Journal of drugs in dermatology
`v. 15, no. 2 (Feb. 2016)
`General Collection
`W1 J0626G
`2016-03-03 09:55:55
`
`1
`
`AMN1047
`Amneal v. Almirall, LLC
`IPR2019-00207
`
`

`

`FEBRUARY 20I6
`
`COPYIUGIIT © 2016
`
`132
`
`VoLUME 15
`
`• IssuE 2 - -
`ocY
`jOUI(NAL 01' DIWCS IN ])EHMATOL
`'
`
`RESIDENT ROUNDS (CONTD)
`247 PART II: High Yield Cutaneous Drug Reactions
`Ben M. Perry DO, Scott Thomas DO, and Bryce L. Desmond DO
`
`251 PART Ill: Case Report: Crohn's Disease Discovered by Granulomatous Chelitis
`Bryce L. Desmond DO, Scott Thomas DO, and Stephanie S. Howerter DO
`
`FEATURED CONTENT
`
`253 Clinical Trial Review
`
`J>UBLISIIUHS
`Shelley N. Tarmer
`Lawrence E. Robins
`
`ExEcUTIVE EmToH
`Karin lkehkr
`
`AssociATE Punus!IEH
`Nick Gillespie
`
`SCJENTII'IC PullLICATIONS LIAisoN
`Luz Figueroa
`
`RJ SKIN OF COLOR
`tll SEMINAR SERIES
`. f ns) bY the
`.
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`Journal of Drugs in Dermato/ogy(JDD) (ISSN 1545-9616) IS published monthly for $300 per year (US subscriptions)/$350 per year (International subscnp 1°
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`© 2016 Journal of Drugs in Dermatology
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`I! II ~rNtS S
`
`2
`
`

`

`C:oi'YIUC;IIT KJ 2010
`
`JuunNAL <>I' Dnuc;s IN DEnMATOLOCY
`
`1 !) 1
`
`VoLUME 15
`
`•
`
`Issun 2
`
`Use of Dapsone So/o Gel as Maintenance Treatment of Acne
`Vulgaris Following Completion of Oral Doxycycline and
`Dapsone So/o Gel Combination Treatment
`
`Leon H. Kircik MD
`Icahn School of Medicine at Moullt Sinai, New York, NY; Indiana University School of Medicine, Indianapolis, IN;
`Physicians Skin Care, l'LLC, Louisville, KY
`
`Background: Acne vulgaris is a common, chronic skin disease that requires long-term therapy. Oral antibiotics are a mainstay of treat(cid:173)
`ment, but extended use is associated with the development of bacterial resistance. Topical therapies are often combined with oral anti(cid:173)
`biotics to achieve an initial improvement. after which the oral agents may be discontinued and the topical therapy used as maintenance.
`Objective: To assess the safety and efficacy of combination therapy with dapsone 5% gel with oral doxycycline hyclate 100mg,
`followed by monotherapy with dapsone 5% gel in improving and maintaining response in patients with moderate to severe acne.
`Methods: In this open-label study, all patients applied dapsone 5% gel twice daily along with doxycycline hyclate 100mg once daily for 12 weeks.
`Subjects who achieved a qualifying improvement at week 12 continued to the second phase of the study in which they applied only dapsone 5%
`gel twice daily for maintenance therapy of 12 more weeks. Subjects were evaluated for safety and efficacy at weeks 4, 8, 12, 16, 20, and 24.
`Results: All subjects (n=30) in the initial phase qualified to enter the maintenance phase. 82% of participants maintained their treat(cid:173)
`ment response (Investigator's Global Assessment score) at week 24. The regimen was safe and well tolerated.
`Conclusions: The combination oral doxycycline hyclate 100 mg with topical dapsone 5% gel twice daily is an effective and well(cid:173)
`tolerated regimen to treat moderate to severe acne vulgaris. After discontinuation of doxycycline, topical dapsone 5% gel is effective
`at maintaining a therapeutic response. These data suggest that topical dapsone 5% gel can be used effectively for long-term acne
`maintenance treatment without the risk of developing antibiotic resistance.
`
`J Drugs Derma to!. 2016;15(2): 191-195.
