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`(cid:127) Clinical Focus: Acne
`
`By Dina Anderson, MO
`
`Finding a Place for Topical Anti-inflammatory
`Acne Therapy
`
`Dermatologists and patients are discovering how a novel topical therapy offers a
`different way to target acne in certain individuals.
`
`5 everal months after the market
`
`launch of topical dapsone gel 5%
`(Acrone, Allergan), clinicians still
`seem co be t rying to acquaint them(cid:173)
`selves with the agent and identify its
`ideal place in the management of acne
`patients. Patients, too, may be trying
`to familiarize themselves with this new
`and as yet not readily identified pre(cid:173)
`scription product. A cursory review of
`some Internet discussion boards for
`acne reveal quite a bit of dialogue
`about topical dapsone but few factual
`details. The following review high(cid:173)
`lights what we know about topical
`dapsone and its potential role in acne
`management.
`
`Efficacy and Safety
`Use of dapsone for the management of
`acne is not entirely new. It had been
`considered a possible acute, systemic
`intervention for severe, nodu!ocystic,
`inflammatory acne, and its use for this
`indication has been advocated as
`recently as last year.' However, due to a
`lack of data to support the use of oral
`dapsone for severe acne and the risk of
`adverse effects associated with the
`agent, including hematologic effects, its
`use for acne has been limited.2
`Topical dapsone expands the poten(cid:173)
`tial utility of the drug for acne. Several
`publications have presented and
`reviewed the efficacy of topical dap(cid:173)
`sone gel 5% in treating mild co mod(cid:173)
`erately severe acne. M In 12-week clini(cid:173)
`cal trials comparing topical dapsone to
`vehicle, treated patients had greater
`improvements in investigator's global
`
`acne assessment and mean percentage
`reduction in inflammatory, non(cid:173)
`inflammatory, and total lesion counts,
`compared to controls. Statistically sig(cid:173)
`nificant improvement in lesion counts
`was evident by week four/
`Topical application is associated
`with low systemic exposure and obvi(cid:173)
`ates concerns about hematologic side
`effects, with studies showing that only
`two of 50 study participants with glu(cid:173)
`cose-6-phosphate dehydrogenase
`(G6PD) deficiency experienced a drop
`in hemoglobin levels; those fluctua(cid:173)
`tions were similar to changes observed
`in non-G6PD deficient subjects.5 As
`dermatologists are aware, FDA
`dropped an initial requirement for
`screening for G6PD prior to topical
`dapsone therapy.
`
`A Context
`While data support the efficacy of topi(cid:173)
`cal dapsone gel, there are no trials com(cid:173)
`paring the intervention to other avail(cid:173)
`able topical therapies. Additionally,
`there may be some confusion regarding
`the agent's method of action in acne
`vu!garis and, thus, its therapeutic role.
`Dapsone is a su!fone and has long
`been used to manage leprosy, caused
`by bacteria Mycobacterium /eprae and
`Mycobacterium lepromatosis. The drug
`has been recognized as conferring anti(cid:173)
`inflammatory effects-beneficial in
`the management of leprosy- bur cur(cid:173)
`rent evidence questions the degree to
`which dapsone provides antimicrobial
`effects. One trial found that even at
`very high concentrations, dapsone
`
`demonstrated no antibacterial effects
`against Streptococcm pyogenes,
`Staphylococcus a11rem, or Escherichia
`coli.6 No published data report anti(cid:173)
`bacterial effects of dapsone against P
`acnes. Though, as the maxim holds,
`absence of evidence is not evidence of
`absence, these facts present interesting
`questions. Publications describe topi(cid:173)
`cal dapsone gel as an antibacterial
`agent;' marketing materials for the
`new formulation do not mention anti(cid:173)
`bacterial effects.
`Marketing emphasires the anti(cid:173)
`inflammatory properties demonstrated
`by topical dapsone gel in trials.
`Among 486 patients who used topical
`dapsone gel twice daily for up to 12
`months, there was a 58.2 percent
`reduction in mean inflammatory
`lesions at the end of the study period,
`compared to a 19.5 percent reduction
`in mean non-inflammatory lesions.•
`Overall reduction in mean total lesion
`counts was 49 percent. Investigations
`are reportedly underway to examine
`the use of topical dapsone for rosacea,
`a disease with a significant inflamma(cid:173)
`tory component.' Precisely how dap(cid:173)
`sone confers anti-inflammatory effects
`is not fully understood.
`Given that recent recommendations
`from the Global Alliance co Improve
`Outcomes in Acne group emphasize
`that acne is a chronic, inflammatory
`disease, similar to atopic dermatitis or
`psoriasis,' the availability of a topical
`anti-inflammatory agent may prove
`helpful in the clinic. Persistent con(cid:173)
`cerns about developing microbial
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`Almirall EXHIBIT 2009
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`Amneal v. Almirall
`IPR2019-00207
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`(cid:127)
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`(cid:127)
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`(cid:127) Clinical Focus: Acne
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`Rosacea Flare Forecast
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`If you notice an influx of rosacea patients during the summer months, your practice probably isn't unique. According to a recent
`survey of rosacea patients conducted by the National Rosacea Society (NRS), about half of respondents said their skin condition is
`worse in the summer months. Results of the survey of 1,190 rosacea patients, published in Rosacea Review, show that a majority
`(85 percent) said their rosacea is affected by changes in seasons; 46 percent said they have to make the most lifestyle adjustments
`during summer months to reduce the likelihood of a flare -up of signs and symptoms. The cold poses problems, as well. Thirty-five
`percent of all respondents and 46 percent of those who live in the northern US said their symptoms are at their worst during cold
`weather.
