scholarly journals Tofacitinib, an Oral Janus Kinase Inhibitor: Analysis of Malignancy (Excluding Nonmelanoma Skin Cancer) Events Across the Ulcerative Colitis Clinical Program

2020 ◽  
Author(s):  
Gary R Lichtenstein ◽  
Gerhard Rogler ◽  
Matthew A Ciorba ◽  
Chinyu Su ◽  
Gary Chan ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Skin Cancer ◽  
Kinase Inhibitor ◽  
Development Program ◽  
Clinical Development ◽  
Nonmelanoma Skin Cancer ◽  
Janus Kinase ◽  
Phase 3 ◽  
Janus Kinase Inhibitor ◽  
Clinical Development Program

Abstract 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.

scholarly journals Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Nonmelanoma Skin Cancer Rates From the Ulcerative Colitis Clinical Program

2021 ◽  
Author(s):  
Bruce E Sands ◽  
Millie D Long ◽  
Walter Reinisch ◽  
Julian Panés ◽  
Edward V Loftus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ulcerative Colitis ◽  
Skin Cancer ◽  
Cox Regression ◽  
Kinase Inhibitor ◽  
Tumor Necrosis Factor Inhibitor ◽  
Nonmelanoma Skin Cancer ◽  
Cox Proportional Hazards Model ◽  
Janus Kinase ◽  
Clinical Program

Abstract Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present integrated analyses of nonmelanoma skin cancer (NMSC) incidence in the tofacitinib UC clinical program. Methods Nonmelanoma skin cancer events were evaluated from 3 randomized, placebo-controlled studies: 2 identical, 8-week induction studies (NCT01465763, NCT01458951), a 52-week maintenance study (NCT01458574), and an open-label, long-term extension study (NCT01470612). Cohorts analyzed were: Induction, Maintenance, and Overall (patients receiving ≥1 dose of tofacitinib 5 mg or 10 mg twice daily [BID]). An independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique patients with events per 100 patient-years of exposure) for NMSC were evaluated. A Cox proportional hazards model was used for risk factor analysis. Results Nonmelanoma skin cancer was evaluated for 1124 patients (2576.4 patient-years of tofacitinib exposure; ≤6.8 years’ treatment). In the Induction Cohort, NMSC IR was 0.00 for placebo and 1.26 for 10 mg BID. Nonmelanoma skin cancer IR was 0.97 for placebo, 0.00 for 5 mg BID and 1.91 for 10 mg BID in the Maintenance Cohort, and 0.73 (n = 19) in the Overall Cohort. No NMSC was metastatic or led to discontinuation. In the Overall Cohort, Cox regression identified prior NMSC (hazard ratio [HR], 9.09; P = 0.0001), tumor necrosis factor inhibitor (TNFi) failure (3.32; P = 0.0363), and age (HR per 10-year increase, 2.03; P = 0.0004) as significant independent NMSC risk factors. Conclusions For patients receiving tofacitinib, NMSC occurred infrequently. Older age, prior NMSC, and TNFi failure, which are previously reported NMSC risk factors in patients with UC, were associated with increased NMSC risk.

Tofacitinib, an oral Janus kinase inhibitor, in patients from Mexico with rheumatoid arthritis: Pooled efficacy and safety analyses from Phase 3 and LTE studies

2019 ◽  
Vol 15 (1) ◽  
pp. 43-53
Author(s):  
Ruben Burgos-Vargas ◽  
Mario Cardiel ◽  
Daniel Xibillèc) ◽  
Cèc)sar Pacheco-Tena ◽  
Virginia Pascual-Ramos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Janus Kinase Inhibitor

scholarly journals Phase 2 Study of CP-690,550, an Oral Janus Kinase Inhibitor, in Active Ulcerative Colitis

2011 ◽  
Vol 140 (5) ◽  
pp. S-110 ◽  
Author(s):  
William J. Sandborn ◽  
Subrata Ghosh ◽  
Julian Panes ◽  
Ivana Vranic ◽  
Chinyu Su ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Active Ulcerative Colitis ◽  
Phase 2 ◽  
Janus Kinase Inhibitor ◽  
Phase 2 Study

scholarly journals Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-severe Ulcerative Colitis: Results From a Randomised, Phase 2 Study

2018 ◽  
Vol 12 (10) ◽  
pp. 1158-1169 ◽  
Author(s):  
Bruce E Sands ◽  
William J Sandborn ◽  
Brian G Feagan ◽  
Gary R Lichtenstein ◽  
Hongyan Zhang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Phase 2 ◽  
Janus Kinase Inhibitor ◽  
Severe Ulcerative Colitis ◽  
Phase 2 Study

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

2021 ◽  
Vol 14 ◽  
pp. 175628482110057
Author(s):  
David T. Rubin ◽  
Walter Reinisch ◽  
Thomas Greuter ◽  
Paulo G. Kotze ◽  
Marcia Pinheiro ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Extraintestinal Manifestations ◽  
Peripheral Arthritis ◽  
Janus Kinase Inhibitor ◽  
Clinical Program ◽  
History Of ◽  
The Impact ◽  
Maintenance Study

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

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