Abstract
Background
The pan-Janus kinase inhibitor tofacitinib (TFC) has recently been approved for treatment moderate-to-severe ulcerative colitis (UC). Real-life data are limited, especially on endoscopic and histologic outcome. We report the efficacy and safety of TFC in refractory UC patients, and assessed potential clinical predictors of response.
Methods
Thirty-five UC patients, all refractory to anti-TNF and vedolizumab, were prospectively included (Table 1). All received TFC 10mg BID till week 8, and were endoscopically assessed at baseline (Mayo endoscopic sub-score ≥2) and week 8. Biological response was defined as a 50% decrease in faecal calprotectin (fCal) or fCal <250 mg/g, and biological remission as a fCal <250 mg/g at week 8. The endoscopic response was defined as Mayo endoscopic sub-score of ≤1, endoscopic remission as a sub-score of 0. Histologic remission was defined as a numeric Geboes score ≤6 (similar to ≤2A.0). A non-response imputation and last observation carried forward analysis was applied.
Results
The Mayo endoscopic sub-score decreased significantly by week 8 (p = 0.004), resulting in an endoscopic response and remission rate of 22.9% and 17.2% respectively. Histological remission was seen in 14.8% of patients. Faecal calprotectin decreased from 1386 mg/g down to 568 mg/g by week 4 (p = 0.03) (Table 2), but not further down by week 8 (703 mg/g, p = 0.5) with a biological response and remission rate of 52.9% and 38.2%. Half of the patients with a PNR to one anti-TNF (10 out of 20) did discontinue TFC because of PNR. However, PNR to two anti-TNF agents almost exclusively (4 out of 5) resulted in PNR to TFC. In contrast, only 3 out of 8 vedolizumab PNR experienced PNR to TFC. Ultimately, 48.6% of all included patients discontinued TFC therapy after a median of 15.9 [12.4–26.6] weeks, all but one due to PNR, of whom 9/17 (52.9%) required colectomy. In multivariate analysis, a higher baseline albumin and a lower Mayo endoscopic sub-score were independent predictors of endoscopic (OR 1.06, p = 0.02; OR 0.59, p = 0.003) and biological remission (OR 1.06, p = 0.03; OR 0.57, p = 0.01). By week 8, creatinine kinase significantly increased (p = 0.001), whereas the lipid profile was not significantly affected. One patient suffered from vaginal herpes infection, and one patient treated with TFC and high dose steroids developed disseminated nocardia, pneumocystic jiroveci, cutaneous zoster and varicella pneumoniae.
Conclusion
TFC can induce biologic, endoscopic and histologic remission in refractory UC, though clinical and predictive molecular markers are required to identify the right patients. In patients with prior PNR to 2 anti-TNF agents, TFC does not seem an alternative treatment strategy.
Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis
