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Advances in Therapy Dec 2022Nowadays, numerous skincare routines are used to rejuvenate aging skin. Retinoids are one of the most popular ingredients used in antiaging treatments. Among the... (Review)
Review
Nowadays, numerous skincare routines are used to rejuvenate aging skin. Retinoids are one of the most popular ingredients used in antiaging treatments. Among the representatives of retinoids, tretinoin is considered the most effective agent with proven antiaging effects on the skin and can be found in formulations approved as medicines for topical treatment of acne, facial wrinkles, and hyperpigmentation. Other retinoids present in topical medicines are used for various indications, but only tazarotene is also approved as adjunctive agent for treatment of facial fine wrinkling and pigmentation. The most commonly used retinoids such as retinol, retinaldehyde, and retinyl palmitate are contained in cosmeceuticals regulated as cosmetics. Since clinical efficacy studies are not required for marketing cosmetic formulations, there are concerns about the efficacy of these retinoids. From a formulation perspective, retinoids pose a challenge to researchers as a result of their proven instability, low penetration, and potential for skin irritation. Therefore, novel delivery systems based on nanotechnology are being developed to overcome the limitations of conventional formulations and improve user compliance. In this review, the clinical evidence for retinoids in conventional and nanoformulations for topical antiaging treatments was evaluated. In addition, an overview of the comparison clinical trials between tretinoin and other retinoids is presented. In general, there is a lack of evidence from properly designed clinical trials to support the claimed efficacy of the most commonly used retinoids as antiaging agents in cosmeceuticals. Of the other retinoids contained in medicines, tazarotene and adapalene have clinically evaluated antiaging effects compared to tretinoin and may be considered as potential alternatives for antiaging treatments. The promising potential of retinoid nanoformulations requires a more comprehensive evaluation with additional studies to support the preliminary findings.
Topics: Humans; Retinoids; Dermatologic Agents; Cosmeceuticals; Adapalene; Tretinoin
PubMed: 36220974
DOI: 10.1007/s12325-022-02319-7 -
Clinical Interventions in Aging 2006Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the... (Review)
Review
Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy ofretinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confirm their advantage in the delivery of topical retinoids.
Topics: Adapalene; Dermatologic Agents; Dermis; Epidermis; Humans; Naphthalenes; Nicotinic Acids; Retinaldehyde; Retinoids; Skin Aging; Treatment Outcome; Tretinoin; Vitamin A Deficiency
PubMed: 18046911
DOI: 10.2147/ciia.2006.1.4.327 -
Therapeutic Options for the Treatment of Darier's Disease: A Comprehensive Review of the Literature.Journal of Cutaneous Medicine and... 2022Darier's disease (also known as keratosis follicularis or dyskeratosis follicularis) is an autosomal dominant inherited disorder which manifests as hyperkeratotic greasy... (Review)
Review
Darier's disease (also known as keratosis follicularis or dyskeratosis follicularis) is an autosomal dominant inherited disorder which manifests as hyperkeratotic greasy papules in the first or second decade of life. Aside from symptom management and behavioral modifications to avoid triggers, there are currently no validated treatments for Darier's disease (DD). However, a variety of treatments have been proposed in the literature including retinoids, steroids, vitamin D analogs, photodynamic therapy, and surgical excision. The purpose of this review article is to identify therapeutic options for treating DD and to outline the evidence underlying these interventions. A search was conducted in Medline for English language articles from inception to July 4, 2020. Our search identified a total of 474 nonduplicate studies, which were screened by title and abstract. Of these, 155 full text articles were screened against inclusion/exclusion criteria, and 113 studies were included in our review. We identified Grade B evidence for the following treatments of DD: oral acitretin, oral isotretinoin, systemic Vitamin A, topical tretinoin, topical isotretinoin, topical adapalene gel, topical 5-flououracil, topical calciptriol and tacalcitol (with sunscreen), grenz ray radiation, and x-ray radiation. All other evidence for treatments of DD consisted of case reports or case series, which is considered grade C evidence. Considering the quality and quantity of evidence, clinicians may consider initiating a trial of select topical or oral retinoids first in patients with localized or generalized DD, respectively.
Topics: Acitretin; Adapalene; Darier Disease; Humans; Isotretinoin; Sunscreening Agents
PubMed: 34841914
DOI: 10.1177/12034754211058405 -
The Cochrane Database of Systematic... May 2020Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear.
OBJECTIVES
To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne.
SEARCH METHODS
We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers.
SELECTION CRITERIA
Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life.
MAIN RESULTS
We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence).
AUTHORS' CONCLUSIONS
Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs.
