Biologics approved for asthma show efficacy in chronic rhinosinusitis with nasal polyps

Three currently available type 2 biologics approved for asthma appeared effective in treating chronic rhinosinusitis with nasal polyps, according to data published in The Journal of Allergy and Clinical Immunology: In Practice.

Brian J. Lipworth, MD, and Rory Chan, MBChB, from the Scottish Centre for Respiratory Research at University of Dundee, wrote that although chronic rhinosinusitis with nasal polyps (CRSwNP) is often treated with oral corticosteroids or surgical treatment, many patients often relapse from these interventions.

“There is an unmet need for biologics which target type 2 inflammatory pathways in order to improve disease control and reduce the need for rescue medical and surgical polypectomy, as well as to attenuate the systemic burden of recurrent oral corticosteroid exposure,” Lipworth and Chan wrote. “Corticosteroid-sparing effects of biologics assume even greater relevance in patients who have concomitant severe asthma and CRSwNP.”

The researchers reviewed data from the SINUS 24 and SINUS 52 trials of dupilumab (Dupixent, Sanofi), an anti-interleukin receptor 4 alpha inhibitor; the POLYP 1 and POLYP 2 trials of omalizumab (Xolair; Genentech, Novartis), an anti-IgE monoclonal antibody; and the SYNAPSE trial of mepolizumab (Nucala, GlaxoSmithKline), an anti-IL5 monoclonal antibody.

Nasal polyp score (NPS) — based on a scale from 0 to 8 — served as a co-primary end point in each trial.

All trials showed significant improvements in NPS, with a range from a 15% reduction (–0.8 units) with mepolizumab, 18% (–1.14 units) with omalizumab and 35% (–2.06 units) with dupilumab. Lipworth and Chan noted that dupilumab was the only biologic to consistently improve mean NPS by more than one unit in both its phase 3 trials.

Researchers also evaluated the 22-item sino-nasal outcome test (SNOT-22) score, a secondary outcome in the trials, which measured disease-related quality of life on a scale of 0 to 110. Similar to the NPS outcomes, the lowest change occurred with mepolizumab (–13.7 units), followed by omalizumab (–16.12 units), and the greatest occurred with dupilumab (–21.2 units).

The researchers suggested that a formal meta-analysis could clarify putative differences in efficacy between the biologics from the various phase 3 trials, especially as head-to-head randomized control trials are unlikely to be performed in the near future.

They also noted that real world head-to-head comparisons will be required in severe CRSwNP cases to establish which type 3 endotypes predict the best response to biologics.

“We believe from a pragmatic point of view that it makes sense to tailor treatment according to the underlying endotype and mode of action,” Lipworth and Chan wrote. “For example, in patients with asthma and CRSwNP, one might choose mepolizumab in eosinophilic patients where asthma was the main problem, and in patients with raised FeNO [fractional exhaled breath nitric oxide] with asthma and CRSwNP, one might use dupilumab.”

The researchers concluded that a multidisciplinary approach between physicians and surgeons is the best step forward regarding continued study and application of treatment for CRSwNP.