Treatment and Prophylaxis of Seborrheic Dermatitis of the Scalp With Antipityrosporal 1% Ciclopirox Shampoo
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STUDY
Treatment and Prophylaxis of Seborrheic Dermatitis
of the Scalp With Antipityrosporal
1% Ciclopirox Shampoo
Sam Shuster, MD; Jean Meynadier, MD; Helmut Kerl, MD; Siegfried Nolting, MD
Objective: To demonstrate the efficacy, safety, and tol- Main Outcome Measures: Primary and secondary:
erance of ciclopirox shampoo for treatment and prophy- response of “effectively treated” and “cured,” with in-
laxis of seborrheic dermatitis of the scalp. vestigators and patients rating acceptability and toler-
ance.
Design: Multicenter, randomized, double-blind, vehicle-
controlled study. After treatment with ciclopirox sham- Results: Ciclopirox twice and once weekly produced re-
poo once or twice weekly or vehicle for 4 weeks (study sponse rates of 57.9% and 45.4%, respectively, com-
segment A), responders were randomized to a 12-week pared with 31.6% for vehicle. Relapses occurred in 14.7%
prophylactic study arm (segment B). of patients using prophylactic ciclopirox once weekly,
22.1% of those in the prophylactic group shampooing once
Setting: Forty-five medical centers in Germany (n=19), every 2 weeks, and 35.5% in the vehicle group. The few
France (n = 15), the United Kingdom (n = 8), and Aus- adverse events were evenly distributed among groups. Lo-
tria (n=3). cal tolerance and cosmetic acceptability were “good” in
more than 85% of subjects.
Patients: A total of 1000 patients with stable or exac-
erbating seborrheic dermatitis of the scalp. Conclusions: Seborrheic dermatitis of the scalp re-
sponds well to 1% ciclopirox shampoo once or twice
Interventions: A total of 949 patients were random- weekly for 4 weeks. A low relapse rate is maintained by
ized to receive ciclopirox treatment once or twice weekly once-weekly shampooing or shampooing once every 2
or vehicle for 4 weeks. Thereafter, 428 responders re- weeks. These treatments are safe and well-tolerated.
ceived either ciclopirox prophylaxis once weekly or ev-
ery 2 weeks or vehicle for 3 months. Arch Dermatol. 2005;141:47-52
S
EBORRHEIC DERMATITIS AND ITS Ciclopirox (6-cyclohexyl-1-hydroxy-4-
minorform,dandruff,arecom- methyl-2(1H)-pyridone), an antifungal drug
mondisordersandcanbeprob- of the hydroxypyridone family, is highly ef-
lematic in patients with AIDS fective against Malassezia furfur and many
andneurologicdisease.Because pathogenic dermatophytes, molds, and
of its chronic course with remissions and re- yeasts.10-12 Unlike the imidazoles and allyl-
lapses, the condition requires repeated treat- amines, which inhibit synthesis of fungal cell
ment and regular prophylaxis. Topical ke- walls, ciclopirox complexes polyvalent cat-
Author Affiliations: toconazole became widely used following ions, thus inhibiting metal-dependent en-
Departments of Dermatology,
confirmation of the etiologic relationship be- zymes including those responsible for per-
University Hospital, Norwich,
England (Dr Shuster) and tween seborrheic dermatitis and the yeast oxide degradation in the fungal cell.13 There
Saint-Eloi Hospital, Montpellier, Malassezia furfur1 (formerly Pityrosporum is some evidence of antibacterial and anti-
France (Dr Meynadier); ovale) and the therapeutic response to an- inflammatory activity.11,14
Department of Dermatology tipityrosporal agents.2-5 Effective though ke- The potent antipityrosporal effects of
and Venereology, Graz toconazolemaybeforthetreatmentandpro- ciclopirox combined with its tolerability
University Hospital, Graz, phylaxis of seborrheic dermatitis and and lack of toxic effects make it an ideal
Austria (Dr Kerl); and
dandruff,1,2,6-8 there is always a need for al- alternative to existing antifungal agents
Department of Dermatology,
University of Muenster, ternative therapeutic agents, preferably with both for treatment and prophylaxis of seb-
Muenster, Germany different modes of action and without ke- orrheic dermatitis. There have, of course,
