Immunomodulatory Approaches to Treating Chronic Rhinosinusitis Gain Importance

The most advanced of anti-eosinophilic therapies is anti-IL-5, Dr. Chiu said. “There’s been some major pharmaceutical investment in this over the past 10 years,” he added.

A randomized controlled trial of mepolizumab, involving 362 asthmatics, found a reduction in serum and sputum eosoniphilia but no clinical improvement in the asthma-related objective parameters (Am J Respir Crit Care Med. 2007;176:1062-1071).

A 2011 study of reslizumab found significant improvement in Asthma Control Questionnaire scores compared with a placebo among asthmatics treated for three months, with significantly more improvement in asthmatics with polyps than those without (Am J Respir Crit Care Med. 2011;184:1125-1132).

In a 2006 study, 24 patients with massive nasal polyps received a single dose of reslizumab after a one-month washout and a two-month ban on steroid therapy post-treatment. There was at least one adverse event in 23 of the 24 patients, 14 of whom had upper respiratory infections. There was significantly reduced blood eosinophilia compared with a placebo 12 hours after treatment but a severe rebound 24 weeks later. (J Allergy Clin Immunol. 2006;118:1133-1141).

There were also significantly reduced nasal secretions of eosinophilic cationic protein and IL-5. Additionally, 50 percent of the patients with polyps had a decrease in polyp scores; the responders were those who had increased IL-5 levels in nasal secretions before treatment.

In a 2011 double-blind, placebo-controlled trial of mepolizumab for nasal polyps, 30 patients with severe nasal polyps got two single doses of the drug 28 days apart. The treatment was well tolerated, but the patients experienced side effects, and there was a significant reduction in just 12 of the 20 patients on nasal polyp score. But, as in the reslizumab study, there was no rebound of eosinophilia seen.

Dr. Chiu said that although the treatments show signs of promise, the question of who to treat is still unclear. “It may be the wave of the future if we can actually predict which patients are going to respond,” he added.

Leukotriene Inhibitors

Eric Holbrook, MD, assistant professor of otology and laryngology at Harvard Medical School and a physician at the Massachusetts Eye and Ear Infirmary, reviewed the sparse literature that exists on leukotriene inhibitors. Montelukast, pranlukast and zafirlukast, which are cysteinyl-leukotriene type I receptor inhibitors, are indicated for chronic treatment of asthma and allergic rhinitis but come with a warning about neuropsychiatric events. Zileuton inhibits 5-lipoxygenase, an enzyme that catalyzes leukotrienes from arachidonic acid. It’s indicated for treatment of chronic asthma and comes with warnings about hepatotoxicity and neuropsychiatric events.