Dataset Information

Extraintestinal manifestations at baseline, and the effect of tofacitinib, in patients with moderate to severe ulcerative colitis.

ABSTRACT:

Introduction

Extraintestinal manifestations (EIMs) in patients with ulcerative colitis (UC) are common. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. We evaluated the efficacy of tofacitinib in patients with EIMs, and the impact of tofacitinib on EIMs in patients with UC in the OCTAVE clinical program.

Methods

Data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain) were analyzed. The effect of tofacitinib on efficacy outcomes stratified by EIM status, proportion of predefined prior and active EIMs at baseline, and change from baseline in EIMs were determined at the end of the treatment period (weeks 8 or 52), or at early termination.

Results

At baseline of OCTAVE Induction 1 and 2, and OCTAVE Sustain, 27.0% and 9.0% of patients had a history of EIMs (prior or active), respectively. Patients treated with tofacitinib 10 mg twice daily (BID) achieved remission and had endoscopic improvement in all studies, irrespective of any history of EIMs. A greater proportion of patients had active peripheral arthritis at baseline of OCTAVE Induction 1 and 2 versus OCTAVE Sustain. In OCTAVE Induction 1 and 2, similar proportions of tofacitinib and placebo-treated patients with active peripheral arthritis experienced either no change (81.3% and 85.7%, respectively) or an improvement (15.6% and 14.3%, respectively). By week 52 of OCTAVE Sustain, improvements in active peripheral arthritis were only observed in tofacitinib-treated patients (16.7% and 33.3% with tofacitinib 5 and 10 mg BID, respectively).

Conclusion

Any history of EIMs did not influence the efficacy of tofacitinib 10 mg BID for induction or maintenance of UC. The most common active EIM was peripheral arthritis, for which many patients in OCTAVE Induction 1 and 2, and OCTAVE Sustain, reported improvement or no change from baseline with tofacitinib treatment.Clinicaltrials.gov:NCT01465763; NCT01458951; NCT01458574.

SUBMITTER: Rubin DT

PROVIDER: S-EPMC8132089 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We aimed to describe the real-world treatment experience and corticosteroid utilisation of patients treated with tofacitinib in a US claims database.MethodsPatients with a UC diagnosis who initiated tofacitinib, vedolizumab or tumour necrosis factor inhibitor (TNFi) treatment between May 2018 and July 2019 were identified from the Optum Research Database. Demographic and clinical characteristics of patients who initiated tofacitinib, vedolizumab or TNFi were described. Oral corticosteroid use prior to and following tofacitinib initiation was evaluated. Tofacitinib adherence (proportion of days covered) and continuation was assessed for 6 months following initiation. Analyses were descriptive and stratified by prior biologic use (naïve, 1 or ≥ 2; minimum of 12 months prior to tofacitinib initiation).ResultsAmong patients initiating tofacitinib (N = 225), mean age was 45.6 (SD 16.5) years and 50.2% were female. Of these, 43 (19.1%) patients were biologic-naïve and 182 (80.9%) had prior biologic use (92 [40.9%], 1 prior biologic; 90 [40.0%], ≥ 2 prior biologics). Among patients with 1 prior biologic, 82.6% were previously treated with a TNFi. Among patients with ≥ 2 prior biologics, 54.4% were previously treated with vedolizumab and a TNFi, 16.7% with two TNFi and 28.9% with ≥ 3 prior biologics. In the 6 months prior to tofacitinib initiation, 65.8% of patients had received oral corticosteroids (74.4%, 60.9% and 66.7% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively). The proportion of patients with ongoing oral corticosteroid use 3-6 months after tofacitinib initiation decreased to 13.3% (9.3%, 18.5% and 10.0% for biologic-naïve, 1 and ≥ 2 prior biologics, respectively), and 19.6% of patients discontinued oral corticosteroid use during the 6 months after tofacitinib initiation. Overall, tofacitinib adherence, as determined by the mean proportion of days covered during the 6-month follow-up, was 0.7 (median 0.8). During the 6-month follow-up, 84.9% of patients continued tofacitinib.ConclusionsAmong patients with UC initiating tofacitinib, the majority had prior biologic use. Tofacitinib adherence was high, discontinuation was low and oral corticosteroid utilisation decreased irrespective of prior biologic use. Further research with longer follow-up and a larger sample size is required.

Project description:ObjectiveTofacitinib is an oral Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). The objective of this study was to evaluate the long-term cost-effectiveness of tofacitinib versus current biologics, considering combinations of first-line (1L) and second-line (2L) therapies, from a Japanese payer's perspective in patients with moderate-to-severe active UC following an inadequate response to conventional therapy and in those who were naïve to biologics.MethodsA cost-effectiveness analysis was conducted during the time horizon specified in the Markov model, which considers a patient's lifetime as 60 years and an annual discount rate of 2% on costs and effects. The model compared tofacitinib with vedolizumab, infliximab, adalimumab, golimumab, and ustekinumab. The time of active treatment was divided into induction and maintenance phases. Patients not responding to their biologic treatment after induction or during the maintenance phase were switched to a subsequent line of therapy. Treatment response and remission probabilities (for induction and maintenance phases) were obtained through a systematic literature review and a network meta-analysis that employed a multinomial analysis with fixed effects. Patient characteristics were sourced from the OCTAVE Induction trials. Mean utilities associated with UC health states and adverse events (AEs) were obtained from published sources. Direct medical costs related to drug acquisition, administration, surgery, patient management, and AEs were derived from the JMDC database analysis, which corresponded with the medical procedure fees from 2021. The drug prices were adjusted to April 2021. Further validation through all processes by clinical experts in Japan was conducted to fit the costs to real-world practices. Scenario and sensitivity analyses were also performed to confirm the accuracy and robustness of the base-case results.ResultsIn the base-case, the treatment pattern including 1L tofacitinib was more cost-effective than vedolizumab, infliximab, golimumab, and ustekinumab for 1L therapies in terms of cost per quality-adjusted life year (QALY) gained (based on the Japanese threshold of 5,000,000 yen/QALY [38,023 United States dollars {USD}/QALY]). The base-case results demonstrated that the incremental costs would be reduced for all biologics, and decreases in incremental QALYs were observed for all biologics other than adalimumab. The incremental cost-effectiveness ratio (ICER) was found to be dominant for adalimumab; for the other biologics, it was found to be less costly and less efficacious. The efficiency frontier on the cost-effectiveness plane indicated that tofacitinib-infliximab and infliximab-tofacitinib were more cost-effective than the other treatment patterns. When infliximab-tofacitinib was compared with tofacitinib-infliximab, the ICER was 282,609,856 yen/QALY (2,149,157 USD/QALY) and the net monetary benefit (NMB) was -12,741,342 yen (-96,894 USD) with a threshold of 5,000,000 yen (38,023 USD) in Japan. Therefore, infliximab-tofacitinib was not acceptable by this threshold, and tofacitinib-infliximab was the cost-effective treatment pattern.ConclusionThe current analysis suggests that the treatment pattern including 1L tofacitinib is a cost-effective alternative to the biologics for patients with moderate-to-severe UC from a Japanese payer's perspective.