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Acta Medica Philippina 2024Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by , a normal commensal in the skin. Keratolytic agents are popular, cheap, and...
BACKGROUND
Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by , a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking.
OBJECTIVES
To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review.
METHODS
We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of 12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www.isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes.
RESULTS
We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole, bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment.
CONCLUSION
It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance and occurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.
PubMed: 38939846
DOI: 10.47895/amp.vi0.5605 -
Pharmaceutics Jun 2024Biodegradable aliphatic polyester formulations as carriers for topical drug delivery show the potential to encapsulate structurally different therapeutic compounds....
Biodegradable aliphatic polyester formulations as carriers for topical drug delivery show the potential to encapsulate structurally different therapeutic compounds. Poly(octamethylene suberate) (POS) nanoparticles (POS-NPs) were used as a matrix to encapsulate four therapeutic molecules used to treat skin disorders: caffeine (CF), quercetin (QR), hydrocortisone (HC), and adapalene (AD). Hydrophobicity and chemical structure of bioactive compounds (BCs) influenced the physicochemical stability of drug-loaded nanoparticles. The particle size of drug-loaded nanoparticles was between 254.9 nm for the CF-POS-NP and 1291.3 for QR-POS-NP. Particles had a negative charge from -27.6 mV (QR) to -49.2 mV (HC). Drug loading content for all BC-POS-NPs varies between 36.11 ± 1.48% (CF-POS-NP) and 66.66 ± 4.87% (AD-POS-NP), and their entrapment efficiency is relatively high (28.30 ± 1.81% and 99.95 ± 0.04%, respectively). Calorimetric analysis showed the appearance of polymorphism for AD- and HC-loaded systems and the drug's complete solubilisation into all nanoparticle formulations. FTIR and NMR spectra showed apparent drug incorporation into the polymer matrix of NPs. The encapsulation of BCs enhanced the antioxidative effect. The prepared POS nanoparticles' cytotoxicity was studied using two dermal cell lines, keratinocyte (HaCaT) cells and fibroblasts (HDFn). The nanoparticle cytotoxic effect was more substantial on HaCaT cell lines. A reconstructed human epidermis (RHE) was successfully used to investigate the penetration of polymeric NPs. Based on permeation and histology studies, HC-POS-NPs and CF-POS-NPs were shown not to be suitable for dermal applications with the explored drug concentrations. AD presents a high permeation rate and no toxic impact on RHE.
PubMed: 38931876
DOI: 10.3390/pharmaceutics16060753 -
Crystal Growth & Design Jun 2024Lipophilic aggregation using adamantanes is a widely exploited molecular property in medicinal and materials chemistry. Adamantanes are traditionally installed to...
Lipophilic aggregation using adamantanes is a widely exploited molecular property in medicinal and materials chemistry. Adamantanes are traditionally installed to molecular units via covalent bonds. However, the noncovalent installation of adamantanes has been relatively underexplored and presents the potential to bring properties associated with adamantanes to molecules without affecting their intrinsic properties (e.g., pharmacophores). Here, we systematically study a series of adamantanecarboxylic acids with varying substitution levels of methyl groups and their cocrystals with bipyridines. Specifically, single-crystal X-ray diffraction shows that while the directionality of single-component adamantanes is notably sensitive to changes in methyl substitution, hydrogen-bonded cocrystals with bipyridines show consistent and robust packing due to π-stacking predominance. Our observations are supported by Hirshfeld surface and energy framework analyses. The applicability of cocrystal formation of adamantanes bearing carboxylic acids was used to generate the first cocrystals of adapalene, an adamantane-bearing retinoid used for treating acne vulgaris. We envisage our study to inspire noncovalent (i.e., cocrystal) installation of adamantanes to generate lipophilic aggregation in multicomponent systems.
PubMed: 38911135
DOI: 10.1021/acs.cgd.4c00457 -
Archives of Dermatological Research Jun 2024Acanthosis nigricans (AN), with an estimated prevalence of 19.4% in the U.S., presents as hyperpigmented, velvety plaques in intertriginous regions. Acanthosis... (Review)
Review
Acanthosis nigricans (AN), with an estimated prevalence of 19.4% in the U.S., presents as hyperpigmented, velvety plaques in intertriginous regions. Acanthosis Nigricans negatively affects psychological well-being and particularly impacts skin of color individuals. Addressing the underlying cause of acanthosis nigricans, as current guidelines recommend, is often challenging. This highlights the importance of skin directed treatment for acanthosis nigricans. This systematic review evaluated topical, laser, and oral treatments for acanthosis nigricans and provides evidence-based recommendations for clinical use. Adhering to PRISMA guidelines, we evaluated 19 clinical trials investigating topical, oral, and laser interventions for acanthosis nigricans. Oxford Centre for Evidence-Based Medicine guidelines were used to make clinical recommendations. We strongly recommend topical tretinoin (grade A) and endorse the appropriate use of adapalene gel, urea cream, and fractional carbon dioxide laser therapy (grade B). Further research is essential to enhance our understanding of alternative treatments to determine additional evidence-based recommendations. This review aims to guide clinicians in managing acanthosis nigricans, especially when direct treatment of underlying conditions is impractical.