Topics: Acne Vulgaris; Adapalene; Adolescent; Adult; Anti-Bacterial Agents; Benzoyl Peroxide; Bias; Child; Clindamycin; Dermatologic Agents; Dicarboxylic Acids; Erythromycin; Female; Glycolates; Humans; Keratolytic Agents; Male; Mandelic Acids; Niacinamide; Patient Dropouts; Pyruvic Acid; Quality of Life; Salicylic Acid; Sulfur; Tretinoin; Young Adult; Zinc
PubMed: 32356369
DOI: 10.1002/14651858.CD011368.pub2 -
Cancer Cell Apr 2024Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. The senescence-associated secretory phenotype (SASP), released...
Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. The senescence-associated secretory phenotype (SASP), released by senescent cells, plays a crucial role in this dichotomy. Consequently, the clinical challenge lies in developing therapies that safely enhance senescence in cancer, favoring tumor-suppressive SASP factors over tumor-promoting ones. Here, we identify the retinoic-acid-receptor (RAR) agonist adapalene as an effective pro-senescence compound in prostate cancer (PCa). Reactivation of RARs triggers a robust senescence response and a tumor-suppressive SASP. In preclinical mouse models of PCa, the combination of adapalene and docetaxel promotes a tumor-suppressive SASP that enhances natural killer (NK) cell-mediated tumor clearance more effectively than either agent alone. This approach increases the efficacy of the allogenic infusion of human NK cells in mice injected with human PCa cells, suggesting an alternative therapeutic strategy to stimulate the anti-tumor immune response in "immunologically cold" tumors.
Topics: Male; Humans; Animals; Mice; Cellular Senescence; Prostatic Neoplasms; Receptors, Retinoic Acid; Killer Cells, Natural; Adapalene
PubMed: 38428412
DOI: 10.1016/j.ccell.2024.02.004 -
The Cochrane Database of Systematic... Mar 2020Acne is a common, economically burdensome condition that can cause psychological harm and, potentially, scarring. Topical benzoyl peroxide (BPO) is a widely used acne... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acne is a common, economically burdensome condition that can cause psychological harm and, potentially, scarring. Topical benzoyl peroxide (BPO) is a widely used acne treatment; however, its efficacy and safety have not been clearly evaluated.
OBJECTIVES
To assess the effects of BPO for acne.
SEARCH METHODS
We searched the following databases up to February 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of relevant randomised controlled trials (RCTs) and systematic reviews.
SELECTION CRITERIA
We included RCTs that compared topical BPO used alone (including different formulations and concentrations of BPO) or as part of combination treatment against placebo, no treatment, or other active topical medications for clinically diagnosed acne (used alone or in combination with other topical drugs not containing BPO) on the face or trunk.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane. Primary outcome measures were 'participant global self-assessment of acne improvement' and 'withdrawal due to adverse events in the whole course of a trial'. 'Percentage of participants experiencing any adverse event in the whole course of a trial' was a key secondary outcome.
MAIN RESULTS
We included 120 trials (29,592 participants randomised in 116 trials; in four trials the number of randomised participants was unclear). Ninety-one studies included males and females. When reported, 72 trials included participants with mild to moderate acne, 26 included participants with severe acne, and the mean age of participants ranged from 18 to 30 years. Our included trials assessed BPO as monotherapy, as add-on treatment, or combined with other active treatments, as well as BPO of different concentrations and BPO delivered through different vehicles. Comparators included different concentrations or formulations of BPO, placebo, no treatment, or other active treatments given alone or combined. Treatment duration in 80 trials was longer than eight weeks and was only up to 12 weeks in 108 trials. Industry funded 50 trials; 63 trials did not report funding. We commonly found high or unclear risk of performance, detection, or attrition bias. Trial setting was under-reported but included hospitals, medical centres/departments, clinics, general practices, and student health centres. We reported on outcomes assessed at the end of treatment, and we classified treatment periods as short-term (two to four weeks), medium-term (five to eight weeks), or long-term (longer than eight weeks). For 'participant-reported acne improvement', BPO may be more effective than placebo or no treatment (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.12 to 1.45; 3 RCTs; 2234 participants; treatment for 10 to 12 weeks; low-certainty evidence). Based on low-certainty evidence, there may be little to no difference between BPO and adapalene (RR 0.99, 95% CI 0.90 to 1.10; 5 RCTs; 1472 participants; treatment for 11 to 12 weeks) or between BPO and clindamycin (RR 0.95, 95% CI 0.68 to 1.34; 1 RCT; 240 participants; treatment for 10 weeks) (outcome not reported for BPO versus erythromycin or salicylic acid). For 'withdrawal due to adverse effects', risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment (RR 2.13, 95% CI 1.55 to 2.93; 24 RCTs; 13,744 participants; treatment for 10 to 12 weeks; low-certainty evidence); the most common causes of withdrawal were erythema, pruritus, and skin burning. Only very low-certainty evidence