Journal of Dermatological Treatment
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`Taylor & Francis
`%,lor & ~,.,d, c,,,,~p
`
`ISSN: 0954-6634 (Print) 1471-1753 (Online)Journal homepage: http:llwww.tandfonline.comlloilijdt20
`
`Clinical evaluation of Double Strength IsotrexinTM
`versus Benzamycin ® in the topical treatment of
`mild to moderate acne vulgaris
`
`P Marazzi, GC Boorman, AE Donald & HD Davies
`
`To cite this article: P Marazzi, GC Boorman, AE Donald & HD Davies (2002) Clinical evaluation of
`Double Strength IsotrexinTM versus Benzamycin ® in the topical treatment of mild to moderate acne
`vulgaris, Journal of Dermatological Treatment, 13:3, 111-117, DOI: 10.1080/09546630260199460
`
`To link to this article: https://doi.org/10.1080/09546630260199460
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`Published online: 12Ju12009.
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`Journal of Dermatological Treatment (2002) 13, 111-117
`© 2002 Journal of Dermatological Treatment. All rights reserved. ISSN 0954-6634
`
`¯ - (cid:128) Taylor &Francis
`Martin L)Unl~Z~lhealthsdences 111
`
`Clinical evaluation of Double Strength IsotrexinTM
`versus Benzamycin® in the topical treatment of mild
`to moderate acne vulgaris
`
`P Marazzi1, GC Boorman2,
`AE Donald2 and H D Davies2
`
`7 The Medical Centre, East Horsley, Surrey,
`UK, on behalf of Profiad Ltd, Reading, UK;
`2Stiefel International R & D, Maidenhead,
`Berkshire, UK
`
`inflammatory and non-inflamma-
`BACKGROUND: Topical retinoid
`tory lesions and acne grade) while
`therapy has been shown to be an
`subjective global change assess-
`effective means of treating both
`the inflammatory and non-inflam- ments of facial acne from baseline
`matory lesions of acne vnlgaris,
`and symptom-specific skin toler-
`AIM: To assess the efficacy and anee were assessed by the patient.
`safety of the test product, a gel The investigator recorded an
`containing isotretinoin 0.1% w/w overall global assessment of skin
`and erythromyein 4.0%w/w, with
`tolerability at week 12. Adverse
`a currently used and effective events wererecordedthroughout.
`treatment for mild to moderate RESULTS: The treatments were
`acne vulgaris, a gel containing comparable with regard to their
`benzoyl peroxide 5.0% w/w and effects on inflammatory and non-
`erythromyein3.0%w/w,
`inflammatory lesions and aene
`METHODS: This multi-centre, grade. Few adverse events were
`single-blind (investigator blind), considered to be treatment-
`parallel group study compared the
`related. Both the isotretinoin/ery-
`efficacy
`and
`safety
`of
`thromycin
`and
`benzoyl
`isotretinoin/erythromyein
`gel peroxide/erythromyein gels were
`(Double Strength IsotrexinTM) generally well tolerated. Corn-
`once daily against benzoyl perox- plianee was better with
`the
`ide/erythromyein gel (Benza-
`isotretinoin/erythromyein
`gel,
`myein®) twice daily in the topical which had the advantages of not
`treatment of mild to moderate
`requiring mixing or storage in a
`acne vulgaris. Patients (n = 188)
`refrigerator, and was applied once
`with a history (mean duration 3.3
`rather than twice daily.
`years) of facial acne vulgaris and CONCLUSION~
`Isotretinoin/ery-
`with 15-100 inflammatory
`thromyein gel given only once
`lesions and/or 15-100 non- daily showed comparable efficacy
`inflammatory lesions, but not with benzoyl peroxide/ery-
`more than three noduloeystic
`thromyein given twice daily in the
`treatment of mild to moderate
`lesions, were included. At base-
`line and weeks 2, 4, 8 and 12, the acne vulgaris of the face. (] Derma-
`investigator assessed efficacy
`tol Treat (2002) 13: ] ] ]-] ] 7)
`(total number and severity of
`
`Received 27th February 2002
`Revised 15th April 2002
`Accepted 3rd May 2002
`
`Keywords: Ache vulgaris -- Double Strength Isotrexin
`
`Correspondence:
`Angus E Donald, Clinical Research Manager, Stiefel International R & D, Whitebrook
`Park, Maidenhead, Berkshire SL 6 8XY, UK. Fax: +44 (0) 1628 411590.
