key: cord-0910632-84jv0ljr
authors: Agrawal, Manasi; Brenner, Erica J; Zhang, Xian; Colombel, Jean-Frederic; Kappelman, Michael D; Ungaro, Ryan C
title: Physician practice patterns on holding inflammatory bowel disease medications due to COVID-19 in the SECURE-IBD registry
date: 2020-11-24
journal: J Crohns Colitis
DOI: 10.1093/ecco-jcc/jjaa243
sha: a0088c3cfb5ca1df5e1b51c3bf1f2dc86c177f25
doc_id: 910632
cord_uid: 84jv0ljr

BACKGROUND: We aimed to describe physician practice patterns on holding or continuing IBD therapy in the setting of COVID-19 infection using the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry. METHODS: IBD medications that were stopped due to COVID-19 were recorded in the SECURE-IBD registry in addition to demographic and clinical data. We conducted descriptive analyses to understand characteristics associated with stopping IBD medications in response to active COVID-19 infection. RESULTS: Of 1,499 patients, IBD medications were stopped in 518 (34.6%) patients. On bivariate and multivariable analyses, a diagnosis of ulcerative colitis or IBD-unspecified was associated with a lower odds of stopping medication compared with Crohn’s disease [adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.48, 0.75]. When evaluating specific medications, 5-aminosalicylic acid was more likely to be continued (p<0.001) while anti-tumor necrosis factor therapy and immunomodulator therapy were more likely to be stopped (global p <0.001). Other demographic and clinical characteristics did not impact prescription patters. CONCLUSION: IBD medications other than immunomodulators were continued in the majority of IBD patients with COVID-19 in the international SECURE-IBD registry. Future studies are needed to understand the impact of stopping or continuing IBD medications on IBD- and COVID-19-related outcomes.

A c c e p t e d M a n u s c r i p t Methods IBD medications that were stopped due to COVID-19 were recorded in the SECURE-IBD registry in addition to demographic and clinical data. We conducted descriptive analyses to understand characteristics associated with stopping IBD medications in response to active COVID-19 infection.

Of 1,499 patients, IBD medications were stopped in 518 (34.6%) patients. On bivariate and multivariable analyses, a diagnosis of ulcerative colitis or IBD-unspecified was associated with a lower odds of stopping medication compared with Crohn's disease [adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.48, 0.75]. When evaluating specific medications, 5-aminosalicylic acid was more likely to be continued (p<0.001) while antitumor necrosis factor therapy and immunomodulator therapy were more likely to be stopped (global p <0.001). Other demographic and clinical characteristics did not impact prescription patters.

IBD medications other than immunomodulators were continued in the majority of IBD patients with COVID-19 in the international SECURE-IBD registry. Future studies are needed to understand the impact of stopping or continuing IBD medications on IBD-and COVID-19-related outcomes.

Key words: inflammatory bowel disease; Crohn's disease; ulcerative colitis; Coronavirus disease 2019; IBD therapy. M a n u s c r i p t

The impact of holding immunosuppressive and other therapies for inflammatory bowel diseases (IBD) in the context of Coronavirus Disease 2019 (COVID-19) is unknown. In the interim, expert consensus is to hold corticosteroids, immunosuppressants and biologics, but not 5-aminosalisylic acid (5-ASA), at the time of suspected or confirmed diagnosis of COVID-19 infection until fever and other symptoms are resolved (1) . There are currently no data on physician practice patterns regarding IBD therapy in the setting of COVID-19.

We analyzed data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry to determine physician practice patterns in IBD patients with confirmed COVID-19. Collection and categorization of data have been previously reported (2) . Reporters to SECURE-IBD were asked if any medications were stopped due to active COVID-19 infection and to indicate which specific drugs were stopped.

We conducted bivariate analyses to understand demographic and clinical characteristics associated with stopping ≥ 1 IBD medication due to COVID-19, and subsequently performed multivariable logistic regression to evaluate the independent effects IBD disease activity (specified a priori) and other patient characteristics that were statistically significant on bivariate analyses. We also analyzed country as a variable impacting stopping in multivariate analyses and included any country with ≥50 reported cases in SECURE-IBD. Additionally, among users of each medication class, we compared the proportion of patients who had discontinued treatment after diagnosis of COVID-19. P values ≤0.05 were considered statistically significant.

