Chronic pruritus is a major symptom of atopic dermatitis (AD). Its etiopathogenesis is complex, and an understanding of the driving factors of its pathogenesis allows for the development of new molecule-targeted therapies. Dupilumab, targeting and blocking interleukin-4 (IL-4) and interleukin-13 (IL-13) molecules, has shown great efficacy in treating AD symptoms such chronic itching. We performed a retrospective observational study to evaluate possible chronic-itch-related characteristics and parameters in 356 AD patients who received dupilumab. The objective of the study was to evaluate the factors associated with the level of pruritus reported by patients at each of the 1575 detections in the form of the peak pruritus numerical rating scale (NRSpp) and sleep disturbance numerical rating scale (NRSsd). We focused on: the eczema area and severity index (EASI), dermatology life quality index (DLQI), patient-oriented eczema measure (POEMS), eosinophilia, L-lactate dehydrogenase (LDH), immunoglobulin E (IgE) and the time from the start of dupilumab therapy. NRSpp fell from 8.6 (sd 1.7) at baseline to 1.7 (sd 2.3) at 36 months and NRSsd from 7 (sd 3) to 0. Regarding the parameters that correlate with NRSpp, all the parameters analysed were significantly correlated except for eosinophils (p = 0.136). In the multivariate analysis, both considering and not considering treatment duration, the parameters were correlated (p < 0.001); EASI, DLQI, POEM, and LDH significantly correlated with NRSpp (p < 0.001 for each, except for LDH p = 0.003); while IgE tot lost significance (p = 0.337). Similar results were obtained for the parameters correlating with NRSsd. Our results confirm the efficacy of dupilumab on pruritus. The use of questionnaires such as DLQI and POEM is advisable in clinical practice and is adequate for assessing the impact of itching on AD. The low correlation of IgE and eosinophils, the ambiguity of LDH levels with the level of pruritus, and a poor clinical validity and unclear correlation with disease severity suggest a progressive abandonment of monitoring of these values.

Atopic dermatitis (AD) can be subclassified into the more frequent extrinsic type (EAD), with elevated serum IgE levels and frequent association with other atopic conditions, and the less frequent intrinsic type (IAD), with normal IgE levels and no history of atopy. This retrospective study has the objective to compare the efficacy of dupilumab therapy in patients with IAD versus EAD in a real-life setting. We studied a group of 360 patients treated with dupilumab for moderate-to-severe AD of whom 49 had IAD (IgE < 200 kU/L and no history of other atopic conditions) and 311 had EAD (IgE ≥ 200 kU/L and/or history of atopy). There were no statistically significant differences in the achievement of EASI75 between IAD and EAD patients either at 16, 32, or 48 weeks (61% vs. 50%; 66% vs. 60%; and 53% vs. 65%, respectively). Similarly, there were no statistically significant differences in the achievement of EASI90 or the reduction in NRSpp, NRSsd, and DLQI at each timepoint. Additionally, mean absolute eosinophils and IgE values were significantly higher in the EAD group at all timepoints. This study confirms that dupilumab, targeting the Th2 pathway, which is known to be overexpressed in all AD phenotypes, appears to be equally effective in the two populations regardless of IgE levels.

Background: Dupilumab, an interleukin (IL)-4 receptor-α inhibitor that blocks IL-4 and IL-13 signaling pathways, is an effective and well-tolerated therapy for moderate-to-severe atopic dermatitis (AD). However, an increased incidence of dupilumab-associated conjunctivitis has been reported in patients treated with dupilumab. In contrast, upadacitinib, a selective Janus kinase 1 inhibitor, is reported to have lower incidence of conjunctivitis than dupilumab. Objective: The aim of this retrospective study was to investigate ocular adverse events in adult patients with moderate-to-severe AD treated with upadacitinib after discontinuing treatment with dupilumab. Methods: In total, 33 patients were examined at the start of treatment with upadacitinib after discontinuation of dupilumab, then again after 4 weeks and every 12 weeks up to a maximum of 72 weeks. Results: Among the patients in the study, 14 had developed dupilumab-associated conjunctivitis during dupilumab treatment and had complete resolution of ocular symptoms after the switch to upadacitinib within the 1-month follow-up visit. In addition, only 1 patient treated with upadacitinib developed an episode of conjunctivitis. This condition was of mild severity and it spontaneously resolved quickly. Interestingly, this patient had no history of dupilumab-associated conjunctivitis. Conclusions: All patients who developed dupilumab-associated conjunctivitis experienced complete remission on upadacitinib and only 3% of the patients in our sample developed conjunctivitis after the start of treatment with upadacitinib. In light of this, upadacitinib appears to be a prudent and safe treatment option for AD patients with uncontrolled ocular symptoms associated with dupilumab therapy.

Background: De-escalation strategies have become increasingly used in the treatment of atopic Dermatitis® (AD) patients with dupilumab. Dose spacing (DS) refers to dose reduction by dosage elongation strategies from 2 to 8 weeks between dupilumab injections, in patients with stable response to treatment or affected by numerous adverse events. Objectives: Investigate safety and clinical effectiveness of DS strategy in AD patients treated with dupilumab. Methods: A retrospective cohort study was conducted on AD patients aged ≥18 years treated with dupilumab undergoing DS. Pre–post analyses were conducted on this cohort, termed cohort A, between effectiveness outcomes at baseline, at 16 weeks of treatment, at the index date identified as the mean follow-up time between dupilumab initiation and DS, and at subsequent two follow-up visits: T1 and T2. Based on the index date, a cohort B of AD patients on dupilumab treatment not experiencing DS was then compared with cohort A for the same outcomes at the same time points. Results: Seventy-three out of 452 patients treated with dupilumab underwent DS. The mean time since treatment initiation was 28.6 months. Mean Eczema Area Severity Index (EASI) from the index date remained stable until the second follow-up visit (T2) 0.2–0.8 with no significant pre–post differences ( P > 0.05). Similar considerations can be made for mean number rating scale worst pruritus (NRSp), numerical rating scale disturbs of sleeping/sleeping disturb (NRSsd), mean Dermatology Life Quality Index (DLQI), and EASI Head and Neck. Attainment of relative outcomes remained stable for EASI75, 90, ≤ 7, DLQI ≤ 5, and NRSp ≤ 4. When compared with cohort B, no clinically significant differences were observed in mean reductions in all outcomes analyzed. Conclusions: DS in our study appears to be an effective and safe strategy in treating patients with severe AD after the initial therapeutic response.