`
`2 0f8
`
`

`

`112
`
`P Marazzi et al
`
`Acne vulgaris - Double Strength Isotrexin vs Benzamycin
`
`Introduction
`
`Topical retinoid therapy has been shown to be an effective
`means of treating both the inflammatory and non-inflam-
`matorylesions of acnevulgaris.13
`It can be considered that topical erythromycin therapy
`reduces the percentage of surface free fatty acids, which is
`thought to be due to inhibition of both lipase activity and
`lipase production by Propionibacterium aches.4 Ery-
`thromycin also inhibits leukocyte chemotaxis,s The main
`therapeutic effect of erythromycin is inhibition of inflam-
`mation caused by bacteria.6
`High efficacy and tolerability has previously been
`demonstrated with combined topical retinoid/antibiotic
`preparations in the treatment of acne vulgaris.7q°
`The results of a multi-centre, single-blind, controlled
`study comparing the efficacy and safety of a gel containing
`isotretinoin/erythromycin once daily with benzoyl perox-
`ide/erythromycin twice daily for the topical treatment of
`mild to moderate acne vulgaris are now reported.
`
`Patie n ts a n d m et h o d s
`
`Aims and objectives
`
`3), 8 (visit 4) and 12 (visit 5) weeks. During the study
`period and 1 month prior to recruitment, no other acne
`treatment was allowed.
`The isotretinoin/erythromycin gel was stored at room
`temperature. According to the manufacturer’s instruc-
`tions, patients were requested to store the benzoyl perox-
`ide/erythromycin gel in the fridge.
`
`Selection criteria
`
`A total of 188 patients, aged between 12 and 33 years
`(inclusive), were recruited into the study. To be able to
`detect a 30% absolute difference between active treat-
`ments, at the two-sided 5% significance level, with 95%
`statistical power, a total of 148 patients (74 completing
`each treatment) was required.
`Patients with facial acne vulgaris having 15-100 inflam-
`matory lesions and/or 15-100 non-inflammatory lesions,
`but not more than three nodulocystic lesions, were eligible
`for the study. Counts were made by assessors who were
`trained according to the method of Burke and Cunlifl~.11 The
`baseline numbers of inflammatory and non-inflammatory
`
`lesions and acne grade were recorded at the admission visit.
`
`Assessment of efficacy and safety
`
`The aim of the study was to assess the efficacy and safety
`of the test product, isotretinoin/erythromycin gel, with a
`currently used and effective treatment for mild to moder-
`ate acne vulgaris, benzoylperoxide/erythromycin gel.
`
`The gel containing isotretinoin O. 1% w/w and erythromycin
`4.0% w/w in a vehicle of butylated hydroxytoluene, hydrox-
`ypropylcellulose and ethanol (Double Strength IsotrexinTM),
`was manufactured by Stiefel International R & D (Maiden-
`head, Berkshire, UK). The comparator gel contained benzoyl
`peroxide 5.0%w/w and erythromycin 3.0%w/w (Benza-
`mycin®) and was manufactured by Rhane-Poulenc Rorer,
`Puerto Rico Inc, Puerto Rico and distributed by Bioglan Lab-
`oratories Ltd, Hitehin, Herefordshire, UK.
`
`At weeks 2, 4, 8 and 12, the following assessments were
`performed.
`The primary efficacy variables were the total number
`of inflammatory lesions, non-inflammatory lesions and
`the acne grade. Under standard light conditions, using the
`Test medications methods of Burke and Cunliffe, the assessors counted the
`11
`total number of inflammatory (papules and pustules) and
`non-inflammatory (closed and open comedones) lesions
`on each patient’s face, and also graded the severity of their
`acne. All 22 assessors who counted the lesions and graded
`the acne were trained by Ann Eady (Principal Research
`Fellow, University of Leeds).