Topics: Humans; Acanthosis Nigricans; Administration, Oral; Laser Therapy; Clinical Trials as Topic; Administration, Cutaneous; Evidence-Based Medicine; Dermatologic Agents; Administration, Topical; Lasers, Gas; Tretinoin; Treatment Outcome
PubMed: 38904687
DOI: 10.1007/s00403-024-02931-3 -
Journal of Drugs in Dermatology : JDD Jun 2024Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the first fixed-dose triple-combination approved for the treatment of acne. This... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the first fixed-dose triple-combination approved for the treatment of acne. This post hoc analysis investigated the efficacy and safety of CAB in pediatric (<18 years) and adult (greater than or equal to 18 years) participants.
METHODS
In two multicenter, double-blind, phase 3 studies (NCT04214639 and NCT04214652), participants greater than or equal to 9 years of age with moderate-to-severe acne were randomized (2:1) to 12 weeks of once-daily treatment with CAB or vehicle gel. Pooled data were analyzed for pediatric and adult subpopulations. Assessments included treatment success (greater than or equal to 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 0 [clear] or 1 [almost clear], inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability.
RESULTS
At week 12, treatment success rates for both pediatric and adult participants were significantly greater with CAB (52.7%; 45.9%) than with vehicle (24.0%; 23.5%; P<0.01, both). CAB-treated participants in both subgroups experienced greater reductions from baseline versus vehicle in inflammatory (pediatric: 78.6% vs 50.4%; adult: 76.6% vs 62.8%; P<0.001, both) and noninflammatory lesions (pediatric: 73.8% vs 41.1%; adult: 70.7% vs 52.2%; P<0.001, both). Acne-QoL improvements from baseline to week 12 were significantly greater with CAB than with a vehicle. Most TEAEs were of mild-to-moderate severity; no age-related trends for safety/tolerability were observed. Conclusions: CAB gel demonstrated comparable efficacy, quality of life improvements, and safety in pediatric and adult participants with moderate-to-severe acne. As the first fixed-dose, triple-combination topical formulation, CAB represents an important new treatment option for patients with acne. J Drugs Dermatol. 2024;23(6):394-402. doi:10.36849/JDD.8357.
Topics: Humans; Acne Vulgaris; Clindamycin; Child; Double-Blind Method; Adolescent; Female; Male; Gels; Adult; Drug Combinations; Benzoyl Peroxide; Treatment Outcome; Young Adult; Dermatologic Agents; Quality of Life; Administration, Cutaneous; Severity of Illness Index
PubMed: 38834226
DOI: 10.36849/JDD.8357 -
Archives of Dermatological Research May 2024Topical adapalene gel is an effective and well tolerated acne treatment that transitioned from prescription to over-the-counter (OTC) availability in 2016. Historically,...
Topical adapalene gel is an effective and well tolerated acne treatment that transitioned from prescription to over-the-counter (OTC) availability in 2016. Historically, prescription to OTC transitions have lowered costs to patients and payers and increased access to medications. This study used sales and prescriber data to assess access to topical retinoid therapies and their costs in the pre- and post- Rx-to-OTC transition. We demonstrate that the prescription to OTC transition of adapalene gel increased access to this medication, while lowering costs to patients and payers, including Medicare patients. These results provide a necessary call to action for future OTC shifts with other high safety profile, well-tolerated medications in ultimate efforts and hopes of cost savings for patients, insurers, and Medicare within our healthcare industry.
Topics: Humans; Adapalene; Nonprescription Drugs; Acne Vulgaris; Dermatologic Agents; United States; Administration, Topical; Prescription Drugs; Drug Costs; Medicare; Health Services Accessibility; Cost Savings
PubMed: 38734769
DOI: 10.1007/s00403-024-02890-9 -
Cureus Apr 2024Acne vulgaris, commonly called acne, is a skin condition affecting many individuals globally. It is a chronic condition characterized by developing pimples, blackheads... (Review)
Review
Acne vulgaris, commonly called acne, is a skin condition affecting many individuals globally. It is a chronic condition characterized by developing pimples, blackheads (open comedones), whiteheads (closed comedones), and other skin lesions. Acne usually appears on the face, neck, chest, and back. It is commonly associated with puberty and adolescence but can also affect adults of all ages. Acne can be very frustrating and embarrassing, leading to low self-esteem and social isolation. The condition arises from various factors, including clogged pores, excessive sebum production, bacteria, and inflammation. This systematic review assesses the effectiveness of topical antibiotics, retinoids, niacinamide, azelaic acid, and clascoterone in treating mild-to-moderate acne vulgaris. A comprehensive search across PubMed, PubMed Central, and Google Scholar yielded 10 articles focused on topical antibiotics, with findings from 198 subjects indicating the efficacy of doxycycline against inflammatory lesions. Retinoids, such as tretinoin and adapalene, significantly improved both lesion types (open and closed comedones). Niacinamide, examined in a randomized controlled trial involving 41 participants, reduced sebum production. Another study with 60 patients revealed that azelaic acid effectively reduced both inflammatory and non-inflammatory lesions. Clascoterone emerged as a promising antiandrogenic treatment, supported by a randomized controlled trial involving 4,440 patients. It is essential that individualized therapy, incorporating patient preferences and considering adverse effects, is emphasized for optimizing acne management.
