Stelara (Ustekinumab) for the Treatment of Moderate to Severe Crohn’s Disease, United States of America
Developed by Janssen Biotech, Stelara (Ustekinumab) is indicated for the treatment of moderate to severely active Crohn's disease.
A new drug application (NDA) for Stelara was submitted to the US Food and Drug Administration (FDA) on 30 November 2015, which was approved on 26 September 2016.
In addition, a Grouped Type II variation or extension application was submitted to the European Medical Agency (EMA) in November 2015, which was approved on 11 November 2016.
Stelara was earlier approved in the US for the treatment of plaque psoriasis and active psoriatic arthritis.
Crohn's disease causes and symptoms
Crohn's disease is a type of inflammatory bowel disease (IBD) that causes inflammation and irritation in the digestive tract. It is a chronic disease mainly affecting the small intestine and the beginning of the large intestine. It begins gradually with subtle symptoms that aggravate over time.
The disease may be associated with complications such as intestinal obstruction, fistulas, abscesses, anal fissures, ulcers, malnutrition, and inflammation in other parts of the body. It can also be associated with diarrhoea, cramps and abdominal pain, weight loss, anaemia, redness in the eyes, fatigue, joint pains, nausea, and skin rashes.
The exact cause of the disease is unknown, but researchers suggest it may be caused due to an auto immune reaction, genetics, and other factors such as smoking and the use of non-steroidal anti-inflammatory drugs.
Stelara's mechanism of action
Stelara is a human IgG1K monoclonal antibody, which inhibits the mediated signals generated by interleukin (IL)-12 and IL-23 cytokines. These are associated with inflammatory and immune responses such as killer cell activation and CD4+ T-cell differentiation and activation.
The drug binds to the p40 protein subunit of the IL-12 and IL-23 cytokines to disrupt their mediated signalling and interaction with the cell surface receptor chain IL-12Rß1.
Clinical trials on Stelara
The US FDA and EMA approved Stelara based on results obtained from three phase III clinical studies UNITI-1, UNITI-2 and IM-UNITI. The trials were conducted to evaluate the safety and efficacy of the drug.
UNITI-1 was a phase III, randomised, double-blind, placebo-controlled, parallel group, and multi-centre trial conducted on 741 patients with moderate to severely active Crohn's disease, who already received tumour necrosis factor (TNF) antagonists.
Subjects were randomised to receive either 130mg of Stelara as a single dose, 6mg/kg of Stelara as a single dose, or placebo as a single dose. The trial met primary and secondary end points for reduction of the activity index of the Crohn's disease from baseline and clinical remission at week eight in the arms treated, with Stelara 130mg and Stelara 6mg/kg, when compared to the arm treated with placebo.
UNITI 2 was a phase III, randomised, double-blind, placebo-controlled, parallel group and multi-centre trial conducted on 628 patients with moderate to severely active Crohn's disease, who had failed conventional treatment and received TNF antagonists.
The subjects in this trial were randomised to receive either Stelara 130mg as a single dose, Stelara 6mg/kg as a single dose, or placebo as a single dose. The trial arms treated with Stelara 130mg and Stelara 6mg/kg met the primary endpoints of reduction of the activity index of the Crohn's disease from baseline and secondary end points of clinical response and clinical remission at week eight.
IM-UNITI was a maintenance study, which enrolled 388 patients who showed positive response to single IV dose of Stelara either in UNITI 1 or UNITI 2 studies. The patients in the trial were randomised to receive either Stelara 90mg subcutaneously every eight weeks, Stelara 90mg subcutaneously every 12 weeks, or placebo.
The trial demonstrated that the arms receiving Stelara were superior to placebo in achieving the primary and secondary endpoints.