`For each patient, the investigator subjectively assessed
`the overall facial acne condition as a global change score
`(very much improved, much improved, minimally
`improved, no change, minimally worse, much worse, very
`much worse) after 2, 4, 8 and 12 weeks of therapy. This
`assessment was intended as a secondary efficacy variable;
`however, it is recognized that the global change scores are
`exploratory in this clinical trial because baseline photo-
`graphs werenottaken.
`The secondary efficacy variable was the patient’s self-
`rating assessment, where patients self-rated the overall
`change in their facial acne as a patient’s self-rating assess-
`ment (improved, no change or worse) after 2, 4, 8 and 12
`weeks of therapy. The investigator asked the patient how,
`in his/her opinion, his/her condition had changed since
`commencing therapy.
`
`Study design
`
`This multi-centre, single-blind, parallel group study was
`conducted by 11 primary care centres throughout
`England, Wales and Ireland. The primary care centres
`were coordinated by Profiad Limited.
`
`Patients recruited for the study were assigned accord-
`ing to a pre-determined randomization schedule to receive
`either isotretinoin/erythromycin gel or benzoyl
`peroxide/erythromycin gel. Each patient was given verbal
`and written instructions by the investigator regarding the
`correct use of study gel, which was to be applied as a thin
`layer to the entire affected areas of skin (15 minutes after
`washing) for 12 consecutive weeks. Patients were Adverse events
`required to return for assessment after 2 (visit 2), 4 (visit
`Adverse events were classified into body system and pre-
`
`3 of 8
`
`

`

`P Marazzi et al
`
`Acne vulgaris - Double Strength Isotrexin vs Benzamycin 113
`
`ferred term using COSTART (Coding Symbols for a The-
`saurus of Adverse Reaction Terms).12 Any skin tolerability
`parameters (erythema, scaling, dryness, burning or pruri-
`tus) were graded as ’none’, ’mild’, ’moderate’ or ’severe’
`and, if present, whether intermittent or persistent. Any
`skin tolerability parameter graded as severe was also
`recorded as an adverse event,
`
`Compliance with dosage regimen
`
`Patients kept diary cards in which they noted the number
`of applications. The study nurse/pharmacist noted on the
`case report forms whether or not the patients had applied
`the medication according to the protocol (yes/no). If no,
`the approximate per cent of applications was noted
`(>75%, >50% and ~<75%, >25% and ~<50% and
`~<25%). Major violations were defined as less than or
`equal to 50% compliant at their last visit. The weight of
`the medication (~<25%, >25%, ~<50%, >50%, ~<75%,
`>75%) was recorded at each return visit,
`
`Statistical methods
`
`The results of the study were analysed by Hartington Stat-
`istics and Data Management, UK. Efficacy data were com-
`pared using analysis of variance (ANOVA) and logistical
`regression analysis. The chi-squared test or the Fisher’s exact
`test (where frequencies were small) and 95% confidence
`intervals (95% CIs) were used to compare safety data on all
`randomized patients receiving at least one application of
`study medication. Treatment groups were compared using
`two-tailed hypothesis tests at the 5% significance level.
`
`the study and randomized to Featment (intention-to-Feat
`population) with isoFetinoin/erythromycin (n = 95) or
`benzoyl peroxide/erythromycin (n = 93). See Table I.
`Patients were excluded from the per-protocol popu-
`lation from the visit at which the major violation was
`recorded, if applicable. Major violationswere less than 50%
`compliance, attendance more than 15 days before or after
`their scheduled visits, and use of concomitant medication
`before study start. If the violation was recorded at visits 1
`or 2, the patient was completely excluded from the per-pro-
`tocol population. Major protocol violations at visits 1 or 2
`occurred in three patients in the isoFetinoin/erythromycin
`group and seven patients in the benzoyl peroxide/ery-
`thromycin group, leaving 178 efficacy-evaluable patients
`(per-protocol population). In all, 21 patients (22%)from
`the isoFetinoin/erythrosmycin and 30 (32%) from the
`benzoyl peroxide/erythromycin groups discontinued at
`various times during the study, due to lack of Featment
`efficacy (n=0 and 2, respectively), adverse events (n=8
`and 9, respectively), refusal to cooperate (n = 6 and 12,
`respectively), development of exclusion criteria (n =4 and
`8, respectively), and other reasons (n = 3 and 0, respec-
`tively). One patient in the benzoyl peroxide/erythromycin
`group had two reasons for withdrawal.
