AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis

Abstract

This document presents the official recommendations of the American Gastroenterological Association (AGA) on the management of moderate to severe ulcerative colitis (UC). The guideline was developed by the AGA Institute’s Clinical Guidelines Committee and approved by the AGA Governing Board. It is accompanied by a technical review that provides a detailed synthesis of the evidence from which these recommendations were formulated.1Singh S. Allegretti J.R. Siddique S.M. et al.AGA Technical review on the management of moderate to severe ulcerative colitis.Gastroenterology. 2019; 158: 1465-1496Abstract Full Text Full Text PDF Scopus (34) Google Scholar Development of this guideline and the accompanying technical review was fully funded by the AGA Institute without additional outside funding. Members of the guideline panel and technical review panel were selected by the AGA Governing Board in consultation with the Clinical Guidelines Committee with careful consideration of all Institute of Medicine recommendations for clinical guideline development. Joseph Feuerstein was the guideline panel chair and Siddharth Singh was the methodologist and co-chair of the guideline panel. A patient representative was also included in the development and review process and had no recommended changes. The guideline and accompanying technical review underwent independent peer review, and a 30-day open public comment period; all comments were collated by the AGA staff, and were reviewed and carefully considered by the guideline panel and technical review teams, respectively. Changes were incorporated in revised documents, and where changes were not accepted, a thoughtful response document was created. After the public comment period, 2 pivotal clinical trials (VARSITY, UNIFI) were published and a critical safety update on tofacitinib was issued by the US Food and Drug Administration (FDA). At the recommendation of the Clinical Guidelines Committee, the technical review and clinical guidelines were updated to incorporate this new evidence as presented here. In accordance with the Clinical Guidelines Committee policies, all clinical guidelines are reviewed annually at the AGA Clinical Guideline Committee meeting for new information. The next update for these guidelines is anticipated in 3 years from publication. UC is a chronic inflammatory bowel disease with peak onset in early adulthood.2Fumery M. Singh S. Dulai P.S. et al.Natural history of adult ulcerative colitis in population-based cohorts: a systematic review.Clin Gastroenterol Hepatol. 2018; 16: 343-356 e3Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar Untreated, the natural history of the disease is one of relapsing and remitting mucosal inflammation. Based on population-based cohort studies, the majority of patients with UC have a mild to moderate course, generally most active at diagnosis and then in varying periods of remission or mild activity. Approximately 15% patients may experience an aggressive course, and 20% of these patients may require hospitalization for severe disease activity.2Fumery M. Singh S. Dulai P.S. et al.Natural history of adult ulcerative colitis in population-based cohorts: a systematic review.Clin Gastroenterol Hepatol. 2018; 16: 343-356 e3Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar,3Narula N. Marshall J.K. Colombel J.F. et al.Systematic review and meta-analysis: infliximab or cyclosporine as rescue therapy in patients with severe ulcerative colitis refractory to steroids.Am J Gastroenterol. 2016; 111: 477-491Crossref PubMed Scopus (105) Google Scholar The 5- and 10-year cumulative risk of colectomy is 10%–15%, primarily limited to patients with moderate to severe disease activity; a subset of hospitalized patients with acute severe ulcerative colitis (ASUC) have short-term colectomy rates of 25%–30%.3Narula N. Marshall J.K. Colombel J.F. et al.Systematic review and meta-analysis: infliximab or cyclosporine as rescue therapy in patients with severe ulcerative colitis refractory to steroids.Am J Gastroenterol. 2016; 111: 477-491Crossref PubMed Scopus (105) Google Scholar Predictors of an aggressive disease course and colectomy are the following: young age at diagnosis (<40 years old), extensive disease, severe endoscopic activity (presence of large and/or deep ulcers), presence of extra-intestinal manifestations, early need for corticosteroids, and elevated inflammatory markers.4Dassopoulos T. Cohen R.D. Scherl E.J. et al.Ulcerative colitis care pathway.Gastroenterology. 2015; 149: 238-245Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar For this guideline and the accompanying technical review, moderate to severe UC is defined based on the Truelove and Witts criteria and Mayo Clinic score (Table 1).4Dassopoulos T. Cohen R.D. Scherl E.J. et al.Ulcerative colitis care pathway.Gastroenterology. 