Secukinumab induction and maintenance therapy in moderate‐to‐severe plaque psoriasis: a randomized,double‐blind,placebo‐controlled,phase II regimen‐finding study

Background Interleukin (IL)‐17A has major proinflammatory activity in psoriatic lesional skin. Objectives To assess the efficacy and safety of secukinumab, a fully human IgG1κ monoclonal anti‐IL‐17A antibody, in moderate‐to‐severe plaque psoriasis in a phase II regimen‐finding study. Methods A total of 404 patients were randomized to subcutaneous placebo (n = 67) or one of three secukinumab 150 mg induction regimens: single (week 0; n = 66), early (weeks 0, 1, 2, 4; n = 133) and monthly (weeks 0, 4, 8; n = 138 patients). The primary outcome was ≥ 75% improvement from baseline Psoriasis Area and Severity Index score (PASI 75) at week 12. PASI 75 responders from active treatment arms at week 12 were rerandomized to either a fixed‐interval (secukinumab 150 mg at weeks 12 and 24; n = 65) or a treatment‐at‐start‐of‐relapse maintenance regimen (secukinumab 150 mg at visits at which a start of relapse was observed; n = 67). Results At week 12, early and monthly induction regimens resulted in higher PASI 75 response rates vs. placebo (54·5% and 42·0% vs. 1·5%; P < 0·001 for both). Among PASI 75 responders at week 12 entering the maintenance period, PASI 75 and PASI 90 achievement at least once from week 20 to week 28 was superior with the fixed‐interval regimen [85% (n = 55) and 58% (n = 38), respectively] vs. the start‐of‐relapse regimen [67% (n = 45), P = 0·020, and 21% (n = 14), respectively]. Fifteen weeks after last study drug administration, < 10% of patients in the fixed‐interval and start‐of‐relapse groups experienced a start of relapse. No immunogenicity was observed, and no injection‐site reactions were reported. Reported cases of neutropenia were mild‐to‐moderate (≤ grade 2); none was associated with clinically significant adverse events or resulted in study discontinuation. Due to the brief duration of the safety assessment, no firm conclusions can be drawn regarding long‐term safety. Conclusions Secukinumab shows efficacy for induction and maintenance treatment of moderate‐to‐severe plaque psoriasis.     

Phase 2a,randomized, double‐blind,placebo‐controlled,multicenter, parallel‐group study of a H4R‐antagonist (JNJ‐39758979) in Japanese adults with moderate atopic dermatitis

This trial was conducted to evaluate the safety and efficacy of the H₄R‐antagonist JNJ‐39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ‐39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double‐blind, multicenter, placebo‐controlled study. Primary efficacy was assessed via week‐6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient‐reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty‐eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end‐point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ‐39758979 100 mg (?3.7) and 300 mg (?3.0) versus placebo (?1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ‐39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ‐39758979 and placebo with the exception of two patients (both receiving JNJ‐39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H₄R‐antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ‐39758979 appears to be associated with drug‐induced agranulocytosis, likely an off‐target effect.     

Ixekizumab treatment for psoriasis: integrated efficacy analysis of three double‐blinded,controlled studies (UNCOVER‐1, UNCOVER‐2, UNCOVER‐3)

Psoriasis is a disease that causes the skin to form thick scales that get red, itchy, and dry. About 2–4% of the Western population has psoriasis. We tested if ixekizumab, an approved psoriasis treatment, was better at improving psoriasis symptoms than placebo (a nonactive drug) or etanercept (another approved psoriasis treatment). Patients from 21 countries were included. We combined data from 3 different studies where patients were given 80 mg of ixkeizumab every 2 weeks, 80 mg of ixekizumab every 4 weeks, 50 mg of etanercept twice weekly (only in 2 studies), or placebo. Patients who were given ixekizumab started with a 160‐mg initial dose. We measured psoriasis improvement by the percentage of patients who were rated by their physician as having little or no psoriasis after 12 weeks of treatment [sPGA (0, 1)]. Patients who improved by 75% from their initial (baseline) psoriasis assessment [PASI 75] were also considered to have benefited from treatment. We found that ixekizumab treatment was better than placebo and etanercept when measured by the percentage of patients who had these results [sPGA 0, 1 and PASI 75]. Patients treated with ixekizumab started to do better than those treated with placebo or etanercept as early as Week 1. Patients had some side effects when taking etanercept or ixekizumab, but about 95% stayed in the study. Ixekizumab given every 2 weeks was better than ixekizumab given every 4 weeks during the first 12 weeks. Patients who take ixekizumab for their psoriasis are likely to have a good response.     

Juvenile,insulin‐dependent diabetes mellitus,type 1‐related dermatoses

Juvenile insulin‐dependent diabetes mellitus type 1 (IDDM) is a well‐recognized worldwide entity, the significance of which has increased because of its recent upsurging trends, warranting attention on variety of its clinical expressions, in particular, pertaining to skin, an aspect seldom taken cognizance of. Hence an endeavour to recap the related dermatoses, such as limited joint mobility syndrome including sclerodermoid (scleroderma–like) changes, xerosis, necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic foot syndrome, has been made. Complexities relating to the recently explored issues of atopic dermatitis and drug hypersensitivity syndrome have also been covered adequately. In addition, the current concepts of the physiopathology of type 1 diabetes‐related dermatoses are briefly recapitulated for clarity.