key: cord-1056344-ch6zvnjx
authors: Alexander, James L; Selinger, Christian P; Powell, Nick
title: Third doses of SARS-CoV-2 vaccines in immunosuppressed patients with inflammatory bowel disease
date: 2021-10-13
journal: Lancet Gastroenterol Hepatol
DOI: 10.1016/s2468-1253(21)00374-5
sha: a1710aa0363e3f2123eee9e07f2abc981eb020c0
doc_id: 1056344
cord_uid: ch6zvnjx

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In September, 2021, the UK Joint Committee on Vaccination and Immunisation ( JCVI) produced guidance, accepted by the UK Government, on third primary doses and booster doses of SARS-CoV-2 vaccination. 1,2 The JCVI advises that a third primary dose of a SARS-CoV-2 vaccine is given to individuals who received targeted therapy for an autoimmune disease in the previous 3 months, at least 8 weeks after the second dose. 1 Of the treatments used in inflammatory bowel disease, JAK inhibitors, TNF inhibitors, and IL-12 and IL-23 inhibitors are listed in the guidance; anti-integrin therapy is not, although the list is noted to be non-exhaustive. Individuals taking high-dose corticosteroids (equivalent to ≥20 mg of prednisolone per day), methotrexate at more than 20 mg per week (oral and subcutaneous), azathioprine at more than 3·0 mg/kg per day, or mercaptopurine at more than 1·5 mg/kg per day are also considered eligible for a third primary dose. Third primary doses are distinct from the booster dose programme, which is being offered to other vulnerable groups no earlier than 6 months after second dose.

Clear evidence now exists that patients with inflammatory bowel disease treated with anti-TNF agents have impaired serological responses to SARS-CoV-2 vaccination, 3 and that immunity wanes over time in patients treated with either anti-TNF drugs or anti-integrin agents. 4 Although the CLARITY-IBD study showed inferior serological responses to vaccination in patients receiving anti-TNF therapy compared with those treated with anti-integrin agents, 3,4 how immune responses in the group treated with anti-integrin agents compare with those in the general population is unknown.

The doses of immunomodulator typically used in inflammatory bowel disease (eg, azathioprine 2·0-2·5 mg/kg per day and methotrexate 10-15 mg/week) are beneath the JCVI-stipulated threshold for third primary dose eligibility. Azathioprine monotherapy has been shown to attenuate immune responses to pneumococcal vaccination in patients with Crohn's disease, 5 although other reports suggest no effect on vaccine immunogenicity. 6,7 Importantly, no data currently exist on whether such doses of immuno modulator substantially impair immune responses to SARS-CoV-2 vaccination, although results from CLARITY-IBD suggest that concomitant immunomodulator use further blunts serological responses in patients treated with infliximab. 3 The vast majority of immunos u p p r e s s e d p a t i e n t s w i t h inflammatory bowel disease were prioritised for immunisation early in 2021, and we note that even those who might not meet the JCVI's criteria for a third primary dose will soon be at least 6 months post-second dose, which makes them eligible to receive a booster dose. 2 At the time of writing, recognising the paucity of data on the relative impact of different immunosuppressive therapies on immune responses to SARS-CoV-2 vaccination, and the challenges of communicating a clear message to patients and their care teams, the British Society of Gastroenterology is recommending a pragmatic approach, similar to the position taken by the British Society for Rheumatology. 8 A third dose of a SARS-CoV-2 vaccine should be offered no earlier than 8 weeks after the second dose to all patients with inflammatory bowel disease who are 12 years and over and who are receiving any immunosuppressive treatment, irrespective of current dose, and to all other patients with inflammatory bowel disease who are extremely clinically vulnerable. JLA reports sponsorship from Vifor Pharma for accommodation and travel to the British Society of Gastroenterology 2019 annual meeting, outside the submitted work. CPS reports grants and personal fees from AbbVie and Janssen; and personal fees from Ferring, Pfizer, Takeda, Galapagos, and Arena, outside the submitted work. NP has served as a speaker or advisory board member for Allergan, Falk, Janssen, Tillotts, Takeda, AbbVie, Debiopharm International, Ferring, Pfizer, Galapagos, and Vifor Pharma, outside the submitted work.

Patients with Crohn's disease on anti-tumor necrosis factor therapy are at significant risk of inadequate response to the 23-valent pneumococcal polysaccharide vaccine

Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study

COVID-19 guidance