Discontinuation of tofacitinib in patients with ulcerative colitis in sustained clinical remission on combination therapy with 5-aminosalicylates and tofacitinib: The STOP Trial

Ulcerative colitis (UC) is a chronic relapsing disease requiring long-term therapy. Tofacitinib, an oral Janus kinase inhibitor, is effective for moderate-to-severe UC, while 5-aminosalicylates (5-ASA) remain standard for mild-to-moderate disease. In clinical practice, many patients in sustained remission continue both drugs, though the necessity of combination therapy is uncertain. Prolonged tofacitinib use carries risks such as infections, thromboembolism, cardiovascular events, and high treatment costs. Whether patients in deep remission can safely discontinue tofacitinib while continuing 5-ASA is unknown.

The STOP Trial is a double-blind, randomized controlled study enrolling 110 adult UC patients in composite remission (clinical, biochemical, and endoscopic) on stable 5-ASA and tofacitinib 5 mg twice daily for at least three months. Participants will be randomized (1:1) into two arms: (1) continuation of 5-ASA + tofacitinib, or (2) discontinuation of tofacitinib and continuation of 5-ASA

The primary outcome is the proportion of patients experiencing relapse within 12 months, defined by Partial Mayo score greater than or equal to 2 with rectal bleeding score greater than or equal to 1, Mayo endoscopic score greater than or equal to 1, and fecal calprotectin more than 250 micrograms per gram. Secondary outcomes include time to flare, recapture of response after escalation, maintenance of remission at 12 months, and safety outcomes.

This trial will provide prospective evidence on tofacitinib withdrawal in sustained remission. Results may guide de-escalation strategies, reduce unnecessary drug exposure, lower risks, and improve cost-effectiveness in UC management.