`
`IINTR0DUGTI0NI
`
`I n the real world, acne is a chronic disease that requires
`
`maintenance treatment beyond the 12-week evaluation
`period used in most clinical trials. Combination therapy,
`using different drugs with complimentary mechanisms of ac(cid:173)
`tion is considered standard of care in treating acne. While
`oral antibiotics are commonly used initially to control mod(cid:173)
`erate to severe acne, they should not be used as long-term
`maintenance because of the risk of promoting bacterial re(cid:173)
`sistance. Topical retinoids have traditionally been the pre(cid:173)
`ferred option for maintenance therapyYTopical dapsone 5%
`gel has been approved for treatment of acne vulgaris since
`2005. It has been used for acne vulgaris with proven efficacy
`and safety during post marketing in addition to a long-term
`safety study. 3 However, there is a paucity of data evaluating
`topical dapsone 5% gel as maintenance following a success(cid:173)
`ful course of antibiotics.
`
`The current study investigated whether dapsone 5% gel could be
`used to maintain a therapeutic response in moderate to severe
`acne patients who were assessed to be responsive to initial com(cid:173)
`bination treatment with oral doxycycline hyclate 100 mg once a
`day and dapsone 5% gel twice a day for 12 weeks.
`
`!METH0DSI
`Study Design
`Thirty two subjects with moderate to severe facial acne vul(cid:173)
`garis were enrolled into this two-site, open-label, pilot study.
`Subjects entered into a 12-week initial treatment phase fol(cid:173)
`lowed by a 12-week maintenance phase for qualifying patient.
`In the initial treatment phase, patients received doxycycline
`hyclate 100 mg once daily in combination with dapsone 5%
`gel twice daily. In the maintenance phase, the oral antibiotic
`was discontinued and patients applied dapsone 5% gel twice
`daily as monotherapy. Participants had 7 study visits; baseline
`and weeks 4, 8, 12, 16, 20, and 24. At the week 12 visit, sub(cid:173)
`jects who achieved a qualifying treatment response, moved
`on to the maintenance phase. Subjects who did not achieve a
`qualifying treatment response at week 12 were discontinued
`from the study.
`
`The sample size of 32 subjects was chosen based on the as(cid:173)
`sumption that 66% of subjects (approximately 20 subjects)
`enrolled would achieve treatment response and crossover
`into the second phase of the study. Data from the study will
`highlight any trends regarding the safety and efficacy of the
`study medication.
`
`3
`
`

`

`JouHNAL oi' Dnucs IN DEHMAT<>L<>t:Y
`Pl'lmUAHY 201 (>
`• VoLUME 15 •
`IssuE 2
`
`192
`
`L.H. Kircik
`
`Inclusion Criteria
`Male and female patients at least 12 years old of any race were
`eligible for enrollment. Participants had facial acne vulgaris
`judged to be moderate or severe (3-4 on the Investigator's Glob(cid:173)
`al Assessment (IGA) scale). with 10-50 inflammatory lesions
`(eg, papules, pustules) and 10-100 non-inflammatory lesions
`(eg, open, closed comedones). Female subjects of childbear(cid:173)
`ing potential had to have a negative urine pregnancy test result
`at baseline and were required to practice a reliable method of
`contraception throughout the study.
`
`Exclusion Criteria
`Patients were excluded from participation in the study if they were
`female and pregnant, breast-feeding, or of childbearing poten(cid:173)
`tial but not practicing a reliable method of birth control. Patients
`were also excluded if they had an allergy to any component of
`the dapsone 5% gel, lincomycin, tetracycline, or sulfites. Standard
`wash-out periods of 14 days for topical acne medications, 30 days
`for oral antibiotics or other investigational drugs, and 6 months for
`oral retinoids were used. Patients with a history of clinically signif(cid:173)
`icant anemia, hemolysis, or glucose-6-phosphate dehydrogenase
`(G6PD) deficiency, or enteritis (including regional enteritis, ulcer(cid:173)
`ative colitis, pseudomembranous colitis, or antibiotic-associated
`colitis) were prohibited from participating.