(Dr Nolting). toconazole’s inductive effects and inhibition been studies of the efficacy of this drug,15-21
Financial Disclosure: None. of cytochrome P450.9 but the numbers of patients in each study
(REPRINTED) ARCH DERMATOL/ VOL 141, JAN 2005 WWW.ARCHDERMATOL.COM
47
©2005 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 04/10/2020have not been large, and there have been no direct stud- contained 90 mL of 1% ciclopirox shampoo. By alternating
ies of its prophylactic efficacy, so the likely clinical po- bottles, they used the active shampoo twice a week. Patients
tential of the drug remains to be clearly established. The on treatment A2 received 1 bottle with 90 mL of 1% ciclopirox
present randomized, double-blind clinical trial was there- shampoo and 1 bottle with vehicle to achieve once-weekly sham-
pooing with 1% ciclopirox. The bottles blindly allocated to pa-
fore carried out in a large cohort of patients to defini-
tients in A3 both contained 90 mL of vehicle. Each application
tively establish the efficacy, safety, local tolerance, and dose was 5 mL; patients with longer than shoulder-length hair
cosmetic acceptability of 1% ciclopirox shampoo in the could use up to 10 mL. The vehicle contained the ingredients
treatment and prophylaxis of seborrheic dermatitis of the Genapol LRO liquid (shampoo base) (Clariant, Frankfurt, Ger-
scalp using different application frequencies in compari- many), Rewopol SBFA 30 (Whitco Surfactants, Steinau, Ger-
son with vehicle. many), Arlypon F (Henkel, Düsseldorf, Germany), sodium chlo-
ride, and water. After 4 weeks of double-blind treatment, all
patients were rated as responders or nonresponders according
METHODS
to definition.
This vehicle-controlled, randomized, double-blind, multi- Segment B: Prophylaxis
center clinical trial was conducted at 45 centers in Austria,
France, Germany, and the United Kingdom. The trial was di-
Segment B of the study commenced immediately after seg-
vided into 2 segments: A, treatment; B, prophylaxis. The en-
ment A was completed to assess the prophylactic efficacy of dif-
tire study lasted about 5 months for each subject (6 weeks for
ferent application frequencies of ciclopirox shampoo. A total
segment A, 12 weeks for segment B). The recruitment phase
of 428 responders from segment A proceeded with segment B
lasted 6 months.
before the random code for segment A was opened. The re-
sponders were randomized blindly to 3 equal groups to use ciclo-
PARTICIPANTS AND pirox once every week, once every 2 weeks, or vehicle. The de-
ELIGIBILITY CRITERIA fined relapse rate was assessed as the primary outcome measure.
As in segment A, the patients were instructed to apply the sham-
Otherwise healthy men and women of any ethnic origin, aged poo from 2 different bottles (bottles B I and B II) weekly in a
18 to 88 years with stable or exacerbating seborrheic derma- strictly alternating manner.
titis of the scalp were enrolled. Disease severity had to be at
least moderate, with a score of 3 or more on 6-point ordinal OBJECTIVES AND
scales of “status of seborrheic dermatitis,” “inflammation,” and OUTCOME MEASURES
“scaling” (0, none; 1, slight; 2, mild; 3, moderate; 4, pro-
nounced; 5, severe). All patients who met the inclusion crite- The primary objective of the study was to establish the effi-
ria gave their consent in writing after receiving detailed oral cacy, safety, and tolerance of 1% ciclopirox shampoo in the treat-
and written instructions and explanations about the study, which ment and prophylaxis of seborrheic dermatitis of the scalp. The
was approved by the review board or ethics committee respon- efficacy of ciclopirox treatment was assessed by comparing the
sible for each center and complied with the currently valid Dec- responder rates of active treatment groups with vehicle as odds
laration of Helsinki. ratios (including 95% confidence intervals [CIs]).
Patients with psoriasis, asthma, or diabetes were excluded.