`Of the 188 patients (106 females, 82 males, mean age
`17 years) recruited into the study, 185 were Caucasian;
`the mean duration of their history of acne was 3.7 years
`for the isoFetinoin/erythromycin group and 2.9 years for
`the benzoyl peroxide/erythromycin group. The two
`groups were well matched with respect to inflammatory
`and non-inflammatory lesions as well as for the severity of
`acne grade. The demographic characteristics for the inten-
`tion-to-Feat population are summarized in Table II.
`
`Resu Its
`
`Efficacy
`Between 19 October 1998 and 17 June 1999, a total of Mean changes from baseline (with 95% CI) ofnon-inflam-
`matory lesions, inflammatory lesions and acne grade for
`188 patients, from 11 primary care cenFes in the UK,
`with mild to moderate acne vulgarly were recruited into
`the intention-to-Feat population are presented in Table
`
`Centre no.
`
`Investigator
`
`Study centre
`
`Patients treated
`with isotretinoin/
`erythromycin gel
`
`Patients treated with
`benzoyl peroxide/
`erythromycin gel
`
`1
`2
`3
`4
`5
`6
`7
`8
`9
`10
`11
`
`Dr Chris Kyle
`Dr Malcolm McCaughey
`Dr Adrian Darrah
`Dr Sarah Morgan
`Dr Huw Charles
`Dr Chris Morgan
`Dr Philip Marazzi
`Dr Peter Harvey
`Dr Dayantha Fernando
`Dr Sally Barnard
`Dr Katrina Young
`
`Rosehall Surgery, Co. Antrim
`The Health Centre, Co. Antrim
`Whiteabbey Health Centre, Belfast
`Four Elms Surgery, Cardiff
`Ely Bridge Health Centre, Cardiff
`Old School Surgery, Mid Glamorgan
`The Medical Centre, Surrey
`Crouch Oak Family Practice, Surrey
`The Surgery, Surrey
`Newnham Walk Surgery, Cambridgeshire
`St Mary’s Surgery, Cambridgeshire
`
`9
`8
`8
`15
`9
`8
`8
`12
`8
`4
`6
`
`8
`8
`9
`1 3
`9
`6
`9
`11
`9
`4
`7
`
`Table I
`
`Number of patients treated at each primary care centre
`
`4 of 8
`
`

`

`114
`
`P Marazzi et al
`
`Acne vulgaris - Double Strength Isotrexin vs Benzamycin
`
`Treatment groups
`
`~
`._o
`
`--~
`
`0
`
`-5
`
`~ Isotretinoin (0.1%0)/Frythromycin (4%)
`
`O Benzoyl peroxide (5%)/Erythromycin (3%)
`
`Baseline
`characteristic
`
`Gender, n (%)
`Male
`Female
`
`Race, n (%)
`Caucasian
`Mongoloid
`
`Age, years
`
`Mean (SD)
`Range
`
`Weight, kg
`Mean (SD)
`
`Duration of acne, years
`Mean
`
`Previous acne treatment,
`mean (SD)
`Yes
`
`Benzoyl peroxide/
`Isotretinoin/
`erythromycin gel
`erythromycin gel
`(n = 95) (n = 93) K
`
`o ~"
`
`-10
`~
`
`-
`~
`.-~
`
`-15
`
`-20
`
`-25
`
`-30
`
`~
`~.t
`
`45 (47)
`50 (53)
`
`95 (100)
`0 (0)
`
`37 (40)
`56 (60)
`
`90 (97)
`3 (3)
`
`~ -35
`
`-40 ....
`Week 2 Week 4
`Week 8
`Week 12
`
`17.1 (5.0)
`12-33
`
`16.9 (3.6)
`12-30
`
`Finite 1
`
`63.9 (12.6)
`
`64.4 (10.8)
`
`3.7
`
`2.9
`
`28 (66.7)
`
`30 (69.8)
`
`Mean change from week 0 in non-iF~ammatond lesions at weeks 2,
`
`4, 8 and 12. Population: intention-to-treat.
