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Tofacitinib, an Oral Janus Kinase Inhibitor: Analysis of Malignancy (Excluding Nonmelanoma Skin Cancer) Events Across
Gary R Lichtenstein1, Gerhard Rogler2, Matthew A Ciorba3
1Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Background:
Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we performed an integrated analysis of malignancy events from the tofacitinib phase 3 UC clinical development program (excluding nonmelanoma skin cancer [NMSC]).
Methods:
Data (up to May 2019) were pooled from two phase 3 induction studies, a phase 3 maintenance study, and an ongoing, open-label, long-term extension (OLE) study, and analyzed as 3 cohorts: induction (N = 1139), maintenance (N = 592), and overall (induction, maintenance, and ongoing OLE study; N = 1124). Proportions and incidence rates (IRs; unique patients with events per 100 patient-years [PY] of exposure) for malignancies confirmed by adjudication were calculated.
Results:
The overall cohort consisted of patients who received at least 1 dose of tofacitinib at 5 or 10 mg twice daily, for up to 6.8 years, with an exposure of 2576.4 PY. Of the 1124 overall cohort tofacitinib-treated patients, 20 developed a malignancy (excluding NMSC; IR, 0.75; 95% confidence interval, 0.46-1.16), of which 17 occurred in patients treated with tofacitinib 10 mg twice daily; importantly, more than 80% of patients predominantly received this dose. Furthermore, there was no apparent clustering of malignancy types, and IRs were stable over time.
Conclusions:
In the tofacitinib UC clinical development program, malignancy events were infrequent, and rates were comparable with those in the tofacitinib rheumatoid arthritis and psoriatic arthritis clinical development programs, and for biologic UC treatments. ClinicalTrials.gov: NCT01465763, NCT01458951, NCT01458574, and NCT01470612.
Insights
Malignancy events were infrequent in patients treated with tofacitinib for ulcerative colitis (UC). Rates were comparable to other tofacitinib studies and biologic UC treatments.
Area of Science:
- Gastroenterology
- Pharmacology
- Clinical Trials
Background:
- Tofacitinib is an oral Janus kinase inhibitor used for ulcerative colitis (UC) treatment.
- This study analyzes malignancy events from the tofacitinib Phase 3 UC clinical development program, excluding nonmelanoma skin cancer (NMSC).
Purpose of the Study:
- To conduct an integrated analysis of malignancy events in patients with ulcerative colitis treated with tofacitinib.
- To evaluate the incidence and characteristics of malignancies within the tofacitinib UC clinical development program.
Main Methods:
- Data were pooled from Phase 3 induction, maintenance, and long-term extension studies up to May 2019.
- Malignancy events were analyzed across induction (N=1139), maintenance (N=592), and overall (N=1124) cohorts, calculating incidence rates (IRs) per 100 patient-years (PY).
Main Results:
- In the overall cohort (N=1124) with 2576.4 PY of exposure, 20 malignancies (excluding NMSC) occurred (IR, 0.75).
- Most malignancies (17/20) occurred in patients receiving tofacitinib 10 mg twice daily, the predominant dose.
- No apparent clustering of malignancy types was observed, and IRs remained stable over time.
Conclusions:
- Malignancy events were infrequent in the tofacitinib UC clinical development program.
- Observed malignancy rates were comparable to those in tofacitinib's rheumatoid arthritis and psoriatic arthritis programs, as well as biologic UC treatments.
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