2015; 149: 238-245Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 5Schroeder K.W. Tremaine W.J. Ilstrup D.M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.N Engl J Med. 1987; 317: 1625-1629Crossref PubMed Scopus (1934) Google Scholar, 6Truelove S.C. Witts L.J. Cortisone in ulcerative colitis; final report on a therapeutic trial.Br Med J. 1955; 2: 1041-1048Crossref PubMed Scopus (2106) Google Scholar After excluding concomitant infections (such as Clostridium difficile), patients with moderate to severe disease are those who are dependent on or refractory to corticosteroids, have severe endoscopic disease activity (presence of ulcers), or are at high risk of colectomy. When reported, Mayo Clinic scores of 6–12 with an endoscopic subscore of 2 or 3 were considered moderate to severe disease. ASUC in this guideline is defined as hospitalized patients with the following Truelove and Witts criteria: ≥6 bloody bowel movements/day with at least 1 marker of systemic toxicity, including heart rate >90 beats/min, temperature >37.8°C, hemoglobin <10.5 g/dL, and/or erythrocyte sedimentation rate –30 mm/h.6Truelove S.C. Witts L.J. Cortisone in ulcerative colitis; final report on a therapeutic trial.Br Med J. 1955; 2: 1041-1048Crossref PubMed Scopus (2106) Google ScholarTable 1Disease Severity Scoring SystemsVariableTruelove and Witts criteriaMildSevereFulminantNo. of stools/d<4>6>10Blood in stoolIntermittentFrequentContinuousTemperature, °CNormal>37.5>37.5Pulse, beats/minNormal>90>90HemoglobinNormal<75% normalTransfusion requiredErythrocyte sedimentation rate, mm/h≤30>30>30Colonic features on radiographNoneAir, edematous wall, thumbprintingColonic dilationClinical signsNoneAbdominal tendernessAbdominal distention and tendernessVariableMayo score for UCDefinitionScoreVariableDefinitionScoreStool patternNormal no. of daily bowel movements0Endoscopic findingsNormal/inactive colitis01–2 more bowel movements than normal1Erythema, decreased vascularity13–4 more bowel movements than normal2Friability, marked erythema, erosions25 or more bowel movements than normal3Ulcerations, severe friability, spontaneous bleeding3Most severe rectal bleeding of the dayNone0Physician Global AssessmentNormal0Blood streaks seen in the stool less than half of the time1Mild colitis1Blood in most stool2Moderate colitis2Pure blood passed3Severe colitis3 Open table in a new tab There are a number of different drug classes for long-term management of moderate to severe UC, including TNF-α antagonists, anti-integrin agent (vedolizumab), Janus kinase inhibitor (tofacitinib), interleukin 12/23 antagonist (ustekinumab), and immunomodulators (thiopurines, methotrexate).7Ungaro R. Mehandru S. Allen P.B. et al.Ulcerative colitis.Lancet. 2017; 389: 1756-1770Abstract Full Text Full Text PDF PubMed Scopus (1051) Google Scholar In general, most drugs that are initiated for induction of remission are continued as maintenance therapy, if they are effective. This clinical practice is considered standard of care in this guideline and it is assumed that if a drug (excluding corticosteroids and cyclosporine) is started for and is effective for induction of remission or response, it will be continued for maintenance of remission. This guideline addresses the medical management of adult outpatients with moderate to severe UC, as well as the medical management of adult hospitalized patients with ASUC. The guideline focuses on immunomodulators, biologics, and small molecules for induction and maintenance of remission (for moderate to severe UC) and decreasing the risk of colectomy (for ASUC). As noted, unless otherwise specified, we do not present separate recommendations for induction and maintenance of remission. The drugs are listed in order of FDA approval unless specifically mentioned. The first 7 questions are focused on the medical management of adult outpatients with moderate to severe UC; the subsequent 4 questions are focused on adult patients hospitalized with ASUC, focusing on initial management, and rescue therapy in cases of corticosteroid-refractory disease. We acknowledge challenges in defining moderate disease activity and severity, with variable definitions in clinical practice, and an understanding of this entity may be enhanced reading the AGA guideline on the management of mild to moderate UC.8Ko C.W. Singh S. Feuerstein J.D. et al.American Gastroenterological Association Institute guideline on the management of mild-to-moderate ulcerative colitis.Gastroenterology. 2019; 156: 748-764Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar This guideline does not address surgical management of moderate to severe UC or ASUC. Therapeutic drug monitoring to guide the use of biologic therapy has been addressed in separate AGA guidelines.9Feuerstein J.D. Nguyen G.C. Kupfer S.S. et al.American Gastroenterological Association Institute Guideline on therapeutic drug monitoring in inflammatory bowel disease.Gastroenterology. 