Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo.

BACKGROUND: Vitiligo is a chronic autoimmune disease that causes skin depigmentation. A cream formulation of ruxolitinib (an inhibitor of Janus kinase 1 and 2) resulted in repigmentation in a phase 2 trial involving adults with vitiligo. METHODS: We conducted two phase 3, double-blind, vehicle-controlled trials (Topical Ruxolitinib Evaluation in Vitiligo Study 1 [TRuE-V1] and 2 [TRuE-V2]) in North America and Europe that involved patients 12 years of age or older who had nonsegmental vitiligo with depigmentation covering 10% or less of total body-surface area. Patients were randomly assigned in a 2:1 ratio to apply 1.5% ruxolitinib cream or vehicle control twice daily for 24 weeks to all vitiligo areas on the face and body, after which all patients could apply 1.5% ruxolitinib cream through week 52. The primary end point was a decrease (improvement) of at least 75% from baseline in the facial Vitiligo Area Scoring Index (F-VASI; range, 0 to 3, with higher scores indicating a greater area of facial depigmentation), or F-VASI75 response, at week 24. There were five key secondary end points, including improved responses on the Vitiligo Noticeability Scale. RESULTS: A total of 674 patients were enrolled, 330 in TRuE-V1 and 344 in TRuE-V2. In TRuE-V1, the percentage of patients with an F-VASI75 response at week 24 was 29.8% in the ruxolitinib-cream group and 7.4% in the vehicle group (relative risk, 4.0; 95% confidence interval [CI], 1.9 to 8.4; P<0.001). In TRuE-V2, the percentages were 30.9% and 11.4%, respectively (relative risk, 2.7; 95% CI, 1.5 to 4.9; P<0.001). The results for key secondary end points showed superiority of ruxolitinib cream over vehicle control. Among patients who applied ruxolitinib cream throughout 52 weeks, adverse events occurred in 54.8% in TRuE-V1 and 62.3% in TRuE-V2; the most common adverse events were application-site acne (6.3% and 6.6%, respectively), nasopharyngitis (5.4% and 6.1%), and application-site pruritus (5.4% and 5.3%). CONCLUSIONS: In two phase 3 trials, application of ruxolitinib cream resulted in greater repigmentation of vitiligo lesions than vehicle control through 52 weeks, but it was associated with acne and pruritus at the application site. Larger and longer trials are required to determine the effect and safety of ruxolitinib cream in patients with vitiligo. (Funded by Incyte; TRuE-V1 and TRuE-V2 ClinicalTrials.gov numbers, NCT04052425 and NCT04057573.).

Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.

BACKGROUND: Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods. METHODS: In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months. RESULTS: We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p <  0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p <  0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p <  0.001 and than DMPA (mean percentage difference - 39.45, p <  0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001). CONCLUSIONS: This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study. ECHO TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users' own circulating sex hormones, both the 'female' and the 'male' sex hormones (androgens). In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.

Benefit of Topical Combination Therapy for Acne: Analyzing Effect Size Using Number Needed to Treat.

BACKGROUND: Topical acne trials often are confounded by high vehicle response rates and differing outcome measures, making it difficult to compare treatments. Number needed to treat (NNT) can be a simple, clinically meaningful way to indirectly compare treatment options without head-to-head data. NNT is the number of patients who need to be treated with an intervention to observe one additional patient successfully achieving a desired outcome versus vehicle/placebo. While treatment attributes such as adverse events may not be captured, lower NNT is a good indicator of a more effective treatment. METHODS: Following a search of combination topical treatments for acne vulgaris, all treatments that reported pivotal trial efficacy data consistent with the 2018 FDA definition of success were included in NNT analyses.  Results: Of 13 treatments, 7 reported 12-week treatment success rates in 11 phase 3 trials, with similar baseline demographics/disease severity. Treatment success ranged from 26.8% with tretinoin 0.1%/benzoyl peroxide (BPO) 3% cream to 50% with triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel. NNTs for the triple-combination gel were 4 and 5 (from 2 pivotal trials). Adapalene 0.3%/BPO 2.5% gel had an NNT of 5. Tretinoin/BPO had the largest range between trials, with NNTs of 4 and 9. The other 4 treatments had NNTs ranging from 6 to 8. CONCLUSION: A comparison of combination topical acne treatment trial data, using the same treatment outcome and similar patient populations, resulted in triple-combination clindamycin phosphate/adapalene/BPO gel and adapalene/BPO gel having the most favorable NNTs.J Drugs Dermatol. 2024;23(2):42-49.  doi:10.36849/JDD.7927.