`
`Treatment Regimen
`During the initial treatment phase, patients applied dapsone
`5% gel to the face twice daily in combination with once daily
`doxycycline hyclate 100 mg once a day in the morning. Patients
`were instructed to use a pea-sized amount of dapsone 5% gel
`after washing their face with a gentle cleanser. All patients were
`given the same moisturizer and gentle cleanser. At week 12,
`subjects' global response to therapy was evaluated. Those who
`achieved an IGA score of at least mild (IGA 0, 1, or 2) moved
`on to the second phase of the study. During the maintenance
`phase, subjects discontinued doxycycline therapy and applied
`dapsone 5% gel twice daily as monotherapy for an additional
`12 weeks. Subjects were evaluated to assess whether improve(cid:173)
`ment would remain with topical monotherapy.
`
`Randomization
`This was an open-label investigation, in which all subjects received
`active treatment. Patients who achieved an IGA score of clear, al(cid:173)
`most clear, or mild were advanced into the maintenance phase of
`the study, in which all patients again received active treatment.
`
`Main Outcome Measures
`The primary efficacy outcome was the IGA score, a 6-point
`scale where O=clear, 1=almost clear, 2=mild, 3=moderate, 4=se(cid:173)
`vere, and 5=very severe. (Table 1) Secondary efficacy variables
`included inflammatory lesion (papule/pustule). non-inflamma(cid:173)
`tory lesion (open/closed comedone). and total lesion counts.
`Safety outcomes included collection of all adverse events and
`
`TABLE 1.
`
`0 =Clear Skin
`
`Clear Skin; no inflammatory or non(cid:173)
`inflammatory lesions
`
`1 =Almost
`Clear
`
`2 =Mild
`Severity
`
`3 =Moderate
`Severity
`
`4 =Severe
`
`5 =Very
`Severe
`
`Almost clear; rare non-inflammatory lesions
`with no more than one small inflammatory
`lesion
`
`Mild severity; greater than Grade 1; some
`non-inflammatory lesions with no more than
`a few inflammatory lesions (papules/pustules
`only, no nodular lesions)
`
`Moderate severity; greater than Grade 2;
`some to many non-inflammatory lesions and
`may have some inflammatory lesions, but no
`more than one small nodular lesion
`
`Severe; greater than Grade 3; some to many
`non-inflammatory and inflammatory lesions,
`but no more than a few nodular lesions
`
`Very Severe; greater than Grade 4; many non(cid:173)
`inflammatory and/or inflammatory lesions
`with some or many nodular lesions
`
`evaluation of medication tolerability, including erythema, dry,
`ness, peeling, and oiliness on a five grade scale (Table 2). Finally,
`any application site reactions such as stinging and burning were
`also assessed using a 6-point severity scale (Table 3).
`
`Statistical Analysis
`Statistical analyses were conducted on the intent-to-treat popu,
`lation, ie, all enrolled subjects were included. All statistical tests
`were 2-sided and interpreted at a 5% significance level.
`
`0>'411J4.tl
`Patients
`A total of 32 patients with moderate to severe facial acne were
`enrolled in two United States investigational research centers. The
`majority of patients (62.5%) were female. The mean and median
`ages of subjects were 24.8 and 21.5 years old, respectively. The
`youngest patient enrolled was 12.8 years old and the oldest was
`48.7 years old. The majority (71.9%) of patients were Caucasian.
`The full subject demographic information is summarized in Table 4.
`
`Of the 32 patients, 24 (75%) completed the initial treatment
`phase. All (100%) of the patients who completed the initial
`phase qualified to move into the maintenance phase of the
`study. Of the 24 patients, 22 completed the maintenance phase.
`
`Efficacy
`Investigator's Global Assessment
`The primary outcome measure in this study was the percent
`of subjects who maintained IGA success rate at the end of
`
`4
`
`

`

`J<>UHNAL <>I' DHu<;s IN D~:HMAI <>L<><;v
`ri:IIHUI\I{Y 2() I() • VoLU/\11: 15 • lssu~: 2
`
`L.ll. Kircik
`
`193
`
`TABlE 2.
`~·,,,···.· ~ '
`
`,.,
`
`,· '
`
`':..; "' ': ~ •!. I 1 • i.
