ARTICLES1) Draelos ZDCarter EMaloney JM et al. Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for the treatment of acne vulgaris . J Am Acad Dermatol 2007;56 (3) 439.e1- 439.e10 Background A new aqueous gel formulation of dapsone has been developed that allows clinically-effective doses of dapsone to be administered topically with minimal systemic absorption. Objectives The goal of these studies was to evaluate the efficacy and safety of dapsone gel, 5% in the treatment of acne. Methods Patients 12 years of age and older with acne vulgaris (N = 3010) participated in two identicallydesigned 12-week, randomized, double-blind studies of twice-daily monotherapy with dapsone gel, 5%, versus a vehicle gel. Results Dapsone gel–treated patients achieved superior results in terms of the investigator's global acne assessment (P < .001) and the mean percentage reduction in inflammatory, noninflammatory, and total lesion counts (all, P < .001) at week 12. Reductions in inflammatory lesion counts favoring dapsone gel over vehicle were apparent as early as 2 weeks and reached statistical significance by 4 weeks. No clinically significant changes in laboratory parameters, including hemoglobin, even among glucose-6-phosphate dehydrogenase–deficient patients, were observed. Adverse events were comparable between the treatment groups and rarely led to discontinuation. Limitations Adjunctive topical treatments and their impact on acne were not studied in this trial. Conclusions Dapsone gel, 5% appears to be an effective, safe, and well-tolerated treatment for acne vulgaris, with a rapid onset of action. 2)Lucky AW, Maloney JM, Roberts J, et al. Dapsone gel 5% for the treatment of acne vulgaris: safety and efficacy of long-term (1 year) treatment . J Drugs Dermatol. 2007;6:981– 987. Abstract Dapsone gel 5%, a topical formulation of dapsone, was shown to deliver clinically effective doses of dapsone with minimal systemic absorption in 2 randomized, vehicle-controlled, 12-week studies of patients with acne vulgaris. A 12-month, open-label, long-term safety study further evaluated the safety and efficacy of dapsone gel. Patients at least 12 years of age with acne vulgaris (N = 486) applied dapsone gel twice daily for up to 12 months. Application site reactions related to treatment were reported in 8.2% of the patients and were mostly mild to moderate in severity. Common nonapplication site adverse events included headache (20%) and nasopharyngitis (15%). No significant changes in hematology or blood chemistry parameters were observed. At one month, mean reduction from baseline in inflammatory lesion counts was 30.6%. At 12 months, mean reduction from baseline was 58.2%, 19.5%, and 49.0% for inflammatory, noninflammatory, and total lesion counts, respectively, (all P=.002 compared to baseline). These results show that dapsone gel 5% is safe and effective for long-term treatment of acne vulgaris and has a rapid onset of action. 3)Tanghetti E, Harper JC, Oefelein MG. The efficacy and tolerability of dapsone 5% gel in female vs male patients with facial acne vulgaris: gender as a clinically relevant outcome variable. J Drugs Dermatol.2012;11:1417–1421. Abstract BACKGROUND: Gender differences in skin and acne have been reported. OBJECTIVE: To evaluate the effect of gender on the efficacy and tolerability of dapsone 5% gel. METHODS: This was a pooled analysis of data from 2 identical phase 3 randomized, double-blind, and vehiclecontrolled trials (DAP0203 and DAP0204) of dapsone 5% gel conducted in the United States and Canada between November 2002 and September 2003. A total of 2,898 patients with acne vulgaris were included in the pooled analysis. Of these, 1,453 patients (753 female, 700 male) received dapsone 5% gel twice daily, and 1,445 patients (767 female, 678 male) received vehicle twice daily. End points included the mean percentage reduction from baseline in acne lesion counts and the proportion of patients achieving clinical success (Global Acne Assessment Scale score of 0, clear skin, or 1, almost clear skin). Assessments were performed at baseline and at weeks 2, 4, 6, 8, and 12. RESULTS: The mean percentage reduction in acne lesion counts at 12 weeks was significantly greater in females than males in both treatment groups. The mean reduction in total lesion counts in dapsonetreated females and males was, respectively, 46.6% vs 35.8% (P<.0001). Reductions in papulopustular and comedonal lesion counts were likewise significantly higher in female than male patients (each P<.0001). Significantly more dapsone-treated females than males achieved clinical success (48.6% vs 34.4%; P=.0003). CONCLUSION: The response to dapsone 5% gel appears to be influenced by gender, with female patients experiencing a significantly greater reduction in acne lesion counts and a significantly higher clinical success rate following 12 weeks of treatment. These data suggest that gender is a novel predictor of outcome that should be considered in acne clinical trial design and analysis 4) The efficacy of 5% dapsone gel plus oral isotretinoin versus oral isotretinoin alone in acne vulgaris: A randomized double-blind study Gita Faghihi, Mehrdad Nilforoushzadeh1 Rakhshanpour, Bahareh Abtahi-Naeini, and Mohammad Ali INTRODUCTION Acne vulgaris is a common dermatologic disease that is usually managed by application of topical preparations, systemic medications, or a combination of the two.[1,2] Acne is primarily an inflammatory disease, challenging the current nomenclature of non-inflammatory versus inflammatory acne lesions, suggesting that the nomenclature is outdated and incorrect.[3] The evidence in support of acne as an inflammatory disease also has clinical implications, in that antiinflammatory drugs used to treat the disease can be expected to exert effects against all lesion stages, albeit via distinct mechanisms of anti-inflammation.[3] Today, different topical therapies are available for patients with acne vulgaris, including comedolytic agents, anti-inflammatory medications, antibiotics, systemic retinoid and even herbal preparations. Antibiotics play a pivotal role in treatment.[4] Dapsone (4, 4′-diaminodiphenylsulfone) is a drug of the sulfone class and was discovered in 1908.[5] Oral dapsone has demonstrated efficacy in acne, but was associated with g. Iran. placebo-controlled clinical trial was conducted at Al-Zahra General Hospital. pregnancy or intention of pregnancy. methotrexate and vitamin A supplements) within the previous 3 months. tetracyclines.’ indicating the side on which they should be applied.g. which was particularly serious in patients with glucose-6phosphate dehydrogenase (G6PD) deficiency. . this is the first time to combine topical dapsone gel as an anti-inflammatory agent with oral isotretinoin in treatment of moderate to severe acne in order to enhance the efficacy. The 5% dapsone gel was prepared in Isfahan University's Department of Pharmacy. Japan) in the same physical condition. All patients were administered oral isotretinoin (Roaccutane ®. Trimetoprim-sulfametoxazol) or isotretinoin (e. Topical 5% dapsone gel and non-comedogenic vehicle gel was applied on the face twice daily for 8 weeks in our patients (group A: 5% dapsone gel and group B vehicle gel). Photographic imaging was performed using a camera (Canon power shot G12. F. Dapsone gel was prepared from its powder solved in a little ethanol and mixed with lubricant non-comedogenic gel up to 5% concentration. by one person at base line and on each follow-up visit. During the study period. history of having taken any medication that could interact with dapsone (e. The patients came for follow-up examinations on day 2 and weeks 4. All patients provided written informed consent before participation.