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Pediatric Dermatology 2023This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/OBJECTIVES
This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata (AA) in patients aged 12-17 years.
METHODS
In ALLEGRO-2b/3, patients aged ≥12 years with AA and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (±4-week 200-mg loading dose) or 10 mg or placebo for 24 weeks. In a subsequent 24-week extension period, ritlecitinib groups continued their doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily. Clinician- and patient-reported hair regrowth outcomes and safety were assessed.
RESULTS
In total, 105 adolescents were randomized. At Week 24, 17%-28% of adolescents achieved a Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair) in the ritlecitinib 30 mg and higher treatment groups versus 0% for placebo. At Week 48, 25%-50% of patients had a SALT score ≤20 across ritlecitinib treatment groups (30 mg and higher). Adolescents reporting that their AA "moderately" or "greatly" improved were 45%-61% in the ritlecitinib groups (30 mg and higher) (vs. 10%-22% for placebo) at Week 24 and 44%-80% at Week 48. The most common adverse events in adolescents were headache, acne, and nasopharyngitis. No deaths, major adverse cardiovascular events, malignancies, pulmonary embolisms, opportunistic infections, or herpes zoster infections were reported.
CONCLUSION
Ritlecitinib treatment demonstrated clinician-reported efficacy, patient-reported improvement, and an acceptable safety profile through Week 48 in adolescents with AA with ≥50% scalp hair loss.
Topics: Adolescent; Humans; Alopecia Areata; Carbazoles; Double-Blind Method; Protein Kinase Inhibitors; Severity of Illness Index
PubMed: 37455588
DOI: 10.1111/pde.15378 -
Journal of the American Academy of... Dec 2023
Review
Topics: Humans; Alopecia Areata; Alopecia; Piperidines
PubMed: 37024053
DOI: 10.1016/j.jaad.2023.03.041 -
Pharmacological Research Feb 2024Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one of the most important drug targets in the 21st... (Review)
Review
Owing to the dysregulation of protein kinase activity in many diseases including cancer, this enzyme family has become one of the most important drug targets in the 21st century. There are 80 FDA-approved therapeutic agents that target about two dozen different protein kinases and seven of these drugs were approved in 2023. Of the approved drugs, thirteen target protein-serine/threonine protein kinases, four are directed against dual specificity protein kinases (MEK1/2), twenty block nonreceptor protein-tyrosine kinases, and 43 inhibit receptor protein-tyrosine kinases. The data indicate that 69 of these drugs are prescribed for the treatment of neoplasms. Six drugs (abrocitinib, baricitinib, deucravacitinib, ritlecitinib, tofacitinib, upadacitinib) are used for the treatment of inflammatory diseases (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, and ulcerative colitis). Of the 80 approved drugs, nearly two dozen are used in the treatment of multiple diseases. The following seven drugs received FDA approval in 2023: capivasertib (HER2-positive breast cancer), fruquintinib (metastatic colorectal cancer), momelotinib (myelofibrosis), pirtobrutinib (mantle cell lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma), quizartinib (Flt3-mutant acute myelogenous leukemia), repotrectinib (ROS1-positive lung cancer), and ritlecitinib (alopecia areata). All of the FDA-approved drugs are orally effective with the exception of netarsudil, temsirolimus, and trilaciclib. This review summarizes the physicochemical properties of all 80 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, polar surface area, potency, solubility, lipophilic efficiency, and ligand efficiency.
Topics: Humans; Adult; Protein Kinase Inhibitors; Alopecia Areata; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Protein Serine-Threonine Kinases; Protein Kinases; Neoplasms
PubMed: 38216005
DOI: 10.1016/j.phrs.2024.107059 -
Frontiers in Medicine 2023
PubMed: 37692788
DOI: 10.3389/fmed.2023.1275332 -
Indian Dermatology Online Journal 2023Micropigmentation and microblading is a popular technique now a days which is used as a semi permanent method for camoflaging various dermatological indications. This... (Review)
Review
Micropigmentation and microblading is a popular technique now a days which is used as a semi permanent method for camoflaging various dermatological indications. This article will elaborate upon various indications of micropigmenation. Micropigmentation is used in variety of dermatological conditions like semi permanent make up and vitiligo (stable forms). In this technique, a thorough knowledge of the indication and colour theory is crucial to achieve near to natural output. Micropigmentation or medical tattooing is a novel and easy to learn technique to camouflage various dermatological conditions like stable vitiligo, alopecia (androgenetic alopecia or stable alopecia areata) as well as for semi permanent make up.
