TACOSUC · Acute severe colitis
Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial
Singh A, et al.
Am J Gastroenterol 2024 · PMID 38131615 (PubMed, opens in a new tab) · doi 10.14309/ajg.0000000000002635 (full paper, opens in a new tab)
| Endpoint | Tofacitinib | Placebo | Difference |
|---|---|---|---|
| Response by day 7 (primary endpoint) | 83.01% (44/53) | 58.82% (30/51) | OR 3.42 (95% CI 1.37–8.48); P=0.007 |
The effect lasted: the cumulative probability of needing infliximab or colectomy by day 90 was 0.13 vs 0.38 (log-rank P=0.003).
Source: Singh 2024, abstract (intention to treat).
Structured abstract
BackgroundAbout 30–40% of patients with acute severe UC do not respond to IV corticosteroids. Whether adding a fast-acting oral JAK inhibitor improves early response had not been tested in a randomised trial.
MethodsSingle-centre, double-blind, placebo-controlled randomised trial. 104 patients. Primary endpoint: Response by day 7 (Lichtiger index down by more than 3 points and an absolute score below 10 for 2 consecutive days, without rescue therapy).
ResultsPrimary result. 83.01% (44/53) vs 58.82% (30/51); odds ratio 3.42 (95% CI 1.37–8.48); P=0.007
Take-homeAdding tofacitinib to IV steroids improved day-7 response in acute severe UC in one small single-centre trial; promising, but not yet standard care.
| Patients | 104 |
|---|---|
| Population | Adults with acute severe UC (Truelove and Witts criteria) receiving IV hydrocortisone 100 mg every 6 hours |
| Comparison | Tofacitinib 10 mg three times daily vs placebo for 7 days, added to IV corticosteroids |
| Drugs | tofacitinib |
| Classes | JAK inhibitor |
| Published | Singh A, et al. Am J Gastroenterol 2024;119:1365–72. |
Key points
- Need for rescue therapy by day 7 was lower with tofacitinib: odds ratio 0.27 (95% CI 0.09–0.78); P=0.01.
- Cumulative probability of needing rescue therapy (infliximab or colectomy) by day 90: 0.13 vs 0.38 (log-rank P=0.003).
- Most adverse effects were mild; one patient on tofacitinib developed dural venous sinus thrombosis.
Limitations
- Single centre and small.
- Tofacitinib 10 mg three times daily is an off-label, higher-than-licensed dose.
- Acute severe UC is a high-thrombosis-risk state, and the one cerebral venous thrombosis is a relevant warning for JAK inhibitors in this setting.
Commentary
Context. TACOS is a placebo-controlled randomised trial of a JAK inhibitor in acute severe UC. It tested tofacitinib added to IV steroids during the first 7 days, not as rescue after steroid failure, so it does not replace infliximab or ciclosporin rescue (see CONSTRUCT, PMID 27595142).
In practice. JAK inhibitors for acute severe UC are off-label and best used within specialist protocols, with thromboprophylaxis and attention to thrombotic risk. Systematic reviews and meta-analyses of JAK inhibitors in acute severe UC were published in 2025–26 (for example PMID 41690364), but large randomised trials are still needed.
Journal club
Design
Single-centre, double-blind, placebo-controlled randomised trial. 104 patients.
Primary result. 83.01% (44/53) vs 58.82% (30/51); odds ratio 3.42 (95% CI 1.37–8.48); P=0.007
Validity and applicability
- Single centre and small.
- Tofacitinib 10 mg three times daily is an off-label, higher-than-licensed dose.
- Acute severe UC is a high-thrombosis-risk state, and the one cerebral venous thrombosis is a relevant warning for JAK inhibitors in this setting.
Where it sits now
Adding tofacitinib to IV steroids improved day-7 response in acute severe UC in one small single-centre trial; promising, but not yet standard care.
- ACTIVE (2025): After a steroid-responsive episode of acute severe UC in a thiopurine- and biologic-naive patient, starting infliximab plus azathioprine reduced 1-year treatment failure compared with azathioprine alone.
- PREDICT-UC (2024): In steroid-refractory acute severe UC, a 10 mg/kg first infliximab dose or an accelerated schedule was not better than standard 5 mg/kg dosing.
- CONSTRUCT (2016): In steroid-refractory acute severe UC, infliximab and ciclosporin are equally effective rescue therapies; choose by local experience, patient factors and the maintenance plan.
- CYSIF (2012): Ciclosporin and infliximab perform similarly as rescue therapy for steroid-refractory acute severe UC, in the short and long term.
Questions for discussion
- The dose was 10 mg three times daily, above the licensed dose. How would you weigh it against the thrombotic risk of acute severe colitis?
- Response was judged by the Lichtiger index at day 7. How does that compare with the day-3 criteria you use to decide on rescue therapy?
- If a patient fails steroids plus tofacitinib, how does that affect the next step: infliximab, ciclosporin or colectomy?