Targeting Interleukin-5 or Interleukin-5Rα: Safety Considerations.
Asthma is a highly prevalent chronic disease of the airways; approximately 10% of patients with asthma will experience a severe form of the disease. New understanding of the pathogenesis of asthma has enabled the development of novel drugs and provided hope for patients with asthma. Interleukin (IL)-5 and IL-5 receptor subunit α (IL-5-Rα) plays a crucial role in the development, maturation, and operation of eosinophils so were the first important therapeutic target of these new drugs. While the results of early clinical trials of these drugs were not promising, results improved once researchers discovered the drugs worked best in patients with high eosinophil levels. Patients treated with both anti-IL-5 and IL-5-Rα experienced significant decreases in exacerbations. Trials have also demonstrated promising safety profiles; adverse events have been few and frequently only observed with placebo or considered unrelated to the study drug. The positive efficacy and safety profiles of these drugs has led to trials with interesting results in other diseases that are also secondary to the action of eosinophils: Churg-Strauss syndrome, hypereosinophilic syndrome, nasal polyposis, chronic obstructive pulmonary disease, atopic dermatitis, and esophagitis. In this review, we explore the main clinical trials of anti-IL-5 and IL-5-Rα, both in asthma and in other pathologies, with particular reference to the interesting safety and efficacy results.
Allergy and Respiratory Diseases, Department of Internal Medicine, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
Diego
D
Bagnasco
Allergy and Respiratory Diseases, Department of Internal Medicine, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
Matteo
M
Ferrando
Allergy Unit, University Hospital of Verona, Verona, Italy.
Marco
M
Caminati
Allergy and Respiratory Diseases, Department of Internal Medicine, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
Alice
A
Bragantini
Respiratory Disease Clinic, Department of Internal Medicine, IRCCS Humanitas Clinical and Research Center, Humanitas University, Milan, Italy.
Francesca
F
Puggioni
Division of Clinical Immunology and Allergy, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Gilda
G
Varricchi
Allergy and Respiratory Diseases, Department of Internal Medicine, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
Giovanni
G
Passalacqua
Allergy and Respiratory Diseases, Department of Internal Medicine, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy. canonica@unige.it.|Respiratory Disease Clinic, Department of Internal Medicine, IRCCS Humanitas Clinical and Research Center, Humanitas University, Milan, Italy. canonica@unige.it.
Giorgio Walter
GW
Canonica
D001249:Asthma / Q000188:drug therapy*; D015415:Biomarkers; D006801:Humans; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D053666:Interleukin-5 Receptor alpha Subunit / Q000627:therapeutic use*
D015415:Biomarkers; C485918:IL5RA protein, human; D015848:Interleukin-5; D053666:Interleukin-5 Receptor alpha Subunit