Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the ...pathogenesis of prurigo nodularis.
We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously at baseline, week 4, and week 8, as compared with placebo, in patients with moderate-to-severe prurigo nodularis and severe pruritus. Moderate-to-severe prurigo nodularis was defined as 20 or more nodules, and severe pruritus was defined as a mean score of at least 7 for the worst daily intensity of pruritus on the numerical rating scale (scores range from 0 no itch to 10 worst itch imaginable). The primary outcome was the percent change from baseline in the mean peak score for pruritus on the numerical rating scale at week 4. Secondary outcomes included additional measures of itching and disease severity. Safety assessments were performed through week 18.
A total of 70 patients were randomly assigned in a 1:1 ratio to receive nemolizumab (34 patients) or placebo (36). The initial pruritus score on the numerical rating scale was 8.4 in each group. At week 4, the peak pruritus score on the numerical rating scale was reduced from baseline by 4.5 points (change, -53.0%) in the nemolizumab group, as compared with a reduction of 1.7 points (change, -20.2%) in the placebo group (difference, -32.8 percentage points; 95% confidence interval, -46.8 to -18.8; P<0.001). Results for secondary outcomes were in the same direction as for the primary outcome. Nemolizumab was associated with gastrointestinal symptoms (abdominal pain and diarrhea) and musculoskeletal symptoms.
Nemolizumab resulted in a greater reduction in pruritus and severity of skin lesions than placebo in patients with prurigo nodularis but was associated with adverse events. Larger and longer trials are needed to determine the durability and safety of nemolizumab for the treatment of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT03181503.).
Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically ...targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis.
We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16). The primary end point was a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12.
At week 12, the percentage of patients with a 90% or greater reduction in the PASI score was 77% (64 of 83 patients) for risankizumab (90-mg and 180-mg groups, pooled), as compared with 40% (16 of 40 patients) for ustekinumab (P<0.001); the percentage of patients with a 100% reduction in the PASI score was 45% in the pooled 90-mg and 180-mg risankizumab groups, as compared with 18% in the ustekinumab group. Efficacy was generally maintained up to 20 weeks after the final dose of 90 or 180 mg of risankizumab. In the 18-mg and 90-mg risankizumab groups and the ustekinumab group, 5 patients (12%), 6 patients (15%), and 3 patients (8%), respectively, had serious adverse events, including two basal-cell carcinomas and one major cardiovascular adverse event; there were no serious adverse events in the 180-mg risankizumab group.
In this phase 2 trial, selective blockade of interleukin-23 with risankizumab was associated with clinical responses superior to those associated with ustekinumab. This trial was not large enough or of long enough duration to draw conclusions about safety. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT02054481 ).
Summary
Background
Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs and symptoms of moderate‐to‐severe atopic dermatitis (AD).
Objectives
To ...evaluate the efficacy and safety of baricitinib with background topical corticosteroids (TCS) in patients with moderate‐to‐severe AD and inadequate response, intolerance or contraindication to ciclosporin A (CA).
Methods
In this double‐blind, randomized, placebo‐controlled, phase III study, patients were randomized 1: 1: 2: 1 to placebo (N = 93), baricitinib 1 mg (N = 93), 2 mg (N = 185) or 4 mg (N = 92) with background TCS. The primary endpoint was the proportion of patients receiving baricitinib 4 mg or 2 mg (+ TCS) vs. placebo + TCS who achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index (EASI 75) at week 16.
Results
Baricitinib 4 mg + TCS was superior to placebo + TCS for EASI 75 (4 mg: 32%, placebo: 17%, P = 0·031) at week 16 and for improvements in itch, skin pain and number of night‐time awakenings owing to itch. Improvements were maintained through 52 weeks of treatment. Treatment‐emergent adverse events (TEAEs) were more common with baricitinib than placebo (+ TCS); most were mild or moderate. The most frequent TEAEs with baricitinib 4 mg + TCS were nasopharyngitis, herpes simplex, influenza and headache. No deaths or deep vein thromboses were reported.
Conclusions
Baricitinib 4 mg + TCS improved the signs and symptoms of moderate‐to‐severe AD through 52 weeks of treatment in patients with inadequate response, intolerance or contraindication to CA. The safety profile was consistent with previous studies of baricitinib in moderate‐to‐severe AD.
What is already known about this topic?
Ciclosporin A is indicated for the treatment of atopic dermatitis that is refractory to topical therapies. However, its use is limited by safety concerns and it may not provide adequate response for some patients.
Baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor, has been shown to improve the signs and symptoms of moderate‐to‐severe atopic dermatitis as a monotherapy or in combination with topical corticosteroids.
What does this study add?
Baricitinib combined with background low‐ or moderate‐potency topical corticosteroids provided improvements in the signs and symptoms of moderate‐to‐severe atopic dermatitis through 1 year of treatment in patients with a contraindication, intolerance or failure to respond to ciclosporin A.
The most common treatment‐emergent adverse events with baricitinib 4 mg were nasopharyngitis, herpes simplex, influenza and headache.
The safety profile was consistent with previous studies in patients with moderate‐to‐severe atopic dermatitis.