`
`0 =Absent
`
`No redness
`
`. '··
`-.. ~;' .
`
`-:J·,'J•'·
`
`\
`
`None
`
`1 =Trace
`
`2 =Mild
`
`Faint red or pink
`coloration, barely
`perceptible
`
`Barely perceptible dryness by palpation with no
`accentuation of skin markings, skin desquamation
`(flakes) or fissure formation
`
`Light red or pink
`coloration
`
`Easily perceptible dryness by palpation with
`accentuation of skin markings but no skin
`desquamation (flakes) or fissure formation
`
`1
`
`Smooth
`
`Fine peeling, barely
`perceptible
`
`Slight peeling
`
`Normal
`
`Mild and
`localized
`
`Mild and
`diffuse
`
`3 =Moderate
`
`4 =Severe
`
`Medium red
`coloration
`
`Beet red
`coloration
`
`Easily noted dryness with accentuation of skin
`markings and skin desquamation (small flakes) but no
`fissure formation
`
`Definitely
`noticeable peeling
`
`Moderate and
`diffuse
`
`Easily noted dryness with accentuation of skin markings,
`skin desquamation (large flakes) and/or fissure formation
`
`Extensive peeling
`
`Prominent and
`dense
`
`maintenance phase (week 24) compared to the end of initial
`treatment phase (week 12). The success was defined as an
`IGA score of 0, 1, or 2. This was first assessed after the initial
`phase at week 12 compared to baseline, then again after the
`maintenance phase at week 24 compared to week 12. Com(cid:173)
`bination therapy with doxycycline 100 mg daily with topical
`dapsone gel 5% twice daily resulted in a treatment response
`in 30% of subjects by week 4, 67% of subjects by week 8, and
`100% of subjects at week 12. 100% of subjects qualified to en(cid:173)
`ter the maintenance phase, during which the doxycycline was
`discontinued and subjects were treated with topical dapsone
`gel 5% twice daily as monotherapy. 78.3%, 87%, and 82% of
`subjects maintained their treatment response at weeks 16
`(4 weeks post-phase 1), 20 (8 weeks post-phase 1 ), and 24
`( 12 weeks post-phase 1 ), respectively. At week 24, topical
`
`TABlE 3.
`KftmMtifjjffiOO@rttiijffiffiiAtifti?:.~"/·:·;::·:.::;>.li·~'\::·:.-.·'::·',~.:<.·1
`
`!
`
`!
`
`.::. ·)~.
`
`• r ~
`
`-
`
`•
`
`I
`
`t{.~ i~l·!~~~~-~.
`
`0 =Absent
`
`Normal, no discomfort
`
`1 =Trace
`
`2 =Mild
`
`An awareness, but no discomfort and no
`intervention required
`
`Noticeable discomfort causing intermittent
`awareness
`
`3 =Moderate
`
`Noticeable discomfort causing continuous
`awareness
`
`4 =Marked
`
`Definite discomfort causing continuous
`awareness, interfering occasionally with
`normal daily activities
`
`5 =Severe
`
`Definite, continuous discomfort interfering
`with normal daily activities
`
`dapsone 5% gel twice daily did not maintain therapeutic re(cid:173)
`sponse in only a minority (18%) of patients.
`
`Inflammatory Lesion Count
`Compared to baseline, combination therapy resulted in a 39.8%
`and 54.7% mean reduction in inflammatory lesions at weeks 4
`and 8. By week 12, there was a 79.4% mean reduction in inflam(cid:173)
`matory lesions, which was maintained throughout the second
`phase of the study. After discontinuation of doxycycline, twice
`daily application of dapsone 5% gel provided a sustained re(cid:173)
`duction in inflammatory lesions; at weeks 16, 20, and 24, there
`was a mean percent reduction of 80.5%, 78%, and 77.8% com(cid:173)
`pared to baseline. All inflammatory lesion count reductions
`were statistically significant compared to baseline (P <0.0001 ).
`In addition, there were no statistical differences in the overall
`mean percent change in inflammatory lesions at any point dur(cid:173)
`ing the maintenance phase compared to week 12.
