and OPA serotype assays systematically collected and clinical activity was reported by the gastroenterologist at the same time. Correlate of protection in adults using serology testing was classically defined as at least 9 out of 13. Serotypes > 1µg/mL. For functional testing of antibodies using the Opsonophagocytic assays, we apply the well-defined 4 times increase of titer between pre and post-vaccination against at least 70% of serotypes. ClinicalTrials.gov Identifier: NCT02255227

Results

51 patients in the normal vaccination arm and 53 in the intensified vaccination arm were included (mean age: 42.9 years, male: 63%, CD: 68%, active smoking: 21%, duration of IBD: 10.2 years, 98% IBD inactive). Around 88% of patients were under anti-TNF monotherapy (28% on combotherapy) and 12% under vedolizumab. Serology criteria for good responders at M5 were 57.5% for the intensified regimen vs 25.6% for the standard regimen (RR: 2.25 (1.26;4.00), p = 0.003). For OPA correlate of protection, vaccine response was significantly greater in the intensified arm at all-time points: M5 (96% vs. 89%), M12 (76 vs. 58%) and M36 (68% vs. 36.8%). In multivariate analysis, two factors reduced vaccine response: anti-TNF use (RR: 6.84; CI95: 1.01-46.1; p=0.048) and CD type (RR: 9.48; CI95: 2.74-32.8; p:0.0004). The tolerability of the vaccine regimens was comparable throughout follow-up. In terms of IBD activity, percentage of clinical relapse was similar during follow-up (16.8% under the intensified regimen versus 25% under the normal regimen (p:NS).

Conclusion

In IBD on biotherapy and/or IS, the intensified pneumococcal vaccine regimen (2 injections of Prevenar followed by one of Pneumo 23) is significantly more immunogenic than a standard regimen, especially when using functional correlate of protection. The duration of the response is also greater in this intensified arm.