Baseline Disease Activity and Steroid Therapy Stratify Risk of COVID-19 in Patients With Inflammatory Bowel Disease

Abstract

New York City is the epicenter of the US coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with local population infection rates estimated at 25%.1Saplakoglu Y. 1 in 5 people tested in New York City had antibodies for the coronavirus. LiveScience.https://www.livescience.com/covid-antibody-test-results-new-york-test.htmlGoogle Scholar The impact of COVID-19 on patients with inflammatory bowel disease (IBD) within an epicenter is not well understood. Our study aims were to compare clinical outcomes between COVID-19 patients with and without IBD and to investigate the prevalence and risk factors of COVID-19 in IBD patients. A matched cohort design was used to compare clinical outcomes in COVID-19 patients with or without IBD. The source cohort of all COVID-19-positive patients at 2 New York hospitals has been described previously2Hajifathalian K. Krisko T. Mehta A. et al.Gastrointestinal and hepatic manifestations of 2019 novel coronavirus disease in a large cohort of infected patients from New York: clinical implications [published online ahead of print May 7, 2020]. Gastroenterology.https://doi.org/10.1053/j.gastro.2020.05.010Google Scholar (Supplementary Material). The exposure of interest was defined as a pre-existing diagnosis of IBD. Cases (COVID-19 patients with IBD) were matched for decade of age and sex in a 1:2 ratio to unexposed controls (COVID-19 patients without IBD). Outcomes of interest were clinical manifestations of COVID-19, and intensive care unit admission, endotracheal intubation, and death among admitted patients. COVID-19 was defined as confirmed (positive SARS-CoV-2 polymerase chain reaction), or highly suspected (new-onset fever >37.8°C and more than 1 new symptom, including cough, sore throat, dyspnea, anosmia, or diarrhea, with a known close contact with COVID-19).3Haberman R. Axelrad J. Chen A. et al.Covid-19 in immune-mediated inflammatory diseases—case series from New York.N Engl J Med. 2020; 383: 85-88Crossref PubMed Scopus (322) Google Scholar A separate longitudinal cohort of active IBD patients was used to estimate the prevalence of COVID-19 in IBD patients and evaluate the effects of disease activity and treatment on risk of COVID-19 infection. Exposures of interest were IBD type, clinical, biochemical, and endoscopic indices of disease activity, and IBD treatment. The outcome of interest was diagnosis of COVID-19, as defined above. The details of methods and description of cohorts are available in the Supplementary Material. Eighty confirmed or highly suspected COVID-19 cases with IBD were matched with 160 COVID-19 controls without IBD. Disease characteristics for the IBD cases are reported in Supplementary Table 1. IBD cases and controls had similar prevalence of comorbidities (Table 1), except IBD cases had significantly lower body mass index, chronic obstructive pulmonary disease, and asthma, but higher prevalence of malignancy and immunosuppressive medication use. At presentation, vital signs, hypoxemia, and inflammatory markers were similar between cases and controls (data not shown). IBD cases more frequently presented with gastrointestinal symptoms of diarrhea (45% vs 19%; P < .001), and abdominal pain (20% vs 5%; P = .001) compared with non-IBD matched controls (Table 1). The primary outcome, a composite of death, ICU admission, or intubation, was similar but numerically lower in IBD cases compared with matched controls (24% vs 35%; P = .352) (Table 2). Among IBD cases, diagnosis of ulcerative colitis (UC) was associated with emergency department visit or admission (adjusted odds ratio, 12.7; P = .009) in multivariable analysis adjusted for age, fever, and gastrointestinal symptoms. Additionally, the proportion of patients on vedolizumab or receiving