Treatments for Moderate-to-Severe Acne Vulgaris: A Systematic Review and Network Meta-analysis.

BACKGROUND: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values.  Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle). CONCLUSIONS: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8148.

Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

International Dermatology Outcome Measures (IDEOM): Report from the 2020 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) initiative is a non-profit organization that aims to develop evidence-based outcome measurements to evaluate the impact of treatments for patients with dermatological disease. IDEOM includes all key stakeholders in dermatology (patient, physician, industry, insurer, and government) during the process of developing such outcome measurements. SUMMARY: Here, we provide an update of IDEOM activities that were presented at the 2020 IDEOM Virtual Annual Meeting (October 23-24, 2020). During the meeting, multiple IDEOM workgroups (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) shared their progress to date, as well as future directions in developing and validating Patient-Reported Outcome Measures. Updates on demonstrating efficacy in clinicals trials by the US Food and Drug Administration are also summarized. KEY MESSAGES: In this report, we summarize the work presented by each IDEOM workgroup (psoriasis, psoriatic arthritis, hidradenitis suppurativa, acne, pyoderma gangrenosum, and actinic keratosis) at the 2020 IDEOM Virtual Annual Meeting.

Current Concepts in Acne Pathogenesis: Pathways to Inflammation.

Acne is a disease of pilosebaceous inflammation. Pivotal in pathogenesis are the roles of hormones (insulin, insulin-like growth factor-1, androgens), Propionibacterium acnes, lipogenesis, and a proinflammatory lipid profile. Innate immune responses are induced through interaction with toll-like receptors and inflammasome activation initially and subsequently through adaptive immune activation. These insights into pathogenic inflammatory pathways can translate into novel therapeutic approaches for acne. Semin Cutan Med Surg 37(supp3):S60-S62 ©2018 published by Frontline Medical Communication.

Advances in Acne and Rosacea Therapy.

New topical therapies have demonstrated efficacy in patients with moderate or severe acne who might otherwise have required therapy with systemic antibiotics or isotretinoin. Increasing knowledge about the pathogenesis of acne has facilitated the development of therapies with novel modes of action. New and investigational therapies also are available or in development for the treatment of both the papulopustular and erythematous manifestations of rosacea. Semin Cutan Med Surg 37(supp3):S63-S66 © 2018 published by Frontline Medical Communications.

Treating Acne in Adult Women.

Acne can persist into adulthood or erupt de novo at any point after adolescence. Adult acne is more common in women than in men. Considerations for treating acne in adult women include childbearing potential, pregnancy, lactation, and concomitant skin conditions. Semin Cutan Med Surg 37(supp3):S67-S70 © 2018 published by Frontline Medical Communications.

Treating Acne in Patients With Skin of Color.

Patients with skin of color are more likely to develop acne and postinflammatory hyperpigmentation (PIH). Many therapies for acne have demonstrated efficacy in darker skin types and in the treatment of PIH. Semin Cutan Med Surg 37(supp3):S71-S73 © 2018 published by Frontline Medical Communications.

Quality appraisal of acne clinical practice guidelines, 2008-2013.

BACKGROUND: Acne vulgaris is a common chronic disease, and evidence-based clinical practice guidelines (CPGs) can provide credible treatment information. METHOD: A literature search for acne CPGs published between January 2008 and September 2013 was conducted. Two reviewers independently applied the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. METHODological quality was evaluated by ranking in AGREE II domains and the highest number of items scoring above the neutral threshold score. RESULTS: Four CPGs fulfilled the selection criteria, and the highest ranked were the European and Malaysian. Highest scores achieved by the former were for scope/purpose, stakeholder involvement, and rigor of development and by the latter were for scope/purpose, clarity of presentation, and applicability. Applicability was the lowest scoring of all domains for all CPGs. CONCLUSION: European and Malaysian acne CPGs were ranked highest for methodological quality and may serve to inform clinical practice and guideline adaptation.

