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Background: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA)., Research Design and Methods: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure., Results: Candida infections had an IR of 1.9 per 100 PY in patients with PsO ( N  = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA ( N  = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA ( N  = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit., Conclusions: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications., Trial Registration: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.

Background: Baricitinib treatment in adults with moderate-to-severe atopic dermatitis (AD) has demonstrated rapid improvements in itch as well as AD sign severity and affected body surface area as assessed by the Eczema Area and Severity Index (EASI) total score, whether administered as monotherapy or in combination with topical corticosteroids (TCS). As EASI clinical signs differ in time course and associated antecedents, the effects of baricitinib on each individual clinical sign are of interest., Objectives: In this post hoc analysis, we aimed to investigate the effects of baricitinib on individual EASI subscores, namely excoriation, oedema/papulation, erythema and lichenification, in both monotherapy and TCS combination therapy trials., Methods: We analysed the percent change from baseline in individual EASI subscores from three phase-III, double-blind, 16-week trials of baricitinib in monotherapy (BREEZE-AD1/BREEZE-AD2) and TCS combination therapy (BREEZE-AD7) cohorts via mixed model repeated measures (MMRM)., Results: Baricitinib 4 mg showed rapid and sustained improvements in all four clinical signs in both cohorts. Significant effects emerged at week 1 for excoriation, oedema/papulation and erythema scores in monotherapy (p < 0.001) and TCS combination therapy (p < 0.001, p < 0.01, p < 0.001), plateaued at week 4, and remained significant versus placebo through week 16. The effect on lichenification scores also emerged early, at week 1 in monotherapy (p < 0.05) and week 2 in combination therapy (p < 0.001), with scores continuously improving without a clear plateau. Effect magnitude was highest in excoriation scores, exhibiting near-maximal reduction in week 1 of monotherapy and remaining highest across all timepoints in combination therapy., Conclusions: Rapid and sustained improvements were observed across clinical signs of inflammation and particularly on excoriation following baricitinib treatment. Our findings suggest that selective inhibition of janus kinases 1 and 2 leads to rapid and sustained control of skin inflammation, and that rapid reductions in itch translate into early disruption of the itch-scratch cycle., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Introduction: Psoriasis localized at the scalp, face, nails, genitalia, palms, and soles can exacerbate the disease burden. Real-world studies comparing the effectiveness of treatments for these special areas are limited., Methods: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional, study comparing the effectiveness of anti-interleukin (IL)-17A biologics (ixekizumab and secukinumab) compared to other approved biologics and the pairwise comparative effectiveness of ixekizumab relative to five other individual biologics for patients with moderate-to-severe psoriasis. To determine special area involvement, physicians answered binary questions at baseline and week 12. The proportion of patients who achieved special area clearance at week 12 was assessed. Missing outcome data were imputed as non-response. Comparative treatment analyses were conducted using frequentist model averaging., Results: Of the 1,978 patients included, 83.4% had at least one special area involved at baseline with the scalp (66.7%) as the most frequently affected part, followed by nails (37.9%), face/neck (36.9%), genitalia (25.6%), and palms and/or soles (22.2%). Patients with scalp, nail, or genital, but not palmoplantar or face/neck psoriasis, had significantly higher odds of achieving clearance at week 12 in the anti-IL-17A cohort compared to the other biologics cohort. Patients with scalp psoriasis had a 10-20% higher response rate and significantly greater odds (1.8-2.3) of achieving clearance at week 12 with ixekizumab compared to included biologics., Conclusion: Biologics demonstrate a high level of clearance of special areas at week 12 in a real-world setting. Patients with scalp, nail, or genital involvement have significantly higher odds of clearance at week 12 with anti-IL-17A biologics compared to other biologics., Competing Interests: SP received consulting fees from Abbvie, Almirall, Celgene, Janssen, Leo-pharma, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz, UCB; speaker payments from Abbvie, Almirall, Celgene, Janssen, Leo-pharma, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz, UCB; support for attending meetings or travel from Abbvie, Almirall, Celgene, Janssen, Leo-pharma, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Pfizer, Sandoz, UCB. LP received consulting fees from AbbVie, Janssen Biotech, Novartis Pharmaceuticals Corporation, Eli Lilly, Bristol Myers Squibb; payment or honoraria for lecturers or presentations from AbbVie, Janssen Biotech, Novartis Pharmaceuticals Corporation, Eli Lilly and Company, Bristol Myers Squibb; participated on data safety monitoring board or advisory boards of AbbVie, Janssen Biotech, Novartis Pharmaceuticals Corporation, Eli Lilly, Bristol Myers Squibb. The institution of LP received funding for the present study. The institution of PB received funding from Pfizer. PB received consulting fees from LEO Pharma, Pfizer, Sanofi Genzyme, Eli Lilly, Novartis, Celgene, UCB Pharma, Biotest, Boehringer Ingelheim, AbbVie, Amgen, Arena Pharmaceuticals, GSK and Regeneron; received payment or honoraria for lectures and presentations from LEO Pharma, Pfizer, Sanofi Genzyme, Eli Lilly, Novartis, Celgene, UCB Pharma, Biotest, Boehringer Ingelheim, AbbVie, Amgen, Arena Pharmaceuticals, GSK and Regeneron; was a board member of the Austrian Society for Allergology and Immunology. RV was employed by Dermatrials Research Inc. and Venderm Consulting. RV has received grants from Abbvie, Amgen, Arcutis, Bausch, Health, Boehringer, Ingelheim, BMS, Celgene, Centocor, Dermira, Dermavant, Galderma, GlaxoSmithKline, Innovaderm, Janssen, LEO Pharma, Eli Lilly and Company, Mediji, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, Takeda and USB; Consulting fees from Abbvie, Actelion, Amgen, Aralez, Arcutis, Bausch-Health, Boehringer Ingelheim, BMS, Celgene, Cipher, Janssen, Galderma, GSK, Kabo-Care, LEO Pharma, Eli Lilly and Company, Merck, Novartis, Palladin, Pfizer, Sandoz, SUN, UCB and Viatris-Mylan; payment or honoraria for lectures or presentations from Abbvie, Actelion, Amgen, Arcutis, Bausch-Health, BMS, Celgene, Cipher, Janssen, Galderma, GSK, LEO pharma, Eli Lilly and Company, Merck, Novartis, Pfizer, Sun and USB; support for attending meetings or travel from Abbvie, Arcutis, Janssen and UCB. CM is a contractor of HaaPACs GmbH and conducted statistical analysis for this project on behalf of Eli Lilly and Company. NH, NT, GG, and CS are employees and minor shareholders of Eli Lilly and Company. ER is a former employee of Eli Lilly and Company and a minor stockholder and has also been a speaker and consultant for Eli Lilly and Company. The authors declare that this study received funding from Eli Lilly and Company. The funder was involved in study design, analysis and interpretation of data, the writing of this article and the decision to submit it for publication., (Copyright © 2023 Piaserico, Riedl, Pavlovsky, Vender, Mert, Tangsirisap, Haustrup, Gallo, Schuster and Brunner.)