Tofacitinib Through the Eyes of Patients: Rapid Response After Treatment Initiation
How does tofacitinib fare in the treatment of ulcerative colitis in real clinical practice from the patients' perspective? This was addressed in a recent study published in the journal Inflammatory Bowel Diseases.
What JAK?
Tofacitinib is an oral selective inhibitor of Janus kinases (JAK), which form the intracellular domain of cytokine receptors. Tofacitinib preferentially inhibits signaling mediated by receptors involving JAK3 and/or JAK1, thus suppressing the effects of interleukins (IL-2, IL-4, IL-6, IL-7, IL-9, IL-15, IL-21) and type I and II interferons. This modulation of immune and inflammatory responses is utilized in the treatment of rheumatoid and psoriatic arthritis, ankylosing spondylitis, polyarticular juvenile idiopathic or psoriatic arthritis, and also ulcerative colitis.
In the treatment of these chronic diseases, it is important to gain the perspective of patients in addition to objective clinical efficacy. Therefore, clinical research programs often include studies focused on parameters directly assessed by patients (PRO – patient-reported outcomes).
Methodology of the Study and Evaluated Population
Adult patients with ulcerative colitis who started treatment with tofacitinib as part of standard care and agreed to be monitored for at least one year were included in the prospective multicenter cohort study TOUR. Monitored parameters included the Simple Clinical Colitis Activity Index (SCCAI), PRO Measurement Identification System (PROMIS), and the occurrence of adverse events. SCCAI was evaluated daily during the first 2 weeks of therapy and then on days 28 and 56. PROMIS was evaluated on the day of treatment initiation and subsequently on days 14, 28, and 56. Patients used a special web platform to evaluate these parameters.
The study included 96 patients with a slight predominance of men (56.3%) with an average age of 37.3 years and an average BMI of 25.4 kg/m2. In 67% of these patients, therapy with ≥ 2 biologics had already failed, and 61.5% were simultaneously using corticosteroids. The most common prior medications used, besides corticosteroids, included tumor necrosis factor inhibitors (94.8%). A large portion of patients had also been pre-treated with mesalazine (92.7%), vedolizumab (58.3%), azathioprine (45.8%) or methotrexate (21.9%), and a total of 6 patients (6.3%) had been treated with ustekinumab before entering the study.
Findings
Significant and sustained reductions in average SCCAI scores (-1.1; p < 0.0001) as well as in SCCAI sub-scores for stool frequency (-0.3; p < 0.003), bleeding (-0.3; p < 0.0002), and urgency (-0.2; p < 0.001) were observed from day 3 after starting tofacitinib therapy. Remission without the need for corticosteroids was achieved by 25% of patients after 14 days, 30.2% after 28 days, and 29.2% after 56 days. By day 56, there was also numerical improvement in all parts of PROMIS (depression, anxiety, social satisfaction).
The effects of previous biological treatments and endoscopically assessed disease intensity were also tested. Neither of these factors proved to be independent predictive factors for treatment response.
Within the first 56 days, 2 patients discontinued tofacitinib due to adverse events, 4 due to insufficient efficacy, and 5 due to colectomy. Four patients were excluded from the study for other reasons – 1 withdrew consent, and 3 due to incomplete questionnaires.
The occurrence of adverse events was low and consistent with published data. A total of 3 patients were hospitalized for exacerbation of ulcerative colitis, 3 developed shingles during the follow-up period, and 6 used antibiotic therapy during the observation period.
Conclusion
Patients with ulcerative colitis reported a very early onset of tofacitinib’s effect. During the first 2 weeks of therapy, there was a significant improvement in urgency and incontinence, stool bleeding, and frequency of bowel movements. This improvement was maintained throughout the follow-up period. Thus, the treatment of ulcerative colitis with tofacitinib, in usual clinical practice, led to a rapid and sustained clinical effect as perceived by the patients themselves.
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Source: Long M. D., Afzali A., Fischer M. et al. Tofacitinib Response in Ulcerative Colitis (TOUR): early response after initiation of tofacitinib therapy in a real-world setting. Inflamm Bowel Dis 2023; 29 (4): 570–578, doi: 10.1093/ibd/izac121.
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