Should We Continue or Discontinue Inflammatory Bowel Disease Medication in Patients With Coronavirus Disease 2019?

Dear Editors:

We read with great interest the study by Ungaro et al, “Impact of Medications on COVID-19 Outcomes in Inflammatory Bowel Disease: Analysis of More Than 6000 Patients From an International Registry.” The authors compared the association between inflammatory bowed disease (IBD) medications during coronavirus disease 2019 (COVID-19) diagnosis and COVID-19 adverse events in the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)-IBD database and showed that the prognosis of patients receiving steroids for IBD at the time of COVID-19 diagnosis was poor. In addition, the authors suggested that use of IBD medications, specifically tumor necrosis factor (TNF) antagonists, interleukin (IL) 12/23 antagonists, and integrin antagonists, may be a favorable prognostic factor for COVID-19.

However, the authors noted that measurement bias may occur if patients voluntarily discontinued their medication. SECURE-IBD has not accumulated real data on the withdrawal or postponement of IBD medication during the COVID-19 pandemic. The International Organization for the study of Inflammatory Bowel Disease (IOIBD), European Crohn’s and Colitis Organisation (ECCO)-COVID Taskforce, and JAPAN IBD COVID-19 Taskforce have provided guidelines on the continuation or withdrawal of IBD medications in patients with COVID-19 based on transitional evidence. However, the correct method of continuation/withdrawal of medications remains unclear. This is because only a few reports have been published on the clinical outcomes of IBD patients with COVID-19 who have stopped their IBD medications.

A retrospective multicenter registry study of Japanese patients with inflammatory bowel disease with COVID-19 (Japan COVID-19 surveillance in inflammatory bowel disease [J-COSMOS], UMIN000040656) has collected data regarding IBD disease activity, medications at COVID-19 diagnosis, withdrawal during COVID-19, and outcome of COVID-19. We performed an interim analysis of the risk of postponing/discontinuing IBD medications during concomitant COVID-19 in 187 patients enrolled in J-COSMOS from June 2020 to October 2021. Of the 187 patients, the diagnosis of patients was ulcerative colitis in 104, Crohn’s disease in 74, IBD unclassified in 3, and intestinal Behçet’s disease in 6. First, we found that the percentage of Japanese patients with IBD and severe COVID-19 based on the World Health Organization classification was 7%. No deaths were recorded.

In this survey, among 144 patients receiving mesalamine at the time of COVID-19 diagnosis, 7.9% (11 of 140) of patients who continued it and 25% (1 of 4) of those who discontinued it had severe COVID-19. Of 57 patients receiving thiopurines, 3.6% (1 of 28) of patients who continued them and 3.4% (1 of 29) of those who discontinued them had severe COVID-19. In addition, none of the 48 patients who continued TNF inhibitors had severe COVID-19, and 3.8% (1 of 26) of the patients who discontinued them had severe COVID-19. The Fisher exact test showed no significant difference between the continuation and discontinuation of IBD drugs and COVID-19 severity (Supplementary Table 1). No patient receiving budesonide, ustekinumab, vedolizumab, or tofacitinib for IBD at the time of COVID-19 diagnosis had severe COVID-19. Furthermore, we examined whether continuation and discontinuation of IBD medications could contribute to worsening IBD clinical activity based on the partial Mayo score or the Harvey-Bradshaw Index. We found that neither continuation nor discontinuation of any medication during COVID-19 affected the exacerbation of IBD activity (Supplementary Figure 1). Meanwhile, 6.1% (10 of 163) of patients with IBD who continued medication had mild exacerbation of disease activity. Our current registry indicates that the continuation or discontinuation of IBD medications does not contribute to COVID-19 disease outcomes.

Despite the significance of our data, the limitation are (1) the number of IBD patients with COVID-19 in Japan was small, (2) we did not collect any data regarding when IBD medications were stopped or restarted and how long the patients with IBD had COVID-19, and (3) the number of patients with severe COVID-19 was too small to analyze the confounding factors of the relationship between continuation or discontinuation of IBD medications and COVID-19 severity.

In summary, our interim data suggest that neither continuation nor discontinuation of IBD medications affects COVID-19 severity. In addition, discontinuation of IBD medications did not contribute to flares of IBD during COVID-19. The SECURE-IBD and J-COSMOS data show 3 factors are implicated in the continuation or discontinuation of IBD medications in IBD patients with COVID-19: severity of COVID-19, IBD refractoriness, and type of IBD medications. Therefore, further accumulation of real-world data is required to manage IBD during the COVID-19 pandemic.