Effectiveness and Safety of Ustekinumab for Moderate to Severely Active Crohn’s Disease: Results from an Early Access Program in Brazil

Abstract

This prospective, observational, open-label study aimed to provide access to ustekinumab prior to market authorization and assess its safety and effectiveness in patients with Crohn’s disease (CD) refractory to anti-tumor necrosis factor-α and conventional drugs in Brazil. Patients with a diagnosis of moderate-to-severe active CD for ≥ 3 months before screening received ustekinumab in a single intravenous induction dose (~6 mg/kg) at week 0, and a 90 mg maintenance dose, subcutaneously, every 8 or 12 weeks, from week 8 through to 80. Serious adverse events (SAE), adverse drug reactions (ADR), clinical response (per CD Activity Index and Harvey Bradshaw Index (HBI) scores), remission (per HBI scores), biomarkers (C-reactive protein (CRP) and fecal calprotectin (FC)) and endoscopic improvement rate over 80 weeks were assessed. Patients with a mean age of 39.9 years were assessed. Discontinuation rate was low (23%) and most adverse events were mild (68.7%). The SAE rate was 21% (mostly infections/infestations or gastrointestinal disorder), and ADR rate was 44%. The CD Activity Index and HBI scores decreased (by 74% and 81%, respectively) with 50% of patients showing normalized CRP and FC, and 63% achieved endoscopic improvement. Ustekinumab was fairly safe, well tolerated and effective in a Brazilian cohort of CD patients.

Long-term effectiveness and safety of ustekinumab in Crohn’s disease: a prospective cohort study

“…These studies were however restricted by a retrospective design and follow-up data beyond 52 weeks was available in only a small number of patients. Recently, a small prospective study showed persistency rates of 77% at week 80 with clinical remission in 88% of these patients and endoscopic improvement in 63% of patients with a follow-up endoscopy [22]. Furthermore, a recent prospective study described outcomes at 104 weeks for 252 Crohn’s disease patients initiated on ustekinumab with a similar design as our study.…”

“…Corticosteroid-free remission rates after 52 weeks ranged from 12.2 to 47.4% [6,9,13,17,18]. Long-term outcomes beyond 52 weeks have only been assessed in a few real-world studies which were often restricted by small numbers or a retrospective design [19][20][21][22]. Recently, a large Dutch prospective cohort study reported a corticosteroid-free clinical remission rate of 34% at week 104 [17].…”

Efficacy, drug sustainability, and safety of ustekinumab treatment in Crohn’s disease patients over three years

“…In a Brazilian prospective study, the UST discontinuation rate was 23% which is closer to our results of drug sustainability. Their treatment was also well tolerated during the 80 weeks of follow-up, though they mention a serious adverse event rate of 21% with mostly infectious causes 23 . Comparing these results of the different studies is challenging.…”

Research progress of Ustekinumab in the treatment of inflammatory bowel disease

“…The post‐marketing surveillance in Japan ( 63 ) shown that the overall incidences of ADRs and SADRs were 5.3% and 2.1%, respectively. A study in Brazil shown that, although most of patients might experience at least one AE, most of the AEs were mild or moderate and were not connected to the UST, with the SAE rate being 21% and with the ADR rate being 44% ( 64 ). A prospective cohort study conducted in The Netherlands ( 65 ) revealed that the ADRs associated with UST were 13.4 per 100 patient-years, and only 7% of patients discontinued UST due to ADRs.…”