Of 1,499 patients with available medication-related data in the SECURE-IBD registry, IBD medications were stopped in 518 (34.6%) patients and continued in 981 (65.4%) patients. Baseline characteristics of patients who stopped and did not stop at least 1 medication are reported in Table 1 . On bivariate and multivariable analyses, a diagnosis of ulcerative colitis (UC) or IBD-unspecified (IBD-U) was associated with a lower odds of stopping medication compared with Crohn's disease (CD) [adjusted odds ratio (aOR) 0.6, 95% CI 0.48, 0.75] ( Table 2) . Compared with cases from other countries, those from Italy and Brazil were associated with higher odds of stopping IBD medication on bivariate analysis, but this was not significant in the multivariable model. Other demographic variables, physician global assessment of IBD activity, COVID-19-related emergency room visit or hospitalization were not associated with stopping IBD therapy in the setting of COVID-19.

When evaluating specific medications, 5-ASA was more likely to be continued (p<0.001) while anti-tumor necrosis factor (anti-TNF) therapy and immunomodulator therapy [6mercaptopurine (6MP), azathioprine, methotrexate] were more likely to be stopped (global p <0.001) (Figure) . Of 156 patients on combination therapy with an anti-TNF and an immunomodulator, the anti-TNF alone was stopped in 10 (6.4%), immunomodulator alone in M a n u s c r i p t Manuscript Doi: 10.1093/ecco-jcc/jjaa243 6 33 (21.2%), and both medications in 53 (34%) patients. Sixty (38%) patients continued on combination therapy.

In this brief report, we describe physician practice patterns on holding IBD medications in an international registry of IBD patients with confirmed COVID-19. IBD medications were more likely to be continued in those with UC or IBD-U than with CD. This is likely due, at least in part, to a higher proportion of UC patients on 5-ASA therapy, which was the most likely medication to be continued. Conversely, anti-TNFs and immunomodulators, used alone or in combination, were the most frequently stopped classes of medications. These practice patterns are largely concordant with expert guidance on IBD medication management in setting of COVID-19 (1).

However, IBD medications were continued for nearly two-thirds of patients, and combination therapy with an anti-TNF and immunomodulator in nearly 40% of patients. It is important to note that biweekly or less frequent dosing of certain biologics could impact decision and feasibility to stop. Emergency room visit or hospitalization due to COVID-19 did not impact IBD medication management. While variation in the discontinuation of IBD medications was significant by country in bivariate analyses, these associations did not remain statistically significant in a multivariable model. Notable trends that may have been limited by sample size include lower odds of medication discontinuation in patients from Italy and higher odds of discontinuation in patients from Brazil. These findings suggest the need to further study international variation in practice patterns and patient outcomes. In the absence of these data, we suggest following guidance laid out per expert consensus (1).

Strengths of this study include the use of a large, international registry with a diverse adult and pediatric IBD patient population. Limitations include the considerable risk of reporting bias in this voluntary registry of IBD patients with COVID-19 patients. Another limitation is missing data, although this was <4% for all variables except ethnicity. In the present study, we were not able to evaluate the impact of holding or continuing medications on COVID-19 outcomes, due to issues related to unmeasured confounding of COVID-19 severity and lack of data regarding duration of holding medication and timing of medication restarting.

In summary, we found that IBD medications other than immunomodulators were continued in the majority of IBD patients with COVID-19 in the international SECURE-IBD registry. Future studies are needed to understand the impact of stopping or continuing IBD medications on IBD-related outcomes as well as COVID-19-related outcomes. M a n u s c r i p t Manuscript Doi: 10.1093/ecco-jcc/jjaa243 8 

Management of Patients With Crohn's Disease and Ulcerative Colitis During the Coronavirus Disease-2019 Pandemic: Results of an International Meeting

but not TNF Antagonists, are Associated with Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results from an International Registry

We acknowledge the physicians and other healthcare providers worldwide who have reported cases to the SECURE-IBD database and the organizations who supported or promoted the SECURE-IBD database (Reporter names available at www.covidibd.org/reporter-acknowledgment/. Partnering organizations available at https://covidibd.org/our-partners/).

Proportion of patients who stopped IBD therapy