`
`0,
`
`.o -5
`
`~,
`o
`
`~ Isotretinoin (0.1%)/Erythromycin (4%)
`
`O Benzoyl peroxide (5%)/Erythromycin (3%)
`
`Non-inflammatory lesions
`Mean (SD)
`Minimum
`Maximum
`
`45.3 (25.0)
`3
`111
`
`43.6 (22.0)
`7
`95
`
`Inflammatory lesions
`36.2(18.8)
`33.2(17.5)
`Mean (SD)
`7
`Minimum
`15
`Maximum 90 93
`
`-I0
`
`K
`
`~ K
`--15
`I C
`
`"-
`
`..~ ............................
`
`~’
`o~c
`
`-20
`
`~ -25
`O2
`
`-30
`
`Acne grade
`
`Mean (SD)
`Minimum
`Maxim um
`
`Table II
`
`1.25 (0.55)
`0.3
`3.0
`
`1.25 (0.63)
`0.1
`3.0
`
`Week 2 Week 4
`
`Week 8
`
`Week 12
`
`Figure 2
`Mean change from week 0 in inflammatory lesions at weeks 2, 4, 8
`and 12. Population: intention-to-treat.
`
`Demographic characteristics for the intention-to-tree t population at
`
`baseline according to treatment group
`
`-0.1
`
`~ Isotretinoin (0.1 Yo)/Erythromycin (4%)
`o
`
`-0.2 O Benzoyl peroxide (5%)/Erythromycin (3%)
`
`III. ANOVA was used to compare Featment groups with -~
`.~ -0.3
`respect to the changes from week 0 in the total number of
`non-inflammatory lesions, inflammatory lesions and acne
`grade at week 12. A total lesion count was not performed
`in the analysis and this can be derived from the data pro-
`vide& The numbers of non-inflammatory lesions, inflam-
`matory lesions and acne grade for the intention-to-Feat
`population are shown in Figures 1, 2 and 3, respectively.
`
`oa
`
`-0.4
`
`,~
`._= -0.5 ....
`~ -0.6
`
`,o -0.7
`g
`:~ -o.8
`
`Noniinflammatory lesions
`In the analysis of change from week 0 to week 12 in the
`total number of non-inflammatory lesions, no statistically
`significant difference was observed between the
`isoFetinoin/erythromycin and benzoyl peroxide/
`
`Week 2 Week 4
`
`Week 8
`
`Week 12
`
`Figure 3
`Mean change from week 0 in acne grade at weeks 2, 4, 8 and 12.
`Population: intention-to-tree t.
`
`-0.9
`
`-1.0
`
`5 of 8
`
`

`

`P Marazzi et al
`
`Acne vulgaris - Double Strength Isotrexin vs Benzamycin 115
`
`Efficacy assessment
`
`Week
`
`Isotretinoin/erythromycin gel (a = 95)
`
`Benzoyl peroxide/erythromycin gel (a = 93)
`
`Treatment groups
`
`Non-inflammatory lesions
`
`Inflammatory lesions
`
`Ache grade
`
`2
`4
`8
`12
`
`2
`4
`8
`12
`
`2
`4
`8
`12
`
`-9.3 (-13.0, -5.5)
`-16.0 (-20.2, -11.7)
`-25.0 (-29.6, -20.4)
`-28.3 (-33.2, -23.3)
`
`-9.6 (-12.6, -6.5)
`-11.4 (-is.o, -7.8)
`-16.9 (-20.8, -13.0)
`-20.5 (-24.3, -16.8)
`
`-0.23 (-0.29, -0.18)
`-0.32 (-0.39, -0.25)
`-0.54 (-0.63, -0.45)
`-0.72 (-0.83, -0.61)
`
`-11.0 (-14.0, -7.9)
`-14.8 (-18.6, -10.9)
`-20.1 (-24.9, -15.2)
`-26.0 (-33.2, -23.3)
`
`-13.9 (-17.2, -10.6)
`-20.6 (-24.0, -17.1)
`-23.0 (-26.5, -19.4)
`-24.5 (-29.1, -20.0)
`
`-0.36 (-0.41, -0.30)
`-0.51 (-0.58, -0.44)
`-0.65 (-0.74, -0.56)
`-0.78 (-0.90, -0.66)
`
`Table III
`Mean change from baseline in the number (with 95% CI) of non-ir~ammator!j lesions, inflammatory lesions and in acne grade for the intention-
`to-treat population at weeks 2, 4, 8 and 12 according to treatment group
`
`erythromycin groups. Similar results were obtained for the
`efficacy-evaluable population.
