The Role of Dapsone Gel in the Acne Armamentarium | The Dermatologist
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`The Role of Dapsone Gel in the Acne
`Armamentarium
`The authors discuss how this agent’s dual anti­inflammatory and anti­microbial
`effects may make it a safe and effective multimodal monotherapy for acne. How­
`ever, they add, further studies are needed. Acne vulgaris, which is characterized by inflam­
`matory and non­inflammatory lesions beginning during adolescence, is most often manifested on
`the face and neck. Acne formation is multi­factorial, and includes: disordered keratinocyte desqua­
`mation, sebum secretion, inflammation, and Propionibacterium acnes. Most current treatments for
`acne focus on limiting one or more of these factors.1 Many topical and oral acne treatments involve
`anti­bacterial action, but problems arise when bacteria develop resistance, rendering treatment less
`effective. Benzoyl peroxide (BPO) is widely considered first­line topical antibacterial
`treatment for acne, but it can cause irritation at high concentrations and bleaches clothing and/or
`hair. Topical and oral antibiotics are also common treatments for inflammation in acne,
`but present a problem due to the aforementioned resistance. A newer therapy for acne is 5% dap­
`sone gel, with initial studies indicating that it is both effective and safe; but further studies remain.
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`Dapsone Properties
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`Dapsone is a sulfone that has been used mainly as an oral medication for leprosy and less com­
`monly as a treatment for acne vulgaris. Although dapsone is classified as an antibiotic due to its
`inhibition of bacterial DNA synthesis, it is also an effective anti­inflammatory agent. Never­
`theless, due to the concerning side effects that come along with ingestion of the drug (hematologic
`and hepatic issues), a topical formulation has been produced. Blood dapsone levels following topi­
`cal dapsone gel treatment at steady state was demonstrated to be approximately 100­fold
`lower than exposure to a single 100­mg dose of orally administered dapsone.2 In 2005, the FDA
`approved dapsone for acne patients under the condition that they test negative for G6PD deficiency;
`however, following a phase IV trial, the FDA removed this restriction, improving feasibility. Dap­
`sone’s dual anti­inflammatory and anti­microbial effects may offer physicians a novel
`multimodal monotherapy for targeting acne. Aczone, the trade name for 5% dapsone gel, is
`marketed by Allergan and is available to prescribers and their patients.
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`Dapsone Efficacy
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`Clinical trials have demonstrated reductions in acne lesions with 5% dapsone gel use, particularly
`for inflammatory lesions. One such study enrolled 506 patients older than 12 years of age with a
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`The Role of Dapsone Gel in the Acne Armamentarium | The Dermatologist
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`clinical diagnosis of moderate to moderately severe acne vulgaris.1 Patients applied treatment twice
`daily to affected areas. The clinical trial lasted 12 months. There was a 58.2% decrease in inflam­
`matory lesions, a 19.5% reduction in non­inflammatory lesions, and a total lesion reduction of 49%
`(P values all below 0.05). Acne lesion counts decreased over the first 6 months, then leveled out
`over the next 6 months. Of note, almost 20% of the participants used prohibited acne medications
`in addition to twice daily dapsone gel. Another study assessed the efficacy of 5% daspone gel in
`treating acne vulgaris using global acne assessment score (GAAS) and mean lesion count reductions.
`Two similar 12­week studies of 3,010 patients were combined to generate the data.3 In the first
`study, 44% of the experimental group (vs. 36% of the control group) achieved success using the
`GAAS scale. In the second study, 37% of the experimental group (vs. 30% of the control group)
`achieved success using this scale. Combined, 40% had success with dapsone gel, and 33% had suc­
`cess in the control group (P <0.001). In comparing the mean lesion counts, the dapsone group
`demonstrated greater reductions in inflammatory (48% vs. 42%), non­inflammatory (32% vs.
