2. Summary of clinical characteristics and conflicts of interest of included studies.

Study ID	Disease type	Definition of refractory	Definition of clinical remission/improvement	Conflicts of interest
Aoki 2012	UC	NR	Clinical remission: participants who achieved a CAI score of ≥ 3 were considered to have achieved remission. Clinical improvement: a decrease in CAI by ≥ 4 points was considered clinical improvement.	NR
Lawrance 2017	UC	People who failed conventional therapies of oral or rectal (or both) 5‐aminosalicylate or oral and rectal steroids (or both), or were intolerant of these medications.	Clinical remission: observed by a Mayo score ≤ 2 with no subscore > 1. In addition to endoscopic score of 0 or 1 indicating mucosal healing. Clinical improvement: a reduction in Mayo score ≥ 3 points and a decrease of > 30% from the baseline score. In addition, a reduction of ≥ 1 on the rectal bleeding subscale, or alternatively an absolute rectal score of 0 or 1.	Authors declared no conflicts of interest.
Lie 2020	UP	Mesalamine‐refractory UP (defined as a failure to at least the use of mesalamine suppositories of a maximum of 1 g for ≥ 21 days) or recurring UP (defined as a relapse within 3 months after stopping adequate local mesalamine therapy).	Clinical remission: defined as a Mayo score ≤ 2, and endoscopic remission as no visible inflammation (i.e. Mayo subscore 0). Clinical response: defined as an absolute decrease in Mayo score of 3 points, with a relative decrease of 30% of the total score and ≥ 1 point decrease in the rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1.	Authors declared no conflicts of interest.
Ogata 2006	UC	Steroid resistance defined as unresponsiveness to oral or intravenous corticosteroid therapy. Steroid dependency was defined as either chronic active UC for > 6 months or frequent recurrence (> once a year, or ≥ 3 times every 2 years regardless of intensive medical therapy).	Clinical remission: defined as a DAI score ≤ 2, with no individual subscore > 1, and mucosal healing was defined as an endoscopy subscore (≥ 2 at entry) of 0 or 1. Clinical improvement: defined as combination of partial and complete response. Partial response was defined as a reduction of > 4 points on DAI with improvement in all categories. Complete response was defined as resolution of all symptoms (all assessment scores 0).	Authors declared no conflicts of interest.
Ogata 2012	UC	Steroid resistance was when the disease failed to respond to a systemic daily dose of 1 mg/kg bodyweight, or ≥ 40 mg of prednisolone given over ≥ 7 days, or the equivalent of a daily dose of prednisolone of ≥ 30 mg over ≥ 2 weeks. Steroid‐dependent participants were defined as people with active UC in whom attempts to taper steroids had been unsuccessful.	Clinical remission: defined as a DAI score ≤ 2, with an individual subscore 0 or 1, and mucosal healing defined as an endoscopy subscore of 0 or 1. Clinical response: defined as a reduction in DAI by ≥ 4 points and improvements in all categories (stool frequency, rectal bleeding, mucosal appearance, and physician’s overall assessment).	Authors declared no conflicts of interest.

CAI: Clinical Activity Index; DAI: Disease Activity Index; NR: not reported; UC: ulcerative colitis; UP: ulcerative proctitis.