Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs
| Autor: | Soumya D. Chakravarty, Kamyar Farahi, Zijiang Yang, Lianne S. Gensler, Bruce Strober, Subrata Ghosh, Elyssa Ott, Chris Gasink, P. Ramachandran |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Arthritis Psoriatic Toxicology 030226 pharmacology & pharmacy Severity of Illness Index Antibodies law.invention 03 medical and health sciences Psoriatic arthritis 0302 clinical medicine Randomized controlled trial Crohn Disease law Psoriasis Ustekinumab Severity of illness Monoclonal medicine Humans Pharmacology (medical) Original Research Article 030212 general & internal medicine Pharmacology & Pharmacy Pharmacology Crohn's disease business.industry Pharmacology and Pharmaceutical Sciences Middle Aged medicine.disease Dermatology Clinical trial Methotrexate Treatment Outcome Female business medicine.drug |
| Zdroj: | Drug safety, vol 42, iss 6 Drug Safety Ghosh, Subrata; Gensler, Lianne S; Yang, Zijiang; Gasink, Chris; Chakravarty, Soumya D; Farahi, Kamyar; et al.(2019). Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs.. Drug safety. doi: 10.1007/s40264-019-00797-3. UCSF: Retrieved from: http://www.escholarship.org/uc/item/5mj3g2mw |
| Popis: | INTRODUCTION:Theoretical risks of biologic agents remain under study. OBJECTIVE:The aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials. METHODS:Patients had moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) (± methotrexate), or moderate-to-severe Crohn's disease (CD; failed/intolerant of immunomodulators/corticosteroids). Psoriatic patients received subcutaneous ustekinumab 45/90 mg or placebo, generally at week 0, week 4, then every 12 weeks thereafter, while those with CD received a single intravenous ustekinumab dose (130 mg or weight range-based dosing of approximately 6 mg/kg) or placebo induction dose at week 0, followed by subcutaneous ustekinumab 90 mg at week 8 and every 8/12 weeks thereafter. The incidence rates of a priori-defined safety events were integrated post hoc (adjusted for duration of follow-up, reported per 100 patient-years [PYs]). RESULTS:Among 6280 enrolled patients, 5884 ustekinumab-treated patients (psoriasis: 3117; PsA: 1018; CD: 1749) contributed 4521 PYs versus 674 PYs in placebo-treated patients through year 1 (829 PYs and 385 PYs during 8- to 16-week controlled periods). Combined across diseases among ustekinumab- versus placebo-treated patients, respective incidences/100 PYs (95% confidence intervals) of infections were 125.4 (122.2-128.7) versus 129.4 (120.9-138.3) through year 1, and not meaningfully increased in patients who did versus those who did not receive methotrexate (92.5 [84.2-101.5] vs. 115.3 [109.9-121.0]), or significantly increased in patients who did versus those who did not receive corticosteroids (116.3 [107.3-125.9] vs. 107.3 [102.0-112.8]) at baseline. Major adverse cardiovascular events (0.5 [0.3-0.7] vs. 0.3 [0.0-1.1]), malignancies (0.4 [0.2-0.6] vs. 0.2 [0.0-0.8]), and deaths (0.1 [0.0-0.3] vs. 0.0 [0.0-0.4]) were rare across indications. CONCLUSIONS:Ustekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications. TRIAL REGISTRATIONS:ClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355. |
| Databáze: | OpenAIRE |
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