PubMed: 38725769
DOI: 10.7759/cureus.57909 -
Dermatology and Therapy May 2024A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially...
INTRODUCTION
A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data.
METHODS
In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated.
RESULTS
At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12.
CONCLUSIONS
The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT04214639 and NCT04214652.
PubMed: 38724841
DOI: 10.1007/s13555-024-01155-7 -
Briefings in Bioinformatics Mar 2024Gliomas are the most common type of malignant brain tumors, with glioblastoma multiforme (GBM) having a median survival of 15 months due to drug resistance and relapse....
Gliomas are the most common type of malignant brain tumors, with glioblastoma multiforme (GBM) having a median survival of 15 months due to drug resistance and relapse. The treatment of gliomas relies on surgery, radiotherapy and chemotherapy. Only 12 anti-brain tumor chemotherapies (AntiBCs), mostly alkylating agents, have been approved so far. Glioma subtype-specific metabolic models were reconstructed to simulate metabolite exchanges, in silico knockouts and the prediction of drug and drug combinations for all three subtypes. The simulations were confronted with literature, high-throughput screenings (HTSs), xenograft and clinical trial data to validate the workflow and further prioritize the drug candidates. The three subtype models accurately displayed different degrees of dependencies toward glutamine and glutamate. Furthermore, 33 single drugs, mainly antimetabolites and TXNRD1-inhibitors, as well as 17 drug combinations were predicted as potential candidates for gliomas. Half of these drug candidates have been previously tested in HTSs. Half of the tested drug candidates reduce proliferation in cell lines and two-thirds in xenografts. Most combinations were predicted to be efficient for all three glioma types. However, eflornithine/rifamycin and cannabidiol/adapalene were predicted specifically for GBM and low-grade glioma, respectively. Most drug candidates had comparable efficiency in preclinical tests, cerebrospinal fluid bioavailability and mode-of-action to AntiBCs. However, fotemustine and valganciclovir alone and eflornithine and celecoxib in combination with AntiBCs improved the survival compared to AntiBCs in two-arms, phase I/II and higher glioma clinical trials. Our work highlights the potential of metabolic modeling in advancing glioma drug discovery, which accurately predicted metabolic vulnerabilities, repurposable drugs and combinations for the glioma subtypes.
Topics: Humans; Glioma; Cannabidiol; Brain Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Animals; Models, Biological; Cell Line, Tumor; Organophosphorus Compounds
PubMed: 38701414
DOI: 10.1093/bib/bbae199 -
International Journal of Dermatology Jun 2024Acne, a highly prevalent skin disease, can be particularly bothersome for patients of Asian background because of its impact on self-confidence and social interactions.... (Review)
Review
Acne, a highly prevalent skin disease, can be particularly bothersome for patients of Asian background because of its impact on self-confidence and social interactions. In addition to active acne lesions, some patients may develop sequelae such as scarring, macular/postinflammatory hyperpigmentation, or erythema. The tendency of Asian skin to develop sequelae because of its increased susceptibility to irritation, cultural preferences for lighter skin phototypes, and differences in skincare regimens may all contribute to the increased burden of acne. Moreover, many Asia-Pacific countries do not have their own guidelines for acne management, and those that do often have no schedule in place for regular updates. In this article, we provide a critical review of the published guidance for the management of acne and its sequelae in the Asia-Pacific region, identifying gaps in current recommendations that could be addressed to enhance standards of acne care in Asia-Pacific countries. Along with highlighting the importance of a comprehensive skincare regimen to increase treatment efficacy and adherence, we discuss topical retinoids and retinoid combination options in the acne armamentarium that may be beneficial for sequelae prevention and management, such as adapalene 0.3% ± benzoyl peroxide 2.5%, tretinoin 0.05%, tazarotene 0.1%, and trifarotene 0.005%. In particular, trifarotene 0.005% has been observed to significantly reduce acne scar counts in a Phase 4 study. The recent data highlight the need to establish up-to-date guidance for acne and acne sequelae management in Asia-Pacific countries to provide optimal care to Asian patients.
Topics: Humans; Acne Vulgaris; Dermatologic Agents; Retinoids; Asia; Hyperpigmentation; Administration, Cutaneous; Cicatrix; Practice Guidelines as Topic; Skin Care; Erythema
PubMed: 38643368
DOI: 10.1111/ijd.17141