Treatment with ustekinumab (Stelara, Janssen) induced clinical response and clinical remission in adult patients with moderate-to-severe Crohn’s disease who had previously failed or were intolerant to treatment with one or more anti-tumor necrosis factor (TNF)-alpha therapies, according to phase 3 data presented at the 11th Congress of the European Crohn’s and Colitis Organization (ECCO).
The phase 3 UNITI-1 study, which included 741 patients, achieved its primary endpoint, with ustekinumab treatment groups demonstrating significantly higher rates of clinical response at week 6 when compared with the placebo group. Major secondary endpoints of clinical response and clinical remission at week 8 were also significantly higher among patients receiving ustekinumab compared with patients receiving placebo.
These latest findings follow phase 3 results from the UNITI-2 study, which demonstrated the efficacy and safety of ustekinumab in patients who had previously failed conventional therapy, the majority of whom were naïve to treatment with anti-TNF-alpha therapy.
Applications seeking approval of ustekinumab for the treatment of moderately to severely active Crohn’s disease are under review in Europe and the United States. Ustekinumab, approved for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis in many countries, is a monoclonal antibody that targets interleukin (IL)-12 and IL-23 cytokines, which are believed to play a role in immune-mediated diseases, including Crohn’s disease.
Patients participating in the phase 3 UNITI-1 study received a single intravenous (IV) infusion of placebo, ustekinumab 130 mg, or ustekinumab at approximately 6 mg/kg (weight-tiered dosing: patients weighing less than or equal to 55 kg received 260 mg; patients weighing more than 55 kg and less than or equal to 85 kg received 390 mg; and patients weighing more than 85 kg received 520 mg) at week 0. All enrolled patients had previously failed or were intolerant to treatment with at least one anti-TNF-alpha therapy, and half of the enrolled patients had failed two or more anti-TNF-alpha therapies.
At week 6, 34% of patients receiving ustekinumab 130 mg and 34% of patients receiving ustekinumab at approximately 6 mg/kg achieved clinical response, as defined by a reduction from baseline in the Crohn’s Disease Activity Index (CDAI) score of at least 100 points, compared with 22% of patients receiving placebo (P = 0.002 for ustekinumab 130 mg; P = 0.003 for ustekinumab of about 6 mg/kg). CDAI is a symptom-based disease assessment tool commonly used in clinical trials to quantify Crohn’s disease activity.
At week 8, 34% and 38% of patients receiving ustekinumab 130 mg and ustekinumab at approximately 6 mg/kg, respectively, achieved clinical response, compared with 20% of patients receiving placebo (P < 0.001). In addition, 16% of patients receiving ustekinumab 130 mg and 21% of patients receiving ustekinumab at about 6 mg/kg achieved clinical remission at week 8, as defined by a CDAI score of less than 150 points, compared with 7% of patients receiving placebo (P = 0.003 for ustekinumab 130 mg; P < 0.001 for ustekinumab at approximately 6 mg/kg).
In addition to significant improvements in signs and symptoms as measured by CDAI, both doses of ustekinumab resulted in significant improvements in the Inflammatory Bowel Disease Questionnaire (IBDQ), a health-related quality-of-life measure for patients with IBD, as well as significant reduction in markers of inflammation, including C-reactive protein, fecal lactoferrin, and calprotectin.
Through week 8 (the placebo-controlled period), adverse events (AEs), serious AEs, and infections were reported in similar proportions across ustekinumab and placebo treatment groups. One case of Listeria meningitis infection was reported in the ustekinumab at about 6 mg/kg group. No malignancies, deaths, cases of tuberculosis, or major adverse cardiovascular events were observed in patients treated with ustekinumab.
Source: Janssen; March 18, 2016.
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