Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials.

BACKGROUND: Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials. METHODS: ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349). FINDINGS: Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred. INTERPRETATION: Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved. FUNDING: Galderma.

An anti-hair loss treatment in the management of mild androgenetic alopecia: Results from a large, international observational study.

Androgenic alopecia (AGA) is a common and chronic condition. It may impact self-esteem, self-image and quality of life. Benefit, tolerability, cosmetic acceptance and patient satisfaction are key to ensure good treatment outcome. Hair loss improvement and hair quality with AC5 (2,4-Diamino-Pyrimidine-N-Oxyde, arginine, 6-O glucose linoleate (SP94), piroctone olamine and Vichy mineralizing water) once daily was assessed in 527 subjects with mild AGA in an open-label, observational, international real-life study. After 3 months, investigators evaluated the impact of AC5 on hair loss, product satisfaction and asked subjects about local tolerance; subjects assessed hair growth and quality and satisfaction. Data from 357 subjects were evaluable for the benefit analysis; 59.9% of subjects were female; the mean age was 33.6±8.7 years. Duration of hair loss was 1.62±2.24 years. 71.3% of women had a Ludwig score of 1 and 40.8% of men had a Hamilton Norwood score of 2. At the end of study, hair loss was reduced in 89.0% of subjects; it was slightly higher in women (92.5%) than in men (83.8%). Subject satisfaction on a scale from 0 (not satisfied at all) to 10 (completely satisfied) was 7.9±1.7. Tolerance was rated good to very good by 98.6% of all subjects. In conclusion, AC5 reduces mild AGA in both men and women with a pleasant texture. AC5 was well tolerated and highly appreciated.

[Prevention of hand dermatoses in small catering enterprises]. / Profilaktyka dermatoz rak w malych zakladach gastronomicznych.

BACKGROUND: Work in catering and food processing is mostly performed by hands. Mechanical, thermal and chemical agents, as well as damp working conditions and frequent hand washing aggravate skin irritation. The aim of the study was to test the efficacy of hydrophobic skin protection measure at these workplaces. MATERIALS AND METHODS: We recommended the prevention of contact skin disorders by using hydrophobic skin protection measure. The study was conducted in a group of 20 food service sector workers, They were interviewed about skin problems and skin protection measures. Tolb assess the effect of the protective preparation on the skin dermatological test procedures, corneometry and sebumetry, were applied, as well as the level of transepidermal water loss (TEWL) was measured. The same survey was performed in the control group composed of 10 workers who used and 10 who did not use barrier preparation. RESULTS: The respondents declared dryness, roughness, peeling, burning, redness, erythema of the skin. All who had applied barrier cream observed a significant improvement of the skin hydration increased by about 30%, and lubrication of the skin - by 11 times on average. Also the level of TEWL decreased by about 25%. CONCLUSIONS: The improvement of skin conditions and reduction of skin disorders were observed confirming the effectiveness of the protection of the skin from exposure to harmful factors. Knowledge about prevention of skin diseases should be promoted among employees of catering enterprises.

A survey of work-related skin diseases in different occupations in Poland.

Occupational skin disorders, in particular inflammations, dryness and erythema, in 80% of cases affect the skin of hands. The most frequent diagnosis, in over 90% of cases of occupational skin diseases, points to an irritant or allergic contact dermatitis. Our aim was to study the prevalence of self-reported skin symptoms on hands and forearms in different populations. The study was conducted on 581 healthcare workers, 61 hair stylists, 149 beauticians, 90 food services workers, 90 cleaners, 181 metal factory workers and 69 textile workers. Healthcare workers had greatest exposure. Eighty-six percent of dentists, 67% of midwives, 51% of nurses and 41% of physicians reported skin disorders. Problems with latex gloves were declared by 30% of healthcare workers. Thirty-four percent of food services workers, 24% of textile workers, 30% of metal factory workers, 21% of hair stylists and beauticians, and 64% of cleaners reported skin manifestations during the time of employment, which they thought could be work-related.