`
`Inflammatory lesions
`In the analysis of change from week 0 to week 12 in the
`total number of inflammatory lesions, no statistically
`significant difference was observed between the
`isotretinoin/erythromycin and the benzoyl peroxide/ery-
`thromycin groups. Similar results were obtained for the
`e fficacy-evaluable population,
`
`Acne grade
`In the analysis of change from week 0 to week 12 in the
`acne grade, no statistically significant difference was
`observed between the isotretinoin/erythromycin and the
`benzoyl peroxide/erythromycin groups. Similar results
`were obtained for the efficacy-evaluable population,
`
`Patients’ self-rating assessment
`In the intention-to-treat population, the great majority of
`patients considered their acne had improved by week 2.
`By week 12, 95-98% of patients considered their con-
`dition had improved. Similar results were obtained for the
`efficacy-evaluable population. At week 12, no statistically
`significant difference was observed between the
`isotretinoin/erythromycin and benzoyl peroxide/ery-
`thromycin groups (odds ratio 0.279, 95% CI 0.030,
`2.573; p=0.260). Similar results were obtained for the
`efficacy-evaluable population. However, in the efficacy-
`evaluable last observation carried forward (LOCF) analy-
`sis, the odds of an improvement were greater for those in
`the benzoyl peroxide/erythromycin group. See Table IV.
`
`Compliance with dosage regimen
`
`The great majority of patients were more than 75% com-
`pliant. In the intention-to treat population, at least 89% of
`the isotretinoin/erythromycin group and 70% of the
`benzoyl peroxide/erythromycin group were 76-100%
`compliant at eachassessment time.
`The following percentages of patients were 100% com-
`pliant in the isotretinoin/erythromycin and benzoyl per-
`oxide/erythromycin groups, respectively:
`
`weeks 0-2: 58 % and 39 %
`weeks 2~J~: 59% and 48%
`weeks 4-8: 52% and 39%
`weeks 8-12: 55% and 44%.
`
`The following percentages of patients were less than 50%
`compliant in the isotretinoin/erythromycin and benzoyl
`peroxide/erythromycin groups, respectively:
`
`weeks 0-2: 2% and 7%
`weeks 2~J~: 4% and 6%
`weeks 4-8: 4% and 11%
`weeks 8-12: 2% and 11%.
`
`Skin tolerability and overall tolerance
`
`In general, the groups were well matched with respect to
`the skin tolerance indicators. The majority of symptoms
`were mild and intermittent. Additionally, all the syrup-
`toms were’absent’ or’mild’ for >~92% of patients in both
`treatment groups. However, a higher proportion of the
`isotretinoin/erythromycin group than the berlzoyl per-
`oxide/erythromycin group experienced burning. Addi-
`tionally, a slightly higher proportion of patients in the
`
`6 of 8
`
`

`

`116
`
`P Marazzi et al
`
`Acne vulgaris - Double Strength Isotrexin vs Benzamycin
`
`Efficacy assessment
`
`Week
`
`Isotretinoin/erythromycin gel (n = 95)
`
`Benzoyl peroxide/erythromycin gel (n = 93)
`
`Treatment g roups
`
`Global change scorea
`
`2
`4
`8
`12
`
`2
`4
`Patients’ self-rating assessment 8
`12
`
`81
`78
`93
`96
`
`77
`69
`89
`95
`
`93
`97
`95
`100
`
`87
`90
`86
`98
`
`aThese results are not discussed, due to the absence of baseline photographs.
`
`Table IV
`
`Per cent of patients rated as ’improved’ (’very much’, ’much’ and ’minimally’) using the investigator subjecti ve global change score and the
`
`patients’ self-rating assessment (’improved’) for the intention-to-tree t population at weeks 2, 4, 8 and 12 according to treatment group
`
`Adverse events
`
`were associated with a reduction in the number of non-
`benzoyl peroxide/erythromycin group experienced pru-
`inflammatory and inflammatory lesions as well as in acne
`titus. See Table V.
