Comment on ‘Efficacy and tolerance of dupilumab in patients with moderate‐to‐severe atopic dermatitis and obesity’ by Dupuis et al.

We read with great interest the manuscript recently published by Dupuis et al. entitled 'Efficacy and tolerance of dupilumab in patients with moderate-to-severe atopic dermatitis and obesity', reporting that the efficacy of dupilumab in 96 patients with a body mass index (BMI) ≥ 30 kg/m2 was like that of the general population of adult atopic dermatitis (AD) patients.1 In our opinion, the manuscript is very interesting, and some strengths should be highlighted, particularly the detailed outcome measures (several AD scores used), the comparative data with non-obese patients, the longer follow-up (median duration of treatment of 18 months) and the multicentre design.1 However, some limitations should be discussed, mainly the limited data on obese subtypes (no sub-analysis based on classes of BMI were performed), the sample size and the lack of evaluation with previously published studies. In this context, we want to report a comparison with our experience assessing the effectiveness and safety of dupilumab for the management of 750 non-obese AD patients as compared with 89 subjects with a BMI ≥25 km/m2.2 In our study, non-obese patients showed a significant better improvement of all the investigated scores (Eczema Area Severity Index, Body Surface Area, Dermatology Life Quality Index) at week (W)16 as compared with obese subjects, becoming comparable from W24.2 Moreover, a subgroup analysis involving only obese patients with a BMI ≥ 30 (12 of 89, 13.48%) showed that clinical improvement was even more reduced in these cohort, being comparable to patients with BMI < 30 between W24 and 52.2 Therefore, according to Dupuis et al., we found a lower response in obese patient, particularly in short term. Reviewing current literature, data shown by Dupuis et al. and ours are in line with other real-life experiences which reported that a greater BMI was associated with a lower probability of reaching an improvement of Investigator Global Assessment (IGA) ≥2 points at W52 (p = 0.049),3 and that patients with a BMI < 24 seemed to have a better response to dupilumab (odds ratio: 2.36; EASI75 at W16).4 Moreover, Kato et al.5 reported that obesity might reduce the effectiveness of dupilumab in the long term. Finally, a base and covariate population pharmacokinetic analyses using data derived from Phase III studies on dupilumab use showed that body weight had a notable effect on central volume, explaining interindividual variability during dupilumab treatment,6 confirming the results of a recent study evaluating the exposure–response relationship of dupilumab in patients with AD and collecting data from six trials which found that older age, higher body weight and Asian race were associated with slightly lower Eczema Area Severity Index response.7 However, no clear covariates were identified on IGA response.7 Finally, an interesting result regarding the unexpected weight changes observed under dupilumab has been reported by Dupuis et al., confirming previous data by a Swedish study.8 In this context, the patient's weight should be considered during the choice of drug for AD management, also considering the emerging role of leptin and other adipokines.9 Certainly, further studies evaluating the weight changes during dupilumab treatment are mandatory to evaluate the potential impact of this drug on body weight. To sum up, current literature seems to suggest that a higher BMI is correlated with a lower effectiveness of dupilumab, especially during the first weeks of therapy. However, long-term effectiveness results are contradictory. The authors have nothing to report. None. None to declare. Not required. Data are reported in the current study.