[6] A unique property of dapsone is that it has dual therapeutic activity and demonstrates antimicrobial and anti-inflammatory properties. it will be helpful to add a topical anti-inflammatory agent to treatment regime to fasten the onset of clinical response and control initial exacerbation of symptoms. Hoffmann-La Roche Ltd. a referral clinic of dermatology in Isfahan. Reasons for exclusion were: Acne being secondary to other problems. The dapsone gel and vehicle noncomedogenic neutral gel were filled in similar tubes that were marked ‘A’ or ‘B. taking any other acne treatment. The patients were divided into groups randomly: (group A: 5% dapsone gel and group B vehicle neutral gel). Cannon components Inc. the patients and the examiner were blind to the topical compounds.severe side-effects such as anemia. other dermatological diseases of the face. Due to a delay in starting of isotretinoin response. Topical dapsone was developed to overcome this limitation. 58 young adults (age range: 18-25 years) with moderate to severe facial acne vulgaris according to the Global Acne Assessment Score (GAAS) were recruited from September 2012 through July 2013.[8] There are a very limited number of studies on the topical use of anti-inflammatory agent in combination with other systemic medications such as isotretinoin in acne vulgaris. and known hypersensitivity to the study medication. Isfahan. breastfeeding. The study protocol was approved by the Ethics Committee of Isfahan University of Medical Sciences. Hence this study aimed to evaluate the efficacy of 5% dapsone gel with systemic isotretinoin in facial acne vulgaris in Iranian patients.). To the best of our knowledge. MATERIALS AND METHODS This double-blind. G6PD deficiency. only a caregiver who was not involved in the experiment was aware of the contents of the tubes. 8 and 12. 20 mg once a day for 8 weeks.[7] Dapsone 5% gel (Aczone) was developed to treat acne vulgaris and today has Food and Drug Administration (FDA) approval. Iran (NO: 392090). Finally. Presence of any possible complications/side effects was assessed and documented on each visit by a skilled dermatologist. II. USA). Data were shown as frequency (percentage) or mean ± standard deviation.001 was considered to be statistically significant. All patients had normal of G6PD level. CONSORT flow chart of the study was showed in one diagram [Figure 1]. Table 1 Global acne assessment scale Figure 1 CONSORT flow chart of the study Statistical evaluation was done using SPSS® for Windows version 18. Decrease in the mean inflammatory and non-inflammatory lesion counts was significantly more in . the two groups were compared with regard to baseline counts. RESULTS Fifty eight patients. The repeated-measures analysis (ANOVA) and the Chi-square test were used as the appropriate measures. range: 18-25 years were enrolled in this study.The numbers of acne lesions were counted manually by the investigator for both the treatment site and control site at baseline and on each follow-up visit.8 years (range: 2-5 years).9%). The patients were divided into groups randomly: (group A: 5% dapsone gel and group B vehicle neutral gel). Demographic data and number of inflammatory. The global severity of acne was assessed by the investigator using the 5-point scale at base line and the end of the study[9] [Table 1]. 25 males (43. non-inflammatory facial lesions and GAAS are summarized in Table 2 and compared between the two groups at baseline [Table 2]. P ≤ 0. All patients completed the study period. there were no significant differences between the two groups (P > 0. The counting was assessed by marking each counted lesion with a pen to ensure that each lesion was only registered once.0 (SPSS Inc..1%) and 33 females (56. The mean duration of acne in the study population was 3.001).19 ± 1. number of lesion) in topical dapsone plus oral isotretinoin group in female patients are significantly superior to the male ones after treatment at the end of the study (P < 0.001. One patient developed contact conjunctivitis due to application of dapsone too close to the eye.264) [Table 3].001). No clinically significant changes were made in laboratory parameters including hemoglobin (P = 0. mild erythema of the skin and mild dryness in 4 (13. The side-effects are summarized and compared in the two groups on different occasions are shown in Table 4. The side-effects on the dapsone-treated group were a mild burning sensation in 7 patients (24. none of these side-effects led to discontinuation of treatment and all the participants completed the study.13%).34%) cases respectively (P < 0. Our result showed that clinical efficacy (i.001) [Figures 2]. However.79%) and 3 (10.345). Table 2 Baseline demographics and disease characteristics Figure 2 The number of inflammatory and non-inflammatory lesions reduced significantly after 8 weeks of treatment with topical dapson gel plus isotretinoin as shown in these pictures . Although reduction in GAAS was not significant on all follow-up visits (P = 0.group A compared to group B on all follow-up visits (P < 0.e. in our study. the significant efficacy observed in the use of topical 5% dapsone in a similar setting in reducing the count of lesions in weeks 4.Table 3 Mean GAAS: Weeks 4. Dhir et al. 8 and 12. 5% dapsone gel was an effective and safe topical medication for patients that received isotretinoin for acne vulgaris treatment with a significant reduction in the number of lesions but this combination applied to therapy did not alter the final outcome and The GAAS. found no significant benefit in the combination of topical anti-acne and isotretinoin over isotretinoin alone in improving nodulocystic acne vulgaris. 8 and 12 Table 4 AEs occurring during the course of treatment DISCUSSION In the present study. is probably due to the additional anti-inflammatory effect of dapsone. In a study by Tanghetti et al. compared the efficacy and tolerability of dapsone 5% gel in female versus male . There are only a limited number of studies that have similarly examined the effect of the combination of isotretinoin and topical application on acne vulgaris and the results are incongruous.[4] However. and safety of dapsone gel 5% in this specific group who often complain of sensitive skin. USA) has been approved by the FDA for the treatment of acne vulgaris but the risks of serious side effects have made it an undesirable drug for use in the relatively healthy acne population. with female patients experiencing a significantly greater reduction in acne lesion counts and a significantly higher clinical success rate following 12 weeks of treatment. even among G6PD-deficient patients. Our findings show significant reduction in both “inflammatory” and “non-inflammatory” (comedonal) lesions in all weeks. documented efficacy of topical 5% dapsone gel for the reduction of both inflammatory and non-inflammatory acne lesions.11. such as anti-inflammatory and anti-interleukin 8 actions. The women were instructed to apply dapsone 5% gel twice daily after washing their face with a standard noncomedogenic soap-free cleanser.12] Mechanisms other than bactericidal action may underlie the therapeutic effect of dapsone.. The limitations of our study were short duration of treatment and lack of more objective methods for result assessment. as was the case in our study.[11] CONCLUSION The results suggest that anti-inflammatory agents such as dapsone can effectively reduce the count of lesions but do not alter the final outcome and The GAAS treat when used in combination with systemic isotretinoin. 5) Cohort study on the treatment with dapsone 5% gel of mild to moderate inflammatory acne of the face in women. including hemoglobin. Andriessen A. Dapsone has multiple anti-inflammatory properties.[10] Our findings are in concordance with the results of Tanghetti's study. Ninety-three . Draelos et al. Treatment outcome was evaluated using physician-scored Global Acne Assessment Scale (GAAS) and patient-reported facial skin condition. Allergan. there is no significant difference between before and after hemoglobin level. Draelos et al.14] Although a topical formulation of dapsone (Aczone.[13. so the anti-inflammatory dapsone is effective in treatment of both “inflammatory” and “non-inflammatory” lesions. Other adverse events were comparable between the treatment groups and rarely led to discontinuation of the topical drug. Inc. tolerability. showed no clinically significant changes in laboratory parameters.patients with facial acne vulgaris and reported that the response to dapsone 5% gel appears to be influenced by gender.