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Effect of IBD Medications on COVID-19 Outcomes: Results from an International Registry

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Effect of IBD Medications on COVID-19 Outcomes: Results from an International Registry Inflammatory bowel disease ORIGINAL RESEARCH Gut: first published as 10.1136/gutjnl-2020-322539 on 20 October 2020. Downloaded from Effect of IBD medications on COVID-19 outcomes: results from an international registry Ryan C Ungaro ,1 Erica J Brenner,2 Richard B Gearry,3 Gilaad G Kaplan ,4 Michele Kissous- Hunt,1,5 James D Lewis,6 Siew C Ng ,7 Jean- Francois Rahier,8 Walter Reinisch ,9 Flávio Steinwurz,10 Fox E Underwood,4 Xian Zhang,2 Jean- Frederic Colombel,1 Michael D Kappelman2 ► Additional material is ABSTRACT Significance of this study published online only. To view Objective We sought to evaluate COVID-19 clinical please visit the journal online course in patients with IBD treated with different (http:// dx. doi. org/ 10. 1136/ What is already known on this subject? gutjnl- 2020- 322539). medication classes and combinations. Design Surveillance Epidemiology of Coronavirus Under ► Patients with IBD who are older, have For numbered affiliations see additional comorbidities and are on oral end of article. Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created corticosteroids appear to be at increased risk of adverse outcomes from COVID-19. Correspondence to to monitor outcomes of IBD patients with confirmed Dr Ryan C Ungaro, The COVID-19. We used multivariable regression with a ► Prior data have suggested that patients with Henry D. Janowitz Division of generalised estimating equation accounting for country IBD on mesalamine/sulfasalazine may be at Gastroenterology, Icahn School as a random effect to analyse the association of different increased risk for severe COVID-19, while of Medicine at Mount Sinai, medication classes with severe COVID-19, defined as patients on tumour necrosis factor (TNF) New York, NY 10029, USA; antagonists do not appear to be at increased ryan. ungaro@ mssm. edu intensive care unit admission, ventilator use and/or death. risk. MK- H and J- FC contributed Results 1439 cases from 47 countries were included What are the new findings? equally. (mean age 44.1 years, 51.4% men) of whom 112 ► Based on data on over 1400 patients with IBD Received 15 July 2020 patients (7.8%) had severe COVID-19. Compared with from an international registry, compared with Revised 28 September 2020 tumour necrosis factor (TNF) antagonist monotherapy, TNF monotherapy, thiopurine monotherapy Accepted 29 September 2020 thiopurine monotherapy (adjusted OR (aOR) 4.08, 95% and the combination thiopurines with TNF CI 1.73 to 9.61) and combination therapy with TNF antagonists are associated with significantly http://gut.bmj.com/ antagonist and thiopurine (aOR 4.01, 95% CI 1.65 to increased risk of severe COVID-19. 9.78) were associated with an increased risk of severe ► Mesalamine/sulfasalazine may be associated COVID-19. Any mesalamine/sulfasalazine compared with an increased the risk of severe COVID-19, with no mesalamine/sulfasalazine use was associated particularly when compared with TNF with an increased risk (aOR 1.70, 95% CI 1.26 to 2.29). antagonists. This risk estimate increased when using TNF antagonist ► There are no significant differences between on September 23, 2021 by guest. Protected copyright. monotherapy as a reference group (aOR 3.52, 95% CI biological classes (TNF, interleukin-12/23 and 1.93 to 6.45). Interleukin-12/23 and integrin antagonists integrin antagonists) on the risk of severe were not associated with significantly different risk than COVID-19. TNF antagonist monotherapy (aOR 0.98, 95% CI 0.12 to 8.06 and aOR 2.42, 95% CI 0.59 to 9.96, respectively). How might it impact on clinical practice in the Conclusion Combination therapy and thiopurines may foreseeable future? be associated with an increased risk of severe COVID-19. ► These findings provide data to help clinicians No significant differences were observed when and patients with IBD make informed, shared comparing classes of biologicals. These findings warrant decisions about risks of medications in the confirmation in large population- based cohorts. COVID-19 era. MKH should be changed to MDK for co- last author line COVID-19 requiring hospitalisation or intensive © Author(s) (or their care unit (ICU) admission have at least one comor- employer(s)) 2020. No INTRODUCTION bidity.4 Specific risk factors for severe COVID-19 commercial re- use. See rights and permissions. Published COVID-19, caused by SARS-CoV -2, was first include increasing age, high fever, cardiovascular by BMJ. reported in December 2019 and has rapidly spread disease, diabetes, obesity, chronic obstructive throughout the world leading to an international pulmonary disease and chronic kidney disease.2 