Janssen’s Psoriasis Drug STELARA® Promises Cure for Crohn's Disease
In one year study, clinical remission was seen in significant proportion of adult patients with moderate to severe Crohn’s disease who received STELARA® (ustekinumab) subcutaneous (SC) maintenance therapy.
Crohn’s disease and ulcerative colitis, together known as inflammatory bowel disease (IBD) affects about five million people throughout the world. Crohn’s disease affecting about 7, 00,000 Americans is a chronic inflammatory disease commonly affecting the ileum and the beginning of colon. However it may affect other parts of GI tract as well leaving patches of diseased intestine among normal tissue.
Figure 1. Inflammatory bowel disease and difference between ulcerative colitis & Crohn’s disease (Photo credit: Digestive Health Center of Louisiana.)
Though the actual cause of this disease looks enigmatic, it is found that it is linked to abnormalities in immune system that gets triggered due to alterations in diet, genetic predisposition or other etiological factors. The symptoms include persistent diarrhoea, abdominal cramps and pain, rectal bleeding, fever, fatigue, weight loss and night sweats.
STELARA® was originally approved for the treatment of active psoriatic arthritis in 71 countries and moderate to severe plaque psoriasis in 87 countries. This drug is prescribed for people who are 18 years and above.
STELARA® is a human monoclonal antibody. It works by targeting interleukin (IL)-12 and IL-23 cytokines that play a major role in activating T-cells and in regulating immune-mediated inflammatory disorders. It binds to p-40 subunit of both IL-12 and IL-23 blocking them and preventing their binding to corresponding receptors.
Figure 2. Mechanism of action of STELARA® (Photo credit: Janssen Biotech, Inc.)
However, it greatly suppresses the immune system making the patient prone to bacterial, viral, fungal infections and some types of cancers as well.
About 50% of the STELARA® treated patients achieved clinical remission. Phase III IM-UNITI maintenance study evaluated the efficacy and safety of STELARA® maintenance therapy in patients suffering from moderate to severe Crohn’s Disease. Phase III UNITI-1 induction study was carried out to study the safety and efficacy of the drug in patients who were previously intolerant to anti-TNF-alpha therapies. This study was also carried out to demonstrate the drug safety and efficacy in patients who were not exposed to anti-TNF-alpha therapy but failed conventional therapies.
Patients responding to a single dose of intravenous STELARA® after 8 weeks in the above trials (388 patients) were re-randomized in the IM-UNITI maintenance study to receive STELARA® 90 mg SC Q8W, STELARA® 90 mg SC Q12W or placebo treatment for a year.
At week 44, 53% of patients showed clinical remission who received a STELARA® 90 mg SC injection every eight weeks (Q8W). 49% of patients showed clinical remission who were on STELARA® 90 mg SC injection every 12 weeks (Q12W) and 36% of patients in placebo.
Crohn’s Disease Activity Index (CDAI), a disease assessment tool to quantify the activity of this disease projected a score less than 150 points.
The secondary end points of this study at 44 week were clinical response, corticosteroid-free remission, clinical remission among patients in remission after induction, and clinical remission in patients refractory or intolerant to anti-TNF-alpha therapies.
William Sandborn, Chief of Division of Gastroenterology, Professor of Medicine, University of California, San Diego, and study investigator commented, “The totality of the induction and maintenance data over the course of one year show the potential of this biologic therapy in inducing and maintaining a clinically relevant therapeutic effect in patients with moderate to severe Crohn’s disease. The results of this comprehensive Phase 3 program-which included anti-tumor necrosis factor (TNF)-alpha naïve, exposed and failure patients-demonstrate the potential of STELARA® to provide significant benefit for patients in need of an effective therapy.”
STELARA® and placebo treatment groups reported the same kind of adverse effects at 44th week. Serious side effects were reported in 10 %, 12 % and 15 % of patients under STELARA® 90 mg SC Q8W, STELARA® 90 mg SC Q12W and placebo, respectively. However, no serious cardiovascular events or mortality were observed in placebo controlled period. Basal cell carcinoma one in each of the placebo and STELARA® 90 mg SC Q8W groups were recorded.
The Managing Director & Head of Immunology Development, Janssen Research & Development, LLC, Newman Yeilding says, “These maintenance data complement the induction data previously presented and provide important insights into the efficacy and safety profile of STELARA® for the treatment of moderately to severely active Crohn’s disease. Pending approval, we look forward to bringing STELARA® to patients who may benefit from this new therapeutic option and providing gastroenterologists with a new alternative to treat Crohn’s disease.”
Applications soliciting approval of STELARA® to treat moderate to severe active Crohn’s disease is being reviewed in US and Europe.
Featured image credit: Inflammatory Bowel Disease, Athersys Inc., USA