`grade. There were no statistically significant differences
`Overall tolerance at week 12 was rated as excellent by
`between the treatments with respect to these changes. The
`37 (50%) patients in the isotretinoin/erythromycin group
`secondary efficacy results show that the analysis of the
`compared with 32 (51%) patients in the benzoyl perox-
`patients’ self-rating assessment revealed greater improve-
`ide/erythromycin group. Statistical analysis using the chi-
`squared test to compare treatment groups with respect to ment in the benzoyl peroxide/erythromycin group.
`There was a high number of withdrawals from the
`overall tolerance (’poor’, ’fair’, vs ’good’, ’excellent’) at
`study. The study was conducted in the autumn, winter
`week 12 showed no statistical difference between groups
`and spring (to avoid the improvement associated with
`(difference4%, 95% CE-5%, 14%;p =0.357).
`sunlight during the summer months), and many of the
`withdrawals were associated with concurrent infections
`that required treatment with antibiotics. The proportions
`of patients with erythema, scaling or dryness were similar
`in the two groups at all assessment times. However, pruri-
`tus was more common in patients using benzoyl perox-
`ide/erythromycin, while burning was more common in
`patients using isotretinoin/erythromycin.
`Compliance data revealed better compliance with
`isotretinoin/erythromycin gel than with benzoyl perox-
`ide/erythromycin gel. Unlike benzoyl peroxide/ery-
`thromycin, isotretinoin/erythromycin is applied once
`daily (rather than twice daily) and does not have to be
`refrigerated.
`In conclusion, isotretinoin/erythromycin gel given
`only once daily showed comparable efficacy with benzoyl
`peroxide/erythromycin given twice daily in the treatment
`of mild to moderate acne vulgaris of the face. The treat-
`ments did not differ significantly with regard to their
`effects on inflammatory and non-inflammatory lesions.
`
`Sixty-four out of 91 (70%) patients in the isotretinoin/
`erythromycin group and 53 out of 92 (58%) patients in
`the benzoyl peroxide/erythromycin group experienced at
`least one adverse event during the study period. Few of the
`reported adverse events were treatment-related. The most
`common treatment-related events were pain (burning:
`reported for five patients using isotretinoin/erythromycin
`and three patients using benzoyl peroxide/erythromycin)
`and rash (itching or redness: four patients using
`isotretinoin/erythromycin and three patients using
`benzoyl peroxide/erythromycin),
`Seventeen patients (eight from the isotretinoin/ery-
`thromycin and nine from the benzoyl peroxide/ery-
`thromycin group) withdrew due to adverse events. In
`several cases, the event leading to withdrawal was an
`infection requiring treatment with antibiotics. Five
`patients using isotretinoin/erythromycin and two using
`benzoyl peroxide/erythromycin withdrew because of skin
`reactions to the products. There were no treatment-
`related serious adverse events.
`
`Acknowledgements
`
`Discussion
`
`Thanks are due to Profiad Limited for coordinating this
`study and Cynthia Haliburn of Hartington Statistics &
`Data Management for valuable assistance in analysing the
`The primary efficacy results show that both treatments results of this study.
`
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`

`P Marazzi et al
`
`Acne vulgaris - Double Strength Isotrexin vs Benzamycin 117
`
`Symptoms
`
`Week
`
`Isotretinoin/erythromycin gel (n = 95)
`
`Benzoyl peroxide/erythromycin gel (n = 93)
`
`Treatment groups
`
`Erythema
`
`Scaling
`
`Dryness
`
`Burning
`
`Pruritus
`
`2
`4
`8
`12
`
`2
`4
`8
`12
`
`2
`4
`8
`12
`
`2
`4
`8
`12
`
`2
`4
`8
`12
`
`15
`17
`9
`9
`
`35
`24
`15
`11
`
`48
`29
`24
`27
`
`46
`30
`15
`14
`
`14
`9
`7
`7
`
`15
`8
`7
`8
`
`32
`23
`9
`10
`
`47
`38
`26
`25
`
`21
`8
`8
`8
`
`21
`20
`12
`8
`
`Table F
`Per cent of patients with s!lmptoms for the intention-to-trea t population at weeks 2, 4, 8 and 12 according to treatment group
`
`References
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