no biologic therapy was numerically higher among IBD cases needing emergency department visit or hospitalization compared with those who did not (no biologic: 29%; vedolizumab: 30%; ustekinumab 8%; tumor necrosis factor antagonist: 6%; P = .197; Supplementary Tables 2 and 3).Table 1Characteristics of Ambulatory and Inpatient Patients With COVID-19 and Inflammatory Bowel Disease and Matched ControlsVariableTotal (N = 240)IBDP valueControls (n = 160)Cases (n = 80)Age, y, mean (SD)48.7 (17.9)48.9 (17.7)48.3 (18.3)NABody mass index, kg/m,2 mean (SD)27.5 (8.1)29.2 (10)25.7 (5.2).048Inpatient, n (%)51 (21.3)34 (21.3)17 (21.3)NAMale, n (%)135 (56.3)90 (56.3)45 (56.3)NAComorbidities, n (%) Hypertension52 (21.7)38 (23.8)14 (17.5).248 Diabetes24 (10)20 (12.5)4 (5).074 Chronic kidney disease12 (5)7 (4.4)5 (6.3).542 Cardiovascular disease15 (6.3)10 (6.3)5 (6.3)1 COPD/asthma21 (8.8)19 (11.9)2 (2.5).032 Obstructive sleep apnea2 (0.8)1 (0.6)1 (1.3).624 Venous thromboembolism6 (2.5)3 (1.9)3 (3.8).396 Cancer13 (5.4)4 (2.5)9 (11.3).012 Chronic liver disease7 (2.9)2 (1.3)5 (6.3).054 Solid organ transplantation2 (0.8)1 (0.6)1 (1.3).624Presenting symptoms, n (%) Fever156 (65)103 (64.4)53 (66.3).775 Cough150 (62.5)96 (60)54 (67.5).237 Shortness of breath93 (38.8)70 (43.8)23 (28.8).028 Myalgia/fatigue51 (21.3)44 (27.5)7 (8.8).002 Anorexia33 (13.8)26 (16.3)7 (8.8).11 Altered mental status5 (2.1)5 (3.1)0 (0).114 Nausea36 (15)24 (15)12 (15)1 Vomiting20 (8.3)10 (6.3)10 (12.5).103 Diarrhea67 (27.9)31 (19.4)36 (45)<.001 Abdominal pain24 (10)8 (5)16 (20).001 Anosmia14 (5.8)7 (4.4)7 (8.8).179 Dysgeusia11 (4.6)7 (4.4)4 (5).814Medication history, n (%) Chronic steroids11 (4.6)1 (0.6)10 (12.5).004 Immunosuppressant22 (9.2)0 (0)22 (27.5)<.001 Statin19 (7.9)15 (9.4)4 (5).224NOTE. P values are calculated using conditional logistic regressions or Mantel–Haenszel test for in matched controlled cohort, and Student t and χ2 tests in SMART-IBD cohort.COPD, chronic obstructive pulmonary disease; NA, not applicable. Open table in a new tab Table 2Clinical Outcomes of Patients With Inflammatory Bowel Disease Admitted With COVID-19 and Matched ControlsOutcomeTotal (n = 51)IBDP valueControls (n = 34)Cases (n = 17)ICU admission14 (27.5)11 (32.4)3 (17.6).226Death2 (3.9)2 (5.9)0 (0).221Intubation13 (25.5)11 (32.4)2 (11.8).117ICU admission, intubation or death16 (31.4)12 (35.3)4 (23.5).352Length of stay, d, (median [SD])6 (2.9)6 (3.4)6 (1.7).426NOTE. Data are n (%). P values are calculated using conditional logistic regressions or Mantel–Haenszel test for in matched controlled cohort, and Student t and χ2 tests in SMART-IBD cohort.ICU, intensive care unit. Open table in a new tab NOTE. P values are calculated using conditional logistic regressions or Mantel–Haenszel test for in matched controlled cohort, and Student t and χ2 tests in SMART-IBD cohort. COPD, chronic obstructive pulmonary disease; NA, not applicable. NOTE. Data are n (%). P values are calculated using conditional logistic regressions or Mantel–Haenszel test for in matched controlled cohort, and Student t and χ2 tests in SMART-IBD cohort. ICU, intensive care unit. In a separate longitudinal cohort of active IBD patients (n = 119; median age was 44 years, 66 were female, 65 had Crohn’s disease, and 54 had UC), 24.4% (n = 29) met criteria for COVID-19 (9 confirmed and 20 highly suspected), consistent with rates estimated in the general population of New York City (Table 3).1Saplakoglu Y. 1 in 5 people tested in New York City had antibodies for the coronavirus. LiveScience.https://www.livescience.com/covid-antibody-test-results-new-york-test.htmlGoogle Scholar,4Bezzio C. Saibeni S. Variola A. et al.Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study.Gut. 2020; 69: 1213-1217Crossref PubMed Scopus (222) Google Scholar The distribution of age, sex, race/ethnicity, smoking, IBD type, disease location, or extraintestinal manifestations was similar between the IBD patients with or without COVID-19. New-onset diarrhea (19.3% vs 11.1%; P < .001) and abdominal pain (12.6% vs 8.9%; P = .03) were significantly more frequent in IBD patients with COVID-19 than without. A higher proportion of IBD patients with COVID-19 had clinically active UC (92.9% vs 62.5%; P = .035), endoscopically active Crohn’s disease (92.3% vs 45.7%; P = .004) or UC (85.7% vs 48.4%; P = .018), and elevated baseline biomarker levels (C-reactive protein >0.9 mg/dL; P = .01; fecal calprotectin >50 μg/mg; P = .002) compared with those without COVID-19. Proportional baseline corticosteroid use was higher among COVID-19 patients (P = .04), but no overall differences were noted based on biologic, immunomodulator, or aminosalicylate use. Of 83 patients receiving biologic therapy, COVID-19 infection was similar across therapeutic classes (P = .315), with fewer overall cases among patients on ustekinumab (13.8%) compared with vedolizumab (30.4%), tumor necrosis factor antagonists (25.0%), or tofacitinib (42.9%).Table 3Characteristics of the Longitudinal Inflammatory Bowel Disease CohortVariableTotal of IBD cases (N = 119)COVID-19P valueYes (n = 29)No (n = 90)Age.295 <40 y51 (42.9)10 (34.5)41 (45.6) >40 y68 (57.1)19 (65.5)49 (54.4)Male53 (44.5)12 (41.4)41 (45.6).694Smoking status.238 Never smoker84 (70.6)18 (56)66 (68) Current11 (9.2)2 (6.9)9 (10) Former24 (20.2)9 (20.2)15 (31)IBD type0.291 UC46 (38.7)14 (48.3)32 (35.6) Crohn’s disease69 (58)15 (51.7)54 (60) Unclassified4 (3.4)0 (0)4 (4.4)Biomarkers C-reactive protein >0.9 g/dL35 (29.4)14 (48.2)21 (23.3).010 Fecal calprotectin >50 μg/mg66 (64.7)24 (88.9)42 (56).002Symptoms New diarrhea23 (19.3)13 (44.8)10 (11.1)<.001 New abdominal pain15 (12.6)7 (24.1)8 (8.9).031TreatmentaBiologic therapy includes anti–tumor necrosis factor medications, Vedolizumab, ustekinumab, and tofacitinib; steroids and budesonide include both oral and rectal formulations; aminosalicylates include mesalamine and sulfasalazine; Immunomodulators include azathioprine, 6- mercaptopurine, and methotrexate. Biologic therapy.804Yes84 (70.6)21 (72.4)63 (70)No35 (29.4)8 (27.6)27 (30) Steroids35 (29.4)13 (44.8)22 (24.4)<.036 Budesonide22 (18.5)6 (20.7)16 (17.8).73 Aminosalicylate38 (31.9)11 (37.9)27 (30.9).43 Immunomodulators5 (4.2)2 (6.9)3 (3.3).41 Combination therapy4 (3.4)2 (6.9)2 (2.2).25Patients with Crohn’s disease Clinical disease activity.060HBI >451 (75)14 (93.3)37 (69.8)HBI ≤417 (25)1 (6.7)16 (30.2) Endoscopic disease activity.004SES-CD >628 (58.3)12 (92.3)16 (45.7)SES-CD ≤620 (41.7)1 (7.7)19 (54.3)Patients with ulcerative colitis Clinical disease activity.035PMS >133 (71.7)13 (92.9)20 (62.5)PMS ≤113 (28.3)1 (7.1)12 (37.5) Endoscopic disease activity.018MES >127 (60)12 (85.7)15 (48.4)MES ≤118 (40)2 (14.3)16 (51.6)NOTE. Data are n (%). P values are calculated using conditional logistic regressions or Mantel–Haenszel test for in matched controlled cohort, and Student t test and χ2 tests in SMART-IBD cohort.HBI, Harvey Bradshaw Index; MES: Mayo endoscopic subscore; PMS: partial Mayo score; SES-CD, Simple Endoscopic Score-Crohn’s disease.a Biologic therapy includes anti–tumor necrosis factor medications, Vedolizumab, ustekinumab, and tofacitinib; steroids and budesonide include both oral and rectal formulations; aminosalicylates include mesalamine and sulfasalazine; Immunomodulators include azathioprine, 6- mercaptopurine, and methotrexate. Open table in a new tab NOTE. Data are n (%). P values are calculated using conditional logistic regressions or Mantel–Haenszel test for in matched controlled cohort, and Student t test and χ2 tests in SMART-IBD cohort. HBI, Harvey Bradshaw Index; MES: Mayo endoscopic subscore; PMS: partial Mayo score; SES-CD, Simple Endoscopic Score-Crohn’s disease. With the onset of the COVID-19 pandemic, there was initial