The coronavirus disease 2019 (COVID-19) pandemic has significantly altered how patients with all conditions are treated, especially those with inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC). While navigating the COVID-19 pandemic, numerous questions have been encountered in patients with IBD, including how to manage a patient’s immunosuppression regimen, especially those receiving biologics, as well as the potential efficacy and safety of the COVID-19 vaccines. 

Although each biologic class has a unique mechanism of action, the end result is typically to attenuate the patient’s immune system. There is growing concern that those patients with IBD who are receiving biologics may have impaired antibody responses to either the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself and/or the vaccination. This type of blunted response could lead to increased transmission (via chronic nasopharyngeal colonization), subsequent development of new variants, as well as increased susceptibility for reinfection.1

This topic was recently evaluated by a group led by Kennedy et al who conducted the CLARITY study. This was a multicenter, prospective observational cohort study in the United Kingdom (UK) that included 92 hospitals and 6935 patients with IBD.1 The researchers aimed to determine the impact of infliximab (IFX) and vedolizumab (VDZ) and/or concomitant immunomodulators (methotrexate, thiopurines) on SARS-CoV-2 immunity, disease course, and susceptibility in patients with IBD. These patients were followed for 2 months, between September and December 2020.


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Rates of patients who reported symptoms of suspected or probable COVID-19 (8.3% vs 8.9%; P =.38), positive PCR test (5.2% vs 4.3%; P =.39), and hospitalization with confirmed COVID-19 (0.2% vs 0.2%; P =.77) were similar between the IFX and VDZ groups, respectively. Despite these similarities, there were lower seroprevalence rates of anti-SARS-CoV-2 antibodies in the IFX group compared with VDZ (3.4% vs 6.0%; P <.0001). There were multiple patient characteristics associated with seropositivity, including younger age, history of UC, no concomitant immunodulator use, and recent steroids. Both IFX (vs VDZ, odds ratio [OR], 0.66; 95% CI, 0.51-0.87; P =.0027) and immunomodulator use (OR, 0.70; 95% CI, 0.53-0.92; P =.012) were independently associated with lower seropositivity. 

For those patients with confirmed SARS-CoV-2 infections, there were lower rates of seroconversion in the IFX group compared with VDZ (48% vs 83%; P =.00044). The seroconversion rate was higher in those patients treated with IFX alone (60%) compared with IFX and an immunomodulator (37%; P =.0460). In addition, patients treated with IFX had significantly lower magnitude of anti-SARS-CoV-2 antibody responses compared with VDZ. The authors concluded that patients treated with IFX had lower responses to SARS-CoV-2 infection as shown by lower rates of seroprevalence, seroconversion, and antibody reactivity. It is important to recognize that as this study was conducted only in the UK, it may not represent the exact patient population seen in the United States (US). 

It is important to note the findings from the Kennedy et al study and evaluate them in conjunction with additional studies that have reviewed the impact of IBD medications on COVID-19 outcomes. Ungaro et al published data from a large international registry (SECURE-IBD) that is monitoring the outcomes of patients with IBD and confirmed COVID-19.2 This study included 1439 patients with IBD, of which 7.8% were diagnosed with severe COVID-19. When compared against tumor necrosis factor (TNF) antagonist monotherapy, thiopurine monotherapy and thiopurine combination therapy with TNF agents had higher rates of severe COVID-19 with ORs of about 4. There were no significant differences between the 3 primary biologic classes (TNF, interleukin [IL]-12/23, and integrin inhibitors) and development of severe COVID-19. 

Both the Kennedy et al and Ungaro et al studies ultimately lead to the question of how patients with IBD will respond to COVID-19 vaccines. This data is still accumulating and will continue to be closely followed as more patients are vaccinated. Wong et al recently published a small study evaluating the serological response to both of the currently available messenger ribonucleic acid (mRNA) COVID-19 vaccines in patients with IBD.3 A total of 48 patients with IBD (23 CD, 25 UC) were included in this study, of which 85.4% of patients were receiving biologics of any kind. Of the 26 patients with IBD who received two doses of vaccine, there was 100% seropositivity. There were, however, lower levels of all antibodies tested in patients receiving VDZ, while those treated with TNF agents had lower anti-receptor binding domain (RBD) total immunoglobulin (Ig) only. 

Several societies have published recommendations regarding COVID-19 vaccinations and IBD. The British Society of Gastroenterology and the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) both support the use of the COVID-19 vaccines in patients with IBD.4,5 The risks of vaccination in patients with IBD is anticipated to be very low, with lack of antibody response more of a concern, as discussed earlier. 

As more patients with IBD inquire about receiving COVID-19 vaccines, there are several logistical issues that should be kept in mind. It is not clear when the “best” time for a patient with IBD receiving biologics should receive a vaccine. Many patients may choose to schedule their vaccine several days or weeks before and/or after their typical infusion to avoid any potential confounding reactions. There are not enough data to support if one vaccine (or mechanism) may be the best option for patients with IBD.

It is important to note that patients with IBD have a higher baseline risk of thrombosis compared with the general population, especially if their IBD is not under control. The need for COVID-19 vaccine “boosters” is still under debate for the general population. Thus, close monitoring of updated guidelines should be noted, especially considering the findings of the Kennedy et al study. The COVID-19 pandemic and the resulting management of chronic conditions such as IBD remain very fluid, with registries hopefully providing clearer answers on management in the near future. 

References

  1. Kennedy NA, Goodhand JR, Bewshea C, et al. Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab. Gut. 2021;70(5):865-875. doi: 10.1136/gutjnl-2021-324388
  2. Ungaro RC, Brenner EJ, Gearry RB, et al. Effect of IBD medications on COVID-19 outcomes: results from an international registry. Gut. 2021;70(4):725-732. doi: 10.1136/gutjnl-2020-322539
  3. Wong SY, Dixon R, Martinez Pazos V, et al.  Serological response to mRNA COVID-19 vaccines in IBD patients receiving biological therapies. Gastroenterol. Published online April 19, 2021. doi: 10.1053/j.gastro.2021.04.025
  4. Siegel CA, Melmed G, McGovern DPB, et al.  SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting. Gut.  2021;70(4):635-40. doi: 10.1136/gutjnl-2020-324000
  5. Alexander JL, Moran GW, Gaya DR, et al. SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement. Lancet Gastroenterol Hepatol. 2021;6(3):218-224. doi: 10.1016/S2468-1253(21)00024-8