SARS-CoV-2 vaccination for patients with inflammatory bowel disease - Authors' reply.

We thank Garcia Garrido and colleagues for their comments on the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) and IBD Clinical Research Group section position statement and the studies cited in their Correspondence, including the valuable meta-analysis of the impact of immunosuppression on pneumococcal vaccination. However, the results of this meta-analysis should be interpreted with caution in patients with IBD, as most of the studies included (18 of 22) were from patients with other immune-mediated inflammatory diseases (mostly rheumatoid arthritis), in which the only conventional immunomodulator reported was methotrexate. Additionally, in the few IBD studies included, anti-TNF treatment significantly impaired vaccine responses, whereas immunomodulators did not. The 2020 study by van Aalst and colleagues also substantiates impaired pneumococcal vaccine (PCV13) responses in patients receiving anti-TNF agents. The key message is that there is clear evidence of impaired pneumococcal vaccine responses in patients with IBD taking anti-TNF therapy, with less clear or conflicting evidence available for conventional immunomodulators.

We agree that any impact of immunosuppression is likely to be specific to vaccines. Fortunately, data are now emerging on the effects of immunosuppressive therapies on anti-SARS-CoV-2 vaccine immunogenicity in patients with IBD. Results from 1283 patients with IBD in the CLARITY IBD study have shown that rates of seroconversion are lower after the first dose of both the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 nCoV-19 (Oxford/AstraZeneca) vaccines in patients treated with infliximab than in patients treated with vedolizumab. Anti-TNF monotherapy and immunomodulator monotherapy were not compared; however, the combination of infliximab and immunomodulator therapy was associated with the lowest rates of seroconversion with both vaccines. Whether any particular vaccine should be favoured in patients with IBD is more contentious. No major serological differences were observed in CLARITY IBD between the two vaccines, but there are conceptual reasons to suspect that adenovirus vector vaccines might elicit favourable T-cell responses, which could be important for durable immunity. Data regarding the effects of immunosuppressive therapies on T-cell responses are eagerly anticipated.

Important unanswered questions remain. Although early data from small cohorts of patients with IBD treated with anti-TNF agents completing two doses of mRNA vaccination in CLARITY IBD and in the USA report robust vaccination responses, larger studies, including those incorporating data on adenovirus vector vaccines, are urgently needed. Furthermore, the effects on vaccine immunogenicity of other immunosuppressive regimens used in IBD are yet to be systematically investigated.

JLA reports sponsorship from Vifor Pharma for accommodation and travel to British Society of Gastroenterology 2019. NAK reports personal fees from Dr Falk, Janssen, Takeda, and Tillotts; and grants and personal fees from Pharmacosmos. TA reports grants from F Hoffmann-La Roche AG, Janssen, and Galapagos; grants and personal fees from Biogen, Celltrion, and Celgene; non-financial support from AbbVie and Tillotts; personal fees from Arena, Adcock Ingram, Gilead, Pfizer, and Genentech; and grants, personal fees, and non-financial support from Takeda. CWL reports grants and personal fees from Gilead; and personal fees from AbbVie, Takeda, Janssen, Ferring, Trellus Health, Pfizer, Galapagos, and Iterative Scopes. NP reports serving as a speaker for Allergan, Bristol Myers Squibb, Falk, Ferring, Janssen, Pfizer, Tillotts, and Takeda, and as a consultant and/or an advisory board member for AbbVie, Allergan, Celgene, Bristol Myers Squibb, Ferring, and Vifor Pharma.