was available for the following comparisons: BPO versus adapalene (RR 1.85, 95% CI 0.94 to 3.64; 11 RCTs; 3295 participants; treatment for 11 to 24 weeks; causes of withdrawal not clear), BPO versus clindamycin (RR 1.93, 95% CI 0.90 to 4.11; 8 RCTs; 3330 participants; treatment for 10 to 12 weeks; causes of withdrawal included local hypersensitivity, pruritus, erythema, face oedema, rash, and skin burning), erythromycin (RR 1.00, 95% CI 0.07 to 15.26; 1 RCT; 60 participants; treatment for 8 weeks; withdrawal due to dermatitis), and salicylic acid (no participants had adverse event-related withdrawal; 1 RCT; 59 participants; treatment for 12 weeks). There may be little to no difference between these groups in terms of withdrawal; however, we are unsure of the results because the evidence is of very low certainty. For 'proportion of participants experiencing any adverse event', very low-certainty evidence leaves us uncertain about whether BPO increased adverse events when compared with placebo or no treatment (RR 1.40, 95% CI 1.15 to 1.70; 21 RCTs; 11,028 participants; treatment for 10 to 12 weeks), with adapalene (RR 0.71, 95% CI 0.50 to 1.00; 7 RCTs; 2120 participants; treatment for 11 to 24 weeks), with erythromycin (no participants reported any adverse events; 1 RCT; 89 participants; treatment for 10 weeks), or with salicylic acid (RR 4.77, 95% CI 0.24 to 93.67; 1 RCT; 41 participants; treatment for 6 weeks). Moderate-certainty evidence shows that the risk of adverse events may be increased for BPO versus clindamycin (RR 1.24, 95% CI 0.97 to 1.58; 6 RCTs; 3018 participants; treatment for 10 to 12 weeks); however, the 95% CI indicates that BPO might make little to no difference. Most reported adverse events were mild to moderate, and local dryness, irritation, dermatitis, erythema, application site pain, and pruritus were the most common.
AUTHORS' CONCLUSIONS
Current evidence suggests that BPO as monotherapy or add-on treatment may be more effective than placebo or no treatment for improving acne, and there may be little to no difference between BPO and either adapalene or clindamycin. Our key efficacy evidence is based on participant self-assessment; trials of BPO versus erythromycin or salicylic acid did not report this outcome. For adverse effects, the evidence is very uncertain regarding BPO compared with adapalene, erythromycin, or salicylic acid. However, risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment. Withdrawal may be linked to tolerability rather than to safety. Risk of mild to moderate adverse events may be higher with BPO compared with clindamycin. Further trials should assess the comparative effects of different preparations or concentrations of BPO and combination BPO versus monotherapy. These trials should fully assess and report adverse effects and patient-reported outcomes measured on a standardised scale.
Topics: Acne Vulgaris; Adolescent; Adult; Benzoyl Peroxide; Cicatrix; Dermatologic Agents; Female; Humans; Male; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32175593
DOI: 10.1002/14651858.CD011154.pub2 -
American Journal of Clinical Dermatology Jan 2022A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.
BACKGROUND
A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance.
OBJECTIVES
We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne.
METHODS
In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed.
RESULTS
A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity.
CONCLUSIONS
Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).
Topics: Acne Vulgaris; Adapalene; Administration, Topical; Adolescent; Adult; Benzoyl Peroxide; Child; Clindamycin; Dermatologic Agents; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Young Adult
PubMed: 34674160
DOI: 10.1007/s40257-021-00650-3 -
Drug and Therapeutics Bulletin Dec 2023Acne vulgaris is very common and can have significant negative impact on people. While sometimes a transient problem, acne may persist for many years and often leads to... (Review)
Review
Acne vulgaris is very common and can have significant negative impact on people. While sometimes a transient problem, acne may persist for many years and often leads to permanent scars or pigment changes. Guidelines unanimously advise topical treatments as first-line, although differ in recommending either topical benzoyl peroxide or topical retinoid (mainly adapalene) alone or in combination. Guidance published by the National Institute for Health and Care Excellence advises counselling patients regarding avoidance of skin irritation when starting topical treatments and promoting adherence (treatments take 6-8 weeks to work). Oral antibiotics are currently overprescribed for acne but have a role when coprescribed with a non-antibiotic topical treatment. Hormonal treatments, such as the combined contraceptive pill, are also effective and there is growing evidence for the use of spironolactone for women with persistent acne. Recent guidance from the Medicines and Healthcare products Regulatory Agency regarding isotretinoin has implications for specialist prescribing and monitoring, and increasing public awareness of potential risks of mental health problems and sexual dysfunction. Although acne is associated with psychiatric disorder, the mental health effects of isotretinoin remain controversial.
Topics: Humans; Female; Isotretinoin; Acne Vulgaris; Benzoyl Peroxide; Anti-Bacterial Agents; Adapalene
PubMed: 38154809
DOI: 10.1136/dtb.2023.000051