A medical research study in adult patients who have moderate to severe Crohn\'s disease designed to determine whether or not treatment with an experimental drug called ustekinumab (or CNTO1275) is safe or not and to determine if the treatment will reduce the symptoms of Crohn\'s disease.
ANTECEDENTES: En los pacientes con enfermedad de Crohn, la eficacia de ustekinumab, un anticuerpo monoclonal humano contra la interleucina-12 y la interleucina-23, se desconoce.
MÉTODOS: Se evaluó ustekinumab en adultos con moderada a severa enfermedad de Crohn que era resistente al factor de necrosis antitumoral del tratamiento (TNF). Durante la inducción, 526 pacientes fueron asignados al azar para recibir ustekinumab intravenosa (a una dosis de 1, 3, o 6 mg por kilogramo de peso corporal) o placebo en la semana 0. Durante la fase de mantenimiento, 145 pacientes que tenían una respuesta a ustekinumab a las 6 semanas fueron sometidos a una segunda aleatorización para recibir inyecciones subcutáneas de ustekinumab (90 mg) o placebo en las semanas 8 y 16. El punto final primario fue una respuesta clínica a las 6 semanas.
RESULTADOS: La proporción de pacientes que alcanzaron el punto final primario fueron 36,6%, 34,1% y 39,7% para 1, 3 y 6 mg de ustekinumab por kilogramo, respectivamente, en comparación con 23,5% para placebo (p = 0,005 para la comparación con el grupo 6-mg). La tasa de remisión clínica con la dosis de 6 mg no difirió significativamente de la tasa con el placebo a las 6 semanas. La terapia de mantenimiento con ustekinumab, en comparación con el placebo, se tradujo en un aumento significativo de las tasas de remisión clínica (41,7% vs. 27,4%, p = 0,03) y la respuesta (69,4% vs. 42,5%, p <0,001) a las 22 semanas. Las infecciones graves ocurrieron en 7 pacientes (ustekinumab 6 receptora) durante la inducción y 11 pacientes (4 recibir ustekinumab) durante el mantenimiento. El carcinoma de células basales desarrolló en 1 paciente ustekinumab recibir.
Conclusiones: Los pacientes con enfermedad moderada a severa de Crohn que era resistente a los antagonistas del TNF tenido una mayor tasa de respuesta a la inducción con ustekinumab, en comparación con el placebo. Los pacientes con una respuesta inicial a ustekinumab habían aumentado significativamente las tasas de respuesta y remisión con ustekinumab como terapia de mantenimiento. (Financiado por Janssen Investigación y Desarrollo;. CERTIFI número ClinicalTrials.gov, NCT00771667).
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.
BACKGROUND: Ustekinumab is currently approved globally in Crohn's disease (CD) and psoriatic diseases. Recent phase 3 data demonstrate safety/efficacy in ulcerative colitis (UC). Crohn's disease and UC phase 3 programs had similar study designs, facilitating integrated safety analyses. METHODS: Data from 6 ustekinumab phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year. Patients received 1 placebo or ustekinumab (generally 130 mg or ~6 mg/kg) intravenous induction, then subcutaneous (90 mg) maintenance every 8/12 weeks. Analyses incorporated all patients who received ≥1 ustekinumab dose. Safety outcomes are presented as percentages of patients (induction) and as number of patients with events per 100 patient‐years of follow‐up (through 1 year). For key safety events, 95% confidence intervals (CIs) are provided, as appropriate. Hazard ratios with 95% CIs from time‐to‐event analyses for serious adverse events and serious infections were also performed. RESULTS: Through 1 year, 2574 patients received ustekinumab (1733 patient‐years of follow‐up). The number of patients with adverse events per 100 patient‐years (placebo 165.99 [95% CI, 155.81‐176.67] vs ustekinumab 118.32 [95% CI, 113.25‐123.55]), serious AEs (27.50 [95% CI, 23.45‐32.04] vs 21.23 [95% CI, 19.12‐23.51]), infections (80.31 [95% CI, 73.28‐87.84] vs 64.32 [95% CI, 60.60‐68.21]), serious infections (5.53 [95% CI, 3.81‐7.77] vs 5.02 [95% CI, 4.02‐6.19]), and malignancies excluding nonmelanoma skin cancer (0.17 [95% CI, 0.00‐0.93] vs 0.40 [95% CI, 0.16‐0.83]) were similar between placebo and ustekinumab. CONCLUSIONS: The safety profile of ustekinumab across the pooled inflammatory bowel disease population through 1 year was favorable and generally comparable to placebo. These data are consistent with the established safety profile of ustekinumab across indications. CLINICALTRIALS.GOV NUMBERS: NCT00265122; NCT00771667; NCT01369329; NCT01369342; NCT01369355; NCT02407236.
A medical research study in adult patients who have moderate to severe Crohn\'s disease designed to determine whether or not treatment with an experimental drug called ustekinumab (or CNTO1275) is safe or not and to determine if the treatment will reduce the symptoms of Crohn\'s disease.
Diseño del estudio»Ensayo controlado aleatorizado (ECA)
País»Australia,Austria,Belgium,Canada,France,Germany,Israel,Netherlands,New Zealand,Spain,United Kingdom,United States
