Abstract
Background
Tofacitinib is an oral JAK inhibitor approved for the treatment of ulcerative colitis (UC). Its efficiency was proven in registration trials; however, data from clinical practice are insufficient. Our aim was to evaluate response to tofacitinib after 8 weeks in UC patients, and to assess potential predictors of response including early cytokine production shifts.
Methods
Data from consecutive UC patients who started tofacitinib 10 mg b.i.d. were evaluated. Disease activity was assessed by Mayo score at baseline and week 8 together with C-reactive protein (CRP) and faecal calprotectin (FC). Production of IL-4, IL-10, IL-17, TNFα and IFNγ in T-helper cells was determined at baseline and week 4. At week 8, patients with total Mayo 0–5 with endoscopic subscores 0–1 were considered responders. Adverse events were registered at every visit.
Results
Twenty-four patients (41.7% males, 58.3% females), mean age 35.3 ± 11.8 years were included. Mean disease duration was 8.3 ± 5.2 years. In median, the patients were previously treated with two biologic agents; however, 25% of the patients were naive to any biologic therapy. Systemic corticosteroids were present in 41.7% patients at baseline and no patient had concomitant biologic or other immunosuppressive therapy. At week 8, 52.9% of patients responded to therapy. Total Mayo decreased in responders from mean 5.9 ± 3.5 to 1.1 ± 1.3 (p = 0.01), while in nonresponders it changed from 8.0 ± 2.5 to 8.9 ± 2.1 (p = 0.86). Endoscopic subscore decreased from 2.0 ± 1.0 to 0.6 ± 0.7 (p = 0.02) in responders, however, remained stationary in nonresponders (2.9). CRP and FC dropped significantly in responders (6.7 ± 6.2 vs. 2.0 ± 2.2 mg/l, p = 0.04; 1195 ± 1189 vs. 578 ± 654 μg/g, p = 0.05), but not in nonresponders. The responding and nonresponding groups differed significantly in baseline triglycerides, which were higher in nonresponders. Other baseline parameters were comparable. In responders, there was a significant decrease in IL-4 and no change in IL-10, while in nonresponders, there was no change in IL-4 and a significant decrease in IL-10. Tofacitinib was stopped in 23.5% of patients at week 8 due to insufficient response. Two patients reported headaches after treatment initiation and single events of CMV colitis, C. diff. colitis and oral candidiasis occurred.
Conclusion
Tofacitinib was efficient in inducing clinical response with mucosal healing in about 50% of UC patients after 8 weeks of therapy. There was no clear baseline predictor of response, however, considering limited sample, there was also no indication of even multiple biologics failure negatively affecting the response. Preliminary results of cytokine dynamics suggest early IL-4 decrease as a potential biomarker of response, warranting further investigation.
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