`Advising patients on preventive skincare and sun protection as well as recommending appropriate seasonal or pre-seasonal
`therapeutic modifications may help minimize exacerbations.
`
`- PD Staff
`
`resistance associated with the use of
`antibiotics also support the need for
`alternative therapeutic agents for acne
`management.
`
`Finding a Niche
`Based on the available data, topical
`dapsone seems especially well-suited
`to the management of primarily
`inflammatory mild to moderate acne.
`Use of the product is not associated
`with cutaneous irritation, such as
`burning or peeling common with the
`use of topical benzoyl peroxide or
`retinoids. Therefore, it is a suitable
`option for patients with sensitive skin.
`Given that the trend in acne thera(cid:173)
`py is to target as many pathogenic
`factors as possible, monotherapy is
`rarely indicated. In fact, guidelines
`suggest that most patients with mild
`to moderate acne should be managed
`or maintained with a topical retinoid.
`Topical antimicrobials, particularly
`benzoyl peroxide, are also emphasized
`in recommendations.9 Taken together,
`these various considerations suggest
`that most patients prescribed topical
`dapsone therapy may be candidates
`for additional topical intervention(s).
`There are no published studies on
`the use of topical dapsone in combina(cid:173)
`tion with other topical acne interven-
`
`tions. The Prescribing Information
`indicates that concomitant application
`of benzoyl peroxide and dapsone gel
`produced a yellow or orange discol(cid:173)
`oration of the skin in seven of 95 sub(cid:173)
`jects that lasted up to 57 days in some
`individuals. There is no report of the
`efficacy of the combination or whether
`either agent inactivated the other. Still,
`the risk of skin discoloration is suffi(cid:173)
`cient to recommend against concomi(cid:173)
`tant application. There are no other
`reports of interactions or contraindica(cid:173)
`tions with dapsone gel and standard
`topical acne therapies.
`Dapsone gel is indicated for twice(cid:173)
`daily application. However, if it is
`used in conjunction with other topi(cid:173)
`cal agents, until further evidence is
`available, it may be wise to reduce
`application of dapsone to once daily
`and substitute a retinoid or antimicro(cid:173)
`bial, such as benzoyl peroxide, at the
`other application time.
`Although topical dapsone gel may
`not become a first-line treatment
`option for a majority of people with
`acne, it may be an important treat(cid:173)
`ment option for a number of patients.
`It offers a unique mechanism of action
`and effectively targets inflammation(cid:173)
`one of the key pathogenic features of
`(cid:127)
`this ubiquitous dermatitis.
`
`Dr. Anderson has served as a consultant
`to Allergan; She has not consulted
`regarding Aczone.
`
`1. Ochsendorf FR, Oegitz K. Drug therapy of ame.
`Hautarzt. 2008Jul;59(7):579-89.
`2. Wolf R, Matz H, Orion E, Tuzun 8, Tuzun Y. Oapsone.
`Oermatol Online J. 2002 Jun;8(1): 2.
`3. Oraelos ZO, Carter E, Maloney JM, Elewski 8, Poulin Y,
`Lynde C, Garrett 5; Uniled States/Canada Oapsone Gel
`Study Group. Two randomized studies demonstrate the
`efficacy and safety of dapsone gel, 5% for the trealmenl
`of acne vulgaris. J Am Acad Oermalol. 2007
`Mar;56(3):439.e1-10.
`4. Pickert A, Raimer S. An evaluation of dapsone gel 5%
`in the treatment of acne vulgaris. Expert Opin
`Pharmacother. 2009 Jun;10(9):1515-21
`s. Stolland M, Shalita AR, Kissling RF. Oapsone 5% gel: a
`review of ils efficacy and safety in the trealmenl of ame
`vulgaris. Am J Clin Oermatol. 2009;10(4): 221-7.
`6. Wolf R, Omi-Wasserlauf R. A century of the synthesis
`of dapsone: its anti -infective capacity now and then. lnlJ
`Oermatol. 2000 Oct;39(10):779-83.
`7. Scheinfeld N. Aczone, a topical gel formulation of the
`antibacterial, anli-inflammalory dapsone for the treat(cid:173)
`menl of ame. Curr Opin lnveslig Drugs. 2009
`May;10(5):474-81.
`8. Lucky AW, MaloneylM, RobertsJ, Taylors, Jones T,
`Ling M, Garrett S; Oapsone Gel long -Term Safely Study
`Group. Oapsone gel 5% for the treatment of acnevul(cid:173)
`garis: safety and efficacy of long -term (1 year) treal(cid:173)
`menl. J Drugs Oermatol. 2007 Oct;6(10):981-7.
`9. Thiboutot 0, Gollnick H, Bettoli V, Ore no 8, Kang S,
`Leyden JI, Sha Ii la AR, Lozada VT, Berson 0, Finlay A, Goh
`CL, Herane Ml, Kaminsky A, Kubba R, Layton A, Miyachi Y,
`Perez M, Martin JP, Ramos-E-Silva M, See IA, Shear N,
`Wolf J Jr; Global Alliance to Improve Outcomes in Acne.
`New insights into the management of acne: an update
`from the Global Alliance to Improve Outcomes in Acne
`group. l Am Acad Oermalol. 2009 May;60(5 Suppl):S1-
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