`24%), and total lesion counts (39% vs. 32%) compared to the control group. Like the previous
`study, dapsone was more effective in reducing inflammatory lesions than in reducing noninflamma­
`tory lesions. As early as week 2, a small difference could be seen between control and experimental
`groups, and this difference grew to statistical significance by week 8. To put this data in perspec­
`tive, we compared the results from the three large clinical trials to those seen with other commonly
`used acne treatments. Table 1 — which focuses on inflammatory lesion reduction — displays results
`from the clinical trials involving dapsone gel, as well as those from selected trials of other acne
`preparations. Although we found trials testing the efficacy of other topical gels — as opposed to
`creams, lotions, solutions, etc.— it is impossible to make a clear comparison, as gel formulations can
`contain a wide variety of ingredients. Thus, the relative efficacy (found by subtracting lesion reduc­
`tion percentage in the vehicle group from that of the drug treatment group) may not be comparable
`between treatments.4 As stated above, although the listed trials are each quite different in charac­
`ter, dapsone gel appears to be similarly effective in reducing inflammatory acne lesions to benzoyl
`peroxide, topical retinoids, topical antibiotics and oral antibiotics. Its relative efficacy, which
`appears somewhat lower than other agents, is questionable, as the gel formulations themselves may
`be promote or inhibit acne formation.4 Furthermore, other confounding variables, including study
`design and study population, may be responsible for this finding, and further head­to­head compar­
`ative trials are called for. In the meantime, dapsone may serve an important function in those who
`develop intolerance to the currently established acne agents or are unable to use them secondary to
`side effects.
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`Dapsone Tolerability
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`The primary tolerability concern with dapsone is hematological reactions. Patients with glu­
`cose­6­phosphate dehydrogenase (G6PD) deficiency in particular are at increased risk of hemolysis
`and hemoglobin denaturation with oral dapsone. These worries led the FDA to initially condition
`topical dapsone approval on mandatory G6PD deficiency screening. However, the aforementioned
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`trials of dapsone gel indicated that patients are not at increased risk of hemolytic anemia,
`methemogoblinemia, or drops in hemoglobin levels, including those with G6PD deficiency.3 Fur­
`thermore, a 12­week study examining 64 patients with G6PD deficiency (14 were severely deficient)
`using twice daily 5% dapsone gel found a clinically insignificant 0.32 g/dL decrease in Hb level 2
`weeks after beginning therapy, which was no longer observed at 12 weeks of treatment.5 Addition­
`ally, no relationships were found between changes in Hb level and bilirubin, haptoglobin, LDH lev­
`els and relative reticulocyte count, arguing against clinically relevant hemolysis. Finally, no clinical
`signs of hemolytic anemia were observed in subjects applying the dapsone gel. There are local side
`effects associated with 5% dapsone gel. The most common local adverse reactions are oiliness, dry­
`ness and erythema — each in nearly 20% of the patients.3 A much smaller proportion (2% or less)
`of the participants reported burning, pruritus, and irritation at the application site. However, it is
`important to note that these adverse reactions were reported at comparable rates in the control
`group, which received vehicle gel treatment. Thus, adverse reactions are probably attributable to
`the gel vehicle rather than dapsone.
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`Limitations — Studies Needed (Table 2)
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`Due to the fact that dapsone was only recently approved for use in acne treatment, there remains a
`lack of studies on the bacterial resistance caused by dapsone gel. Oral dapsone used in
`leprosy does result in resistance and must be given in combination with other drugs.6 What remains
`to be seen is whether dapsone gel will cause similar resistant strains in acne vulgaris. Such studies
`have been performed in the past with other acne treatments.7 Another study that could help put
`dapsone’s efficacy into better perspective would be a controlled head­to­head clinical trial
`comparing different acne treatments, including BPO, tetracycline agents, clindamycin, eryth­
`romycin and topical retinoids, to dapsone gel. Such a study would help clinicians determine which
`drug is best under a given circumstance, as well as where dapsone fits in the plethora of effective
`acne agents (Figure 1). In comparing other topical treatments with dapsone gel, we must realize
`that acne treatment vehicles are not placebos, oftentimes exhibiting considerable activity.4 In order
`to appropriately compare topical acne agents to each other, it would be prudent to use the same
`vehicle (ie, other topical gels of the same formulation). In this regard, we must also examine the
`interactions of different drugs, both oral and topical, with dapsone, and how they can
`work with or against each other. Such a study would make it possible to understand dapsone combi­
`nations are effective and/or safe and which are not. We are most interested to see if dapsone, in
`combination with other agents, improves efficacy, or if dapsone deactivates or is deactivated by
`another agent. Furthermore, data are also needed on the effect of combination use on side effects.
`Michael Ghods is a medical student at the University of California at Davis, School of Medicine, Sacra­
`mento, CA.
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`Dr. Alikhan is a medical resident at MacNeal Hospital in Berwyn, IL.
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`Dr. Feldman is with the Departments of Dermatology, Pathology, and Public Health Sciences; Wake
`Forest University School of Medicine; Winston­Salem, NC.
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`Disclosures: Michael Ghods and Drs. Alikhan and Feldman have no conflict of interest with any mate­
`rial presented in this month’s column.
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