`
`Non-inflammatory Lesion Count
`Statistically significant decreases in the mean percent reduction
`of non-inflammatory lesion counts were achieved throughout
`the initial study phase compared to baseline (P<0.0001 ). There
`was a 32.2%, 60.6%, and 75.6% mean reduction in non-inflam(cid:173)
`matory lesions at weeks 4, 8, and 12.The mean percent reduction
`in non-inflammatory lesions was sustained with dapsone 5%
`gel monotherapy twice daily. At weeks 16, 20, and 24, there was
`a 77.8%, 81.5%, and 84.7% decrease compared to baseline (P
`<0.0001 ). In addition, there was a statistically significant reduc(cid:173)
`tion in non-inflammatory lesions at week 24 compared to week
`12 (52.6% mean percent reduction, P=0.038).
`
`Total Lesion Count
`At weeks 4, 8, and 12, there was a 36.5%, 59.2%, 78.6% de(cid:173)
`crease, respectively, in mean total lesion count compared to
`
`5
`
`

`

`JouJ!NAL OJ' Dnuc:s IN DJ:I!MAmLoc:v
`FE!li!UAI!Y 201 (J
`• VoLUME 15 • IssuE 2
`
`194
`
`L.H. Kircik
`
`TABLE 4.
`
`Gender
`
`N
`
`Male
`
`Female
`
`Age (years)
`
`N
`
`Mean± SO
`
`', ,••
`
`32
`
`12 (37.5%)
`
`20 (62.5%)
`
`24
`
`11 (45.8%)
`
`13 (54.2%)
`
`32
`
`24
`
`24.8 ± 10.9
`
`24.9 ± 10.8
`
`Median (P25, P75)
`
`21.5 (15.9, 34.1)
`
`21.5 (16.0, 34.1)
`
`Min, Max
`
`12.8, 48.7
`
`13.0, 48.7
`
`Race
`
`N
`
`White
`
`Black
`
`Hispanic
`
`32
`
`23 (71.9%)
`
`7 (21.9%)
`
`2 (6.3%)
`
`24
`
`18 (75.0%)
`
`6 (25.0%)
`
`0 (0.0%)
`
`baseline. Similarly, at weeks 16, 20, and 24, there was a 79.4%,
`79.9%, and 81% decrease, respectively, compared to baseline.
`All results were statistically significant (P<0.0001 ). The follow(cid:173)
`ing changes were observed: At week 16, 7.7% mean percent
`increase compared to week 12 (P=0.4477); at week 20, 20% de(cid:173)
`crease compared to week 12 (P=0.02); at week 24,27% decrease
`compared to week 12 (P=0.0385). In addition, statistically sig(cid:173)
`nificant decreases in total lesion counts were observed during
`maintenance phase compared to week 12. At week 20, there
`was a 20.1% mean percent reduction in total lesions (P=0.0201)
`compared to week 12. This decrease was sustained to week 24,
`with a 27.4% mean percent reduction (P=0.0385) compared to
`week 12.
`
`Tolerabilty
`The regimen was well-tolerated. There were no serious ad(cid:173)
`verse events during the study. Six patients (18.1 %) experienced
`a treatment related adverse event (TRAE), 4 of which (12.5%)
`led to withdrawal from the study. The TRAE's included nausea
`(n=3), headache (n=2), vomiting (n=1 ). There were only 2 skin(cid:173)
`related TRAE's in the study (pruritus (n=1) and skin burning
`(n=1 )).
`
`!DISGUJSSI0NI
`Dermatologists commonly prescribe antibiotics for both infec(cid:173)
`tious diseases and inflammatory conditions. Increasing use,
`coupled with few new antibiotic drugs being developed, make
`antibiotic resistance is a growing health challenge. 3 In the United
`States, the Centers for Disease Control and Prevention (CDC)
`
`promote the idea of antibiotic stewardship, an intervention to
`ensure that antibiotics are prescribed at the correct dose, at the
`correct time, and for the correct duration.4·5 Antibiotics are a core
`component of treatment for inflammatory and widespread acne.
`They are effective and should be judiciously used as part of ini(cid:173)
`tial therapy, but should be discontinued once patients are stable
`and transitioned into a maintenance regimen in concordance
`with acne treatment guidelines.'
