Tofacitinib in the Treatment of Ulcerative Colitis in Real-World Practice in the USA

Tofacitinib in the Treatment of UC

Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiology. It requires lifelong treatment. Its outcomes are not optimal, especially in terms of frequent corticosteroid dependence and the need for colectomy.

Tofacitinib is an oral Janus kinase inhibitor used in the treatment of UC. Its efficacy and safety were evaluated in induction treatment in an 8-week phase II study and the 8-week phase III OCTAVE Induction study, and in maintenance treatment in the 52-week phase III OCTAVE Sustain study and open-label long-term extension OCTAVE Open. In real-world practice, tofacitinib has so far been evaluated in the treatment of UC in several small European studies, and a prospective registry is also being prepared.

Study Aims and Methodology

The aim of this study was to evaluate the demographic and clinical characteristics of patients with UC treated with tofacitinib, vedolizumab, or tumor necrosis factor inhibitors (TNFi), adherence, and persistence with tofacitinib and its impact on corticosteroid (CS) use in the USA, stratified by prior biological treatment.

This was a retrospective cohort study utilizing data from the Optum Research Database (covering 111 million insured individuals) for the period from May 30, 2018, to July 31, 2019. The analysis included patients over 18 years old diagnosed with UC and newly treated with tofacitinib, vedolizumab, or TNFi. They were stratified into subgroups based on previous treatment: no prior biological treatment, one prior biological agent, and ≥ 2 prior biologics. During the study period, only vedolizumab, adalimumab, infliximab, and golimumab were approved for the treatment of moderate to severe UC in the USA.

Data was analyzed over 6 months following the initiation of the assessed treatment. CS use was defined as ongoing if the patient used CS in both the first and second 3 months of follow-up; as initiation if they did not use CS in the first 3 months but did in the second 3 months; and as discontinuation if they used CS in the first 3 months but not in the second 3 months. Adherence to tofacitinib was evaluated based on the proportion of days covered by treatment, and persistence was defined as the duration until discontinuation of tofacitinib.

Analyzed Population and Characteristics of Patients Treated with Tofacitinib

A total of 1538 patients were included in the analysis, of whom 225 (14.6%) initiated treatment with tofacitinib, 373 (24.3%) with vedolizumab, and 940 (61.1%) with TNFi. Characteristics were comparable across these three groups except for prior biological treatment. The majority of patients who were started on vedolizumab (82.3%) or TNFi (93.7%) had not previously used any biological treatment, whereas in the tofacitinib cohort, the proportion without prior biological treatment was only 19.1%. Tofacitinib was also more often initiated following previous treatment with ≥ 2 biological agents compared to vedolizumab or TNFi.

Of the 225 UC patients newly started on tofacitinib, 19.1% were receiving their first targeted treatment. For 40.9%, it was the second targeted therapeutic agent, and 40.0% had been previously treated with ≥ 2 biologics. The majority of patients (88.4%) were prescribed tofacitinib at a dose of 20 mg/day and 11.6% at a dose of 10 mg/day. The average age of patients started on tofacitinib was 45.6 years, with 50.2% being women. In the 6 months prior to starting tofacitinib, 65.8% of patients used CS and 44.4% had extraintestinal manifestations of UC, most commonly arthralgia.

Outcome Findings

Impact of Tofacitinib on Corticosteroid Use

During the 6 months following the initiation of tofacitinib, 58.7% of patients did not need CS, 19.6% discontinued CS, and 13.3% continued to use CS. CS initiation (during the second 3 months of tofacitinib treatment) was noted in 8.4% of patients.

Of the 148 patients who used CS in the 6 months before starting tofacitinib, 49.3% were completely off CS, 25% discontinued CS, and 18.9% continued to use CS during the 6 months post-initiation. CS use decreased across all tofacitinib subgroups regardless of prior biological treatment.

Adherence and Persistence with Tofacitinib Treatment

Adherence to tofacitinib treatment (proportion of days covered by treatment over 6 months) averaged 70% (median 80%). This proportion did not differ in subgroups based on prior biological treatment. More than 4 months of tofacitinib use was maintained by 84.9% of patients, with 79.1% without prior biological treatment, 83.7% following prior treatment with one biological agent, and 88.9% following prior treatment with ≥ 2 biologics.

The average time to discontinuation of tofacitinib was 42.4 days and was comparable across the mentioned subgroups.

Conclusion

The authors summarize their real-world data analysis by stating that the majority of UC patients initiated on tofacitinib had a history of biological treatment. Adherence to tofacitinib was high, the proportion of patients who discontinued treatment was low, and oral corticosteroid use decreased regardless of prior biological treatment.

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Source: Chiorean M. V., Allegretti J. R., Sharma P. P. et al. Real-world characteristics, treatment experiences and corticosteroid utilisation of patients treated with tofacitinib for moderate to severe ulcerative colitis. BMC Gastroenterol 2022 Apr 9; 22 (1): 177, doi: 10.1186/s12876-022-02215-y.