[8] In our study. Irvine.[10. Lynde CW. The high efficacy of 5% dapsone gel in female patients suggests that gender is an important predictor of the therapeutic outcome in acne treatment and should be considered in acne clinical trial design and analysis. CA. Abstract Topical dapsone 5% gel for the treatment of mild to moderate acne has been shown to be effective in randomized controlled studies. as well as the inhibition of neutrophil adherence. A total of 101 adult women with mild to moderate facial inflammatory acne participated in a 12-week cohort study to evaluate the efficacy. 4% (n = 75) of women (t94 = 4. the potential for systemic toxicity prevented its widespread adoption in the treatment of acne. Of the total of 50 patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency in all the studies. improving patient-reported quality-of-life aspects. Bourcier M. and those shifts in values were consistent with fluctuations observed for other study participants. open-label study was also conducted to assess the safety and efficacy of topical dapsone over the long term. With regard to safety.85. This topical formulation was approved in the US based on two randomized. United .women completed the study (6 were lost to follow-up and 2 had mild skin irritation). Prior to the general acceptance of isotretinoin. At 12 weeks. significant physician GAAS scores (t55 = 8. Finally. the studies demonstrated that the concentrations of dapsone and N-acetyl dapsone remain low and do not accumulate over time once steady state is reached. Maloney JM. A recent study evaluating the risk of hemolysis in patients with G6PD deficiency found topical dapsone 5% gel to be safe to use in this patient population. Dapsone 5% gel (Aczone) was recently developed to treat acne vulgaris. Based on the observations noted in the above-mentioned studies.001). only two experienced a drop in hemoglobin levels. has been used to treat a myriad of cutaneous disorders. vehiclecontrolled studies. Topical dapsone gel 5% was shown to be safe.17. P = . A 12-month. Stotland M1. Papp K. P = . 12) Efficacy and safety of dapsone gel 5% for the treatment of acne vulgaris in adolescents. oral dapsone had been reported to be effective in the treatment of nodulocystic acne. Abstract Dapsone. and effective in the treatment of mild to moderate inflammatory facial acne in adult women with sensitive skin. Wilson States/Canada Dapsone Gel Study Group.001) and patient-reported lesion reductions were shown. For many years scientists explored the possibility of developing a topical formulation of dapsone for the treatment of acne in the hope of minimizing the adverse hematologic effects of oral dapsone. Kissling RF. Raimer S1. Shalita AR. This article reports the results of these studies. we conclude that topical dapsone 5% gel is safe and effective in the treatment of acne vulgaris. a synthetic sulfone that has been available for over 60 years. minimally irritating. two open-label phase I pharmacokinetic studies were conducted to evaluate the systemic absorption of topical dapsone compared with oral dapsone. Garrett S. which show a reduction in acne lesion count comparable to those observed in clinical trials of other approved topical acne therapies. 8) Dapsone 5% gel: a review of its efficacy and safety in the treatment of acne vulgaris. D. Such a formulation had been unavailable until recently. However. Siegfried E. Treatment success (GAAS 0 or 1) at 12 weeks was achieved in 69. 001). an anti-inflammatory agent. including application-site events. Draelos Z.1%. Kasteler JS. Kircik L. . open-label. The incidence of adverse events. Green L. was low and similar between treatment groups in the pivotal studies and was similarly low in the long-term safety study.2%. randomized. Tanghetti E1.1% for treatment of acne vulgaris. vehicle-controlled. Abstract BACKGROUND: Acne pathogenesis is multifactorial and includes inflammation. double-blinded pivotal studies and a 12-month. Results from the large number of adolescent participants in these 3 studies show that dapsone gel is an effective and safe topical therapy for the treatment of acne vulgaris in adolescents aged 12 to 15 years for up to 12 months. Downie J. Oefelein MG. Participants randomly were assigned to twice-daily treatment with dapsone gel (n=578) or vehicle gel (n=547) in the pivotal studies and received open-label treatment with dapsone gel in the longterm safety study (n=181).1% in patients with acne vulgaris. Combining drugs targeting multiple components of acne pathogenesis is standard practice. 13) Clinical evidence for the role of a topical anti-inflammatory agent in comedonal acne: findings from a randomized study of dapsone gel 5% in combination with tazarotene cream 0. Germain MA.Abstract Two 12-week. 232/578) compared with the vehicle gel-treated adolescent participants (28. Treatment with dapsone gel in adolescents also resulted in clinically meaningful improvements in acne lesion counts by week 12 in the pivotal studies and for up to 12 months in the long-term safety study. 154/547) (P<. in combination with tazarotene cream 0. longterm. In the pivotal studies. OBJECTIVE: To assess the safety and efficacy of dapsone gel 5%. Dhawan S. 1306 participants (37%) were adolescents aged 12 to 15 years and comprised the subgroup reported here. success based on achieving a Global Acne Assessment Score (GAAS) of 0 (none) or 1 (minimal) at week 12 was significantly greater for the dapsone gel-treated adolescent participants (40. noncomparative safety study were conducted to evaluate the efficacy and safety of dapsone gel 5% in patients with acne vulgaris. Ling M. Of 3516 participants enrolled in the 3 trials. Efficacy and safety data were collected after 1. CONCLUSION: Combination therapy with dapsone gel 5% plus tazarotene cream 0. Garrett S. P=.01).METHODS: Patients were randomized to receive combination therapy (dapsone gel 5% twice-daily plus tazarotene cream 0. 2. 4.6%.2%) than in tazarotenetreated patients (21.1% was more effective than tazarotene monotherapy for treatment of comedonal acne.P=. At 12 weeks. Dapsone Gel in Combination Treatment Study Group. Eichenfield LF. 53.3% vs. dapsone + tazarotene. Abstract PURPOSE: To evaluate the safety and efficacy of dapsone gel 5% in the treatment of acne when used in combination with adapalene gel 0. Lucky A.5 percent. patients treated with dapsone plus tazarotene showed a greater reduction from baseline in noninflammatory (comedonal) and total lesion counts than tazarotene-treated patients (noninflammatory. Fleischer AB Jr1. 59.7 percent vs. total. and 12 weeks of treatment.01. The results suggest that anti-inflammatory agents such as dapsone can effectively treat early stages of acne (both comedonal and noncomedonal) when used in combination with a retinoid 14) Dapsone gel 5% in combination with adapalene gel 0. randomized.1%. Both treatments were well tolerated. Abramovits W. 63. double-blind study.8%.1% daily) or monotherapy (tazarotene cream 0.02). benzoyl peroxide gel 4% or moisturizer for the treatment of acne vulgaris: a 12-week.001 for all). P=. RESULTS: Patients in both arms (n=86. Shalita A. tazarotene) showed significant reductions from baseline in inflammatory. The percentage of patients achieving treatment success (an investigator subjective score of 0 [none] or 1 [minimal]) was greater in dapsone plus tazarotene?treated patients (42. 8. . benzoyl peroxide gel 4% or moisturizer. noninflammatory and total lesion counts (P is less than .1%.1% daily). n=85. 46. as the frequency of office visits for AV affecting post-adolescent women appears to be increasing. comedones) and visibly inflammatory lesions (i.2 Additionally. respectively. Kircik L. Gallagher CJ Acne vulgaris (AV) in adult women has been receiving increased attention both in the United States and globally. skin types (oily.Del Rosso JQ. and 26 percent of women report having AV in their 20s. RESULTS: By week 12. combination.e.. 17) Comparative efficacy and tolerability of dapsone 5% gel in adult versus adolescent females with acne vulgaris. 