Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-severe Ulcerative Colitis: Results From a Randomised, Phase 2 Study
| Autor: | Gary R. Lichtenstein, Richard Strauss, Colleen Marano, Jewel Johanns, Kirk Bertelsen, Brian G. Feagan, Christopher D. O'Brien, Philippe Szapary, Zijiang Yang, Julián Panés, Bruce E. Sands, Hongyan Zhang, William J. Sandborn, Severine Vermeire |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Niacinamide medicine.medical_specialty Administration Oral Adamantane Placebo Gastroenterology Inflammatory bowel disease Severity of Illness Index law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine medicine Humans Janus Kinase Inhibitors Intestinal Mucosa Adverse effect Janus kinase inhibitor Dose-Response Relationship Drug Surrogate endpoint business.industry General Medicine Middle Aged medicine.disease Ulcerative colitis Clinical trial 030104 developmental biology C-Reactive Protein Treatment Outcome Quality of Life 030211 gastroenterology & hepatology Colitis Ulcerative Female Drug Monitoring business Biomarkers |
| Zdroj: | Journal of Crohn'scolitis. 12(10) |
| ISSN: | 1876-4479 |
| Popis: | Background and aims Janus kinase [JAK] inhibitors have shown efficacy in ulcerative colitis [UC]. We studied the dose-response, efficacy, and safety of peficitinib, an oral JAK inhibitor, in patients with moderate-to-severe UC. Methods In this Phase 2b, dose-ranging trial, we evaluated peficitinib at 25 mg once daily [o.d.], 75 mg o.d., 150 mg o.d., and 75 mg twice daily versus placebo for efficacy and safety in 219 patients with moderate-to-severe UC. The primary outcome was peficitinib dose-response at Week 8, with response assessed using Mayo score change from baseline. Secondary endpoints were clinical response, clinical remission, mucosal healing, change from baseline in Inflammatory Bowel Disease Questionnaire [IBDQ], and normalisation of inflammatory biomarkers at Week 8; other secondary endpoints were treatment response through Week 16 and through Week 32 for patients in clinical response at Week 8. Safety was assessed through Week 36 or 4 weeks after the last dose. Results A statistically significant peficitinib dose-response was not demonstrated at Week 8, although a numerically greater proportion of patients receiving peficitinib ≥75 mg o.d. achieved clinical response, remission, and mucosal healing at Week 8, supported by IBDQ improvement and inflammatory biomarker normalisation. Treatment-emergent adverse event [TEAE] rates reported through Week 8 and the final safety visit were higher in the combined peficitinib group than in the placebo group; patients receiving doses of ≥75 mg o.d. peficitinib reported TEAEs more frequently. Conclusions No dose-response in patients with moderate-to-severe UC was demonstrated with peficitinib, but evidence of efficacy was suggested at doses ≥75 mg o.d. The safety profile of peficitinib was consistent with current information. ClinicalTrials.gov NCT01959282. |
| Databáze: | OpenAIRE |
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