Current Data of Tofacitinib in the Treatment of IBD: What Improvements in Endoscopic and Histologic Outcomes Can Be Achieved?

Study Methodology and Patient Population

The retrospective study was conducted at the IBD center of the University of Chicago. All patients with idiopathic inflammatory bowel diseases (IBD) who were part of the center's registry and were using tofacitinib were included.

Demographic, clinical, laboratory, and endoscopic data of participants were evaluated. The clinical data set included the patient's age at disease onset, its duration, phenotype, potential abuse, previous medications and surgeries, extraintestinal manifestations, and disease activity. Tofacitinib use in patients with Crohn's disease (CD) and with J-pouch was off-label, while for UC patients, the drug was approved for this indication during the follow-up. Tofacitinib efficacy was assessed only in UC patients, while safety analysis included data from all participants.

Clinical disease activity was determined using the partial Mayo score at weeks 8, 24, and 52 of follow-up. A decrease of 2 points was considered a response to treatment, and a value < 2 was considered remission. Endoscopic evaluation used the endoscopic Mayo score. Histological data came from reports of pathological examinations of material obtained during colonoscopies.

A total of 119 patients with an average age of 39.4 years (45% male) were included in the study between 2014 and 2021. A total of 97 were treated for UC, 12 for CD, and 10 for pouchitis. Median follow-up was 32 weeks. Before starting tofacitinib, 75 patients had extensive colitis, 97% had undergone biological treatment, and 38% had ≥ 3 cycles.

Results

At week 8 of treatment, clinical response or remission was observed in 70% and 21% of patients, respectively. At week 24, response was achieved in 59% and remission in 33% of patients. At week 52, response and remission were seen in 49% and 37% of participants, respectively. In 17 patients in clinical remission, the dose was reduced from 10 mg twice daily to 5 mg twice daily, and no relapse occurred in 11 of them despite the dose reduction.

Thirty-six patients also had extraintestinal manifestations of IBD (peripheral arthralgia, primary sclerosing cholangitis, pyoderma gangrenosum). At week 24, 74.6% of patients experienced improvement in arthralgia, and 40% saw these symptoms completely resolve. A significant decline in fecal calprotectin levels was also observed during treatment.

At week 52 of treatment, endoscopic response was seen in 79% of the 24 patients who had repeat endoscopic evaluation, and 58% were in endoscopic remission. Histological remission was observed in 24% of patients (n = 21) in endoscopic remission at week 24 of treatment.

During therapy, 27 cases (25%) of adverse events were reported, six of which led to treatment discontinuation. The spectrum of adverse events mainly comprised infections (11 cases), with Clostridium difficile being the causative agent in 3 cases. No cases of herpes zoster infection or cardiovascular complications were observed. One patient with severe UC developed low-grade adenocarcinoma of the colon.

Conclusion

The study results confirmed the safety and efficacy of tofacitinib in the treatment of UC. Its effect was demonstrated on clinical, endoscopic, and histological levels as early as 8 weeks after initiating treatment, and the drug's use also led to improvement in peripheral arthralgia. 

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Source: Cohen N. A., Steinberg J. M., Silfen A. Endo‑histologic normalization is achievable with tofacitinib and is associated with improved clinical outcomes. Dig Dis Sci 2023; 68 (4): 1464–1472, doi: 10.1007/s10620-022-07716-0.