Efficacy and safety of microencapsulated benzoyl peroxide and microencapsulated tretinoin for the treatment of acne vulgaris: Results from two phase 3 double-blind, randomized, vehicle-controlled studies.

BACKGROUND: Benzoyl peroxide and tretinoin are commonly prescribed acne treatments. Historically, they have been difficult to combine in a single formulation due to chemical instability, and both medications are potentially irritating. Microencapsulation helps overcome these challenges. OBJECTIVE: Examine efficacy, safety, and tolerability of encapsulated BPO/encapsulated tretinoin (E-BPO/T) cream, 3%/0.1%. METHODS: Subjects ≥9 years old with moderate to severe acne were enrolled in 2 multicenter, double-blind, vehicle-controlled, parallel trials and randomized (2:1) to 12 weeks of once-daily E-BPO/T (n = 571) or vehicle cream (n = 287). RESULTS: E-BPO/T was significantly superior to vehicle in both studies, with more subjects achieving IGA success with E-BPO/T (38.5%/25.4%) versus vehicle (11.5%/14.7%; P < .001/P = .017). The change from baseline in inflammatory lesion count for E-BPO/T was -21.6 versus -14.8 for vehicle (P < .001) in study 1 and -16.2 versus -14.1 (P = .018) in study 2. The changes from baseline in noninflammatory lesions for E-BPO/T were -29.7 versus -19.8 for vehicle (P < .001) and -24.2 and -17.4 (P < .001) in studies 1 and 2, respectively. E-BPO/T was well tolerated in both studies. LIMITATIONS: Long-term data are not available. CONCLUSION: E-BPO/T provided statistically significant and clinically relevant improvements in IGA and inflammatory and noninflammatory lesion counts and was well tolerated in subjects with moderate to severe acne.

Isotretinoin and the risk of psychiatric disturbances: A global study shedding new light on a debatable story.

INTRODUCTION: Isotretinoin-related risk of depression and suicidal behavior is a topic of inconclusiveness. A crucial knowledge gap exists in defining the association of isotretinoin with other psychiatric comorbidities. OBJECTIVE: To evaluate the risk of psychiatric outcomes among patients with acne treated with isotretinoin versus oral antibiotics. METHODS: A global population-based retrospective cohort study enrolled 2 groups of patients with acne managed by isotretinoin (n = 75,708) and oral antibiotics (n = 75,708). Patients were compared regarding the risk of 9 psychiatric outcomes. RESULTS: Relative to those treated with oral antibiotics, patients prescribed isotretinoin experienced lower risk of depression (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.93; P < .001), but comparable risk of major depressive disorder (HR, 0.97; 95% CI, 0.92-1.03; P = .318). Risk of suicidal attempts was comparable between groups (HR, 0.97; 95% CI, 0.85-1.11; P = .663), despite the elevated risk of suicidal ideation in those under isotretinoin (HR, 1.41; 95% CI, 1.32-1.50; P < .001). Patients under isotretinoin had lower risk of post-traumatic stress disorder (HR, 0.75; 95% CI, 0.68-0.82; P < .001), anxiety (HR, 0.84; 95% CI, 0.82-0.87; P < .001), bipolar disorder (HR, 0.65; 95% CI, 0.59-0.72; P < .001), schizophrenia (HR, 0.60; 95% CI, 0.48-0.76; P < .001), and adjustment disorder (HR, 0.82; 95% CI, 0.77-0.87; P < .001). LIMITATIONS: Retrospective data collection. CONCLUSION: Isotretinoin confers lower risk of 6 psychiatric comorbidities and comparable risk of suicidal attempts.

