A new study published on May 5, 2016, in the New England Journal of Medicine has found that ulcerative colitis when treated with a daily dose of 1mg of Ozanimod can help alleviate the symptoms and induce remission of the disease with a clinical response in 51% of the patients. However, due to the preliminary nature and small scale of the trial, the efficacy and safety of the drug were not established.
The study conducted from December 2012 to April 2015 was a double blind, randomized, placebo controlled phase 2 trial of drug induction and maintenance therapy in nearly 13 countries and 57 different centers within those countries.
The total 199 participants of the trial, aged 18-75, were selected on the basis of several factors such as presence of ulcerative colitis with a Mayo Clinic Score of 6-12 and endoscopic score of two or three, continued treatment with oral amino salicylates or prednisone at less than 30 mg a day, discontinued treatment of any azathioprine, mercaptopurine or methotrexate agents, and a detected presence of varicella-zoster virus IgG antibody or a complete vaccination course administration of varicella-zoster virus.
Ulcerative colitis, a chronic immune mediated disease of the colon, is usually treated with anti-inflammatory drugs like glucocorticoids, thiopurines, mesalamine and biological agents like tumor necrosis factor blockers.
Issues like risks of neoplasia and infection, lack of universal response, and parenteral administration requirement are common with these therapies.
Ozanimod (RPC1063), an oral agonist for a sphingosine-1-phosphate receptor in the body with subtypes S1P1 and S1P5 in comparison to a previously administered drug fingolimod specific to subtypes S1P1, S1P3, S1P4, and S1P5 can produce a more selective response by inducing peripheral lymphocyte sequestration and decreasing the activated lymphocytes numbers circulating the gastrointestinal tract especially the colon, thus potentially ensuring a remission of ulcerative colitis.
Currently, ozanimod is being used as an experimental drug for the treatment of multiple sclerosis due its same specific action for sphingosine receptors.
The trial used the same principle as the basis for the study and divided the subjects with 1:1:1 ratio into three groups who received 0.5 mg of oral ozanimod drug, 1 mg of oral ozanimod drug, or a placebo once daily. The doses were designed as such, on the basis of data from phase 1 of the trial.
After the analysis of the data for 197 of the patients with severe to moderate disease, the researchers at University of California San Diego School of Medicine observed that nearly 16% of the patients with 1 mg dose daily achieved primary outcome (set at clinical remission of the disease at week 8). Patients with 0.5 mg dose daily and a placebo achieved the same primary outcome of 14% and 6% remission in their respective groups.
At 32 weeks, the rates were 21%, 26%, and 6% for each respective group along with rate of clinical response at 51%, 35%, and 20%.
Another observation showed that lymphocyte count fell by 49% percent for the 1 mg group and by 32% for the 0.5 mg group.
Headache and anemia were reported as the most common adverse events observed in the patients. The authors made note that trial was not long enough or extensive enough for a safety analysis of the drug.
These results were termed preliminary, as the researchers noted that there is a need for further study in the area with larger study groups with longer periods before this drug can be used to treat the colitis patients in routine settings.
The chief researcher Dr William J Sandborn, Director Inflammatory Bowel Disease Center at UC San Diego Health and Professor of Medicine at UC San Diego School of Medicine, observed that unlike other available drugs for colitis treatment in the market currently, ozanimod can be administered easily as an oral drug that does not suppress the immune system, which in turn can increase the chances of infection or cancer in the patient.
He added that beside clear clinical remission observed in the patients treated with the drug, there was also a decreased incidence of rectal bleeding and an increase in healing of mucosal lining of the intestine in the patients.
The trial was sponsored by Receptos and the researchers disclosed their relationship with the company when publishing the results.
Attending physician at Massachusetts General Hospital Digestive Healthcare Center in Boston, Vijay Vajnik, MD, PHD, shared his views that the results of the study seems in line with the ‘therapeutic rationale for lymphocyte trafficking agents’, but additional trials are needed for establishing safety and effectiveness of the drug. Dr Vijay was not involved in the trial and did not disclose any financial relationship with the company Receptos.
Ulcerative colitis is different from Crohn’s disease which can affect any part of the gastrointestinal tract, can cause symptoms like weight loss and intestinal bleeding which can also result in bowel obstruction, malnutrition, and cancer. The treatment can involve hospitalization and sometimes, in serious cases, surgical interventions such as removal of portions of bowel and colon can be carried out.
Centers for Disease Control and Prevention (CDC) estimates the current prevalence rates of 37 to 246 cases per 100,000 people and the incidence rates of 2.2 to 14.3 cases per 100,000 person-years, for the disease in the United States.
Statistically the patients with ulcerative colitis are a higher risk of dying from gastrointestinal and lung diseases (not including lung cancer), due to extensive inflammation.