2017; 153: 827-834Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar The guideline is intended for the use of gastroenterology providers, primary care providers, surgeons, patients, and policymakers. For this guideline, critical outcomes for decision-making for adults with moderate to severe UC were induction and maintenance of remission, and for hospitalized adults with ASUC was short-term colectomy risk (within 3 months of hospitalization), and are reported in the evidence profiles. Important outcomes of interest were induction and maintenance of endoscopic remission, maintenance of corticosteroid-free remission, serious adverse events (including serious infections and malignancy), and treatment tolerability (drug discontinuation due to adverse events). These were considered in evidence synthesis especially if inadequate or conflicting data was observed for critical outcomes. Safety considerations with these medications have been synthesized in the accompanying technical review. In the recommendations presented in this guideline, estimates of effects of different medications are presented as the risk for failure to induce or maintain remission, that is, a relative risk (RR) or odds ratio (OR) <1 suggests that the drug under consideration is more effective than the comparison drug or placebo for induction or maintenance of remission. This guideline was developed using a process described elsewhere.10American Gastroenterological AssociationAGA Institute Clinical Practice Guideline Development Process. American Gastroenterological Association, Bethesda, MD2018Google Scholar Briefly, the AGA process for developing clinical practice guidelines incorporate Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology11Sultan S. Falck-Ytter Y. Inadomi J.M. The AGA Institute process for developing clinical practice guidelines part one: grading the evidence.Clin Gastroenterol Hepatol. 2013; 11: 329-332Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar and best practices as outlined by the Institute of Medicine.12Institute of MedicineClinical Practice Guidlines We Can Trust. National Academies Press, Washington, DC2011Google Scholar GRADE methodology was used to prepare the background information for the guideline and the accompanying technical review.1Singh S. Allegretti J.R. Siddique S.M. et al.AGA Technical review on the management of moderate to severe ulcerative colitis.Gastroenterology. 2019; 158: 1465-1496Abstract Full Text Full Text PDF Scopus (34) Google Scholar Optimal understanding of the guideline will be enhanced by reading the applicable portions of the technical review. The guideline panel and the authors of the technical review met face to face on December 14, 2018 to discuss the findings from the technical review. The guideline authors subsequently formulated the guideline recommendations using the GRADE evidence-to-decision framework guidance. New evidence was presented to the guideline panel by the technical review team on October 16, 2019, and was reviewed and approved in a virtual face-to-face meeting on November 1, 2019. Although the quality of evidence (Table 2) was a key factor in determining the strength of the recommendations (Table 3), the panel also considered the balance between benefit and harm of interventions, patients’ values and preferences, and overall resource utilization. The recommendations, quality of evidence, and strength of recommendations are summarized in Table 4.Table 2GRADE Definitions of Quality and Certainty of the EvidenceQuality gradeDefinitionHighWe are very confident that the true effect lies close to the estimate of the effectModerateWe are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different.LowOur confidence in the estimate is limited. The true effect may be substantially different from the estimate of effect.Very lowWe have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effectEvidence gapAvailable evidence is insufficient to determine true effect Open table in a new tab Table 3GRADE Definitions on Strength of Recommendation and Guide to InterpretationStrength of recommendationWording in the guidelineFor the patientFor the clinicianStrong“The AGA recommends…”Most individuals in this situation would want the recommended course and only a small proportion would not.Most individuals should receive the recommended course of action. Formal decision aids are not likely to be needed to help individuals make decisions consistent with their values and preferences.Conditional“The AGA suggests…”The majority of individuals in this situation would want the suggested course, but many would not.Different choices would be appropriate for different patients. Decision aids may be useful in helping individuals in making decisions