30s. and the anatomic distribution of AV is similar overall in both subpopulations.3-7 Although a U-shaped pattern of predominantly inflammatory papules involving the lower cheeks. applied once daily. AV is common in adult women of all ethnicities.013 respondents in the United States showed that 51.1A survey of 1.3-7 Available data and clinical observation have shown that the relative quantities of facial AV lesion types (i. CONCLUSION: Dapsone gel in combination with adapalene gel or benzoyl peroxide gel is safe and well tolerated for the treatment of acne vulgaris. dry. pustules) are found in both adolescent females and adult women with AV. However. Patients treated with dapsone gel combined with adapalene showed a significantly better response in reduction in non-inflammatory and total acne lesion count than those who received the moisturizer combination.4-8 . sensitive).. dapsone gel combined with any of the three additional treatments reduced the mean number of inflammatory lesions. and it has been stated that AV in adult women presents predominantly as inflammatory lesions.. double-blind study. papules. Patients aged 12 years and older (n=301) applied dapsone gel twice daily and were randomly assigned (1:1:1) to one of three additional treatments.METHODS: This was a twelve-week.e. 35. and 40s.052 for both versus moisturizer combination). papules) overlap among patients in both age-related subsets. comedones.1. and anterior and lateral neck has been noted in some adult women with AV.e. and skin colors (Fitzpatrick skin type I-VI). jawline. Local adverse reactions in all three treatment groups were minimal and generally mild in severity. the authors did not detect a significant difference in the reduction of inflammatory lesions when dapsone was used in combination with adapalene gel or with benzoyl peroxide gel compared to the dapsone plus moisturizer combination group (P=0. both visibly noninflammatory lesions (i. randomized. it has been reported that approximately three-fourths of adult women with AV present with a mixed pattern of comedonal and inflammatory facial acne lesions that are often found more diffusely on the face and not just in the U-shaped region. the authors report the outcome of a subgroup analysis from the two Phase 3 pivotal trials in female subjects with facial AV treated with dapsone 5% gel or vehicle in two agebased subgroups. This subgroup analysis was based on data from two identically designed 12-week. and total lesions from baseline.12.8 Dapsone is a sulfone derivative that has been reported to demonstrate a variety of anti-inflammatory properties.0003) and the vehicle-treated study arm (p=0.9.5.14 No differences in adverse events (AEs) were observed between the dapsone-treated and vehicle-treated study groups. noninflammatory. A subgroup analysis of outcomes in men compared with women from the two Phase 3 trials demonstrated that efficacy and tolerability were favorable in both sexes.14.16 In this manuscript.0001).0013). multicenter. dapsone 5% gel was found in clinical studies to be effective for AV for at least 12 months. The authors hypothesized before completion of this subgroup analysis that the response to dapsone 5% gel would be similar in efficacy and safety in both the adolescent and adult female populations for facial AV.9-11 Overall. 12-week trials in subjects ≥12 years of age with facial AV. noninflammatory lesions (p<0.6. vehicle-controlled.6. dapsone 5% gel applied twice daily proved to be superior to vehicle gel in reducing inflammatory.010). controlled trials evaluating the efficacy and safety of topical agents specifically in adult women with AV are lacking. such as oral contraceptives and spironolactone.13 When applied topically to the face twice daily. the majority exhibit normal values when laboratory testing is performed.5. Subjects included in the trials had clinically . randomized. double-blind Phase 3 studies of dapsone 5% gel twice daily versus vehicle gel (n=3. with little emphasis on topical therapies.16 The percentage of subjects achieving endpoint success (clear or almost clear) based on global acne assessment score (GAAS) was statistically significantly superior in females compared with males in both the dapsone-treated study arm (p=0. however. The outcomes of these Phase 3 studies led to the approval of dapsone 5% gel twice daily for AV by the United States Food and Drug Administration (FDA) in 2005.0001).14 Subjects (≥12 years of age) were randomly assigned to either treatment and instructed to apply the test material twice daily to the face after washing with a standardized soap-free cleanser. MATERIALS AND METHODS Study design and participants. with subgroup analyses completed with only a few therapeutic agents and formulations. as described previously.10 Most of the discussions about treatment of AV in adult women focus on the use of systemic therapies. ≥18 years of age) females.It is important for the clinician to consider the possibility of underlying disorders that cause androgen excess in adult women presenting with AV. and total AV lesions (p<0.0001) in both the actively treated and vehicle-treated study arms in females (n=1520) compared with males (n=1378). adolescent (12-17 years of age) and adult (post-adolescent. randomized.1.14 However.15 In two large Phase 3.6. doubleblind. a subgroup analysis showed significantly greater reductions in inflammatory lesions (p<0. . l=minimal. efficacy was evaluated based on the proportion of subjects achieving success on GAAS. STATISTICAL METHODS Within-group change from baseline was analyzed and comparisons were performed using the Wilcoxon signed-rank test. 4. and 12. Enrolled subjects were evaluated at baseline and at Weeks 2.diagnosed AV. Ranked analysis of covariance was used to analyze the percentage of reduction in acne lesion counts. Women taking oral contraceptives were required to have been using them for at least three months prior to study entry. defined as achieving a rating of none (0) or minimal. 781 female subjects in the dapsone 5% gel group. Tolerability and safety monitoring. adolescent girls 12–17 years of age. total) at Week 12.e. and 4=severe). Efficacy assessments. AEs. Subjects were also excluded if they used other treatments (i. Subjects were excluded if severe cystic acne or conglobate acne was present or if any emerging nodular lesions above the mandible were noted. were monitored and captured throughout the study at each study visit or if reported otherwise by the study subject. (n=347.507 evaluable subjects who completed the two Phase 3 pivotal trials. Endpoint success for AV lesions was defined as a significantly greater mean percentage reduction from baseline in at least two of the three types of AV lesions (inflammatory.14 The GAAS was scored on a 5-point scale (0=none. Among the 2. female subjects treated with dapsone 5% gel twice daily and vehicle gel were stratified by age: ≥18 years (adult or post-adolescent) and 12 to 17 years (adolescent). Efficacy at the 12-week time point (study endpoint) was assessed by comparing the mean GAAS score at baseline and at study endpoint as well as change from baseline. To be included in this subgroup analysis. topical. 3=moderate.1 Efficacy was also determined via acne lesion counts. Women of childbearing potential could not be pregnant or nursing and had to be using an effective form of contraception as determined by the investigator. including and signs and symptoms of application site reactions (local skin tolerability). . n=434. along with the total AV lesion count. 8. systemic. adult women ≥18 years of age) were eligible for this analysis (Table 1). all subjects underwent investigator global assessment using GAAS and counting of inflammatory and noninflammatory AV lesions. Study visits and assessments. At each visit. noninflammatory. In addition. 2=mild. RESULTS Subject disposition and characteristics. 