A propensity score matched cohort study identifying an association of acne, but not oral antibiotic or isotretinoin use, with risk of incident inflammatory bowel disease.

BACKGROUND: Concerns remain regarding whether oral antibiotic or isotretinoin use for acne is associated with increased risk of inflammatory bowel disease (IBD); little is known about whether acne itself is associated with IBD. OBJECTIVE: To determine whether isotretinoin exposure, oral tetracycline-class antibiotic exposure, and/or acne itself are associated with IBD. METHODS: A propensity score matched cohort study was performed using TriNetX between 2001 and 2022 to compare the 1-year incidence of IBD between those without acne compared to those with acne managed without systemic medications, acne managed with oral tetracycline-class antibiotics, and acne managed with isotretinoin. RESULTS: There was a statistically significant association between acne and risk of incident IBD (odds ratio: 1.42; 95% confidence interval: 1.23-1.65). There was no statistically significant association between oral tetracycline-class antibiotic or isotretinoin exposure and IBD. LIMITATIONS: Use of electronic health data; potential for misclassification bias. CONCLUSION: This matched cohort study identifies an association between acne and IBD. These data provide further reassurance regarding the use of isotretinoin in the treatment of acne.

Self-Reported Long-Term Side Effects of Isotretinoin: A Case Series.

CITATION: Ghadimi TR, Martinez MJ, Rieder EA. Self-reported long-term side effects of isotretinoin: A case series. J Drugs Dermatol. 2023;22(4):423-424. doi:10.36849/JDD.2303.

Individual Article: Clascoterone Cream 1%: Mechanism of Action, Efficacy, and Safety of a Novel, First-in-Class Topical Antiandrogen Therapy for Acne.

Acne is a prevalent chronic inflammatory disease that can cause severe psychiatric effects and physical scarring of the skin. Historically, although systemic antiandrogen acne medications have been effective in women, the utility of these systemic medications has been limited due to potential systemic side effects in men and pregnant women. Therefore, research has been focused on developing topical formulations of antiandrogen therapy for acne. Topical clascoterone cream 1% is the first topical anti-androgen medication approved for the treatment of acne vulgaris in patients 12 years and older and represents a breakthrough in acne treatment. Clascoterone, or cortexolone-17α propionate, is an androgen receptor inhibitor with highly localized activity. Thismedication is thought to compete with dihydrotestosterone (DHT) for androgen receptors located in pilosebaceous units, thus inhibiting the acnegenic downstream effects of DHT such as lipid synthesis and inflammatory cytokine production in a dose-dependent manner. Two phase III clinical trials have been conducted thus far; both trials have shown clascoterone 1% cream applied BID to be significantly more effective than placebo cream at treating acne vulgaris in patients ages 12 and older with moderate-to-severe acne. Clascoterone has also been shown to have a similar safety profile to that of placebo cream in clinical studies, without any systemic antiandrogenic effects observed in the clinical setting. Due to its novel mechanism of action and activity limited to the skin, clascoterone presents an exciting opportunity for dermatologists to further optimize care for eligible acne patients, either as a monotherapy or in combination with other anti-acne medications. J Drugs Dermatol. 2023;22:56(Suppl 1):s7-14.

Management of Acne Vulgaris With Trifarotene.

Topical retinoids have an essential role in treatment of acne. Trifarotene, a topical retinoid selective for retinoic acid receptor (RAR) γ, is the most recent retinoid approved for treatment of acne. RAR-γ is the most common isoform of RARs in skin, and the strong selectivity of trifarotene for RAR-γ translates to efficacy in low concentration. Trifarotene, like other topical retinoids, acts by increasing keratinocyte differentiation and decreasing proliferation, which reduces hyperkeratinization. Retinoids have also been shown to inhibit inflammatory pathways via effects on leukocyte migration, toll-like receptors, and Activator Protein (AP)-1. Large-scale randomized, controlled clinical trials have demonstrated trifarotene to be safe, well tolerated, and efficacious in reducing both comedones and papules/pustules of acne. However, unlike all other retinoids, trifarotene is the first topical retinoid with rigorous clinical data on safety and efficacy in truncal acne. Data supporting use of trifarotene to manage acne are reviewed in this publication.

