Response to COVID‐19 vaccine is reduced in patients with inflammatory bowel disease, but improved with additional dose

BACKGROUND: Coronavirus disease 2019 (COVID‐19) vaccination is recommended for patients with inflammatory bowel disease (IBD); however, suppressed immune responses have been reported for fully vaccinated patients under immunosuppressive therapy, mainly from Western countries. We prospectively analyzed antibody titers of IBD patients in Asia induced by two‐dose and additional dose of messengerRNA COVID‐19 vaccine. METHODS: After measuring high‐affinity antibody titers, factors associated with antibody titers were identified by multiple regression analyses using the following covariates: sex, age (≥60 or <60 years), disease type (Crohn's disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA‐1273), time from second/third vaccination, molecular‐targeted agent (anti‐tumor necrosis factor [TNF] agents, ustekinumab, vedolizumab, tofacitinib, or no molecular‐targeted agents), thiopurine, steroid, and 5‐aminosalicylic acid. RESULTS: Among 409 patients analyzed, mean titer was 1316.7 U/mL (SD, 1799.3); 403 (98.5%) were judged to be seropositive (≥0.8 U/mL), and 389 (95.1%) had neutralizing antibodies (≥15 U/mL). After the third vaccination, mean titer raised up to 21 123.8 U/mL (SD, 23 474.5); all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies. In 248 patients with genetic data, there was no difference in mean titer after two/third doses between carriers and non‐carriers of HLA‐A24 associated with severe disease during COVID‐19 infection. A multiple regression analyses using covariates revealed that older age, vaccine type (BNT162b2), time from second/third dose, anti‐TNF agent, tofacitinib, and thiopurine were independently associated with lower antibody titers. CONCLUSIONS: Our findings further support the recommendation for COVID‐19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti‐TNF agents and/or thiopurine or tofacitinib.