consistent with their values and preferences. Clinicians should expect to spend more time with patients when working towards a decision.No recommendation“The AGA makes no recommendation…”—The confidence in the effect estimate is so low that any effect estimate is speculative at this time. Open table in a new tab Table 4Summary of Recommendations of the AGA Clinical Guidelines Committee for the Management of Moderate to Severe Ulcerative ColitisRecommendationsStrength of recommendationQuality of evidence1. In adult outpatients with moderate to severe UC, the AGA recommends using infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment. (Medications are ordered based on year of approval by the US FDA.)StrongModerate2a. In adult outpatients with moderate to severe UC who are naïve to biologic agents, the AGA suggests using infliximab or vedolizumab rather than adalimumab, for induction of remission.Comment: Patients, particularly those with less severe disease, who place higher value on the convenience of self-administered subcutaneous injection, and a lower value on the relative efficacy of medications, may reasonably chose adalimumab as an alternative.ConditionalModerate2b. In adult outpatients with moderate to severe UC who are naïve to biologic agents, the AGA recommends that tofacitinib only be used in the setting of a clinical or registry study. (No recommendation, knowledge gap)Comment: Updated FDA recommendations (July 26, 2019) on indications for use of tofacitinib in UC recommends its use only after failure of or intolerance to TNF-α antagonists.No recommendationKnowledge gap2c. In adult outpatients with moderate to severe UC who have previously been exposed to infliximab, particularly those with primary nonresponse, the AGA suggests using ustekinumab or tofacitinib rather than vedolizumab or adalimumab for induction of remission.ConditionalLow3a. In adult outpatients with active moderate to severe UC, the AGA suggests against using thiopurine monotherapy for induction of remission.ConditionalVery low3b. In adult outpatients with moderate to severe UC in remission, the AGA suggests using thiopurine monotherapy rather than no treatment for maintenance of remission.ConditionalLow3c. In adult outpatients with moderate to severe UC, the AGA suggests against using methotrexate monotherapy for induction or maintenance of remission.ConditionalLow4a. In adult outpatients with active moderate to severe UC, the AGA suggests using biologic monotherapy (TNF-α antagonists, vedolizumab, or ustekinumab) or tofacitinib rather than thiopurine monotherapy for induction of remission.ConditionalLow4b. In adult outpatients with moderate to severe UC in remission, the AGA makes no recommendation in favor of or against using biologic monotherapy or tofacitinib rather than thiopurine monotherapy for maintenance of remission.No recommendationKnowledge gap5a. In adult outpatients with moderate to severe UC, the AGA suggests combining TNF-α antagonists, vedolizumab or ustekinumab with thiopurines or methotrexate rather than biologic monotherapy.Comment: Patients, particularly those with less severe disease, who place higher value on the safety of biologic monotherapy and lower value on the efficacy of combination therapy may reasonably chose biologic monotherapy.ConditionalLow5b. In adult outpatients with moderate to severe UC, the AGA suggests combining TNF-α antagonists, vedolizumab, or ustekinumab with thiopurines or methotrexate rather than thiopurine monotherapy.ConditionalLow6. In adult outpatients with moderate to severe UC, the AGA suggests early use of biologic agents with or without immunomodulator therapy rather than gradual step up after failure of 5-ASA.Comment: Patients, particularly those with less severe disease, who place higher value on the safety of 5-ASA therapy and lower value on the efficacy of biologic agents or tofacitinib may reasonably chose gradual step therapy with 5-ASA therapy.ConditionalVery low7. In adult outpatients with moderate to severe UC who have achieved remission with biologic agents and/or immunomodulators or tofacitinib, the AGA suggests against continuing 5-ASA for induction and maintenance of remission.ConditionalVery low8. In hospitalized adult patients with ASUC, the AGA suggests using intravenous methylprednisolone dose equivalent of 40–60 mg/d rather than higher doses of intravenous corticosteroids.ConditionalVery low9. In hospitalized adult patients with acute severe UC without infection, the AGA suggests against adjunctive antibiotics.ConditionalVery low10. In hospitalized adult patients with ASUC refractory to intravenous corticosteroids, the AGA suggests using infliximab or cyclosporine.ConditionalLow11. In hospitalized adult patients with acute severe UC being treated with infliximab, the AGA makes no recommendation on routine use of intensive vs standard infliximab