Evaluation of essential clinical components and features of current acne global grading scales.

BACKGROUND: Acne research is hindered by the absence of a universal, consistently applied standard for severity grading. Acne experts recently identified 4 essential clinical components and 2 features for an ideal acne global grading scale (AGGS). OBJECTIVE: This study evaluated current AGGSs against consensus criteria previously identified as necessary. METHODS: AGGSs were identified by systematic literature search and then evaluated independently by 4 raters against criteria (components and subcomponents; features and subfeatures) identified as essential. RESULTS: Eighteen AGGSs fulfilled selection criteria. Three scored 1 full SD above the mean for categorical scores. We also identified highest-ranked AGGSs for subcategory scores. LIMITATIONS: Only English-language scales were selected. Efficiency and acceptance were not evaluable. CONCLUSION: Although no singular scale fulfilled all essential criteria, this study did identify highly ranked AGGSs. Incorporation and rationalization of their components and features should facilitate development of an ideal standard.

Biologic therapy in psoriasis: perspectives on associated risks and patient management.

BACKGROUND: Previous publications have described practical considerations for initiating biologic therapy in psoriasis patients. However, most publications have focused on anti-tumor necrosis factor (TNF) therapy. OBJECTIVE: To create an evidence-based, practical tool that provides guidance on patient management for all biologics currently approved in Canada and the United States. METHODS: Psoriasis publications regarding safety issues in the initiation or monitoring of adalimumab, alefacept, etanercept, infliximab, or ustekinumab therapy were identified through a PubMed search. Phase III trials and open-label extensions (regardless of indication) and relevant guidelines from Health Canada were used to compile this review. RESULTS: Although these biologic agents have demonstrated efficacy in patients with psoriasis and are generally considered safe and well tolerated, rare but serious safety issues (ie, demyelination, infection, tuberculosis, malignancy, lymphoma, cardiovascular outcomes, hepatitis, pregnancy, surgery, and vaccination) have been observed. Attention to specific aspects of patient management (ie, prescreening requirements, symptoms to watch for, appropriate treatment, and referrals) is required to mitigate risk. CONCLUSION: Much of the evidence regarding the long-term safety of these agents has been based on experience in other patient populations. However, it does serve to guide us in understanding the risks that may impact the management of psoriasis patients.

Three-dimensional, Full-sized, Silicone-based, Facial Replicas for Teaching Outcome Measures in Acne.

BACKGROUND: The scientific integrity of outcome measurements is dependent upon reproducibility and accuracy. In acne assessments, there is no current gold standard for accuracy in lesion counting and global grading. PURPOSE: The purpose of this study was to create facial acne replicas for use in acne training and for evaluation of rater accuracy. METHODS: Two full-sized, three-dimensional, silicone-based, facial replicas with predetermined acne lesion type and number were created. Their teaching value was evaluated by dermatologists and clinical coordinators undergoing training in acne evaluations. A questionnaire after the training session addressed realism, preferences, and ease of assessments with the facial replicas compared to live subjects. RESULTS: Of 55 potential respondents, 32 questionnaires were completed and analyzable. Of these, 23 were from dermatologists and nine were from clinical research coordinators performing acne assessments. The facial replicas were considered sufficiently realistic for acne lesion counting by 91 percent (29/32) and for global grading by 94 percent (30/32). Of these, 66 percent preferred to have both real subjects and replicas for training (21/32), 31 percent preferred real subjects only (9/32), and one preferred replicas only. Replicas were considered easier to evaluate for noninflammatory and inflammatory lesions (p=0.002 and p=0.013, respectively) and equivalent to live models for global grading (p=0.001). LIMITATIONS: Shortcomings include the limited spectrum of acne that could be represented due to production of only two prototypes, the relative paucity of secondary lesions, and production time and cost. CONCLUSION: These facial replicas provide a realistic and practical method for teaching and evaluating raters in acne outcome measures as they provide a gold standard for acne lesion counts. Furthermore, their use may obviate some of the shortcomings inherent in recruitment of human acne volunteers for acne training sessions.