PubMed: 37727553
DOI: 10.4103/idoj.idoj_767_21 -
Journal of the American Academy of... Aug 2023Trichoscopy is currently regarded as an essential part of the hair loss consultation. It allows visualization of morphologic structures that are not obvious to the naked... (Review)
Review
Trichoscopy is currently regarded as an essential part of the hair loss consultation. It allows visualization of morphologic structures that are not obvious to the naked eye, including peri- and interfollicular skin surface abnormalities and changes to hair shaft thickness and shape. In this paper, we aim to discuss current knowledge on trichoscopy of the most common forms of scarring and nonscarring alopecias.
Topics: Humans; Cicatrix; Alopecia; Hair; Ambulatory Care Facilities; Referral and Consultation
PubMed: 37591567
DOI: 10.1016/j.jaad.2023.04.033 -
Dermatology and Therapy Oct 2023Alopecia areata (AA) is a complex autoimmune disease manifesting as a chronic inflammatory disease characterized by non-scarring patches of hair loss over the face,... (Review)
Review
Alopecia areata (AA) is a complex autoimmune disease manifesting as a chronic inflammatory disease characterized by non-scarring patches of hair loss over the face, scalp, and body. Several treatments have been proposed for AA, but none are curative nor achieve a state of remission. The present consensus statement aims to present the evidence- and experience-based recommendations on the diagnosis and management of AA in Saudi Arabia. The Ministry of Health in Saudi Arabia has opted to initiate a meeting of a multidisciplinary group to discuss and concede on this topic. Eight dermatology experts and clinical pharmacists convened in eight consensus meetings. All content presented in this document was agreed upon by this working group, including diagnosis and severity assessment, prognostic indicators, and therapeutic options for AA. Special consideration was given to special patient populations including pediatric patients and patients with less frequent presentations of AA. Updates of the current recommendations will take place as new evidence evolves in the treatment of AA.
PubMed: 37558830
DOI: 10.1007/s13555-023-00991-3 -
Journal of the American Academy of... Sep 2023Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up).
BACKGROUND
Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed.
OBJECTIVE
To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab.
METHODS
Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included. All patients received 30-mg upadacitinib during the open-label period. We report results of a prespecified interim OLE 16-week analysis.
RESULTS
Patients (n = 239) continuing upadacitinib maintained high levels of skin and itch response. Patients (n = 245) switching from dupilumab experienced additional incremental improvements in clinical responses within 4 weeks of starting upadacitinib. Most patients who did not achieve adequate clinical responses with dupilumab did so with upadacitinib. The safety profile of upadacitinib up to 40 weeks (week 16 of OLE) was consistent with previous phase 3 AD studies, with no new safety risks observed.
LIMITATIONS
Open-label study design.
CONCLUSIONS
Clinical responses are maintained with continuous upadacitinib through 40 weeks and patients regardless of prior dupilumab response experienced improved outcomes when switched to upadacitinib. No new safety risks were observed.
Topics: Adult; Humans; Dermatitis, Atopic; Treatment Outcome; Double-Blind Method; Severity of Illness Index
PubMed: 37230366
DOI: 10.1016/j.jaad.2023.05.033 -
Nature Genetics Aug 2023Genome-wide association studies have identified many loci associated with hair and skin disease, but identification of causal variants requires deciphering of...
Genome-wide association studies have identified many loci associated with hair and skin disease, but identification of causal variants requires deciphering of gene-regulatory networks in relevant cell types. We generated matched single-cell chromatin profiles and transcriptomes from scalp tissue from healthy controls and patients with alopecia areata, identifying diverse cell types of the hair follicle niche. By interrogating these datasets at multiple levels of cellular resolution, we infer 50-100% more enhancer-gene links than previous approaches and show that aggregate enhancer accessibility for highly regulated genes predicts expression. We use these gene-regulatory maps to prioritize cell types, genes and causal variants implicated in the pathobiology of androgenetic alopecia (AGA), eczema and other complex traits. AGA genome-wide association studies signals are enriched in dermal papilla regulatory regions, supporting the role of these cells as drivers of AGA pathogenesis. Finally, we train machine learning models to nominate single-nucleotide polymorphisms that affect gene expression through disruption of transcription factor binding, predicting candidate functional single-nucleotide polymorphism for AGA and eczema.
Topics: Humans; Scalp; Chromatin; Genome-Wide Association Study; Transcriptome; Alopecia Areata; Hair Follicle; Eczema
PubMed: 37500727
DOI: 10.1038/s41588-023-01445-4