Efficacy of topical 30% salicylic acid in combination with minocycline in moderate to severe acne.

To evaluate the efficacy of topical 30% salicylic acid plus minocycline in moderate to severe acne. One hundred patients with moderate to severe acne from February 2020 to February 2021 were retrospectively analyzed. They were assigned (1:1) to receive either topical 30% salicylic acid plus minocycline (combination group) or minocycline (mono therapy group). The acne scores, physician subjective and objective scores, efficacy, quality of life, incidence of adverse reactions, recurrence and satisfaction in both groups were compared. The combination group had lower Global Acne Grading System (GAGS) scores, erythema scores and papulopustular scores than the mono therapy group. Combined therapy was associated with lower erythema absolute value and erythema index, more skin water content and less transcutaneous water loss versus minocycline. Higher efficacy, acne symptoms scores, and quality of life were observed with combination therapy versus mono therapy (P<0.05). The two groups had a similar incidence of adverse reactions and recurrence. Combination therapy showed a higher appearance satisfaction versus mono therapy. The efficacy of topical 30% salicylic acid plus minocycline for moderate to severe acne was better versus minocycline.

A systematic review and network meta-analysis of topical pharmacological, oral pharmacological, physical and combined treatments for acne vulgaris.

BACKGROUND: Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity. OBJECTIVES: To identify best treatments for mild-to-moderate and moderate-to-severe acne, as determined by clinician-assessed morphological features. METHODS: We undertook a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, published up to May 2020. Outcomes included percentage change in total lesion count from baseline, treatment discontinuation for any reason, and discontinuation owing to side-effects. Risk of bias was assessed using the Cochrane risk-of-bias tool and bias adjustment models. Effects for treatments with ≥ 50 observations each compared with placebo are reported below. RESULTS: We included 179 RCTs with approximately 35 000 observations across 49 treatment classes. For mild-to-moderate acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with benzoyl peroxide (BPO) [mean difference 26·16%, 95% credible interval (CrI) 16·75-35·36%]; physical - chemical peels, e.g. salicylic or mandelic acid (39·70%, 95% CrI 12·54-66·78%) and photochemical therapy (combined blue/red light) (35·36%, 95% CrI 17·75-53·08%). Oral pharmacological treatments (e.g. antibiotics, hormonal contraceptives) did not appear to be effective after bias adjustment. BPO and topical retinoids were less well tolerated than placebo. For moderate-to-severe acne, the most effective options for each treatment type were as follows: topical pharmacological - combined retinoid with lincosamide (clindamycin) (44·43%, 95% CrI 29·20-60·02%); oral pharmacological - isotretinoin of total cumulative dose ≥ 120 mg kg-1 per single course (58·09%, 95% CrI 36·99-79·29%); physical - photodynamic therapy (light therapy enhanced by a photosensitizing chemical) (40·45%, 95% CrI 26·17-54·11%); combined - BPO with topical retinoid and oral tetracycline (43·53%, 95% CrI 29·49-57·70%). Topical retinoids and oral tetracyclines were less well tolerated than placebo. The quality of included RCTs was moderate to very low, with evidence of inconsistency between direct and indirect evidence. Uncertainty in findings was high, in particular for chemical peels, photochemical therapy and photodynamic therapy. However, conclusions were robust to potential bias in the evidence. CONCLUSIONS: Topical pharmacological treatment combinations, chemical peels and photochemical therapy were most effective for mild-to-moderate acne. Topical pharmacological treatment combinations, oral antibiotics combined with topical pharmacological treatments, oral isotretinoin and photodynamic therapy were most effective for moderate-to-severe acne. Further research is warranted for chemical peels, photochemical therapy and photodynamic therapy for which evidence was more limited. What is already known about this topic? Acne vulgaris is the eighth most common disease globally. Several topical, oral, physical and combined treatments for acne vulgaris exist. Network meta-analysis (NMA) synthesizes direct and indirect evidence and allows simultaneous inference for all treatments forming an evidence network. Previous NMAs have assessed a limited range of treatments for acne vulgaris and have not evaluated effectiveness of treatments for moderate-to-severe acne. What does this study add? For mild-to-moderate acne, topical treatment combinations, chemical peels, and photochemical therapy (combined blue/red light; blue light) are most effective. For moderate-to-severe acne, topical treatment combinations, oral antibiotics combined with topical treatments, oral isotretinoin and photodynamic therapy (light therapy enhanced by a photosensitizing chemical) are most effective. Based on these findings, along with further clinical and cost-effectiveness considerations, National Institute for Health and Care Excellence (NICE) guidance recommends, as first-line treatments, fixed topical treatment combinations for mild-to-moderate acne and fixed topical treatment combinations, or oral tetracyclines combined with topical treatments, for moderate-to-severe acne.