concern that IBD and immunosuppressive medications would place patients at high risk for infection with and complications from SARS-CoV2. Using one of the largest reported cohorts of COVID-19–positive patients, this matched case–control analysis reveals IBD patients did not experience more severe COVID-19. Older age was a risk for emergency care or hospitalization. Although UC was associated with greater risk of severe disease in our cohort, neither baseline IBD activity nor biologic medication predicted need for higher level of care. Reflecting lower rates of obesity and pulmonary disease, IBD patients with COVID-19 experienced less dyspnea or severe outcomes than matched non-IBD controls. However, the increased prevalence of gastrointestinal manifestations of COVID-195Zhou F. Yu T. Du R. et al.Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.Lancet. 2020; 395: 1054-1062Abstract Full Text Full Text PDF PubMed Scopus (16310) Google Scholar within the IBD population highlights the need for COVID-19 evaluation in IBD patients with new gastrointestinal symptoms. These data provide early evidence tracking incident infection and clinical COVID-19 in a longitudinal IBD cohort. Despite similar overall infection rates in IBD patients and the general pandemic epicenter population, moderate-to-severe IBD activity and corticosteroid use were found to be associated with higher rates of COVID-19. Limitations in SARS-CoV-2 testing and asymptomatic carriage might underestimate the true prevalence in this cohort. These data support societies’ guidelines to continue effective steroid-sparing IBD therapy in the epicenter of a pandemic to minimize active disease. Our data support the emerging idea that IBD and/or medications used for its treatment are not associated with severe outcomes in COVID-19.3Haberman R. Axelrad J. Chen A. et al.Covid-19 in immune-mediated inflammatory diseases—case series from New York.N Engl J Med. 2020; 383: 85-88Crossref PubMed Scopus (322) Google Scholar,4Bezzio C. Saibeni S. Variola A. et al.Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study.Gut. 2020; 69: 1213-1217Crossref PubMed Scopus (222) Google Scholar Within the IBD subset of the inpatient cohort, severe sequelae of COVID-19 were lower than in matched non-IBD controls. Despite the small number of admitted IBD patients, these findings are consistent with a possible blunting of the cytokine release syndrome, associated with severe morbidity and mortality in COVID-19,6Burgueno J.F. Reich A. Hazime H. et al.Expression of SARS-CoV-2 entry molecules ACE2 and TMPRSS2 in the gut of patients with IBD.Inflamm Bowel Dis. 2020; 26: 797-808Crossref PubMed Scopus (109) Google Scholar by altered immune function or immunosuppressive therapy, which can limit disease progression. No significant differences were detected regarding biologic type on COVID-19 risk. These data support the need for further study of intestinal inflammation associated with SARS-CoV-2 infection and gastrointestinal symptoms.7Zhang C. Wu Z. Li J.-W. et al.Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality.Int J Antimicrob Agents. 2020; 55: 105954Crossref PubMed Scopus (1158) Google Scholar,8Potdar AA, Dube S, Naito T, et al. Reduced expression of COVID-19 host receptor, ACE2 is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn′s disease. Preprint. Posted online April 23,2020. medRxiv 2020.04.19.20070995. doi: https://doi.org/10.1101/2020.04.19.20070995.Google Scholar Jill Roberts Center Study Group: Gabriela Funez-dePagnier, Lucia Duenas-Bianchi, Vinita Jacob, and Robert J Battat. Weill Cornell Medicine-Gastrointestinal Study Group: Tibor Krisko, Brett E. Fortune. Dana J. Lukin, Anand Kumar, and Kaveh Hajifathalian contributed equally to this work. Dana J. Lukin, MD, PhD (Conceptualization: Lead; Data curation: Supporting; Supervision: Lead; Writing – original draft: Equal; Writing – review & editing: Lead). Anand Kumar, MD (Data curation: Equal; Formal analysis: Equal; Methodology: Equal; Writing – original draft: Supporting; Writing – review & editing: Equal). Kaveh Hajifathalian, MD (Data curation: Equal; Formal analysis: Equal; Methodology: Equal; Writing – original draft: Supporting; Writing – review & editing: Supporting). Reem Z. Sharaiha, MD, MSc (Conceptualization: Supporting; Supervision: Supporting; Writing – review & editing: Supporting). Ellen J. Scherl, MD (Conceptualization: Equal; Data curation: Equal; Supervision: Equal; Writing – review & editing: Equal). Randy S. Longman, MD, PhD (Conceptualization: Lead; Data curation: Equal; Methodology: Supporting; Writing – original draft: Equal; Writing – review & editing: Lead). The source cohort consisted of 1386 with confirmed or highly suspected COVID-19 patients who presented to our tertiary academic center in New York (including Jill Roberts Center for IBD) or an affiliated smaller nonacademic hospital in New York, between February 1 and April 30, 2020. COVID-19 was defined as confirmed (positive SARS-CoV-2 polymerase chain reaction), or highly suspected (new-onset fever >37.8°C and more than 1 new symptom including cough, sore throat, dyspnea, anosmia, and diarrhea, with a known close contact with COVID-19). Cases consisted of COVID-19 patients with a diagnosis of IBD (exposed, n = 80), and were matched in a 1:2 ratio to the COVID-19 patients without IBD (nonexposed, n = 160) according to their decade of age and sex. Demographic and clinical data including comorbidities relevant to COVID-19 were extracted. Patients were considered to have gastrointestinal manifestations at presentation if they reported any of the symptoms of nausea, vomiting, diarrhea, or abdominal pain at time of presentation. For IBD patients, clinical disease activity at baseline was determined using the Harvey Bradshaw Index for Crohn’s disease or the partial Mayo Score for UC. Endoscopic activity within 6 months was determined if a colonoscopy report was available and reported as Simple Endoscopic Score for Crohn’s Disease or Mayo endoscopic subscore for UC. The main exposure in the matched cohort study was presence of IBD. Outcomes of interest were clinical manifestations of COVID-19 on presentation (including fever, cough, dyspnea, myalgia or fatigue, anorexia, altered mental status, nausea, vomiting, diarrhea, abdominal pain, anosmia, and dysgeusia), as well as the composite of intensive care unit admission, endotracheal intubation, or death among admitted patients. Detailed definitions of individual variables have been described elsewhere.2 Among cases with IBD, the association between disease type or IBD treatment and need for emergency visit or admission was evaluated in secondary analysis. IBD treatment was categorized into biologic therapy (including tumor necrosis factor antagonists, vedolizumab, or ustekinumab), or no biologic use. This consisted of 119 patients with active IBD who were followed prospectively at our center (SMART IBD longitudinal cohort). The exposures of interest were IBD type, clinical, biochemical, and endoscopic indices of disease activity, and IBD treatment. The outcome of interest was diagnosis of COVID-19, as defined above. Clinical IBD disease activity was determined using partial Mayo score for UC and Harvey Bradshaw Index for Crohn’s disease. Biochemical disease activity was evaluated using C-reactive protein, albumin, and fecal calprotectin levels. Endoscopic disease activity was evaluated using last recorded Simple Endoscopic Score for Crohn’s Disease or Mayo endoscopic subscore for UC, and baseline medications used to treat IBD were recorded, as for the matched cohort. IBD treatment was categorized into biologic therapy (including tumor necrosis factor antagonists, vedolizumab, or ustekinumab), oral or rectal steroids (excluding budesonide), oral or rectal budesonide, aminosalicylates (including mesalamine and sulfasalazine), immunomodulators (including azathioprine, 6- mercaptopurine, and methotrexate), and combination therapy (biologics plus immunomodulators) Descriptive statistics were reported as mean (SD), median (interquartile range), or counts and proportions. Conditional logistic regressions and Mantel–Haenszel test were used to compare variables between COVID-19 patients with and without IBD in the matched cohort, and multivariable logistic regression was used to evaluate the effect of IBD type and treatment on emergency visit or hospitalization. In longitudinal IBD cohort, groups were compared using χ2 test for categorical variables and Student t test for continuous variables. All analyses were based on nonmissing data and missing data were not imputed. All tests were 2-tailed with a significance level of α = .05. Analyses were performed with STATA, version 13.0 for Windows (StataCorp LP, College Station, TX) and SPSS, version 25.0 (IBM Corp, Armonk, NY).Supplementary Table 1Disease Characteristics of COVID-19 Cases With Inflammatory Bowel DiseaseCharacteristicData,aData available on 64 of the 80 cases. n (%)IBD type UC26 (40.6) CD38 (59.4)CD CD locationIleal7 (18.4)Colonic8 (21.1)Ileocolonic22 (57.9) Perianal disease8 (21.1) Prior intestinal resection18 (47.4) Clinical disease activity CDActive (HBI >4)24 (63.2)Moderate to severe (HBI >7)15 (41.7) Endoscopic disease activity CDActive (SES-CD >4)22 (84.6)Moderate to severe (SES-CD >6)19 (73.1)UC UC extentProctitis2 (7.7)Left-sided8 (30.8)Pancolitis16 (61.5) Ostomy or pouch3 (11.5) Clinical disease activity UCActive (PMS >1)13 (52)Moderate to severe PMS >4)5 (20) Endoscopic disease activity UCActive (MES >0)16 (61.5)Moderate to severe (MES >1)14 (53.8) C-reactive protein >0.9 mg/dL16 (25.8) Fecal calprotectin >50 μg/mg26 (48.1) Biologic therapyTumor necrosis factor antagonist16 (25)Vedolizumab10 (15.6)Ustekinumab12 (18.8)Tofacitinib1 (1.6)Dual (vedolizumab + tofacitinib)1 (1.6)Trial drug3 (4.7)None21 (32.8) Thiopurines (6-mercaptopurine, azathioprine)4 (6.3) Methotrexate3 (4.7) Combination therapy4 (6.3) Oral/rectal aminosalicylate20 (31.3) Any steroid13 (20.3)ComorbidityaData available on 64 of the 80 cases.21 (32.8)CD, Crohn’s disease; HBI, Harvey Bradshaw Index; MES, Mayo endoscopic subscore; PMS, partial Mayo score; SES-CD, Simple Endoscopic Score-CD.a Data available on 64 of the 80 cases. Open table in a new tab Supplementary Table 2Emergency Department Visit or Hospitalization According to Inflammatory Bowel Disease Treatment Among COVID-19 Cases With Inflammatory Bowel DiseaseBiologic useaDetails of treatment available for 64 of 80 cases. Three patients on clinical trials, 1 patient on tofacitinib, and 1 patient on dual biologic were excluded due to small sample sizes.Total, nED visit or hospitalizationP valueYes, n (%)(n = 11)No, n (%)(n = 48)No biologic216 (28.6)15 (71.4).197Tumor necrosis factor antagonist161 (6.3)15 (93.8)—Vedolizumab103 (30)7 (70)—Ustekinumab121 (8.3)11 (91.7)—ED, emergency department.a Details of treatment available for 64 of 80 cases. Three patients on clinical trials, 1 patient on tofacitinib, and 1 patient on dual biologic were excluded due to small sample sizes. Open table in a new tab Supplementary Table 3COVID-19 Diagnosis According to Inflammatory Bowel Disease Treatment in the Longitudinal Inflammatory Bowel Disease CohortBiologic classTotal, n (N = 83)COVID diagnosisP valueYes, n (%)(n = 20)No, n (%)(n = 63)Tumor necrosis factor antagonist246 (25)18 (75).315Vedolizumab237 (30.4)16 (69.6)—Ustekinumab294 (13.8)25 (86.2)—Tofacitinib73 (42.9)4 (57.1)— Open table in a new tab CD, Crohn’s disease; HBI, Harvey Bradshaw Index; MES, Mayo endoscopic subscore; PMS, partial Mayo score; SES-CD, Simple Endoscopic Score-CD. ED, emergency department.