P0593 High-dose Tofacitinib in Acute Severe Ulcerative Colitis: an option to avoid colectomy?
Authors: Sierra Ausín M , Latras Cortés I , Suárez Álvarez P , Cano Sanz N , Elosua González T 
Published: January 2025

Background

30% of patients with ulcerative colitis (UC) develop an acute severe ulcerative colitis (ASUC), which involves risk of colectomy and has limited treatments despite the development of new drugs. 30% of ASUC do not respond to steroids and 25% are refractory to cyclosporine or infliximab (IFX) and precise colectomy. High-dose tofacitinib and recent case series with upadacitinib have demonstrated effectiveness in these refractory scenarios1.

Methods

Retrospective, descriptive and unicentric study of 9 patients admitted to hospital with steroid-refractory ASUC. They received tofacitinib at an off-label dose of 30 mg daily (in bionaive patients, after failure of IFX).

Primary objective

evaluate the rate of early-colectomy (one week&one month since hospital admission) and late-colectomy(after 3,6 and 12 months).

Secondary objective

evaluate early and late clinical response (decrease in the partial Mayo score&gt;3points) and clinical remission (partial Mayo score≤2). Changes in laboratory values such as C-reactive protein(CRP), fecal calprotectin(FC),albumin and hemoglobin were analyzed, as well as dose de-escalation,secondary loss of response and adverse effects.

Qualitative variables are presented as frequencies and percentages;quantitative variables as medians ± interquartile ranges(IQR).

Results

Age on admission was 64.57 years(IQR 21,92) (Figure 1). 6 patients were bio-naïve and 3 were receiving biologic therapy. The patients started tofacitinib at day 10 (IQR 15) since admission.

3 patients (33.33 %)needed early-colectomy (2 one week after initiation of tofacitinib and 1 one month later). Clinical response was 77.78% at week 1, 85.71% at week 4 and 100% at week 12. Clinical remission was 33.33%,57.14% and 83.33% respectively.

4 patients continue treatment with tofacitinib; 1 patient was discontinued after 9.17months due to diagnosis of lung adenocarcinoma,1 patient was discontinued after 2.30months because of partial response and changed to upadacitinib, 1 patient was discontinued after one month because of non-response, was changed to upadacinitib without achieving response and ended up having a colectomy.

Regarding the 4 patients who are still on tofacitinib, 1 was de-escalated to 10 mg/12hours and 3 were de-escalated to 5mg/12h (after 0.97,1.27,2.03 and 12.3 months respectively). None of them lost response.

There was a decrease in partial Mayo, CRP and FC and an increase in albumin and hemoglobin (Figure 2).

Conclusion

High dose (30mg daily) of tofacitinib may be effective to avoid colectomy in steroid and infliximab-refractory ASUC. Tofacitinib allowed to achieve clinical response and clinical remission, as well as a decrease in CRP&FC

References

1.Berinstein JA, Sheehan JL, Dias M, et al. Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study. Clin Gastroenterol Hepatol. 2021 Oct;19(10):2112-2120.e1. doi: 10.1016/j.cgh.2021.05.038. Epub 2021 May 25. PMID: 34048936; PMCID: PMC8760630.