xRead - Olfactory Disorders (September 2023)

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Biologics on CRSwNP-induced olfactory dysfunction

FIGURE3. Forest plots of olfactory measures.

most prominent. Medical treatment options for olfactory dysfunction caused by CRS include topical and systemic steroids and a wide range of other systemic and topical therapies. However, the efficacy of these treatments in im proving olfactory dysfunction, whether alone or in combi nation, remains elusive. A meta-analysis showed subjective improvement with oral, topical, or combined steroid treat ments, and lesser improvement in objective olfactory out comes. All other categories of medical regimens were not considered successful. 20 However, the main clinical prob lem with medical therapy is that, even in cases with a posi tive response, this is not sustained, and after a short period olfactory dysfunction returns. Sinus surgery is suggested when medical treatment fails. One meta-analysis showed olfaction improved in CRS patients undergoing FESS, based on the signifi cant improvement in all subjective and objective olfac tory measurements. 21 However, sinus surgery in a sig nificant percentage of patients may result in no change in olfactory outcome, but it can also cause harm, with some reports showing worsening increasing by up to 9%. 22 In addition, we note that surgery is not indi cated for CRS with anosmia as a sole symptom. We have also to consider that when medical therapy is effec tive, this is in the short term and that surgery is not al ways indicated, having sometimes serious complications. Within this therapeutic frame, novel systemic therapies such as biologics seem to be a very promising therapeutic alternative. It remains unclear when olfactory improvement should be expected. When biologics are given, usually responders can be identified in the relatively short period of about 8 weeks, with improved nasal obstruction being the most

striking change. In the dupilumab studies, olfaction showed similar early improvement, but this was a result of a com bined treatment with nasal steroids. 15,18 In other studies, olfaction showed a slower progression. 19 Thus, we would not recommend olfactory function as an early indicator of response to biologics. In all likelihood, early or later re sponse in olfaction is related to the degree of inflammatory changes of the olfactory epithelium, which varies widely among CRSwNP patients. There are some limitations to our meta-analysis. With the exception of the 3 similar, large-sample, well-conducted dupilumab studies that culminated in a quantitative synthe sis, the studies were characterized by small samples, short study periods, and often incompletely reported data, in ad dition to heterogeneity among study designs, making it im possible to compare the effect of the interventions. Despite the positive results in all 3 biologic categories, we were unable to conclude whether one monoclonal antibody was superior to the other, as all studies compared each category of biologic therapy only with placebo. No comparison was possible among the different subcategories of patients with olfactory dysfunction, such as hyposmics vs anosmics in CRSwNP cohorts. In addition, in most studies, the UPSIT was used as the primary endpoint to measure olfaction. The UPSIT assesses olfactory identification but does not take threshold or discrimination into consideration. Fur thermore, we should consider that psychophysical testing results is preferable to be analyzed using as criterion the clinically significant difference. This type of analysis was not possible with the available data as reported in the in cluded studies. Specifically for the results of our meta-analysis these should be assessed considering that patients who received

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

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