6. with 20 to 50 inflammatory lesions and 20 to 100 noninflammatory lesions located on the face above the mandibular line at baseline. including the use within four weeks of baseline of any systemic or immunosuppressive agents or other therapies known to affect AV or inflammatory responses and/or the use of oral isotretinoin within three months of baseline. devices) that could affect AV. 85. Most subjects were white. dapsone 5%: -0.5%) versus adolescents (45.0426). and 9.3%. At Week 12. no difference was noted between groups in GAAS scores.94. the standard deviation ranges indicate that there was considerable overlap in lesion types and quantities between both age-related female subgroups.80 (p=0. p=0. Both groups showed significantly greater mean changes from baseline in GAAS than their vehicle-treated counterparts: for adolescents.001) in both groups.001) (Figure 1A). TABLE 1 Demographics and clinical characteristics at baseline Efficacy. Figure 1B). However. Mean numbers of AV lesions were higher at baseline in the adolescent subgroup by 1. however.0187). with race/ethnicity definitions and their dispositions outlined in Table 1. 7. for adults.8 noninflammatory lesions. dapsone 5%: -0. the proportion of subjects with clinical success (GAAS score 0 or 1) at Week 12 was greater in adult women (53.The mean age of the adolescent subgroup was 14 years and the mean age of the adult subgroup was 27 years.022. as demonstrated by significantly reduced mean GAAS in both subsets (p<0. . At baseline. dapsone 5% gel improved AV in both the adolescent and adult female subgroups. Dapsone 5% gel significantly reduced mean GAAS from baseline (p<0.5 inflammatory lesions. with no differences in mean change from baseline to Week 12 in GAAS between dapsone-treated adolescent girls and adult women (Figure 1C).2 total lesions.67 (p=0. vehicle: -0. vehicle: -0. (B) Percentage of dapsone 5% gel-treated subjects achieving GASS success (score 0 or 1) at Week 12. The percentage changes from baseline in all lesion endpoints were numerically greater for each type of lesion in adult women compared with adolescent females. statistically significant lesion reductions were observed in the adult-group compared with the adolescent-group for both noninflammatory (p<0. In the dapsone 5% gel study arm. and total lesion counts expressed as percentage change from baseline in both adolescent females and adult women (Table 2).Figure 1 Efficacy of dapsone 5% gel in adolescent and adult females with acne vulgaris.. (A) GAAS rating at baseline and Week 12.0008). TABLE 2 . noninflammatory.. Treatment with dapsone 5% gel resulted in statistically significant reductions in inflammatory.0001) and total lesion counts (p=0. (C) Mean change from baseline in . 3%) and adult females (53.5%) were greater than the overall responder rate (40. although adolescent females had significantly greater numbers of both inflammatory and noninflammatory AV lesions at baseline than did adult women enrolled in the study. and no previously unrecognized safety signals were observed. These results did not reveal any differences from findings observed in the full population of subjects in the two pivotal Phase 3 trials. Interestingly.Percentage (%) change from baseline in acne lesion counts (Week 12) Tolerability and safety. 12-week trials and has also been shown to exhibit a greater clinical success rate in females compared with males.14 This current analysis of AE data from both female subgroups showed no major safety issues. further supporting that dapsone 5% gel was more effective in females overall. although shown to be effective in females aged ≥12 years. dapsone 5% gel was more effective in reducing . Figure 2 Dapsone 5% gel effect on tolerability in adolescent and adult females with acne vulgaris.16The subgroup analysis reported here was designed to compare the efficacy of dapsone 5% gel applied twice daily in two subgroups of female patients based on age: adolescents (12-17 years of age) and adults (≥18 years of age). Tolerability and safety were highly favorable in both subgroups. vehiclecontrolled. whereas reductions in noninflammatory and total AV lesions were greater in adult women compared with adolescents.14. oiliness.16 Dapsone 5% gel was equally effective in both age groups in reducing the percentage change from baseline in inflammatory lesions. GAAS responder rates in both adolescent (45. randomized. BL=baseline DISCUSSION Dapsone 5% gel applied twice daily for facial AV has demonstrated efficacy and safety in both male and female subjects based on outcomes reported from two double-blind. A comparable reduction was observed in inflammatory AV lesions in both adult and adolescent females.14.5%) reported from the combined male and female population in the pivotal Phase 3 studies. and peeling compared with baseline in both adolescent and adult females (Figure 2). may exhibit greater efficacy overall in adult women (≥18 years of age) compared with adolescent females (12-17 years of age). Facial application of dapsone 5% gel for 12 weeks reduced (improved) the percentage of subjects reporting erythema. The results of this sub-analysis demonstrated that dapsone 5% gel was effective in both adolescent and adult females in reducing facial AV. dryness. These data suggest that the efficacy of dapsone 5% gel applied twice daily for facial AV. 14 Outcomes noted in the vehicle-treated female subjects for both age-based subgroups (adolescents and adults) are depicted in Figure 1C and Table 2. If an underlying cause of androgen excess is identified.22 In addition. results observed in vehicle-treated adult women and adolescents were also documented and reported. a dividing line needs to be selected to create a reasonable frame of reference for analysis and discussion. They have not been derived from any established scientific basis to differentiate age-based subgroups. with approximately two-thirds of visits for AV made by females and one-third of visits for AV made by women >25 years of age. skin color. is frequently addressed as an important clinical consideration because of concern regarding persistent residual hyperpigmentation that may be caused by resolved inflammatory AV lesions and/or skin irritation from topically used products. although the severity as an adult may be more severe. However. therapy needs to be directed at treating that disorder. however. often with oral contraceptives and/or oral spironolactone.7 A second limitation of this subgroup analysis is that the comparison of efficacy outcomes between the age-based subgroups was focused on data obtained only from females actively treated with dapsone 5% gel. or less severe than in the past.46 The remaining one-fourth of adult women with AV experienced onset of the disorder after adolescence.4.17. more than 50 percent of females with AV are over the age of 20 years. AV is the most common diagnosis seen in dermatology ambulatory practice in the United States. topical therapy in adult women with AV has not received much direct research to determine whether specific agents and/or vehicle formulations are generally preferred due to more favorable efficacy and/or tolerability. which included females and males ≥12 years of age.2. Dapsone 5% gel has been demonstrated to be more effective than vehicle gel in improving AV in the overall population of enrolled subjects.6. Across all ethnic groups. Nevertheless.18 Although teenagers are the most common group affected overall. most adult women with AV do not have an identifiable underlying disorder and are treated with a variety of conventional therapies for AV.20Unfortunately. some adult women with AV present with .noninflammatory lesions in adult women compared with reductions noted in the adolescent female group. the same.5.9-11.21. One limitation of this analysis is similar to limitations of other age-based subgroup analyses completed with topical agents used to treat AV6-8 The age ranges that define the dividing line to separate the AV subgroups in females have been arbitrarily selected in both previous literature and in subgroup analyses of data from pivotal studies.19 Approximately three-fourths of adult women with AV have had the disorder as an adolescent. The primary design of the subgroup analysis was not focused on outcomes in adolescent and adult females treated with vehicle gel. With regard to topical therapy. the age of 18 years was used as the line dividing adolescent and adult females into two subgroups. often reported as the Fitzpatrick skin phototype. 