Nemolizumab is associated with a rapid improvement in atopic dermatitis signs and symptoms: subpopulation (EASI ≥ 16) analysis of randomized phase 2B study.

BACKGROUND: Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD). OBJECTIVE: Analyse onset of action of nemolizumab 30 mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate-to-severe AD. METHODS: Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores ≥ 16 from a phase 2b trial of moderate-to-severe AD. Endpoints were change in EASI score at week 16, peak pruritus numeric rating scale (PP-NRS), Investigator's Global Assessment (IGA), changes in sleep and responders with ≥ 4-point improvement on PP-NRS. RESULTS: There was a significantly greater itch relief apparent by Day 2 (-22.8% vs -12.3% PP-NRS; P = 0.005) which continued to improve through week 16 (-68.5% vs -30.9% PP-NRS; P < 0.001). At week 16, PP-NRS ≥ 4-point response of itch was observed in 68.0% nemolizumab vs 15.9% placebo patients (P ≤ 0.001). There was also a rapid improvement of sleep disturbance with nemolizumab 30 mg, with a significant separation from placebo by Day 3 (-26.6% vs -9.0%; P < 0.001) which further improved till week 16 (-76.0% vs -36.5%; P < 0.001). Also for the EASI score a separation between groups in favour of nemolizumab was observed by week 1 (P ≤ 0.001), which increased through week 16 (-68.6% vs. -42.6%; P = 0.002). Finally, the degree of response was greater in nemolizumab-treated patients; clinically relevant reductions of 75% EASI were observed in 50.0% of nemolizumab patients versus 15.9% of placebo patients, while 90% reductions were reported for 36.0% and 6.8% of patients, respectively (P < 0.001 for both). IGA success (score of 0/1) was 32.0% for nemolizumab vs 6.8% for placebo (P = 0.002). Nemolizumab was safe and well-tolerated in this population; nasopharyngitis and upper respiratory tract infection were the most common adverse events. CONCLUSIONS: Nemolizumab resulted in very rapid, sustained improvements of inflammation, pruritus and sleep in patients with EASI ≥ 16 at baseline.

The effect of neonatal head-irradiation and subsequent fasting on the mechanisms of catch-up growth.

The heads of 2 day old male and female rats were X-irradiated with 600 rad. Non-irradiated littermates served as controls. At 40 days of age groups of irradiated and non-irradiated rats were subjected to a 48 hour fast. Non-fasted groups of irradiated and non-irradiated rats were fed ad lib. and were used for comparative studies. Growth of body weight and tail length was recorded at intervals through 70 days of age. At sacrifice, pituitary weight, tibial length, and tibial epiphyseal width were also determined. The results confirm earlier findings that whole head irradiation produces reduced growth of body weight and of tail length which remains uncompensated by catch-up growth. After fasting and then refeeding normal catch-up growth acceleration occurred in both male and female irradiated and nonirradiated animals. The fasted non-irradiated animals caught up to the non-irradiated control rat size for both body weight and tail length. Similarly, the fasted irradiated rats caught up to the irradiated, non-fasted rat size, but did not catch up to the size of the non-irradiated controls. Pituitary weight and tibial length were significantly reduced in irradiated males and females. At sacrifice, no significant difference existed between the fasted and non-fasted subgroups. The tibial epiphyseal growth plate was not narrowed in irradiated rats; fasted rats had increased epiphyseal width during recovery in only one group. We conclude that the catch-up growth control is intact in the head-irradiated stunted rat. The findings suggest that the mechanism which recognizes normal body size (set-point for body size) and which determines the limit of catch-up growth acceleration is reset for a smaller body size by the head-irradiation.