Managing Inflammatory Bowel Disease During COVID-19: Summary of Recommendations from Gastrointestinal Societies.

Dear Editor:

We read the recent article by Ungaro et al with great interest. As the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread, gastroenterologists managing patients with inflammatory bowel disease (IBD) face uncertainty amid growing patient concerns regarding risks associated with immunosuppressive medications. Descriptions of initial patient cohorts from China did not include details about concomitant immunosuppressive therapy because immune-mediated diseases did not feature prominently among the reported comorbidities. On the basis of these cohorts, the most important factors associated with poorer outcomes were older age, diabetes, hypertension, and other cardiovascular disease.

An international registry of IBD patients with COVID-19 (Surveillance Epidemiology of Coronavirus [COVID-19] under Research Exclusion) was established. As of April 8, 2020, 382 cases were reported to the registry, of whom 106 had required hospitalization, and 13 had died. In the absence of data to inform decision making, several societies have proposed empiric guidelines for management of IBD patients. These recommendations should be considered in parallel with national/regional guidance from public health authorities, which include instructions for self-isolation that may substantially impact patient livelihoods and thus extend beyond the typical remit of guidelines for disease management. In the context of the rapidly evolving data, we summarize available recommendations from different gastroenterological societies.

To date, public guidance on the management of IBD patients during the COVID-19 pandemic has been issued by the British Society of Gastroenterology (BSG), Crohn’s and Colitis Canada (CCC), European Crohn’s and Colitis Organization (ECCO), , and the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) (Table 1 ).

Table 1

Summarized Recommendations for the Management of Inflammatory Bowel Disease During the Coronavirus Disease 2019 Pandemic

	British Society of Gastroenterology	European Crohn’s and Colitis Organization	International Organization for the Study of Inflammatory Bowel Disease
Mesalamine	• Continue treatment • Optimize treatment in ulcerative colitis patients with uncontrolled symptoms	• Continue treatment	• Continue treatment; also in case of COVID-19
Corticosteroids	• Consider rapid tapering • Consider exclusive enteral nutrition in Crohn’s disease or topical corticosteroids	• Consider tapering • Continued use during infection should be weighed carefully	• Consider tapering • Stop (taper as appropriate) in case of COVID-19 • Do not discontinue topical steroids
Immunomodulators (thiopurines, methotrexate)	• Initiation discouraged • Combination therapy with biologics on a case-by-case basis • Consider stopping in patients ≥65 years and/or comorbidities in stable remission	• Initiation discouraged • Combination therapy with biologics on a case-by-case basis • Reasonable to withhold until resolution if COVID-19 develops	• Continue treatment • Withhold until resolution in case of COVID-19
Biologics (TNF antagonists, anti-integrins, anti-interleukin 12/23)	• Continue treatment • No evidence of increased risk of COVID-19	• Continue treatment with unchanged dosing schedule • Withhold until resolution if COVID-19 develops	• Continue treatment with unchanged dosing schedule • Withhold treatment with TNF antagonists, anti-interleukin 12/23 until resolution in case of COVID-19 • Uncertain if vedolizumab should be stopped in case of COVID-19
TNF antagonists	• Initiation in monotherapy • Elective switching from intravenous to subcutaneous not recommended	• Initiation in monotherapy, consider subcutaneous formulation • Unchanged maintenance dosing schedule • Elective switching from intravenous to subcutaneous not recommended	• Uncertain if patients receiving combination therapy should reduce dose of immunomodulator to prevent COVID-19
JAK inhibitors	• No evidence of increased risk of COVID-19 • Continue treatment	• Continue treatment • Avoid initiation if alternative available • Withhold until resolution if COVID-19 develops	• Continue treatment • Withhold until resolution in case of COVID-19
Endoscopy	• Defer surveillance • Consider alternative methods of disease assessment	• Defer surveillance and regular endoscopic follow-up	• Defer surveillance and regular endoscopic follow-up
Clinical trials	• Continuation of screening and recruiting should be discussed locally • Benefit of avoiding corticosteroids and surgery should be balanced against risk of face-to-face visits • Conduct virtual trial visits if possible • Consider unblinding participants if the information changes treatment or assessment and management of suspected COVID-19	• Only include patients without therapeutic alternatives • Minimize corticosteroid exposure for patients between screening and baseline • Discuss with sponsor: postponing nonessential follow-up visits or replacing them with virtual clinics, performing routine testing in local laboratory, organizing home delivery of study drugs	• Continue treatment • Withhold until resolution in case of COVID-19

COVID-19, coronavirus disease 2019; TNF, tumor necrosis factor.

All aforementioned societies recommend continuing IBD-specific treatment because risk of active disease was perceived to be higher than the uncertain risks of immunosuppression predisposing to higher risk of infection with SARS-CoV-2. Minimizing corticosteroid exposure by rapid tapering whenever possible is universally recommended, with the BSG also suggesting topical corticosteroids or exclusive enteral nutrition as alternatives for patients experiencing a flare. Thiopurine initiation is discouraged by both the BSG and ECCO because of increased perceived risk of viral infection and need for concomitant induction corticosteroid. Both BSG and ECCO advise caution with initiating combination therapy; the former also suggests considering stopping thiopurine treatment in patients ≥65 years and those with significant comorbidities in stable remission. For patients commencing biological therapy, subcutaneously administered drug may be preferred on the basis of local circumstances to maximize social distancing efforts. Forced switching to subcutaneous biologics should only be used in centers unable to provide infusions. There are no data to favor one class of biologics over another in the context of COVID-19. There is some indication that lower T-helper lymphocyte counts are associated with delayed clearance of viral RNA, which led ECCO to recommend against initiation of tofacitinib if therapeutic alternatives are available, in contrast to BSG and IOIBD.

In case an infection develops, ECCO suggests postponing biologic treatment until resolution and considering stopping thiopurines and tofacitinib for the duration of the infection. On the basis of experience with other coronaviruses and early experience with SARS-CoV-2, the benefits and harms of continuing corticosteroid treatment during infection should be weighed carefully. IOIBD suggests withholding all IBD-related medication, except for mesalamine, topical steroids, and possibly vedolizumab until resolution of symptoms in case COVID-19 develops. Alternatively, medication can be restarted after 2 negative nasopharyngeal polymerase chain reaction tests. For general measures to prevent viral transmission, ECCO and IOIBD emphasize hand hygiene and avoiding contact with infected people; CCC also advocates workplace modifications to enable physical distancing for patients using immunosuppressants. Guidance from the BSG is more stringent in suggesting that patients with a comorbidity or >70 years being treated with drugs other than mesalamine/topical corticosteroids should undergo “shielding,” a strict form of social distancing mandating the avoidance of face-to-face contact for at least 12 weeks. This recommendation extends to patients taking daily prednisolone equivalent of ≥20 mg, those during combination therapy induction, those with moderately-to-severely active disease despite treatment, and those with short bowel syndrome or requiring parenteral nutrition. This stricter guidance from the BSG is an outlier with major implications for individual patients and should be taken in the context of the individual case. Patients treated with biologics or immunomodulators, including stable patients on combination therapy, should practice stringent social distancing, whereas patients treated with mesalamine or topical corticosteroids should adhere to standard social distancing. Surveillance endoscopies should be deferred, and disease assessment endoscopies should be carefully assessed for priority, considering the possibility of alternative methods (biomarkers, radiology, and capsule endoscopy).