xRead - Olfactory Disorders (September 2023)

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Tsetsos et al.

olfaction is still unpredictable, being related to multiple factors positively or negatively influencing the outcome. In addition, a positive effect on olfaction after FESS is usually an indirect result, as surgeons avoid surgical manipulations in the olfactory cleft due to possible postoperative fibrosis in this area. More recently, different monoclonal antibodies have been proposed as an alternative therapy targeting type 2 inflammatory response in the subgroup of patients with CRSwNP refractory to standard treatment. Specifically, omalizumab targets immunoglobulin E (IgE), reslizumab and mepolizumab target interleukin (IL)-5, and dupilumab targets the IL-4 receptor- α subunit (IL-4R α ) (inhibit ing signaling of both IL-4 and IL-13). All have shown encouraging results in different randomized, controlled trials (RCTs) by reducing the polyp burden and leading to symptom relief. In addition, biologic therapy has been characterized as a safe and well-tolerated treatment option. 13 The aim of this study was to review all existing evidence concerning the efficacy of monoclonal antibodies on olfac tory dysfunction in adults with CRSwNP. Materials and methods This systematic review was performed according to the Pre ferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) 2009 checklist. MEDLINE, ScienceDi rect, and the Cochrane Library electronic databases were searched from October 1 to 15, 2019, to identify studies that answered the question of interest. In addition, a search was done for eligible trials in multiple trial registries, in cluding www.clinicaltrials.gov, the European Union Clin ical Trials Register, and the International Clinical Trials Registry platforms. The search also included the archives of major recent ear-nose-throat conferences, with the inten tion of identifying grey literature. References of identified studies and relevant review articles were cross-referenced for additional candidate articles. No time or language lim itation was applied. As this study was a systemic review of published articles, neither informed consent nor ethics approval was required. Two reviewers (N.T. and I.K.) independently executed the comprehensive literature search. The following free-text terms were used for the MEDLINE database search: (rhi nosinusitis OR sinusitis OR rhinitis OR “nasal polyps” OR “nasal polyposis” OR smell OR olfaction OR olfactory) AND (“monoclonal antibodies” OR biologics OR human ized OR anti-IgE OR anti-IL5 OR anti-IL4/IL13 OR oma lizumab OR mepolizumab OR dupilumab OR reslizumab) AND (therapy OR treatment OR management) and lim ited to studies of human subjects. This search strategy was modified accordingly to suit the search rules of the other databases. The study selection process was carried out indepen dently by the 2 reviewers and disagreements were resolved by consensus. The inclusion and exclusion criteria of

studies in this systematic review were specified before the literature search. Any studies that met the following criteria were eligible for inclusion: (1) RCTs comparing the use of monoclonal antibody therapy with placebo or another therapy; (2) the study population comprised adult patients ( > 18 years old) with CRSwNP; and (3) outcome measured was change in olfaction. Studies were excluded if they: (1) included patients with medical conditions having an established associa tion with nasal polyposis, such as cystic fibrosis, Churg Strauss syndrome, Kartagener syndrome, and ciliary dysk inesia; and (2) included patients with allergic fungal rhinosinusitis. Two reviewers (N.T. and I.K.) independently reviewed each study according to the predefined criteria for eligibil ity, and, finally, extracted data. Any disagreement in the process of study selection or data extraction was resolved through consensus. A predefined form was used to extract data from each study. The following data were recorded from each of the eligible studies: first author, year of pub lication, country, study design, study sample, diagnosis, length of follow-up, type of intervention, and minor and major reported side effects. The Cochrane risk-of-bias tool was used to assess the quality of included studies. Two independent reviewers performed the quality assessment and any uncertainties were resolved through consensus. A score of “high,” “low,” or “unclear” was assigned to the following items: (1) random sequence generation; (2) allocation conceal ment; (3) blinding of participants and personnel; (4) blind ing of outcome assessment; (5) incomplete outcome data; (6) selective outcome reporting; and (7) other sources of bias. The primary outcome of interest in this study was olfac tory function change from baseline assessment by means of the 40-item University of Pennsylvania Smell Identification Test (UPSIT) or any other objective or subjective measure ment including scoring systems. Safety was assessed on the basis of major and minor adverse events reported in the studies. Researchers decided to include outcome measures reported in at least 2 different studies. If available, statistical data, such as confidence in tervals, standard deviations, p values, etc, were mentioned; if not, results were only narratively described. The ultimate objective of this research was to culminate in a quantitative synthesis of the main outcome measures. Outcomes were analyzed as continuous variables accord ing to Review Manager (RevMan for Windows version 5.3; The Nordic Cochrane Centre, The Cochrane Collab oration, Copenhagen, Denmark, 2014). The standardized mean difference (SMD) and corresponding 95% confidence interval (CI) were calculated. The 95% CI was used and dif ferences were considered significant when p 0.05. Het erogeneity across studies was assessed with the I 2 statistic. If heterogeneity was significant, the random effects model was used. The fixed effects model was used if heterogeneity was nonsignificant.

International Forum of Allergy & Rhinology, Vol. 10, No. 7, July 2020

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