`
`Topical therapies are effective at maintaining acne improvement
`achieved from initial combination therapy with oral antibiotics.
`Such efficacy has demonstrated using topical retinoids 6.7 and
`fixed-dose adapalene 0.1 %-benzoyl peroxide 2.5% gel.8 In fact,
`one study demonstrated equal efficacy of topical tazarotene
`compared to oral minocycline as a maintenance therapy. 7
`
`Topical retinoids have traditionally been the maintenance
`acne therapy of choice because of their anti-inflammatory and
`anti-comedonal properties. 1•2 However, they are commonly
`associated with cutaneous irritation, so alternative topical
`maintenance options may be necessary in some patients. Long
`term use of topical dapsone 5% gel has been evaluated as part
`of a safety study and found to be effective at treating and main(cid:173)
`taining acne improvement over 52 weeks. 9 The current study
`is the first to demonstrate successful use of topical dapsone
`5% gel twice-daily monotherapy as a successful maintenance
`treatment after discontinuation of combination therapy with an
`oral antibiotic.
`
`Dapsone 5% gel is a topical acne medication with an anti(cid:173)
`inflammatory mechanism of action. It has been shown to be
`effective against both inflammatory and non-inflammatory
`acne lesions and has an extremely favorable tolerability pro(cid:173)
`file.10 Studies have shown successful use of topical Dapsone in
`combination with other medications, such as topical retinoids
`and benzoyl peroxide. 11
`12 Moreover, to date there me no pub(cid:173)
`•
`lished reports of bacterial resistance to topical dapsone. These
`characteristics make it a logical option for both initial treatment
`of acne as well as maintenance therapy.
`
`In this study, combination therapy using topical dapsone 5%
`gel with oral doxycycline 100 mg once daily demonstrated out(cid:173)
`standing efficacy after 12 weeks. 100% of subjects achieved a
`treatment response, defined as having an IGA score of at least
`mild (IGA score of 0, 1, and 2). Treatment responses were ob(cid:173)
`served in 30% of subjected by week 4 and in 67% by week 8.
`82% of patients who responded to the combination therapy at
`week 12 maintained their response until week 24 using topical
`dapsone 5% twice daily monotherapy.
`
`Combination therapy resulted in statistically significant reduc(cid:173)
`tions in both inflammatory and non-inflammatory acne lesions.
`By week 12, there was a 79.4% mean percent reduction in
`
`6
`
`

`

`2.
`
`3.
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`Gollnick H, Cunliffe W, Berson D, et a/. Management of acne: a report from
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`a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol.
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`Dreno B, Bettoli V. Ochsendorf F. Layton A, Mobacken H, Degree! H. Euro(cid:173)
`pean recommendations on the use of oral antibiotics for acne. Eur J Derma(cid:173)
`to!. 2004;14:391-399.
`Del Rosso, JO. SPAUD Conference. Cutis. 2007;79(65):6-8.
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`Thiboutot D eta/. Adapalene Gel, 0.1 %, as Maintenance Therapy for Acne
`Vulgaris A Randomized, Controlled, Investigator-Blind Follow-up of a Recent
`Combination Study. Arch Dermatol. 2006;142:597-602.
`Leyden J, et al. comparison of tazarotene and minocycline maintenance
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`group study. Arch Dermatol. 2006;142:605-612
`Tan J, Stein Gold L, Schlessinger J, et al. Short-term con1bination therapy
`and long-term relapse prevention in the treatment of severe acne vulgaris. J
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`Lucky AW, Maloney JM, Roberts J, eta/. Dapsone gel 5% for the treatment
`of acne vulgaris: safety and efficacy of long-term (1 year) treatment. J Drugs
`Dermatol. 2007;6(10):981-7.
`10. Draelos ZD, Carter E, Maloney JM, et al. Two randomized studies demon(cid:173)
`strate the efficacy and safety of dapsone gel, 5% for the treatment of acne
`vulgaris. JAm Acad Derma to/. 2007;56:439-410.
