Comparison of the Efficacy of Tofacitinib and Vedolizumab in the Treatment of Ulcerative Colitis After Anti-TNF Therapy Failure

Introduction

The goal of medication therapy for ulcerative colitis is to induce and maintain remission of the disease and prevent complications. The basis of treatment for ulcerative colitis includes aminosalicylates, which are usually supplemented with corticosteroids during periods of active inflammation, and potentially immunosuppressants. Given the side effects of corticosteroids, there is an effort to avoid long-term use of corticosteroids and to achieve remission by other means, such as by administering immunosuppressants.

The selective Janus kinase inhibitor (JAKi) tofacitinib is indicated for the treatment of several rheumatologic conditions and ulcerative colitis. Vedolizumab is a humanized monoclonal antibody with a selective effect in the intestine, indicated for the treatment of UC, Crohn's disease, and pouchitis. Oral tofacitinib and intravenous vedolizumab are intended for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who did not respond adequately to, could not tolerate, or lost response to previous conventional treatment or anti-tumor necrosis factor-alpha (anti-TNF-α) therapy.

Study Methodology and Objectives

This multicenter retrospective study, involving 11 French hospitals, included all adult UC patients with a partial Mayo index > 2, who had undergone ≥ 1 previous treatment with anti-TNF-α inhibitors and began treatment with tofacitinib or vedolizumab between January 2019 and June 2021. Tofacitinib was initially administered at a dose of 2× 10 mg per day, with a potential dose reduction to 2× 5 mg per day from the eighth week. Intravenous vedolizumab treatment was applied at a dose of 300 mg in weeks 0, 2, 6, 14 (and possibly also in the 10th week).

The primary monitored parameter was disease remission without corticosteroid use (CFREM) with a partial Mayo index ≤ 2 in the 16th week. Additionally, endoscopic improvement (CFREM and an endoscopic Mayo score < 1) and mucosal healing (CFREM and endoscopic and histological remission defined as a Nancy index ≤ 1) were monitored.

All comparisons were made using the propensity score analysis method adjusted for gender, smoking, duration, severity, and extent of UC, the number of previous biological treatments used, the occurrence of previous biological treatment failure, and concurrent use of mesalazine, corticosteroids, or immunosuppressive agents.

Results

Of the first 200 patients included in the study (the target number of patients is 400), 87 received tofacitinib, and 112 received vedolizumab. Baseline characteristics were comparable between both therapeutic arms, except for a higher incidence of pancolitis (54.0 vs. 38.4%; p = 0.028), less frequent use of immunosuppressive therapy (4.6 vs. 27.7%; p < 0.001), and a higher rate of previous exposure to ≥ 2 biological agents in the tofacitinib arm, including concurrent use of mesalazine (10.3 vs. 18.8%) and corticosteroids (23.0 vs. 31.2%).

Vedolizumab infusion in the 10th week was administered to 34.3% of patients, and 42.5% of patients in the tofacitinib arm took a dose of 10 mg 2× daily up to the 16th week.

CFREM was achieved in 54.2% with tofacitinib and 42.5% with vedolizumab (p = 0.089). In the 16th week, CFREM was achieved in 57.4% of patients after one previous biological treatment with tofacitinib vs. 51.1% with vedolizumab (p = 0.77), in 55.4% vs. 41.8% after two biological agents (p = 0.61), and in 56.9% vs. 6.3% after ≥ three biological agents (p = 0.007). In the subgroup with a partial Mayo score ≥ 6, CFREM was achieved in 59.0% vs. 33.3% (p = 0.17).

Tofacitinib was significantly more effective in achieving CFREM in the 16th week than vedolizumab in patients with primary failure of at least one biological agent (71.6 vs. 30.8%; p = 0.049).

Endoscopic improvement was also more frequently achieved in patients treated with tofacitinib (33.6 vs. 7.1%; p = 0.048). Mucosal healing was observed in 6.4% of patients with tofacitinib compared to 3.8% of patients with vedolizumab (p = 0.27).

Conclusion

Both agents, tofacitinib and vedolizumab, represent effective therapy for ulcerative colitis after anti-TNF-α antibody failure. Tofacitinib appears to be more effective than vedolizumab in cases of primary biological treatment failure or failure of multiple biological agents.

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Sources:
1. Buisson A., Nachury M., Fumery M. et al. DOP76 Real-world multicenter comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis after failure to at least one anti-TNF agent. ECCO 2022. Available at: www.ecco-ibd.eu/publications/congress-abstracts/category/dop-session-9-the-atlantic-comparative-effectiveness-biomarkers.html
2. SPC Xeljanz. Available at: www.ema.europa.eu/en/documents/product-information/xeljanz-epar-product-information_cs.pdf
3. SPC Entyvio. Available at: www.ema.europa.eu/en/documents/product-information/entyvio-epar-product-information_cs.pdf