1.1. In this subanalysis. with the recognition that this parameter has been used previously to divide these same subgroups. attitudes and expectations about treatment of AV later in life. which are important to address in how they may or may not apply to each affected woman.3-5. a practical “checklist” of important characteristics that may be helpful during evaluation of each adult woman who presents with AV includes psychosocial factors. with 74 percent indicating that they want treatment for their AV that has been shown to be effective for adult females. a facial skin condition that they thought would never persist after the teenage years or even begin later in life. and beyond are often frustrated and embarrassed by having AV..6. less attractive.6. especially the perioral region.11 Although AV in adult women may be responsive overall to many of the conventional therapies used to treat patients of either gender. TABLE 3 Acne vulgaris (AV) in adult women: management of individual casesa Differentiating factors that can impact It is important to take into account with each patient her age and phase in life. as the presence of AV lesions adversely affects their self-image and self-esteem. salicylic acid) or vehicles that have a propensity to induce cutaneous irritation require more cautious use when applied on the neck and/or to the lower face.inflammatory AV lesions located below the jawline.1. children.1.9. some differentiating considerations need to be taken into account when treating adult women with AV. it is not uncommon for adult women with AV to feel self-conscious. As AV most often involves the face.23 Dedicating time to obtain a detailed history and to carefully evaluate the skin of the patient is important to adult women who are seeking treatment for AV. first age of onset of AV (including any history of adolescent AV).5. involving the submandibular and lateral neck regions. many also report that it is important for the clinician to explain their options for treatment and involve them in the decision. retinoids.23 A survey of adult women with AV (N=409) indicated 54 percent used ≥3 treatments for AV over the past year. attitudes and expectations about having AV later in life. current . and/or fulltime employment. Women who are in their 20s.10.23 Some of the major factors that are important to consider and attempt to differentiate when managing AV in adult women are outlined in Table 3. and less willing to interact socially or professionally. 30s. benzoyl peroxide. such as family. which are sites more prone to irritation from topical medications used to treat AV.10 Certain active ingredients used in topical acne medications (i. From a clinical perspective.5.e.23 Many have the stress of balancing time-consuming responsibilities. 15 More recently. and safe in both adolescent and adult females. anatomic distribution (i. spironolactone.. current medications and any OTC supplements. 1% clindamycin. hirsutism. topical products alone or in combination with systemic products are commonly prescribed. may not be as effective as commonly assumed because the effect of placebo can approach drug effects during the 4 . the mean contribution of vehicle . The mean reduction from drugs and vehicles were 42 ± 7. It was recently pointed out by Chiou that oral tetracyclines.12 weeks of daily administration. 0. facials. diet. respectively.. injectable agents). and the desire for therapies that are effective and well-tolerated specifically in this population is commonly expressed. alopecia. based on female patients actively treated with dapsone 5% gel twice daily.12 weeks of daily administration. and further suggests that efficacy may be greater in the latter subgroup. missed menses.e. this patient population is characterized by specific challenges. and pregnancy considerations.1% adapalene. light therapies.. trunk). microdermabrasion. a combination of benzoyl peroxide with adapalene or clindamycin. overall time course of AV (any flare patterns).Chiou WL Abstract In drug treatment for acne. CONCLUSION The topical treatment of AV in adult women has received little attention until recently. current or previous use of hormonal agent(s) (oral contraceptives. These preparations included 0.1%. 5% dapsone. which most women do not expect to occur. inability to conceive a child). neck. medical history. peels.16 The subgroup analysis data reported here. face. signs and/or symptoms of androgen excess (i. many caused by the presence of AV at a later stage in life. data analysis from the Phase 3 pivotal trials has shown greater efficacy in female than in male subjects. Dapsone 5% gel applied twice daily for facial AV has been shown to be effective and safe in male and female subjects ≥12 years of age in pivotal Phase 3 trials and in a 12-month study in which ∼80 percent of subjects used dapsone 5% gel twice daily as monotherapy over the duration of the study. The present work evaluated the percent contribution of vehicle (placebo) toward the reported efficacy of reduction in total (inflammatory and non-inflammatory) lesion counts of 8 commonly prescribed topical preparations at the end of 10 .AV lesion types. Importantly. Feelings of frustration and embarrassment are common. 18). and 23 ± 5. home use devices). presence of dyschromia (persistent inflammatory erythema or hyperpigmentation). irregular menses.e. use of physical modalities and/or device therapies (i.e.1% tretinoin. previous and current prescription and/or over-the-counter (OTC) therapies used for AV. intrauterine or implanted devices.14. and a clindamycin-tretinoin combination.0%. Low intrinsic drug activity and dominant vehicle (placebo) effect in the topical treatment of acne vulgaris . support that this agent is effective. well-tolerated. presence of acne scarring. the most commonly prescribed systemic drugs. and 25 ± 15%.0%). The potential significance of the above findings in the development of more effective topical anti-acne drugs was discussed.89%).5%. their respective means were 40 ± 9%.82%). Is Dapsone Gel Safe and Effective for the Treatment of Acne Vulgaris? Amy Patel. The present work shows the great importance of vehicle effects in topical therapy. in some cases this effect approached 90%. and vehicletoward-drug contribution was 58 ± 31% (range 9 .toward drug effect was 55 ± 15% (range 35 . PA-S . For 5 benzoyl peroxide preparations evaluated (2 for 2. and 3 for 5. A SELECTIVE EVIDENCE BASED MEDICINE REVIEW In Partial Fulfillment of the Requirements For The Degree of Master of Science In Health Sciences – Physician Assistant Department of Physician Assistant Studies Philadelphia College of Osteopathic Medicine Philadelphia.2012 . Pennsylvania December 14. . controlled trials and the open-label noncomparative study showed that dapsone gel was effective in the treatment of acne vulgaris. Results from the Draelos et al and Raimer et al studies showed patients had success on the GAAS and had a reduction in acne lesion counts. The Lucky et al study showed that patients had a reduction in acne lesions counts. All three studies also demonstrated that dapsone gel was safe when used to treat acne vulgaris. acne. DATA SOURCES: Randomized. controlled trials and open-label noncomparative study indicate that dapsone gel for the treatment of acne vulgaris is safe and effective. double-blind.ABSTRACT OBJECTIVE: The objective of this selective EBM review is to determine whether or not dapsone gel is safe and effective for the treatment of acne vulgaris. controlled trials and one open label. CONCLUSIONS: The results of the randomized. OUTCOMES MEASURED: Success on the Global Acne Assessment Score (GAAS) and reduction in acne lesion counts RESULTS: The two randomized. KEY WORDS: Dapsone. STUDY DESIGN: A review of three English language studies published in 2007. controlled trials comparing dapsone gel to vehicle gel control were found using PubMed and Cochrane database. Includes two randomized. noncomparative study. and environment. and testes secrete androgens. causing hair follicles to be plugged with oil and dead skin cells that further 6 stimulate the development of acne. The incidence of acne vulgaris is 30% to 60% of 10-12 year olds and 4 80% to 95% of 16-18-year olds that are affected. Due to the numerous individuals affected by acne vulgaris. this condition is commonly encountered in the scope of PA practice. Successful and prompt treatment of acne vulgaris can improve an individual’s quality of life. Acne vulgaris can be chronic for some individuals but self-limiting in other cases. self-esteem. The direct costs associated with acne vulgaris 5 surpass $2. It is important to be able to correctly diagnose and treat acne vulgaris. Other known factors that contribute to acne vulgaris are . Contributing factors to developing acne include stress. The prevalence of acne vulgaris peaks during the middle to late teenage period and then steadily decreases. ovaries. acne is the most common skin disorder affecting 40 to 50 million 3 individuals. 