Impact of <scp>BMI</scp> and quality of life on dupilumab response in chronic prurigo: A cohort study

Dupilumab, a human monoclonal antibody that blocks interleukin (IL)-4 and IL-13 signalling, is the first approved treatment for adults with moderate-to-severe chronic prurigo (CP).1 This study aimed to assess the long-term real-life efficacy and safety of dupilumab in adult patients with CP and to explore prognostic factors for treatment response. We conducted a retrospective multicentre cohort study (6 French hospitals and 1 Chinese hospital; July 2023 to November 2024) enrolling adult CP patients who had received dupilumab for more than 12 months. The primary outcome was the percentage of patients who achieved an Investigator Global Assessment Prurigo Nodularis Score of 0 or 1 (IGA PN-S 0–1) at 12 months after dupilumab initiation (M12). The secondary outcomes were: the percentage of patients with a ≥ 4-point reduction in the Worst Itch Numerical Rating Scale (WI-NRS); the median percentage change in the Sleep Visual Analogue Scale (Sleep VAS) and Dermatology Life Quality Index (DLQI); the percentage of patients who achieved an IGA PN-S 0-1 at M24 and M36 and the safety. Confidence intervals around proportions were estimated using Clopper–Pearson's exact confidence intervals. Univariate logistic models were used to assess the impact of baseline characteristics on IGA PN-S improvement at M12. Due to limited sample size, no multivariable analysis could be performed.2 The log-linearity assumption was assessed graphically by transforming the variable with a natural cubic spline. In case of violation, the variable was dichotomized at a threshold determined by a ROC curve analysis using the Youden index. We included 64 patients. At M12, 37 of 56 patients (66%) achieved an IGA PN-S 0-1, a rate that increased to 74% at M24 (20/27 patients) and 89% at M36 (8/9 patients) (Figure 1a). The univariate logistic models identified two variables whose baseline values were associated with the primary outcome (Table 1). A Body Mass Index (BMI) ≥ 25 kg/m2 at baseline (p = 0.009, clinical threshold for overweight) and an initial DLQI ≥18.5 (p = 0.002, threshold determined via ROC curve analysis with AUC = 0.777) were associated with a lower likelihood of achieving an IGA PN-S 0-1 at M12. Subgroup analysis suggested that the effect of BMI on dupilumab response was not explained by the country of origin. At M12, 50 of 61 patients (82%) (95% confidence interval, 70–91%) achieved pruritus improvement on WI-NRS (Figure 1b), the median change in Sleep VAS at M12 compared to M0 was 95% (IQR 68–100%) and the median change in DLQI was 9 (IQR 6–13). No significant differences were observed between patients from the French and Chinese centers. During the follow-up, 25 patients reported minor adverse events possibly related to dupilumab including eosinophilia (n = 2), conjunctivitis (n = 4), injection site reactions (n = 2) and head and neck flare-up (n = 1). One patient discontinued dupilumab because of arthralgia and asthenia. This real-life study highlighted the efficacy of dupilumab in adult patients with CP at 1 year, consistent with pivotal studies and other short-term real-life studies.3, 4 The small number of patients at M24 and M36 limited the robustness of conclusions regarding long-term efficacy. Detailed adherence data were not available in all patients. BMI data were consistent with recent studies suggesting a lower dupilumab response in obese patients with atopic dermatitis,5 raising the question of dose optimization. To our knowledge, there is no literature regarding the impact of initial DLQI on dupilumab response in CP which requires further investigation. In conclusion, exploratory analyses suggested that higher BMI and DLQI at baseline may negatively influence dupilumab response. Given the small cohort size, the retrospective design, the lack of a control group and of multivariate analysis, these findings should be interpreted cautiously and confirmed in larger prospective studies. None. None declared. Not applicable. All data were retrospectively collected and the study did not alter patient care. Patient non-opposition was sought for patient inclusion. The data that support the findings of this study are available from the corresponding author upon reasonable request.