Characterization of acne associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis: A post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials.

BACKGROUND: Acne is the most frequent adverse event associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: To characterize the adverse event of acne associated with upadacitinib. METHODS: This was a post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials of upadacitinib, alone (NCT03569293 and NCT03607422) or in combination with topical corticosteroids (NCT03568318). Data included were from the 16-week placebo-controlled period. RESULTS: Over 16 weeks, 84 of 857 (9.8%), 131 of 864 (15.2%), and 19 of 862 (2.2%) patients randomized to receive upadacitinib 15 mg, upadacitinib 30 mg, and placebo, respectively, experienced acne. All cases of acne, except 1, were mild/moderate in severity; 2 patients discontinued treatment due to moderate acne. Acne occurred at higher rates among younger, female, and non-White patients. Acne required no intervention in 40.5% and 46.6% of patients receiving upadacitinib 15 and 30 mg, respectively; most remaining cases were managed with topical antibiotics, benzoyl peroxide, and/or retinoids. Acne also had no impact on patient-reported outcomes. LIMITATIONS: This study was relatively short in duration and had a small patient population. CONCLUSIONS: Acne associated with upadacitinib for atopic dermatitis treatment is usually mild/moderate in severity and managed with topical therapies or no intervention.

Low-dose oral isotretinoin for the treatment of adult patients with mild-to-moderate acne vulgaris: Systematic review and meta-analysis.

Acne vulgaris is one of the most common dermatologic complaints. Recently, isotretinoin has been used as an off-label indication for the treatment of mild-to-moderate grades of acne not responding to conventional treatment. Its conventional recommended dose is 0.5-1.0 mg/kg per day to the cumulative dose of 120-150 mg/kg. To qualify the state of evidence and analyze the efficacy of the low-daily dose and the pulsed doses of isotretinoin in treating mild-to-moderate acne patients with regards to response and relapse rates. Systematic review and meta-analysis using an electronic literature search were performed. The 320 potentially relevant articles were included and reviewed. The level of evidence is moderate to low as conducted by the GRADE quality of evidence assessment. The pooled statistical estimate for response to treatment in the group comparing low-daily doses with conventional dose showed an overall benefit for conventional dose. On the other hand, pooled data from the group comparing the low-daily dose with the pulsed doses yielded an overall beneficial effect from using the low-daily dose compared with the pulsed doses on achieving the response. Given all of the available studies, the quality of evidence is low. It appears that conventional dose isotretinoin improves the odds of prolonged remission in adults with mild-to-moderate acne vulgaris compared to the low doses.

Evaluation of the efficacy and relapse rates of treatment protocols for moderate acne using isotretinoin based on the global acne grading system: Randomized, controlled, comparative study.