dosing.No recommendationKnowledge gap Open table in a new tab 1. In adult outpatients with moderate to severe ulcerative colitis, the AGA recommends using infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment. (Strong recommendation, moderate quality evidence) 1. In adult outpatients with moderate to severe ulcerative colitis, the AGA recommends using infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment. (Strong recommendation, moderate quality evidence) The panel recommends treating adult outpatients with moderate to severe UC with infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab over no treatment for the induction and maintenance of remission. There were 16 randomized controlled trials (RCTs) comparing the TNF-α antagonists, vedolizumab, tofacitinib, and ustekinumab to placebo (see technical review). Induction of remission was assessed at 6–8 weeks and maintenance of remission was evaluated at 30–54 weeks. All active interventions were superior to placebo for induction of remission, regardless of prior biologic exposure (infliximab: relative risk [RR], 2.85; 95% confidence interval [CI], 2.11–3.86; adalimumab: RR, 1.62; 95% CI, 1.15–2.29; golimumab: RR, 2.49; 95% CI, 1.58–3.93; vedolizumab: RR, 2.22; 95% CI, 1.36–3.64; tofactinib: RR, 3.22; 95% CI, 2.03–5.08; and ustekinumab: RR, 2.91; 95% CI, 1.72–4.94). Likewise, all active interventions were superior to placebo for maintenance of remission (infliximab: RR, 2.25; 95% CI, 1.67–3.05; adalimumab: RR, 2.28; 95% CI, 1.52–3.42; golimumab: RR, 1.88; 95% CI, 1.32–2.68; vedolizumab: RR, 2.31; 95% CI, 1.63–3.28; tofactinib 5 mg twice daily: RR, 3.09; 95% CI, 1.99–4.79; and ustekinumab: RR, 1.83; 95% CI, 1.33–2.49). All medications were well-tolerated with low rates of serious adverse events in both trials of induction and maintenance therapy, not significantly different from placebo. Importantly, the recommended induction dose of tofacitinib is 10 mg twice daily for 8 weeks; in select cases with modest response to initial 8-week therapy, high-dose tofacitinib may be considered for a total of 16 weeks. For long-term maintenance, tofacitinib 5 mg twice daily is recommended for most patients; a higher dose may be considered in patients who lose response at the 5-mg twice-daily dose after careful deliberation of risks and benefits of the medication. At higher doses, an unexpected increase in risk of pulmonary embolism and all-cause mortality has been observed. The overall quality of evidence for this recommendation was moderate for both induction and maintenance of remission. Although the majority of the studies were registration trials sponsored by industry, there was no important bias, inconsistency, or indirectness. The evidence was rated down for imprecision due to the lower number of events (<200) for all comparisons, failing to achieve the optimal information size.2a. In adult outpatients with moderate to severe ulcerative colitis who are naïve to biologic agents, the AGA suggests using infliximab or vedolizumab rather than adalimumab, for induction of remission. (Conditional recommendation, moderate quality evidence)Comment: Patients, particularly those with less severe disease, who place higher value on the convenience of self-administered subcutaneous injection, and a lower value on the relative efficacy of medications, may reasonably chose adalimumab as an alternative.2b. In adult outpatients with moderate to severe ulcerative colitis who are naïve to biologic agents, the AGA recommends that tofacitinib only be used in the setting of a clinical or registry study. (No recommendation, knowledge gap)Comment: Updated FDA recommendations (July 26, 2019) on indications for use of tofacitinib in ulcerative colitis recommend its use only after failure of, or intolerance to TNF-α antagonists. 2a. In adult outpatients with moderate to severe ulcerative colitis who are naïve to biologic agents, the AGA suggests using infliximab or vedolizumab rather than adalimumab, for induction of remission. (Conditional recommendation, moderate quality evidence) Comment: Patients, particularly those with less severe disease, who place higher value on the convenience of self-administered subcutaneous injection, and a lower value on the relative efficacy of medications, may reasonably chose adalimumab as an alternative. 