According to a recently published study, AstraZeneca’s AZD9056 – an orally-available purinergic receptor P2X7 antagonist, may be effective in symptom improvement in patients with moderate to severe Crohn’s disease. The study is titled, “Safety and Efficacy of an Oral Inhibitor of the Purinergic Receptor P2X7 in Adult Patients with Moderately to Severely Active Crohn’s Disease: A Randomized Placebo-controlled, Double-blind, Phase IIa Study“, and is published in the journal Inflammatory Bowel Diseases.
Investigators Jean-Frédéric Colombel, MD, professor of medicine at the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, and Séverine Vermeire, MD, PhD, from the department of gastroenterology at the Catholic University of Leuven in Belgium, and colleagues explained that the P2X7 receptor plays a major role in the conversion and production of a number of proinflammatory cytokines that are known to drive Crohn’s disease.
“AZD9056 is a selective oral inhibitor of P2X7 receptor signaling identified through high throughput screening and has been previously studied in patients with rheumatoid arthritis.” wrote the research team according to a news release.
At the end of the study, researchers found that the CDAI baseline scores decreased from 311 to 242 at day 28 of treatment with AZD9056, compared to the 262 to 239 change in participants that received the placebo, corresponding to a decrease in disease activity, pain and an improved general well-being. It was also found that a higher proportion of patients under AZD9056 treatment were able to achieve remission and exhibit therapeutic response.
“The disconnect between improvement in clinical symptoms, particularly abdominal pain, and lack of change in objective markers of inflammation is of concern and has put the further development of AZD9056 for the indication of [Crohn’s disease] on hold,” the researchers wrote. “Nevertheless, the now well-substantiated role of P2X7 in nociception should rekindle the interest in this pathway for modulating pain in gastrointestinal diseases.”
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