2 In the United States. This subsequently leads to an increase in sebum production. The pathogenesis of acne vulgaris includes many factors and the series of events in the 6 process of development of acne are unclear. the adrenal glands.2 billion each year in the United States. Acne development is initiated during menarche 6 when there is increasing sebum production in the sebaceous glands. During menarche. Acne vulgaris tends to be more severe in males than females. genetics.Patel: Dapsone & Acne Vulgaris 1 INTRODUCTION Acne vulgaris is a common dermatologic condition that presents in adolescence and is characterized by inflammatory lesions (papules and pustules) and non-inflammatory lesions 1 (comedones). Acne vulgaris may negatively impact body 2 image. and mood. Treatment options vary with each patient. OBJECTIVE The objective of this selective EBM review is to determine whether or not “Is dapsone gel safe and effective for the treatment of acne vulgaris?” . but is limited in use due to the potential for systemic absorption leading to toxicity. 4 sulfer. Recently. simply. tretinoin. benzoyl peroxide. azelaic acid. and clindamycin. Thus. self-care. chest. reduce inflammation. Treatment of acne will help to fight bacterial infections. Dapsone has been used orally for the treatment of acne.Patel: Dapsone & Acne Vulgaris 2 6 inflammation. dapsone gel offers a new treatment option for acne vulgaris. Prompt treatment is crucial because acne vulgaris can cause psychological or social dysfunction and long-lasting deformity. Some options include accutane. trimethoprim. or routine face washing with mild soap. and Propionibacterium acnes. Common locations for acne to develop include the face. follicular hyperproliferation. salicyclic acid. neck. Dapsone is a sulfone that has anti-inflammatory and antimicrobial properties. doxycycline. The treatment options that are listed above are all successful ways of treating acne. topical dapsone gel was developed for treatment of acne. depending on the severity of acne. and/or reduce oil production. which would offer the same antimicrobial and anti-inflammatory advantage with minimal systemic absorption. resorcinol. shoulders. and back. accelerate skin turnover. Acne vulgaris can be treated with a variety of medications or. erythromycin. Antibiotics that can be 4 used for acne include tetracycline. Statistics included in the studies were relative risk reduction (RRR). Keywords used in literature search were “dapsone” and “acne”. Inclusion criteria were randomized. The three studies in this review were researched using PubMed and Cochrane database by the author. absolute risk increase (ARI). Patients were randomly assigned dapsone gel or vehicle gel and then instructed to apply a thin layer of dapsone or vehicle gel to the acne-affected areas for 12 weeks. In Lucky et al study. The population in these studies consisted of men and women over the age of 12 years with acne vulgaris. Safety of dapsone gel was specifically evaluated through adverse events and physical examination findings. relative risk increase (RRI).Patel: Dapsone & Acne Vulgaris 3 METHODS This review includes two randomized controlled trials and one open-label noncomparative study. double-blind studies based on an outcome which was important to the patient. if acne cleared up in a particular area. Articles were selected by the author based on their relevance and outcome to the patient. The efficacy and safety of dapsone gel for the treatment of acne vulgaris was measured through success on the GAAS (global acne assessment score) and reduction in acne lesion count. number needed to harm (NNH). Table 1 demonstrates the demographics of the studies included. . In this study. treatment could be discontinued but if acne recurred. number needed to treat (NNT). absolute risk reduction (ARR). then dapsone gel was reapplied. The intervention used was dapsone gel 5%. controlled. The treatment groups receiving dapsone gel were compared to those receiving vehicle gel control treatment. The outcomes measured were those of patient-oriented evidence. patients applied dapsone gel to acne-involved areas for 12 months. and p-values. All articles were published in English in peer-reviewed journals in 2007. Both Draelos et al and Raimer et al studies were designed in a similar way. Studies were excluded if they included patients under the age of 12 years old. Additionally. 6. All three studies assessed patients for dryness. At these visits. blood was drawn for routine laboratory tests and patients were screened for G6PD deficiency. 9. and erythema. 1=minimal. peeling. at baseline and week 12. 2=mild. 3=moderate. noninflammatory and total lesions were counted.4=severe) and reduction from baseline in acne lesion counts. Success on the GAAS is defined as a score of 0 or 1. The Lucky et al study assessed efficacy based on reduction of acne count lesions during a dermatological examination at baseline and months 1. Patients went through a dermatologic examination at baseline and weeks 2. Draelos et al and Raimer et al studies assessed efficacy based on success rates on the GAAS from 0 to 4 (0=none. 3. and 12. a Global Acne Assessment Score was recorded. In addition. . 6. 4. and 12.Patel: Dapsone & Acne Vulgaris 4 OUTCOMES MEASURED Outcomes measured were those of patient-oriented evidence that matters. 8. inflammatory. This was evaluated by the adverse events and physical examination findings. Another outcome measured was safety of dapsone gel. Allergy to dapsone or sulfa drugs .Severe cystic 166 acne.presence of 2050 inflammatory lesions and 20100 noninflammatory lesions above the mandibular line at baseline Open label.Atleast 12 years old with a clinical diagnosis of acne vulgaris involving face 20-50 inflammatory lesions and 20100 noninflammatory lesions above the mandibular baseline 2 Double blind. or active/developi ng nodules . RCT 1306 >12 years old (subgroup presented in this study is 12-15 years old) .Patel: Dapsone & Acne Vulgaris 5 Table 1: Demographics & Characteristics of included studies Study Type # Pts Age Inclusion Criteria 6 Double blind.12 years or old older with a clinical diagnosis of moderate to moderately severe acne vulgaris defined as at least 20 inflammatory lesions at baseline Draelos (2007) Raimer (2007) 1 Lucky (2007) Exclusion W/D Criteria . RCT 3010 > 12 years old .Severe cystic 503 acne or active/ developing nodules .12 years or N/A older with acne vulgaris.Use of drugs that affect acne . . acne conglobate.Use of drugs that affect acne .Allergy to dapsone or sulfa drugs . noncomparative 506 >12 years .Pregnant or nursing women Intervention dapsone gel 5% twice daily or vehicle gel control dapsone gel 5% twice daily or vehicle gel control dapsone gel 5% twice daily .Pregnant or nursing women 22 . Thus. The relative risk reduction (RRR) was 23% and absolute risk reduction (AAR) was 8. In the study done by Raimer et al. .3%. The inclusion criteria for all three studies was similar. non-inflammatory. The difference in control and experimental group was a p-value less than 0. patients treated with dapsone gel had significantly greater reduction