`Fleischer AB, Shalita A, Eichenfield LF. eta/. Dapsone gel 5% in combination
`with adapalene gel 0.1 %, benzoyl peroxide gel 4%, or moisturizer for the
`treatment of acne vulgaris: A 12-week, randomized, double-blind study. J
`Drugs Dermatol 2010;9:33-40.
`12. Tanghetti E, Dhawan S, Green L. eta/. Clinical evidence for the role of a topi(cid:173)
`cal anti-inflammatory agent in comedonal acne: findings from a randomized
`study of dapsone gel 5% in combination with tazarotene cream 0.1% in
`patients with acne vulgaris. J Drugs Dermatol. 2011 ;10(7):783-92.
`
`8.
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`9.
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`11.
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`AUTHOR CORRESPONDENCE
`
`Leon H. Kircik MD
`E-mail: ..................... , .................................. wedoderm@yahoo.com
`
`JouHNAL Ol' DHu<;s IN Du:MATOI.OGY
`l;EBIIUAHY ~0 1 (>
`• VoW ME 15 • IssUI: ~
`
`L.H. Kircik
`
`195
`
`IDIS<:::cOSURESI
`LK has received funding from Allergan either as an investigator,
`speaker, or consultant.
`
`inflammatory and a 75.6% mean percent reduction in non-in(cid:173)
`flammatory lesions. Maintenance therapy with topical dapsone
`5% gel monotherapy maintained the inflammatory lesion
`count reduction for the duration of the study, with no statis(cid:173)
`tically significant changes throughout the maintenance phase
`compared to week 12. Moreover, topical dapsone 5% gel mono(cid:173)
`therapy actually resulted in a statistically significant decrease
`in non-inflammatory lesions at week 24 compared to week
`12. Similarly, statistically significant mean total lesion percent
`count reduction was observed at 24 weeks compared to the ini(cid:173)
`tial improvement from combination therapy at week 12.
`
`Both the initial combination therapy and the maintenance treat(cid:173)
`ment were well-tolerated. There were only 6 treatment related
`adverse events, 4 of which were likely related to the oral dox(cid:173)
`ycycline. One subject discontinued the study due to burning
`and stinging from topical dapsone. One subject reported pruri(cid:173)
`tus which resolved without residual effects and continued the
`study medication without interruption. These data are consis(cid:173)
`tent with safety data from the large, 3000-patient pivotal phase
`Ill dapsone 5% gel studies. 11
`
`Limitations to this study include the small sample size, as this
`was a proof-of-concept study. In future studies, it would be use(cid:173)
`ful to evaluate larger numbers of patients. It is important to note
`that treatment response in this study was defined as an IGA
`score of 0, 1, or 2 (clear, almost clear, or mild), representing a
`real-world approach rather than an FDA-mandated endpoint of
`clear or almost-clear. This study could have also benefited from
`a vehicle arm during the maintenance phase as well as investi(cid:173)
`gator blinding. Another issue is the use of doxycycline hyclate
`100 mg once a day dose rather than a different antibiotic or a
`different dose usage. This decision was made since doxycycline
`hyclate 100mg once daily is the most commonly used antibiotic
`dose for acne globally. Finally, future studies could evaluate ini(cid:173)
`tial combination therapy of topical dapsone 5% gel with other
`complimentary topical preparations for initial therapy, followed
`by topical dapsone maintenance to sustain efficacy but limit po(cid:173)
`tential adverse events from less tolerable topical treatments.
`
`:CON8EBSIONJ
`Combination therapy with oral doxycycline hyclate 100 mg
`plus topical dapsone 5% gel twice daily is an effective and well(cid:173)
`tolerated regimen to treat moderate to severe acne vulgaris.
`After discontinuing the oral antibiotic, the improvement was
`sustained using topical dapsone 5% gel twice-daily monother(cid:173)
`apy for 12 weeks. There was a continued improvement in total
`lesion and non-inflammatory lesion counts at the conclusion of
`study compared to the initial improvement with combination
`therapy seen at week 12. Based on these data, topical dapsone
`5% can be recommended as maintenance therapy of acne vul(cid:173)
`garis, while avoiding the risk of developing antibiotic resistance
`associated with long-term use of oral antibiotics.
`
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