Protocols for treating acne with isotretinoin have varied widely because some factors associated with relapse and treatment duration have not yet been fully determined. This paper evaluates the effectiveness of conventional, low, and intermittent isotretinoin dosage protocols in the treatment of moderate acne and investigates the relationships between GAGS score, treatment duration and relapse rate. The 107 patients with moderate acne were randomly divided into three groups who received isotretinoin for 24 weeks (Group A: 0.5-1 mg/kg/day; Group B: 0.25-0.4 mg/kg/day; Group C: 0.5-0.7 mg/kg/day for 1 week out of every 4 weeks). The results show that both conventional and continuous low doses achieved full clinical effectiveness with minimum relapse rates. However, fewer side effects and better patient satisfaction were reported with the low dose. Significant differences in GAGS scores after 24 weeks were found between groups B and C (p = 0.037) and between groups A and C (p < 0.001), while no significant differences were found between groups A and B (p = 0.153). It was observed that relapse rate increased with initial GAGS score. The average relapse rate was 58.0% for those with initial GAGS scores of 25-30 compared with 5.5% for those with scores of 19-24. It was also noticed that, among the patients who relapsed, the highest percentage (56.3%) were in the age group <20 years. However, GAGS (ß = 0.646, t = 8.323, p < 0.001) was found to be a better predictor of relapse than age (ß = 0.083, t = 1.073, p = 0.286). These results suggest that initial GAGS score is an important factor in determining the treatment protocol for moderate acne. Furthermore, this study recommends that a low-dose treatment is most suitable when GAGS <25, as it can achieve complete clearance of acne with minimal relapses and side effects.

Acne care in health care providers during the COVID-19 pandemic: A national survey.

The medical face mask, widely used by health care providers (HCPs) during the COVID-19 pandemic, is reported to be associated with adverse reactions, among which acne is one of the most common. This study aims to evaluate treatment strategies employed by HCPs affected by acne in association with prolonged medical face mask use, their openness towards accessing telemedicine as a patient, and other lifestyle factors with potential influence on the evolution of their acne. Our online-based cross-sectional survey was distributed between December 17, 2020, and February 17, 2021, and targeted HCPs from different medical centers in Romania. From the n = 134 respondents, 50% reported current acne lesions and 56.7% required treatment. Of the latter, 65.8% self-medicated and 34.2% sought medical advice. The most common treatment associations between anti-acne topical products were: retinoids and salicylic acid (18.18%; n = 8), retinoids and benzoyl peroxide (13.64%; n = 6), salicylic acid and benzoyl peroxide (13.64%; n = 6), and azelaic acid together with salicylic acid (9.09%; n = 4). The health care provider responders were reluctant to use telemedicine, as only 14.2% participants were open to telemedicine. Our results suggest inadequate management of acne in HCPs using medical face masks. As with other occupational hazards and proper usage of personal protective equipment, HCPs should receive adequate screening, training, and treatment for this condition.

Prevention of Acne-Like Eruption Caused by Panitumumab Treatment through Oral Administration of Non-steroidal Anti-inflammatory Drugs.

Acne-like eruption caused by anti-epidermal growth factor receptor (EGFR) antibodies such as panitumumab reduces treatment adherence and patient QOL; an alternative therapy is desired. Meanwhile, the usefulness of oral Non-steroidal Anti-inflammatory Drugs (NSAIDs) for acne-like eruptions caused by low-molecular-weight EGFR inhibitors such as erlotinib has been reported in the treatment of lung cancer. This study aimed to investigate whether the combined use of oral NSAIDs and panitumumab for colorectal cancer patients helps prevent acne-like eruption. We retrospectively investigated 167 colorectal cancer patients who had been treated with panitumumab for three cycles or more. The observation period was set from the start of panitumumab treatment to the end of three cycles. Within this period, the incidence and severity of acne-like eruptions were compared. A total of 59 and 108 patients were in the NSAIDs use and non-use groups, respectively, showing differences in the incidence of acne-like eruption rates (78.0 vs. 90.7%, respectively; p = 0.033). In the use group, eruption severity grades 0, 1, 2, and 3 were observed in 13, 33, 13, and 0 patients, respectively; the corresponding values in the non-use group were 10, 60, 36, and 2, respectively (p = 0.007). Oral NSAIDs may help prevent acne-like eruptions caused by panitumumab.

Patients' Knowledge and Information Needs about Isotretinoin Therapy Use in Jordan.