Development and validation of a Scale for Acne Scar Severity (SCAR-S) of the face and trunk.

BACKGROUND: scarring is an important component of overall acne severity, but there are no global scales for its evaluation inclusive of the face and trunk. OBJECTIVE: our objective was to develop a global scale for acne scar severity inclusive of the trunk and the face. METHODS: a six-category global severity scale (SCAR-S) was developed for assessment of acne scarring at each of the face, chest, and back. We evaluated SCAR-S against acne severity and patient-reported scar severity. RESULTS: of 973 subjects, 73% reported acne scarring. Self-assessment of scarring was associated with facial SCAR-S and overall SCAR-S scores (p < .001, r = .31 and .30, respectively). Acne scarring was observed at the face in 87%, the back in 51%, and the chest in 38%. Clinically relevant scarring (mild or greater) at each of these regions was 55%, 24%, and 14%, respectively. Acne severity correlated with SCAR-S (p < .001) for the back (r = .612), the chest (r = .548), and the face (r = .514). Acne duration correlated with patient-reported severity of scarring (r = .244) and overall SCAR-S scores (r = .152). Clinically relevant scarring increased with acne duration. CONCLUSION: SCAR-S is a practical, validated, global system for acne scar evaluation and is clinically relevant in overall severity grading of acne.

Critical appraisal of quality of clinical practice guidelines for treatment of psoriasis vulgaris, 2006-2009.

Numerous international clinical guidelines for management of psoriasis have recently been published. We evaluated the quality of guidelines published between 2006 and December 2009 using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. Eight guidelines from five separate working groups fulfilled inclusion criteria and were evaluated. Four used the standards established by the AGREE instrument in the process of development of their guidelines. Each of the guidelines uniformly received high domain scores (i.e., > 90%) for scope and purpose (range of 94-100%), and clarity and presentation (range of 92-100%). Nevertheless, each of the eight guidelines had important shortcomings (item scores < or = 2/4, in which 4 indicates strongly agree and 1 indicates strongly disagree that specific items have been adequately addressed) in at least one item including: stakeholder involvement (by lack of piloting and inadequate determination of patient views), development rigor (inadequate procedure for updating), applicability (by lack of discussion on organizational barriers), and editorial independence (from funding body). Despite the use of predefined standards in their development, important deficiencies exist in the most recent clinical treatment guidelines for psoriasis.

The safety profile and sustained remission associated with response to multiple courses of intramuscular alefacept for treatment of chronic plaque psoriasis.

BACKGROUND: Safety and efficacy of up to 3 courses of alefacept intramuscular (IM) in the treatment of chronic plaque psoriasis have been demonstrated in earlier trials. OBJECTIVE: We sought to determine the safety and efficacy of up to 5 courses of alefacept IM in treating plaque psoriasis. METHODS: A standard treatment course was defined as 15 mg of alefacept IM once weekly for 12 weeks, followed by 12 weeks of treatment-free observation. Patients with chronic plaque psoriasis, who had previously received alefacept IM, received up to 3 additional courses (A, B, and C). Efficacy was evaluated by Physician Global Assessment. RESULTS: Safety profiles were similar to those for a single course of treatment. There were no cumulative adverse effects. At 2 weeks postdosing, 16%, 22%, and 19% of patients were rated clear or almost clear by Physician Global Assessment in courses A, B, and C, respectively, with 35%, 42%, and 42% achieving this response at any time during these courses. Patients who achieved clear or almost clear at 2 weeks postdosing remained so for a median duration of 214 and 126 days after courses A and B, respectively. LIMITATIONS: This was an extension study and therefore contained no control group. CONCLUSIONS: Up to 5 courses of alefacept IM may provide extended treatment-free, symptom-free periods in responders while maintaining the safety profile.

Effect of quality of life impact and clinical severity on adherence to topical acne treatment.