in inflammatory. Exclusion criteria included severe cystic acne. Data from the studies was analyzed with the intention to treat.Patel: Dapsone & Acne Vulgaris 6 RESULTS This EBM review was done on two randomized controlled trials and one open-label noncomparative study.001. and total lesion counts from baseline to 12 weeks and achieved success on the GAAS. 9 patients needed to be treated with dapsone gel to improve acne vulgaris in one patient. In the study done by Draelos et al. or the use of other drugs that affect acne. The number needed to treat (NNT) was 13 patients. active/developing nodules. The Draelos et al and Lucky et al studies had similar exclusion criteria whereas the Raimer et al study did not have an exclusion criteria noted. The relative risk reduction (RRR) was 42% and absolute risk reduction was 11. This implies that 13 people needed to be treated with dapsone gel in order to improve acne vulgaris in one patient. dapsone gel was more effective than vehicle gel. making it statistically significant. The results in these reviews were presented as dichotomous data. All participants were at least 12 years old with a clinical diagnosis of acne vulgaris and had the presence of at least 20 inflammatory lesions at baseline.9%. The number needed to treat was 9 patients.001. pregnant or nursing women. allergy to dapsone or sulfa drugs. Testing was statistically significant with a p-value less than 0. At week 12 patients achieved GAAS success and reduction in acne lesion counts from baseline. The study done by Lucky et al is not included in Table 2 because it did not use the GAAS score to evaluate effectiveness.1% 28. Individuals achieving success on GAAS) RRR ARR NNT 44.2% and non-inflammatory lesions decreased by 19.001 Draelos et al (2007) Raimer et al (2007) 23% 8. NNT – number needed to treat The incidence of adverse events was also calculated by each study in regards to the safety of dapsone gel.9% 9 p<0. Total acne lesion counts decreased by 49. RRR – relative risk reduction.2% 42% 11.001. In the study done by Draelos et al. Table 2 shows the efficacy of dapsone gel in the treatment of acne vulgaris in two of the three studies. both dapsone gel and vehicle gel treated groups experienced similar rates of adverse events.3% 13 40. The test was statistically significant with a p-value of less than 0. Table 2.5%. ARR – absolute risk reduction.001 Lucky et al (2007) EER – experimental event rate.9% p<0. Inflammatory lesions decreased the greatest by 58.Patel: Dapsone & Acne Vulgaris 7 In the open-label non-comparative study done by Lucky et al.0%. Clinical efficacy of dapsone gel in the treatment of acne vulgaris Study EER (Dapsone gel. Individuals achieving success on GAAS) 35. Patients treated with dapsone gel had an .2% CER p-value (Vehicle gel control. there was a reduction in acne count lesions from baseline to 12 months with the use of dapsone gel. CER – control event rate. 3% -23 et al (2007) Lucky 1. The relative risk increase (RRI) was 1. Study EER (dapsone gel) CER (vehicle gel control) 16.3%.2% and the absolute risk increase (ARI) was 0. erythema was one of the most common adverse events occurring at week 12. N/A – not applicable . Table 3.Patel: Dapsone & Acne Vulgaris 8 incidence of 58.6% of patients experienced erythema at application site.4% -4. The number needed to harm (NNH) was 23 patients.4% 37. RRI – relative risk increase. 500 patients need to be treated with dapsone gel for one person to have erythema as an adverse event. The number needed to harm (NNH) was 500 patients. Incidence of erythema in dapsone gel group versus vehicle gel control group. In the study done by Raimer et al.3% of dapsone treated patients and 16. Thus.6% N/A N/A N/A N/A et al (2007) EER – experimental event rate. Erythema occurred in 16.4% and absolute risk increase (ARI) was -4. NNH – number needed to harm.6% in terms of adverse events. Table 3 shows the incidence of erythema in patients treated with dapsone gel versus vehicle gel treated groups.1% of vehicle gel treated patients.2%.2% 0. Erythema was a common adverse event in all three studies.2% and patients treated with vehicle gel had an incidence of 58.3% 1. About 1. The study conducted by Lucky et al found 68% of patients experienced at least one adverse event.1% RRI ARI NNH Draelos 16.02% 500 et al (2007) Raimer 33.7% -11. ARI – absolute risk increase. The relative risk increase (RRI) was -11. CER – control event rate. The studies done by Draelos et al and Raimer et al were twelve weeks long.Patel: Dapsone & Acne Vulgaris 9 DISCUSSION Dapsone was shown to be effective for the treatment of acne vulgaris years ago. but was not widespread in use due to its systemic toxicity. Erythema was a common adverse reaction seen in both groups that were treated but declined with the course of treatment. Dapsone has antimicrobial and antiinflammatory properties. which showed similar results between the dapsone gel treated group and vehicle gel treated group. Topical dapsone gel has minimal systemic absorption. Dapsone was known to cause adverse hemolytic reactions. The study done by Draelos et al showed a higher percentage of people having minimal to no acne at the end of the treatment in patients treated with dapsone gel. as noted by the studies discussed. Adverse events and routine blood laboratory values were monitored on patients during the study. this study did assess the use of dapsone gel for twelve months rather than only twelve weeks. In the study done by Lucky et al. The studies in this review have some limitations. In addition. Greatest improvement was seen in inflammatory lesions. The two randomized controlled trials and one open-label noncomparative study showed that dapsone gel 5% is safe and effective for the treatment of acne vulgaris. dapsone gel also caused improvement of acne based on GAAS success and reduction in acne count lesions. more 6 commonly in patients with G6PD deficiency. but no mean change from baseline was seen in the hematology results. it is difficult to assess efficacy without a control group. However. In the study conducted by Raimer et al. which may not be enough time to thoroughly assess . A major concern was patients diagnosed with G6PD deficiency. those treated with dapsone gel had greater success on the GAAS and a reduction in acne lesion counts. many older individuals are also affected and should have been represented. In addition. It was also suggested from these studies that dapsone gel is well-tolerated. as it does not cause significant adverse events. acne can be a chronically debilitating condition where a longer treatment period may be needed. Although these studies do conclude the use of dapsone gel is safe and effective. Even though acne vulgaris is more common in young teenagers and adolescents. dapsone gel has a rapid onset of action. Dapsone gel provides a new treatment option for medial providers and those diagnosed with acne vulgaris. the study done by Raimer et al only focused on a subgroup of participants from 12 to 15 years of age. Also. Regardless of the need for additional studies. which truly matters to the patient. dapsone gel is a safe and effective way of treating acne vulgaris. Lack of a control group can limit findings and be inconclusive about the efficacy and safety of dapsone. Additionally. Patients in all three studies showed improvement in acne vulgaris when applying topical dapsone gel. more trials should be done to assess the safety of using dapsone gel over a chronic time period. CONCLUSION The trials reviewed imply that dapsone gel is safe and effective for the treatment of acne vulgaris. the study done by Lucky et al lacked a control group.Patel: Dapsone & Acne Vulgaris 10 efficacy of dapsone gel. . For many patients. United States . NY. MD. MD. Forest. VA. Carrollton. TX. Alan Shalita. TX. MD. United States. Stephens and Associates.Dapsone gel 5% is an effective. The Educational & Research Foundation. James Herndon. Dallas Associated Dermatologists. United States. safe. David Whiting. Dallas. Inc. State University of New York. Brooklyn. United States. MD. novel topical treatment of acne vulgaris David Wilson..