COVID-19 Vaccination and Inflammatory Bowel Disease: Desired Antibody Responses, Future Directions, and a Note of Caution

Dear Editors:

We have a few thoughts on the important and timely analysis “Serological response to messenger RNA COVID-19 vaccines in inflammatory bowel disease patients receiving biological therapies” by Wong et al.¹ The authors sought to address the concern of COVID-19 vaccine responsiveness among patients with inflammatory bowel disease (IBD) receiving biologic therapy. The analysis included 48 patients with IBD who had received at least 1 vaccination of either the Pfizer-BioNTech or National Institutes of Health (NIH)–Moderna vaccine and assessed the rates of immunoglobulin response to the receptor binding domain (RBD) of the SARS-CoV-2 S protein (using an in-house enzyme-linked immunosorbent assay [ELISA]), comparing results to those of completely vaccinated health care workers and healthy volunteers. All patients with IBD who received both COVID-19 vaccine doses (n = 26) achieved positive anti-RBD results. However, a quantitative comparison of anti-RBD levels between patients with IBD and health care workers showed that use of anti–tumor necrosis factor was associated with lower anti-RBD total immunoglobulin (P = .0299) and that the use of vedolizumab was associated with lower anti-RBD total immunoglobulin, anti-RBD IgG, and anti-S IgG.

The results mirror our own findings using a commercially available ELISA assay for both the COVID-19 nucleocapsid and spike domain antibodies (Roche) among consecutively tested postvaccination patients with IBD on biologic or immunomodulator therapy. The total group included 19 patients, 9 (47%) female, with a mean age of 50 years (range, 27-80 years). Patients’ maintenance therapies varied within the cohort, with most patients on biologic therapy, including 7 (37%) on infliximab, 2 (11%) on adalimumab, 1 (5%) on golimumab, 5 (26%) on ustekinumab, 2 (11%) on vedolizumab, 1 (5%) on tofacitinib, and 1 (5%) on methotrexate. Eleven patients received the Pfizer-BioNTech vaccine, and 8 received the NIH-Moderna vaccine. We observed a 95% (18/19) overall response rate. None of the patients with positive results for spike domain antibodies had elevations of nucleocapsid antibodies, suggesting a true vaccine response rather than prior undiagnosed infection. Of the patients with elevated spike domain antibodies, 89% (17/19) had the highest measurable levels, at >250.00 U/mL, with assay reference ranges of ≤0.79 U/mL indicating negative and ≥0.80 U/mL indicating positive results. The only patient negative for spike domain antibodies was a 78-year-old man on adalimumab 40 mg subcutaneously every 14 days, prednisone 5 mg every third day, and sulfasalazine who had received his second NIH-Moderna vaccination 8 weeks prior.

Both the observations by Wong et al¹ and our own provide important and encouraging early data on the effectiveness of SARS-CoV-2 vaccination. Added to these findings are the report by Kennedy et al² of 27 patients receiving 2 doses of the Pfizer-BioNTech vaccine, with 85% (17/20) of infliximab-treated patients and 86% (6/7) of vedolizumab-treated patients seroconverting. Although our sample size is also small, the additional numbers, expansion to patients not on biologic therapy, and inclusion of a commercially available ELISA add further support to the findings of Wong et al and Kennedy et al. Still, many more data will be needed to determine the true effectiveness of SARS-CoV-2 vaccination in this high-risk population. Notably, Kennedy also observed the lower vaccine response rates after a single dose of the vaccine in infliximab-treated patients and in those with immunomodulator use. Coupling this with reports showing that combination therapy with tumor necrosis factor antagonists and steroid or thiopurines is associated with severe COVID-19 among patients with IBD suggests that specific vaccine protocols (or the requirement for confirmation of a satisfactory neutralizing antibody response) may need to be developed for this highest-risk population.³ Also, as information accumulates on the initial antibody response postvaccination, longer-term follow-up will be needed to track the durability of the antibody response and responses to newer vaccines, in both the IBD and general populations.

There is one critical point to note, particularly at a time when many are still waiting for their first SARS-CoV-2 vaccine dose. Previous studies have shown that patients with IBD have lower serologic response rates to hepatitis B virus,⁴ pneumococcal,⁵ and H1N1 influenza vaccination,⁶ with IBD clinicians encouraged to check serologies and revaccinate those with low or absent antibody responses.⁷ Although we suspect that time and vaccine availability will lead to the same approach with regard to SARS-CoV-2, there is currently no consensus/recommendations on revaccination after a negative serologic response. As post vaccine testing becomes more widely available and requested, patients and their providers should understand that the proper response to a negative serologic response has yet to be determined.