Effectiveness and Safety of Tofacitinib for Ulcerative Colitis

Two-year Results of the ICC Registry

Tessa Straatmijer; Fiona D. M. van Schaik; Alexander G. L. Bodelier; Marijn Visschedijk; Annemarie C. de Vries; Cyriel Y. Ponsioen; Marieke Pierik; Ad A. van Bodegraven; Rachel L. West; Nanne K. H. de Boer; Nidhi Srivastava; Tessa E. H. Romkens; Jildou Hoekstra; Bas Oldenburg; Gerard Dijkstra; Janneke C. van der Woude; Mark Löwenberg; Zlatan Mujagic; Vince B. C. Biemans; Andrea E. van der Meulen-de Jong; Marjolijn Duijvestein


Aliment Pharmacol Ther. 2023;57(1):117-126. 

In This Article

Abstract and Introduction


Background: Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment.

Aim: The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands.

Methods: Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5 mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate.

Results: We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7–34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinib were skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years.

Conclusion: Tofacitinib was effective in 31.8% of patients after 24 months of treatment.


Tofacitinib is the first JAK inhibitor approved for the treatment of moderate to severe ulcerative colitis (UC).[1] Tofacitinib is a small molecule Janus kinase (JAK) inhibitor, which inhibits JAK1 and JAK3. By preventing phosphorylation and subsequent dimerisation of signal transducer and activator of transcription (STATs) proteins, it impairs intracellular signalling in certain immune cells, resulting in reduced inflammatory cytokine production.[2]

In the phase 3 OCTAVE trial, a remission rate (defined as a total Mayo score of ≤2, with no subscore >1 and a rectal bleeding subscore of 0) in 34.3% of UC patients after 52 weeks of treatment with tofacitinib was shown.[1] This drug is administered orally and has a rapid onset of action in most patients.[3] The effect of tofacitinib cannot be reduced by the development of anti-drug antibodies, a potential advantage compared to biologicals, such as anti-tumour necrosis factor (aTNF) agents.[4] However, there are safety concerns about tofacitinib, such as interference with lipid metabolism, increased risk of venous thromboembolisms and infections.[5]

Although in the OCTAVE study it was demonstrated that the therapeutic efficacy of tofacitinib in UC, a study population did not accurately reflect patients who initiate tofacitinib in daily practice. This is partly due to strict in-and exclusion criteria of clinical trials and the pre-specified follow-up period.[6] Therefore, so-called real-world studies evaluating the effectiveness and safety of tofacitinib are of great importance. Several studies demonstrated the effectiveness of tofacitinib in UC patients, but the follow-up did not exceed 1 year.[7–13] In the current era of many (new) therapeutic options for UC, personalisation of an individual's treatment is a beckoning perspective. As much as up to one-third of UC patients lose therapeutic response within a year in the case of modern, complex therapies. This necessitates effectiveness and safety data over longer periods, best with standardisation of disease and clinical characterisation of included patients. In this study, we assessed the effectiveness and safety of 24 months of tofacitinib treatment in UC patients.