ABSTRACT
Introduction: Prostaglandin D2 (PGD2) is a major cyclooxygenase mediator that is synthesized by activated human mast cells and other immune cells. The biological effects of PGD2 are mediated by D-prostanoid (DP1), DP2 (CRTH2) and thromboxane prostanoid (TP) receptors that are expressed on several immune and non-immune cells involved in allergic inflammation. PGD2 exerts various proinflammatory effects relevant to the pathophysiology of allergic disorders. Several selective, orally active, DP2 receptor antagonists and a small number of DP1 receptor antagonists are being developed for the treatment of allergic disorders.
Areas covered: The role of DP2 and DP1 receptor antagonists in the treatment of asthma and allergic rhinitis.
Expert opinion: Head-to-head studies that compare DP1 antagonists with the standard treatment for allergic rhinitis are necessary to verify the role of these novel drugs as mono- or combination therapies. Further clinical trials are necessary to verify whether DP2 antagonists as monotherapies or, more likely, as add-on therapies, will be effective for the treatment of different phenotypes of adult and childhood asthma. Long-term studies are necessary to evaluate the safety of targeted anti-PGD2 treatments.
Article Highlights
Prostaglandin D2 (PGD2), the major cyclooxygenase mediator produced by activated human mast cells, plays a role in allergic inflammation through the engagement of DP1 and DP2 (also known as CRTH2) receptors expressed on several immune and stromal cells.
Several trials have universally found DP1 and DP2 antagonists to be safe and well tolerated.
Only few DP1 antagonists have been reported to be effective in reducing symptoms of allergic rhinitis.
Different DP2 antagonists have demonstrated efficacy in phase II studies in adults with asthma.
Several phase III trials are evaluating the long-term safety and efficacy of DP2 antagonists in adult and pediatric patients with moderate-to-severe asthma.
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Acknowledgments
The authors thank scientists from CISI Laboratory for invaluable collaborations; medical graphic artist Fabrizio Fiorbianco and the administrative staff (Dr. Roberto Bifulco and Dr. Anna Ferraro), without whom we could not function as an integrated team.
Declaration of interest
The authors have no other relevant affiliation or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
One referee has received consultation fees from Novartis Pharma and Teijin Pharma for the development of DP2 antagonists. Other peer reviewers on this manuscript have no relevant financial or other relationships to disclose