Background: Despite being the first-line treatment for severe or moderate acne, isotretinoin has several serious side effects that necessitate the evaluation of patients' knowledge about isotretinoin side effects and its proper use. Objective: The current study aim was to explore information needs about isotretinoin by evaluating patients' knowledge about the appropriate use of isotretinoin and its associated side effects. Methods: In addition to the sociodemographic variables, a validated online questionnaire was adopted from the literature to evaluate patients' knowledge about isotretinoin use and its potential side effects. Independent t-test and one-way analysis of variance (ANOVA) test were implemented to find the correlation between the study variables and the knowledge score. Results: The most recognized side effect of isotretinoin therapy was dryness (98.1%). The study patients showed good knowledge about isotretinoin use with a mean knowledge score of 8.1 (SD = 0.7). However, more than half of them (61.0%) mistakenly thought that isotretinoin therapy should be taken continuously for more than 6 months without stop, and some of them did not know that isotretinoin is recommended to be taken with fatty meal (24%) and sunblock (24.6%). Female gender (8.2 (SD = 0.8)) and using isotretinoin for more than 6 months (8.3 (SD = 1.2)) were significantly associated with a higher knowledge score of isotretinoin use (p=0.01), when compared with male patients (7.8 (SD = 0.7)) and less than 6-month use of isotretinoin (7.7 (SD = 0.7)). Conclusions: The lack of patients' information about the potential side effects, duration of therapy, and some instructions on isotretinoin use, such as taking the medication with fatty meal and sunblock, shed the light on the necessity to prepare leaflets, educational brochures, and educational posts via social media in order to improve patients' knowledge about isotretinoin therapy and its optimal use.

Oral Vitamin A for Acne Management: A Possible Substitute for Isotretinoin.

BACKGROUND: Recent changes to the iPLEDGE platform left providers without the ability to prescribe isotretinoin to their patients. A potential substitute for isotretinoin could be beneficial when the drug is unavailable. Prior to the FDA approval of isotretinoin, a vitamin A derivative, vitamin A was studied for its use in acne management. OBJECTIVE: To review the potential of vitamin A to serve as a substitute for isotretinoin when the latter drug is inaccessible. METHODS: We conducted a review of published literature from 1931 to 2021, regarding the use of vitamin A in acne treatment, using PubMed and Google Scholar databases. Nine studies were selected after reviewing articles for relevancy to our topic. RESULTS: Eight out of the 9 studies noted improvement in patients’ acne with vitamin A use. Ranges of doses used were 36,000 I/U daily to 500,000 I/U daily, with 100,000 I/U daily being the most common. Side effects were mainly mucocutaneous in nature. LIMITATIONS: Many of the trials included in our review were published over 50 years prior and lack standardized components of clinical trials today. CONCLUSION: Oral vitamin A could potentially serve as a substitute for isotretinoin in acne management for select patients. However, due to its teratogenicity, potential for toxicity, and long half-life, strict monitoring under the care of a medical provider is prudent. Since vitamin A is available without a prescription, strict monitoring cannot be assured, and especially careful patient selection and education would be essential. J Drugs Dermatol. 2022;21(6):683-686. doi:10.36849/JDD.6781.

Hormonal Therapies in the Management of Acne Vulgaris.

Acne vulgaris is a multifactorial chronic disorder of the pilosebaceous unit. Established treatments include topical retinoids, antibiotics in mild cases, and oral antibiotics and isotretinoin in moderate to severe cases. Anti-androgens and other hormonal therapies constitute another group of drugs in the armamentarium of acne management. These can be used in patients who do not respond to the aforementioned treatments or when other systemic drugs cannot be tolerated. Recent approval of topical androgen receptor blocker is an additional armamentarium for the management of acne. Considering limited systemic exposure and good efficacy, it has potential for wide usage in patients with acne. In this article, we critically review currently available hormonal treatment options based on published literature search of an electronic database (MEDLINE/PubMed) performed through June 2021. J Drugs Dermatol. 2022;21(6):618-623. doi:10.36849/JDD.6494.