Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis of Results from Phase 2/3 Studies

Abstract

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.

AGA Technical Review on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn’s Disease

“…In an integrated safety analysis of data from 6 phase 2/3 trials of ustekinumab including 2574 patients (1733 PY), incidence of serious infections was 5.02 per 100 PY (vs 5.53 in placebo-treated patients). 34 Extrapolating from other autoimmune diseases like psoriasis, the risk of serious infections with ustekinumab monotherapy may be lower compared with TNFa antagonist monotherapy. However, these findings on the relative safety of ustekinumab in patients with psoriasis should be interpreted with caution, as the dose of ustekinumab approved for use in CD is at least 50% higher than the dose used in psoriasis.…”

Metaanálisis de la eficacia del fármaco ustekinumab en el tratamiento de la enfermedad inflamatoria intestinal en el año 2020

“…Cualquier desacuerdo se resolvió mediante discusión con los autores. Se eliminaron los duplicados, se identificaron mediante la búsqueda electrónica 44 registros, y tras la evaluación de los títulos y resúmenes se eliminaron 37 estudios irrelevantes y se seleccionaron siete informes potencialmente relevantes [7][8][9][10][11][12][13] que fueron identificados y recuperados en texto completo para una evaluación detallada. De los textos indicados, se extrajo la siguiente información: autor, número de sujetos, duración del ensayo clínico, dosificación del fármaco e intervalos, y efectos adversos.…”

“…Así mismo, se confirmó que no hubo mayor riesgo con el uso de ustekinumab en comparación con placebo en cualquiera de los estados de la enfermedad, y que la tasa de respuesta es favorable, con la Figura 1. Ensayos clínicos [7][8][9][10][11][12][13] que evaluaron la respuesta clínica y las tasas de remisión clínica en los pacientes tratados con ustekinumab. salvedad de la comparación entre estudios de heterogeneidad de gravedad de la EII, el esquema de dosificación y los parámetros de respuesta.…”

Cutaneous Manifestations in Biological-Treated Inflammatory Bowel Disease Patients: A Narrative Review

“…Risk factors to develop these skin cancers are: solar exposition, skin phototype, and family history. No increased risk of NMSC has been shown for ustekinumab and the anti-integrin receptors antibodies vedolizumab and natalizumab [ 51 , 52 ].…”