Impact of Medications on COVID-19 Outcomes in Inflammatory Bowel Disease: Analysis of More Than 6000 Patients From an International Registry

Abstract

Bowel Disease (SECURE-IBD) database, an international, collaborative database created to monitor COVID-19 outcomes in patients with inflammatory bowel disease (IBD), has previously reported that corticosteroids and mesalamine or sulfasalazine are associated with an increased risk of severe COVID-19 and tumor necrosis factor (TNF) antagonists do not impact risk. 1 A follow-up report observed that patients on combination therapy with TNF antagonists and thiopurines appeared to be at higher risk of severe COVID-19. 2 However, at that time, the number of reported cases was too low to fully evaluate the risk of other IBD therapies. As the cases reported to SECURE-IBD have increased substantially, more granular analyses evaluating other IBD medication classes (including combination therapies) and adjusting for more covariates are possible. In this study, we compared associations between multiple medication classes and adverse COVID-19 outcomes in the SECURE-IBD database.We analyzed reports to SECURE-IBD from inception (March 13, 2020) through May 21, 2021. Details regarding data and analysis are provided in the Supplementary Material.Demographic and clinical characteristics of 6144 included reports stratified by medication type are provided in Supplementary Table 1. Figure 1 summarizes the independent associations of medication classes on adverse COVID-19 outcomes among all cases reported to SECURE-IBD. Systemic corticosteroids were associated and methotrexate was marginally associated with an increased odds of hospitalization or death or both. Medications associated with a decreased odds of COVID-19-related hospitalization or death or both included TNF, interleukin-12/23, and integrin antagonists. Systemic corticosteroids were significantly associated with increased odds of severe COVID-19, and TNF and interleukin-12/23 antagonists were associated with a decreased odds of severe COVID-19. Systemic corticosteroids were associated with increased odds of death due to COVID-19, and biologics were not. Notably, there were no statistically significant associations between mesalamine or sulfasalazine and any adverse COVID-19 outcome. We also observed that TNF antagonist and thiopurine combination therapy was associated with a significantly increased risk of hospitalization or death (adjusted odds ratio [aOR], 1.82; 95% confidence interval [CI], 1.26-2.62), but not severe 1.63; 95% CI,. In contrast, a combination of TNF antagonist and methotrexate was not significantly associated with risk of either adverse COVID-19 outcome (aOR, 0.82; 95% CI, 0.42-1.60 and OR, 2.44; 95% CI, 0.55-10.74).

Humoral Immunogenicity of 3 COVID-19 Messenger RNA Vaccine Doses in Patients With Inflammatory Bowel Disease

“…Moreover, a recent report from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for IBD (SECURE-IBD) registry demonstrated that among patients with IBD on various forms of IBD-directed therapy, only those on systemic corticosteroid therapy appear to be at relatively greater risk of adverse COVID-19 outcomes. 24 Those who would most likely benefit from a fourth mRNA COVID-19 vaccine dose include solid organ transplant recipients, those on systemic corticosteroids at the time of vaccination, those on concomitant therapies associated with a lower COVID-19 vaccine response (mycophenolate or B cell–depleting therapies), those who have comorbidities associated with adverse COVID-19 outcomes, and potentially those who received their third dose roughly ≥6 months prior.…”

Recent advances in clinical practice: management of inflammatory bowel disease during the COVID-19 pandemic

“…Over the course of the pandemic, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) international registry has helped clinicians and patients better understand outcomes of COVID-19 in patients with IBD. Prior to registry closure in January 2022, 7038 cases of COVID-19 from 74 countries had been reported to determine the impact of IBD treatment regimens on outcomes of COVID-19, including hospitalisation and severe COVID-19, defined as a composite of intensive care unit (ICU) admission, mechanical ventilation and death 33–38. Throughout the pandemic, SECURE-IBD has been a hugely informative resource for the IBD community, however, there are significant limitations with how representative the cohort is, in part secondary to the physician-led opt in nature of the registry.…”

“…Figure created with data from refs. 30 36 and using BioRender.com. 5-ASA, 5-aminosalicylic acid; IBD, inflammatory bowel disease; ICU, intensive care unit; JAK-inhibitor, Janus kinase inhibitor; RR, relative risk; TNF, tumour necrosis factor.…”

“…Although our understanding of risk in patients treated with ustekinumab, an interleukin 12/23 inhibitor, remains limited, in SECURE-IBD, ustekinumab use was associated with a lower risk of hospitalisation or death (RR 0.44, 95% CI 0.36 to 0.54) compared with those not treated with ustekinumab 36. Overall, current evidence highlights that compared with anti-TNF, vedolizumab-treated (RR 0.85, 95% CI 0.56 to 1.28) and ustekinumab-treated (RR 1.25, 95% CI 0.56 to 2.80) patients are not known to be at increased risk of developing severe COVID-19,36 and the relative risk of hospitalisation was similar across patients treated with different biologicals 58…”

Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease

“…The CLARITY IBD study recently reported attenuated serological responses in IBD patients treated with infliximab in comparison to vedolizumab 1 , with the effect greatest in those on infliximab/thiopurine combination therapy. Independently, the global SECURE-IBD registry highlighted that infliximab/thiopurine combination therapy, but not infliximab or vedolizumab monotherapies, was associated with more severe clinical outcomes upon SARS-CoV-2 infection 2,3 .…”