From the AGA Journals

IBD: COVID-19 vaccination still effective in immunosuppressed

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The results are reassuring

There is a need for evidence to clarify the effectiveness of SARS-CoV-2 vaccination in select subpopulations like inflammatory bowel disease (IBD) that were underrepresented in the vaccine clinical trials. Patients on select immune modifying therapies have historically had suboptimal immunologic responses to vaccines in the pre-COVID era, and early data from national and international IBD registries suggest that, while patients generally do mount humoral responses to SARS-CoV-2 vaccination, absolute postvaccination antibody titers may be blunted by specific drug mechanisms such as anti–tumor necrosis factor–alpha therapies or corticosteroids. These reports, however, do not tell the whole story. Postvaccination humoral and cellular (T-cell) immunity appear to be independently mediated, and the thresholds correlating antibody titers with rates of COVID-19 infection or prevention of serious complications have yet to be determined.

Dr. Gil Y. Melmed, MD, MS, is a professor of medicine at Cedars-Sinai in Los Angeles, calif.

Dr. Gil Y. Melmed

Therefore, this study by Mahmud and Khan looking at rates of COVID-19 infection in a large Veterans Affairs cohort of patients with IBD on a variety of immune modifying therapies after SARS-CoV-2 vaccination with an mRNA vaccine is highly clinically relevant and the findings are very reassuring. Patients who received both vaccine doses had significantly lower rates of COVID-19 infection, with an overall vaccine efficacy rates similar to those seen in the general population. Although antibody levels and cellular immunity correlations with protection against infection are still unknown, and the degree of prevention against severe disease has not yet been clarified with larger numbers over time, practitioners can confidently tell their patients with IBD that vaccination has a very high likelihood of protecting them from COVID-19 infection.

Gil Y. Melmed, MD, MS, is a professor of medicine at Cedars-Sinai, Los Angeles. He reports being a consultant to AbbVie, Arena, Boehringer Ingelheim, Bristol-Meyers Squibb/Celgene, Janssen, Pfizer, Samsung Bioepis, Shionogi, and Takeda. He is principal investigator of CORALE-IBD, a registry evaluating postvaccine outcomes in IBD after SARS-CoV-2 vaccination.



In a real-world setting, full vaccination against SARS-CoV-2 was more than 80% effective at reducing infection in people with inflammatory bowel disease (IBD) who were taking immunosuppressive medications.

The study, which examined postvaccine infection rates in a Veterans Affairs cohort, further validates the benefit of COVID-19 vaccines, particularly in a subgroup most at risk for having compromised immune systems. Furthermore, the findings “may serve to increase patient and provider willingness to pursue vaccination in these settings,” wrote study authors Nabeel Khan, MD, of the Corporal Michael J. Crescenz VA Medical Center and Nadim Mahmud, MD, of the University of Pennsylvania, both in Philadelphia. The report was published in Gastroenterology. In addition, the researchers said the findings “should provide positive reinforcement to IBD patients taking immunosuppressive agents who may otherwise be reluctant to receive vaccination.”

Since the onset of the COVID-19 pandemic, concerns have been raised regarding the possible heightened risk of SARS-CoV-2 infection among patients with IBD and other diseases associated with immune system dysregulation. Despite these fears, patients with IBD appear to have comparable rates of SARS-CoV-2 infection to that of the general population.

Pfizer’s BNT162b2 and Moderna’s RNA-1273 vaccines are the most widely used COVID-19 vaccines in the United States. These vaccines have demonstrated over 90% efficacy for preventing infection and severe disease in late-stage trials; however, few trials have examined their pooled effectiveness in immunocompromised patients and those taking immunosuppressive therapies.

To address this gap, researchers conducted a retrospective cohort study that included 14,697 patients (median age, 68 years) from the Veterans Health Administration database who had been diagnosed with IBD before the start date of the administration’s vaccination program. A total of 7,321 patients in the cohort had received at least 1 dose of either the Pfizer (45.2%) or Moderna (54.8%) vaccines.

Approximately 61.8% of patients had ulcerative colitis, while the remaining patients had Crohn’s disease. In terms of medications, vaccinated versus unvaccinated patients in the study were exposed to mesalamine alone (54.9% vs. 54.6%), thiopurines (10.8% vs. 10.5%), anti–tumor necrosis factor (anti-TNF) biologic monotherapy (18.8% vs. 20.9%), vedolizumab (7.2% vs. 6.0%), ustekinumab (1.0% vs. 1.1%), tofacitinib (0.7% vs. 0.8%), methotrexate (2.3% vs. 2.0%%), and/or corticosteroids (6.8% vs. 5.6%).

A total of 3,561 patients who received the Moderna vaccine and 3,017 patients who received the Pfizer vaccine received both doses. The median time between each dose was 21 days for Pfizer and 28 days for Moderna.

Patients who were unvaccinated had significantly fewer comorbidities (P < .001). The majority of patients in the overall cohort were men (92.2%), a group identified as having a much greater risk of worse COVID-19–related outcomes.

Unvaccinated patients in the study had a higher rate of SARS-CoV-2 infection compared with the fully vaccinated group (1.34% vs. 0.11%, respectively) in follow-up data reported through April 20, 2021. Over a median follow-up duration of 20 days, researchers found 14 infections with SARS-CoV-2 (0.28%) in partially vaccinated individuals. Seven infections (0.11%) were reported in fully vaccinated individuals over a median 38-day follow-up period.

Compared with unvaccinated patients, full vaccination status was associated with a 69% reduction in the hazard ratio of infection (HR, 0.31; 95% confidence interval, 0.17-0.56; P < .001). Corresponding vaccine efficacy rates were 25.1% for partial vaccination and 80.4% for full vaccination.

There were no significant interactions between vaccination status and exposure to steroids (P =.64), mesalamine versus immunosuppressive agents (P =.46), or anti-TNFs with immunomodulators or steroids versus other therapies (P =.34). In addition, no difference was found in the association between vaccination status and infection for patients who received the Moderna versus the Pfizer vaccines (P =.09).

Unvaccinated individuals had the highest raw proportions of severe infection with the novel coronavirus (0.32%) and all-cause mortality (0.66%), compared with people who were partially vaccinated or fully vaccinated. In adjusted Cox regression analyses, there was no significant association between vaccination status and severe SARS-CoV-2 infection (fully vaccinated vs. unvaccinated, P = .18) or all-cause mortality (fully vaccinated vs. unvaccinated, P =.11). The researchers wrote that, “future studies with larger sample size and/or longer follow-up are needed to evaluate this further.”

An important limitation of this study was the inclusion of mostly older men who were also predominantly White (80.4%). Ultimately, this population may limit the generalizability of the findings for women and patients of other races/ethnicities.

While the study received no financial support, Dr. Khan has received research grants from several pharmaceutical companies, but Dr. Mahmud disclosed no conflicts.

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