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 Table 2.GRADE Definitions of Quality and Certainty of the Evidence Quality grade Definition High We are very confident that the true effect lies close to the estimate of the effect Moderate We 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. Low Our confidence in the estimate is limited. The true effect may be substantially different from the estimate of effect. Very low We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect Evidence gap Available evidence is insufficient to determine true effect Table 3.GRADE Definitions on Strength of Recommendation and Guide to Interpretation Strength of recommendation Wording in the guideline For the patient For the clinician Strong “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. 1452 Feuerstein et al Gastroenterology Vol. 158, No. 5 CLINICAL PRACTICE GUIDELINES 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 twicedaily dose after careful deliberation of risks and benefits of Table 4.Summary of Recommendations of the AGA Clinical Guidelines Committee for the Management of Moderate to Severe Ulcerative Colitis Recommendations Strength of recommendation Quality of evidence 1. 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.) Strong Moderate 2a. 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. Conditional Moderate 2b. 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-a antagonists. No recommendation Knowledge gap 2c. In adult outpatients with moderate to severe UC