5–7 To cite: Ungaro RC, pandemic.1 Although most cases of COVID-19 are IBDs, including Crohn’s disease (CD) and UC, Brenner EJ, Gearry RB, et al. Gut Epub ahead of print: mild, the disease can become severe and result in are chronic inflammatory conditions of the GI 8–10 [please include Day Month hospitalisation, respiratory failure or death with tract affecting millions of people worldwide. Year]. doi:10.1136/ reported case fatality rates ranging from 2.3% Patients with IBD frequently require treatment with gutjnl-2020-322539 to 7.2%.2 3 The vast majority of patients with immunosuppressant medications that can increase Ungaro RC, et al. Gut 2020;0:1–8. doi:10.1136/gutjnl-2020-322539 1 Inflammatory bowel disease the risk of serious viral and bacterial infections.11–14 However, and practice locations to confirm legitimacy of reports. Reporters it is also possible that immunosuppressive medications may be were confirmed as being healthcare providers through a Google Gut: first published as 10.1136/gutjnl-2020-322539 on 20 October 2020. Downloaded from associated with a decreased risk of adverse COVID-19 outcomes search of the reporter’s name and institution. If we could not by limiting the cytokine storm characteristic of severe COVID- confirm the reporter was a healthcare provider, reports from 19.15 16 non- valid email addresses were excluded from analysis. Using the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE- IBD) database, a large international registry of IBD Statistical analysis patients with COVID-19, we previously reported that cortico- Continuous variables were summarised using means and SD and steroids and mesalamine/sulfasalazine are associated with an categorical variables using proportions. Our primary outcome increased risk of severe COVID-19, defined as requirement was severe COVID-19, defined as a composite of ICU admis- for ICU admission, ventilator support or death, while tumour sion, mechanical ventilation and/or death, consistent with 18 necrosis factor (TNF) antagonists did not impact this risk.17 existing COVID-19 literature. Comorbidities were collapsed However, the number of reported cases available at that time into the following categories: cardiovascular disease (coro- limited the ability to fully evaluate the risk of these and other nary artery disease, heart failure and/or arrhythmia), diabetes, IBD therapies. In this report, we sought to further evaluate the hypertension, stroke, lung disease (asthma, chronic obstructive association of IBD medications and their combinations on the pulmonary disease and other lung disease), kidney disease, liver risk of adverse COVID-19 outcomes. In particular, we aimed to disease and cancer. Medication classes of interest at the time of understand the impact of TNF antagonist monotherapy versus COVID-19 infection included mesalamine/sulfasalazine, thiopu- combination therapy with thiopurines as well as to further rine (mercaptopurine or azathioprine), systemic corticosteroids, explore the effect of mesalamine/sulfasalazine on the risk of TNF antagonists, interleukin (IL) 12/23 antagonists (usteki- severe COVID-19. numab) and integrin antagonists (vedolizumab). Combination therapy was considered coprescription of a TNF antagonist with a thiopurine. METHODS We first evaluated the impact of TNF antagonists and thio- Data source purines, either alone or in combination, on the risk of severe The SECURE- IBD database ( www. covidibd. org) was created to COVID-19. We compared any TNF antagonist use with no monitor outcomes of COVID-19 occurring in paediatric and TNF antagonist use among all patients. Then, using an active adult patients with IBD. SECURE-IBD is an international, collab- comparator design, we compared thiopurine monotherapy and orative effort endorsed and promoted by numerous regional and 17 combination therapy with TNF antagonists to TNF antagonist national organisations as previously described. Physicians and monotherapy.19 other healthcare providers voluntarily reported cases of PCR- We next undertook a series of analyses to further evaluate the confirmed or antibody-confirmed COVID-19 occurring in IBD association of mesalamine/sulfasalazine with severe COVID-19. patients. We instructed healthcare providers to report cases, We first compared any mesalamine/sulfasalazine use with no regardless of severity, after a minimum of 7 days from symptom mesalamine/sulfasalazine use among all patients. Next, as TNF http://gut.bmj.com/ onset and sufficient time had passed to observe the disease course antagonists were the most frequently used medications among through resolution of acute illness or death. In the event that a cases reported to SECURE- IBD, we compared patients treated patient’s status changed after reporting or if there were concerns with mesalamine/sulfasalazine without TNF antagonists
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