xRead - Olfactory Disorders (September 2023)

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Tsetsos et al.

TABLE2. Summary of olfactory outcomes with dupilumab vs placebo

Dupilumab

Placebo

LSmean change from baseline

LSmean change from baseline

LS mean difference for dupilumab vs placebo (95%CI)

Study

Olfactory measure

Mean (SD)

Mean (SD)

p value

Bachert et al (2016) LIBERTYNP SINUS-24

UPSIT

28.7 (8.2)

14.1

16.2 (8.7)

− 0.7

14.8 (10.9 to 18.7)

< 0.001

UPSIT

25.39 (9.49)

11.26

14.56 (8.58)

0.7

10.56 (8.79 to 12.34)

< 0.0001

Loss of smell score (scale 0-3)

1.35 (0.99)

− 1.41

2.50 (0.77)

− 0.29

1.12 ( − 1.31 to − 0.93) < 0.0001

LIBERTYNP SINUS-52

UPSIT

23.89 (9.21)

9.71

13.30 (7.96)

− 0.81

10.52 (8.98 to 12.07)

< 0.0001

Loss of smell score (scale 0-3) − 0.98 ( − 1.15 to − 0.81) < 0.0001 Note : Loss of smell score was reported by participants using a 0 to 3 scale (0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms). CI = confidence interval; CRG = control group; LS = least squares; SD = standard deviation; TRG = treatment group; UPSIT = University of Pennsylvania Smell Identification Test. 1.55 (1.02) − 1.21 2.49 (0.79) − 0.23

Safety and adverse events Six RCTs reported a wide variety of adverse events, the majority of which were negligible, with the most common being upper respiratory tract infection and headache. A total of 39 serious adverse events were reported in 4 of the included RCTs. Three cases of death presented in 3 RCTs, 2 in the TRG (1 in the mepolizumab and 1 in the dupilumab group, respectively) 15,16 and 1 in the CRG, 15 none of which were attributed to the tested drug. Notably, no cases of olfactory deterioration or olfactory loss were reported in any of the 7 included studies. In addition, no qualitative dysfunction, such as parosmia or phantosmia, was reported. Discussion Biologics constitute a novel therapy for the management of several inflammatory conditions such as atopic dermatitis and asthma. Recently they have been suggested in several studies as an alternative therapeutic option for patients with CRSwNP. Overall, our meta-analysis has shown that, with the exception of 1 study, 14 all RCTs proved to be effective in improving olfaction in patients with this debilitating disease. Although a quantitative synthesis was not possible for the studies that assessed omalizumab and mepolizumab, both monoclonal antibody types seem to be an effective and safe therapeutic option for these patients. Moreover, dupilumab was evaluated in 3 large-sample, well-conducted RCTs, where the quantitative analysis undoubtedly showed a remarkable improvement of olfac tion promoting the inclusion of this novel therapy in the treatment of patients with refractory CRSwNP. It is widely accepted that CRSwNP is a disease with a high symptom burden, with loss of smell being one of the

certain period. 16 Similar to omalizumab, a quantitative syn thesis was not possible for mepolizumab due to a significant lack of statistical data.

Dupilumab Three RCTs were included in a meta-analysis of the primary outcome data. 15,18 All 3 had very similar study designs and biases, and their perceived homogeneity regarding the primary outcome was corroborated by an I 2 value of 0%. The fixed-effects model was used to perform statistical analysis. Objective olfactory outcomes after bio logic therapy were measured in the trials using the 40-item UPSIT. The 3 studies were pooled, comprising a total population of 784 patients. All studies used dupilumab in a comparison with placebo. The SMD of the pooled studies was 1.22 (95% CI, 1.06 to 1.37). This indicated a robust improvement in olfaction that clearly favored biologic therapy with dupilumab over placebo ( p < 0.00001) (Fig. 3). Subjective rating of loss of smell (score 0-3) was an additional outcome, having been assessed in 2 of the aforementioned studies. 15 The random-effects model was used to perform statistical analysis of the studies ( I 2 value of 68%). The SMD of the pooled studies was − 1.13 (95% CI, − 1.42 to − 0.84). A significant advan tage of dupilumab vs placebo in reducing loss-of-smell score was noted in patients with CRSwNP ( p < 0.00001) (Fig. 3). Overall, dupilumab use led to striking results in olfaction, as the percentage of anosmic patients decreased from 74% to 24% and from 79% to 30% in the SINUS-24 and SINUS 52 studies, respectively, whereas no change was seen in the placebo groups. 15

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

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