2b. In adult outpatients with moderate to severe ulcerative colitis who are naïve to biologic agents, the AGA recommends that tofacitinib only be used in the setting of a clinical or registry study. (No recommendation, knowledge gap) Comment: Updated FDA recommendations (July 26, 2019) on indications for use of tofacitinib in ulcerative colitis recommend its use only after failure of, or intolerance to TNF-α antagonists. In adult outpatients with moderate to severe UC naïve to biologic agents, the guideline panel suggests using infliximab or vedolizumab rather than adalimumab for induction of remission. Based on updated FDA document on approved indication for tofacitinib use only in patients after failure of, or intolerance to TNF-α antagonists, the guideline panel recommends that any use of tofacitinib in biologic-naïve patients with UC be closely monitored in the setting of a clinical or registry study. Currently, both infliximab and vedolizumab are intravenous medications that require infusions, which may be inconvenient to some patients. For these patients, particularly those with less severe disease who value the convenience of self-administered injection therapy, adalimumab may be a reasonable alternative option as first-line biologic therapy. In the head-to-head trials comparing vedolizumab vs adalimumab in patients with moderate to severe UC (VARSITY), rate of clinical remission at 52 weeks was significantly higher in vedolizumab-treated patients vs adalimumab-treated patients (34.2% vs 24.3%; RR, 1.41; 95% CI, 1.10–1.81) among biologic-naïve patients. For all other comparisons, evidence on comparative efficacy was derived from a network meta-analysis.13Singh S. Murad M.H. Fumery M. Dulai P.S. Sandborn W.J. First- and second-line pharmacotherapies for patients with moderate to severely active ulcerative colitis: an updated network meta-analysis.Clin Gastroenterol Hepatol. 2020; (Jan 13 [Online ahead of print]. https://doi.org/10.1016/j.cgh.2020.01.008.)Abstract Full Text Full Text PDF Scopus (87) Google Scholar Network meta-analysis can help assess comparative efficacy of several interventions and synthesize evidence across a network of RCTs, especially if there is weak (or absent) direct evidence.14Cipriani A. Higgins J.P. Geddes J.R. et al.Conceptual and technical challenges in network meta-analysis.Ann Intern Med. 2013; 159: 130-137Crossref PubMed Scopus (556) Google Scholar Such indirect comparisons of competing interventions, adjusted by a common control, such as placebo, can partially take account of prognostic characteristics of patients in different trials. The analysis included 15 RCTs with a total of 3747 biologic-naïve patients with moderate to severe UC, treated with infliximab (4 trials, 667 patients), adalimumab (4 trials, 1046 patients), golimumab (2 trials, 586 patients), vedolizumab (3 trials, 630 patients), tofacitinib (2 trials, 520 patients), and ustekinumab (1 trial, 298 patients) were included (see technical review). For this body of evidence for induction therapy, trial design, participant characteristics, interventions, comparators, and outcomes for trials of infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab were deemed reasonably similar to facilitate indirect comparison. In contrast, trials of tofacitinib were deemed dissimilar because they used a strict rectal bleeding score of 0 for outcome assessment (in contrast to other trials, which allowed rectal bleeding score of 0 or 1 in outcome assessment). See the technical review and technical review Tables 3–5 for full details regarding this analysis.1Singh S. Allegretti J.R. Siddique S.M. et al.AGA Technical review on the management of moderate to severe ulcerative colitis.Gastroenterology. 2019; 158: 1465-1496Abstract Full Text Full Text PDF Scopus (34) Google Scholar On network meta-analysis, there was moderate confidence in estimates demonstrating the superiority of infliximab over adalimumab (Odds ratio [OR], 2.10; 95% CI, 1.16–3.79) (evidence rated down for serious imprecision). It is important to note that in these clinical trials, treatment was not optimized to suggested drug concentrations; it is possible that the efficacy of infliximab, adalimumab, and golimumab may be comparable in patients who achieve adequate drug concentrations, given their similar mechanism of action.2c. In adult outpatients with moderate to severe ulcerative colitis who have previously been exposed to infliximab, particularly those with primary nonresponse, the AGA suggests using ustekinumab or tofacitinib, rather than vedolizumab or adalimumab, for induction of remission. (Conditional recommendation, low quality evidence)Comment: Patients, particularly those with less severe disease, who place higher value on the potential safety of medications, and a lower value on the relative efficacy of medications, may reasonably chose vedolizumab as an alternative. 2c. In adult outpatients with moderate to severe ulcerative colitis who have previously been exposed to infliximab, particularly those with primary nonresponse, the AGA suggests using ustekinumab or tofacitinib, rather than vedolizumab or adalimumab, for induction of remission. (Conditional recommendation, low quality evidence) Comment: Patients, particularly those with less severe disease, who place higher value on the potential safety of medications, and a lower value on the relative efficacy of medications, may reaso