BACKGROUND: Topical medications are the most commonly prescribed treatments for acne patients. However, adherence to these treatments and possible associations with clinical severity and quality of life (QoL) impact are unclear. PURPOSE: We evaluated the association between sociodemographic factors, clinical severity, and QoL impact and adherence to topical acne treatments. METHODS: This was an observational study of acne patients referred for usual care to community-based dermatologists. Adherence was assessed with questionnaires after 2 months of acne therapy. The associations of adherence with factors of interest were evaluated by chi-square analysis and Spearman rank correlation. RESULTS: In 152 acne patients treated with topical medications, low adherence was observed in 26%, medium in 49%, and high in 24%. Age, gender, duration of acne, education level, third-party drug plan coverage, smoking history, recreational drug use, ingestion of alcohol, and number of prescribed topical agents were not significantly associated with adherence. Adherence was significantly positively correlated with QoL impact (r = .24, p = .003), with the role-emotional and self-perception domains having the highest correlations. In contrast, adherence was weakly negatively correlated with facial acne severity (r = -.16, p = .047). LIMITATIONS: This study focused on facial acne, and adherence was based on patient reporting. CONCLUSIONS: Adherence to topical acne therapy increases with impact on QoL but decreases with increasing acne severity.

Divergence of demographic factors associated with clinical severity compared with quality of life impact in acne.

BACKGROUND: Previous smaller studies suggest that age, gender, and duration of acne may individually be associated with clinical acne severity and quality of life (QoL) impact. OBJECTIVE: Our purpose was to concurrently evaluate the association of demographic factors with clinical acne severity and with QoL impact. METHODS: Clinical acne severity was assessed using the Investigators Global Assessment, whereas QoL impact was evaluated by the patient-completed Acne-QoL. These outcomes were correlated with sociodemographic variables, including age, gender, and duration of acne. RESULTS: In 862 acne patients, clinical severity was associated with younger age, male gender, and shorter acne duration (1-5 years). In contrast, greater impact on QoL was associated with older age, female gender, and longer acne duration (> 5 years). CONCLUSIONS: Clinical and QoL measures each differentiate between groups of patients most severely affected by acne. Our findings reinforce the imperative for clinicians to use both measures for comprehensive patient management. LIMITATIONS: Study limitations include referral population of acne patients and the restriction of outcome measures to facial acne.

Prevalence and severity of facial and truncal acne in a referral cohort.

BACKGROUND: There is a paucity of information on the prevalence and severity of acne of the face, chest, and back. PURPOSE: This study was designed to examine the prevalence and severity of acne on the face, chest, and back in a referral cohort of patients with acne using a validated global acne severity scale. METHODS: Acne patients referred to dermatologists were evaluated at the face, chest, and back. Chi-square testing was performed to assess consistency between patient and physician assessments of each region. The correlation of acne severity between regions was evaluated by Spearman's rank correlation. RESULTS: In 965 patients, the prevalence of acne on the face, chest, and back was 92%, 45%, and 61%, respectively. Acne severity was significantly correlated for all regional pairs (P<.001): face and back (r=0.11); face and chest (r=0.12); and chest and back (r=0.67). The consistency of patient reporting and clinical evaluation for the presence of acne varied by region: face=92%, chest=69%, and back=74%. The proportions of patients reporting no occurrence of acne when clinical acne was indeed absent (negative predictive value) were 67% and 65% for the chest and back, respectively. LIMITATIONS: The operational threshold for clinical acne (>mild) may underestimate the total proportion of affected patients. These patients were referred to dermatologists for care and may represent a more severe cohort. CONCLUSION: Acne affected the face in 92% and the trunk in just over 60% (with the back more frequently and severely affected than the chest). Acne severity was observed to have a much higher correlation between chest and back than face and back or face and chest. Patient-reporting evaluations of absence of acne on the chest and back are frequently erroneous, mandating clinical evaluations of these sites for assessment of overall extent.