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Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open-label, 48-week extension study.
Aliment Pharmacol Ther. 2019 02; 49(3):265-276.AP

Abstract

BACKGROUND

Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease.

AIMS

This 48-week open-label extension study primarily investigated long-term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease.

METHODS

Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks' fixed, open-label treatment.

RESULTS

Sixty-two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non-responder imputation). Study design prevented between-dose efficacy comparisons.

CONCLUSIONS

No new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599.

Links

Authors+Show Affiliations

Inflammatory Bowel Diseases Unit, Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands.

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.

Inflammation & Immunology, Pfizer Inc, Collegeville, Pennsylvania.

Inflammation & Immunology, Pfizer Inc, Collegeville, Pennsylvania.

Inflammation & Immunology, Pfizer Inc, Collegeville, Pennsylvania.

Inflammation & Immunology, Pfizer Inc, Collegeville, Pennsylvania.

Inflammation & Immunology, Pfizer Inc, Collegeville, Pennsylvania.

Inflammation & Immunology, Pfizer Inc, Collegeville, Pennsylvania.

Inflammation & Immunology, Pfizer Inc, Collegeville, Pennsylvania.

MeSH

AdultCrohn DiseaseFemaleHumansMiddle AgedPiperidinesProtein Kinase InhibitorsPyrimidinesPyrroles

Pub Type(s)

Clinical Trial, Phase II

Journal Article

Multicenter Study

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30663107

Clinical Trial Links

Clinical trial which this article describes

Citation

Panés, Julián, et al. "Long-term Safety and Tolerability of Oral Tofacitinib in Patients With Crohn's Disease: Results From a Phase 2, Open-label, 48-week Extension Study." Alimentary Pharmacology & Therapeutics, vol. 49, no. 3, 2019, pp. 265-276.

Panés J, D'Haens GR, Higgins PDR, et al. Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open-label, 48-week extension study. Aliment Pharmacol Ther. 2019;49(3):265-276.

Panés, J., D'Haens, G. R., Higgins, P. D. R., Mele, L., Moscariello, M., Chan, G., Wang, W., Niezychowski, W., Su, C., & Maller, E. (2019). Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open-label, 48-week extension study. Alimentary Pharmacology & Therapeutics, 49(3), 265-276. https://doi.org/10.1111/apt.15072

Panés J, et al. Long-term Safety and Tolerability of Oral Tofacitinib in Patients With Crohn's Disease: Results From a Phase 2, Open-label, 48-week Extension Study. Aliment Pharmacol Ther. 2019;49(3):265-276. PubMed PMID: 30663107.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open-label, 48-week extension study. AU - Panés,Julián, AU - D'Haens,Geert R, AU - Higgins,Peter D R, AU - Mele,Linda, AU - Moscariello,Michele, AU - Chan,Gary, AU - Wang,Wenjin, AU - Niezychowski,Wojciech, AU - Su,Chinyu, AU - Maller,Eric, PY - 2018/04/24/received PY - 2018/05/14/revised PY - 2018/11/01/accepted PY - 2019/1/22/entrez PY - 2019/1/22/pubmed PY - 2020/1/7/medline SP - 265 EP - 276 JF - Alimentary pharmacology & therapeutics JO - Aliment Pharmacol Ther VL - 49 IS - 3 N2 - BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease. AIMS: This 48-week open-label extension study primarily investigated long-term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease. METHODS: Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks' fixed, open-label treatment. RESULTS: Sixty-two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non-responder imputation). Study design prevented between-dose efficacy comparisons. CONCLUSIONS: No new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599. SN - 1365-2036 UR - https://www.unboundmedicine.com/medline/citation/30663107/Long_term_safety_and_tolerability_of_oral_tofacitinib_in_patients_with_Crohn's_disease:_results_from_a_phase_2_open_label_48_week_extension_study_ DB - PRIME DP - Unbound Medicine ER -