Baricitinib 4 mg + TCS improved the signs and symptoms of moderate‐to‐severe AD through 52 weeks of treatment in patients with inadequate response, intolerance or contraindication to CA. The safety profile was consistent with previous studies of baricitinib in moderate‐to‐severe AD.
Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials.
We sought to assess the effectiveness and safety of ...dupilumab in adults with AD in a real-life French multicenter retrospective cohort.
We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up.
We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10−9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10−9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10−6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs.
No control group, missing data.
This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.
Immunoglobulin E (IgE) plays an essential role in many allergic diseases. This review highlights the role of IgE in atopic dermatitis (AD), a common, chronic, and complex skin inflammation, and the ...available therapeutic approaches that target IgE in AD. We examine the existing data showing the use of omalizumab, the only biologic anti-IgE therapy available in clinical use, plasma apheresis, and a combination of both therapeutic approaches for the treatment of AD. Existing data on the efficacy of omalizumab in AD are inconclusive. A limited number of randomised controlled studies, few uncontrolled prospective and retrospective reports, as well as multiple case series and case reports observed varying degrees of the efficacy of omalizumab in AD. Omalizumab displays a trend of higher efficacy in AD patients with low IgE levels compared with those with very high-to-extremely high serum IgE concentrations. Plasma apheresis and its combination with omalizumab show good efficacy, even in patients with unusually high serum IgE concentrations. Combining apheresis and anti-IgE treatment may serve as a comprehensive therapeutic approach for patients with elevated levels of IgE. Dedicated clinical studies with robust study designs are needed to establish the therapeutic efficacy of omalizumab in AD.
Summary
The visible light spectrum is wide, and it can be hypothesized that all the wavelengths between 400–700 nm do not induce the same photobiological effects on pigmentation. We assessed the ...potential pro‐pigmenting effects of two single wavelengths located at both extremities of the visible spectrum: the blue/violet line (λ = 415 nm) and the red line (λ = 630 nm). We made colorimetric, clinical, and histological assessments with increasing doses of those lights on healthy volunteers. Then, we compared these irradiations to non‐exposed and UVB‐exposed skin. Colorimetric and clinical assessments showed a clear dose effect with the 415‐nm irradiation, in both skin type III and IV subjects, whereas the 630 nm did not induce hyperpigmentation. When compared to UVB irradiation, the blue–violet light induced a significantly more pronounced hyperpigmentation that lasted up to 3 months. Histological examination showed a significant increase of keratinocyte necrosis and p53 with UVB, as compared to 415‐ and 630‐nm exposures.
An impaired inhibitory function of circulating CD4+CD25+ regulatory T (Treg) cells was reported to play a key role in alopecia areata (AA). We report the first use to our knowledge of low-dose ...interleukin 2 for treating severe AA by promoting the recruitment of Treg cells.
We conducted a prospective open pilot study in 5 patients with severe AA resistant to previous systemic treatments. Subcutaneous interleukin 2 (1.5 million IU/d) was administered during 5 days, followed by three 5-day courses of 3 million IU/d at weeks 3, 6, and 9. The primary outcome was the evolution of the Severity of Alopecia Tool (SALT) score, evaluated by 2 independent investigators on standardized photographs. Lesional skin biopsy specimens and peripheral blood lymphocyte phenotype were analyzed. The median SALT score went from 82 (range, 63-100) at baseline to 69 (range, 28-100) at 6 months. Immunochemical analysis revealed the appearance or a notable increase in Treg cell count in 4 of 5 patients at the end of the treatment compared with baseline. No serious adverse event was reported.
The partial regrowth achieved in 4 of 5 patients and the recruitment of Treg cells in lesional skin support the interest of promoting Treg cells for treating AA. Further investigations are now required to confirm and to optimize the design in order to enhance the Treg cell response.
clinicaltrials.gov Identifier: NCT01840046.
Findings of increased vascularization in melasma lesions and hyperpigmentation in acquired bilateral telangiectatic macules suggested a link between pigmentation and vascularization. Using ...high-magnification digital epiluminescence dermatoscopy, laser confocal microscopy, and histological examination, we showed that benign vascular lesions of the skin have restricted but significant hyperpigmentation compared with the surrounding skin. We then studied the role of microvascular endothelial cells in regulating skin pigmentation using an in vitro co-culture model using endothelial cells and melanocytes. These experiments showed that endothelin 1 released by microvascular endothelial cells induces increased melanogenesis signaling, characterized by microphthalmia-associated transcription factor phosphorylation, and increased tyrosinase and dopachrome tautomerase levels. Immunostaining for endothelin 1 in vascular lesions confirmed the increased expression on the basal layer of the epidermis above small vessels compared with perilesional skin. Endothelin acts through the activation of endothelin receptor B and the mitogen-activated protein kinase, extracellular signal–regulated kinase (ERK)1/2, and p38, to induce melanogenesis. Finally, culturing of reconstructed skin with microvascular endothelial cells led to increased skin pigmentation that could be prevented by inhibiting EDNRB. Taken together these results demonstrated the role of underlying microvascularization in skin pigmentation, a finding that could open new fields of research for regulating physiological pigmentation and for treating pigmentation disorders such as melasma.
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