Dupilumab shows slow, steady effectiveness for intractable prurigo in patients with atopic dermatitis

Abstract

Prurigo lesions in atopic dermatitis are intractable. This single-center, retrospective study examined dupilumab's clinical effects on intractable prurigo. Twenty adult atopic dermatitis patients (12 with prurigo, eight without) were administrated dupilumab. Its effects on itching and disease severity were examined with Numerical Rating Scale-Itch (NRS-I), Eczema Area and Severity Index (EASI), and Investigator Global Assessment (IGA) scores; body surface areas (BSA); and thymus-and activation-regulated chemokine (TARC), total immunoglobulin (Ig)E, and eosinophil levels. NRS-I scores, EASI scores, TARC levels, and total IgE levels before dupilumab treatment were not statistically different between the prurigo and non-prurigo groups. With dupilumab treatment, NRS-I scores, EASI scores, IGA scores, BSA, TARC levels, and total IgE levels were significantly reduced from baseline in both groups at 1-2 months and onward, but skin symptom improvement in the prurigo group was slower than in the non-prurigo group, as evidenced by significantly higher EASI scores, BSA, and TARC levels at several time points during the 12 months of dupilumab treatment. Prurigo patients were slower in EASI-50 achievement and significantly lower in EASI-90 achievement at 12 months than non-prurigo patients. Adherence to dupilumab was not different, but total equivalent amounts of concomitant therapeutic agents (corticosteroids and tacrolimus) used during dupilumab treatment were significantly higher in the prurigo group (median, 56.2 g/week) than in the non-prurigo group (median, 33.7 g/week). There were 2.2 adverse events per patient on average; ocular complaints were most frequent. Dupilumab was effective in treating intractable prurigo, but despite significantly greater concomitant therapeutic agent use, skin symptom improvement was slower in prurigo patients than in non-prurigo patients. K E Y W O R D S atopic dermatitis, prurigo, pruritus, thymus-and activation-regulated chemokine, treatment 1 | INTRODUC TI ON Atopic dermatitis (AD) is a pruritic, chronically relapsing eczematous condition 1 characterized by T-helper (Th)2-polarized immunity. 2 Dupilumab is a new biologic treatment for AD that interferes with the alpha subunit of the interleukin (IL)-4 receptor, resulting in the blockade of both the IL-4 and IL-13 signaling pathways, which play pivotal roles in the pathogenesis of AD. 3Patients with AD experience itchiness that can affect many aspects of life, 4 and prurigo lesions in those with AD are notably intractable. However, recent case reports have shown a favorable effect of dupilumab in treating intractable prurigo. 5,6 Thus, the purpose of this study was to investigate the clinical effects of dupilumab in the treatment of AD patients with prurigo nodularis (PN) and compare them with the effects of dupilumab in the treatment of AD patients without PN.

RNA sequencing reveals the transcriptome profile of the atopic prurigo nodularis with severe itching

“…Th2 responses, such as IL‐13 and IL‐4R, which were highly expressed in APN, suggest that the novel biologics for AD, dupilumab/tralokinumab/lebrikizumab, may be equally effective in the treatment of prurigo. The latest series of clinical trials confirmed this hypothesis, 20–23 but the onset time of dupilumab in the treatment of APN is often longer than that of AD, 4,12 suggesting the presence of other potential mechanisms underlying the pathogenesis of the former. Tsoi et al reported that IL‐31 plays a critical upstream role in the pathogenesis of PN 8 .…”

“…Prurigo nodularis (PN) is a chronic skin disease characterized by intensely pruritic nodular lesions 1,2 . It has greater itch intensity and causes poorer quality of life than other common skin disorders 2–4 . Traditional therapies such as antihistamines, glucocorticoids and phototherapy are largely ineffective for PN 2,3 .…”

“…1,2 It has greater itch intensity and causes poorer quality of life than other common skin disorders. [2][3][4] Traditional therapies such as antihistamines, glucocorticoids and phototherapy are largely ineffective for PN. 2,3 The morbidity of PN is reportedly associated with race.…”

Safety and effectiveness of dupilumab in the real‐world treatment of atopic dermatitis in Japan: 1‐year interim analysis from a post‐marketing surveillance

“…The present report confirmed this trend with a greater number of patients. Likewise, other real‐world studies in Japanese patients with AD have also shown marked and rapid improvement in skin eruptions and erythema, as well as in TARC and LDH serum levels at 1 month, while there was a gradual improvement in prurigo nodules and serum total IgE level 30–33 …”

Maintenance of response to dupilumab in prurigo nodularis: A retrospective cohort study

“…3 Existing clinical trials have only assessed response until 24 weeks, with long-term impact of therapy (including rates of secondary treatment failure) remaining unclear. 3 , 4 , 5 …”