Dupilumab Efficacy Confirmed in CRSwNP Subgroup Study

Dupilumab efficacy in chronic rhinosinusitis with polyposis (CRSwNP) was further confirmed in a new study out of Germany, with findings showing the monoclonal antibody to have great benefit regarding endoscopic findings, objective smell tests, and subjective findings. The 75 patients in the study, subdivided by disease type—aspirin-exacerbated respiratory disease (AERD), increased histologic eosinophilia, or elevated blood eosinophil or immunoglobulin E (IgE) levels—showed consistent benefit independent of disease characteristics.

Findings were recently published in Medicine, with the study authors noting, “There is little information on several subgroups of dupilumab treatment in CRSwNP. As treatment with dupilumab is associated with considerable costs, accurate knowledge of the expected efficacy is crucial.”

Chronic rhinosinusitis diagnosis was confirmed using American Academy of Otolaryngology Head and Neck Surgery criteria, and their nasal polyps were confirmed via European Forum for Research and Education in Allergy and Airway Diseases criteria. Their screening comprised the following: IgE and eosinophil count, nasal endoscopy, brief identification of smell test (BSIT), short version of the University of Pennsylvania Smell Test, histology, and completion of the Sinus Nasal Outcome Test (SNOT-22). Visual Analogue Scale (VAS) and SNOT-22 scores indicated disease burden. Dupilumab was self-administered using six 300-mg ready-to-use pens, with 1 pen administered every 2 weeks, which was switched to every 4 weeks once adequate disease control was achieved, gauged by at least a one-third score improvement on the VAS or SNOT-22. Follow-up visits took place every 3 months.

Among the 75 original patients (male patients, 65.3%), 55 responded to a follow-up inquiry in March 2021. Their most common disease subtype was histologic eosinophilia, at 85.7%, with 65.3% reporting AERD. The mean (SD) serum eosinophilic level was 0.46 (0.32) x 10³/mcL.

When treatment with dupilumab began, the following mean (SD) measures were seen:

• Endoscopic score: 5.9 (1.7)
• VAS: 8.3 (1.7)
• SNOT-22: 66.9 (15.2)
• BSIT: 3.7 (2.5)

Three of these measures had dropped by the first 2-week follow-up visit, while BSIT rose:

• Endoscopic score: 1.7 (1.8)
• VAS: 2.9 (1.6)
• SNOT-22: 24.4 (15.7)
• BSIT: 7.6 (3.4)

Over the remaining follow-up visits, scores remained consistent, with the endoscopy measures coming in at 1.3 (1.8) and 1.1 (1.9); VAS, 2.7 (1.8) and 2.0 (1.0); SNOT-22, 20.7 (13.5) and 16.6 (10.9); and BSIT, 7.6 (3.4) and 7.4 (3.7). The mean overall eosinophil count was 70.7 (21.9)/HPF.

The study authors noted that they found “very little significant differences in treatment success between different patient groups.” In addition, they only saw a significant difference in SNOT-22 when considering histologic eosinophilia, with the baseline measure being 81.8 (65.4) and the first follow-up visit measure coming in at 24.3 (14.5). Similar results were not seen at the remaining follow-ups.

Forty-one patients were transitioned to dupilumab every 4 weeks following successful therapy initiation, and of this group, 36.5% requested a return to administration every 2 weeks after symptom worsening. However, patients on concomitant medications dropped in all categories following dupilumab initiation (all P = .001):

• Topical steroids: 55 to 44
• Inhalative steroids: 18 to 7
• Oral steroids: 32 to 2
• Intralesional steroids: 2 to 1
• Antileukotrienes: 8 to 2
• Acetylsalicylic acid: 14 to 1

The most common adverse effects with dupilumab were weight gain (21.8%), myalgias (20.0%), and migraines (14.5%).

The authors’ findings are strong in that they echo previous data on dupilumab efficacy and perhaps even show greater benefit from the treatment, which they note “may be due to the fact that a considerable proportion of the patients suffered from substantial type-II inflammation, as is vividly displayed by the extensive eosinophil tissue counts.”

One major limitation on their results is that the patients treated just with dupilumab all had a history of functional endoscopic sinus surgery (FESS) “without longer-lasting disease control, potentially causing a considerable bias.” Therefore, further studies should investigate why patients who have CRSwNP and undergo FESS tend to have disease relapse requiring additional treatment and surgeries despite “adequate postoperative care.”

Reference

Bertlich M, Freytag S, Dombrowski T, et al. Subgroups in the treatment of nasal polyposis with dupilumab: a retrospective study. Medicine (Baltimore). Published online November 11, 2022. doi:10.1097/MD.0000000000031031