Participants were not allowed to receive concomitant topical Segment A
treatments of the scalp or any nonsystemic treatments with an-
tifungal agents, corticosteroids, retinoids, erythromycin, tet-
racycline or derivatives, trimethoprim and/or sulfamethoxa- The efficacy parameters were based on 4 different 6-point or-
zole, or cytostatic or immunomodulating drugs for 4 weeks dinal scales describing the disease manifestations (status, scal-
before the start of treatment. ing, inflammation, and itching). The outcome measures were
Data were collected in 40 locations. Germany provided 19 the 2 response categories derived from the efficacy measures
centers (intent-to-treat [ITT] population, n=585); France, 15 at each patient’s final visit. The primary outcome measure was
centers (ITT population, n=197); United Kingdom, 8 centers effectively treated, defined as a score of 0 (or 1 if the baseline
(ITT population, n=136); and Austria, 3 centers (ITT popu- score was ⱖ3) for status, scaling, and inflammation; the sec-
lation, n=24). ondary outcome measure was cleared, defined as a score of 0
for status, scaling, inflammation, and itching. In addition to their
separate presentations, the results of 3 single scores (itching,
INTERVENTIONS scaling, and inflammation) were added together to form a com-
bined sumscore ranging from 0 to 15.
Segment A: Treatment Phase The 2 active-treatment regimens were compared with the ve-
hicle group in the Holm-Bonferroni sequential procedure. If nei-
All enrolled patients underwent a 2-week run-in during which ther of the 2 P values (2-sided Cochran-Mantel-Haenszel test ad-
they were required to use an open-label shampoo (Prell; Proc- justed for pooled centers) was .025 or lower, then the procedure
ter & Gamble, Cincinnati, Ohio) at least twice weekly. After was stopped without a significant result; if the smallest P value
final selection at the subsequent baseline visit, 1000 patients was .025 or lower, then the second P value was compared with
were enrolled, and a total of 949 were randomized on a 2:2:1 the ␣ level of .05 to guarantee a global ␣ level of .05.
basis to 1 of the 3 parallel groups with different application fre-
quencies of 1% ciclopirox (A1, twice weekly, n=340; A2, once Segment B
weekly, n = 340; A3, vehicle, n = 170). Accordingly, each pa-
tient was given 2 different 90-mL bottles (bottles A I and A II). The primary outcome measure for the prophylactic phase was
The patients were required to use 2 applications per week for the relapse rate, defined as a worsening from the start of seg-
4 weeks strictly alternating use of bottles A I and A II. The pa- ment B by 2 points or more. Secondary outcome measures con-
tients randomized to treatment A1 were given bottles that both sisted of relapses in inflammation, scaling, and itching, de-
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©2005 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 04/10/2020fined as a worsening by more than 2 points from the start of were randomized separately using different sets of randomiza-
segment B. tion numbers.
ASSESSMENTS OF LOCAL TOLERANCE Segment A
AND COSMETIC ACCEPTABILITY
At each center, patients eligible for inclusion after completion
Local tolerance was assessed by the investigators, and cos- of the run-in phase received their randomization number in the
metic acceptability and tolerance were rated by the patients at order in which they entered the study phase. For segment A,
each visit. These assessments were recorded at baseline (visit the number of randomized patients per center ranged from 10
2), 2 weeks ±3 days from baseline (visit 3) and 4 weeks ±3 days to 30. The 3 treatments for segment A, ciclopirox twice a week
from baseline (visit 4). Visit 4 coincided with the end of seg- or once a week or vehicle, were randomized on a 2:2:1 basis,
ment A and with the beginning of segment B. For the segment respectively. The randomization code of segment A was not bro-
A responders enrolled in segment B, investigators’ ratings of ken until this segment was completed and its database was
local tolerance and patient self-ratings of cosmetic acceptabil- closed. Although this took place while segment B was still run-
ity and tolerance were documented at visits 5 and 6 of the study, ning, the code of segment A was not disclosed to the investi-
which took place 4 ±1 weeks and 12±1, respectively, after the gators before the entire study had been completed.
start of segment B.
Segment B
SAMPLE SIZE
In each center selected for continuation, patients eligible for
The sample size was based on the following: (1) sufficient power entry to segment B received their second randomization num-
to discriminate between active treatment and vehicle; (2) esti- ber in the order in which they entered segment B. Inclusions
mates of response rates; and (3) a sufficient number of respond- into segment B were stopped when the scheduled number of
ers from segment A (treatment) for inclusion in segment B (pro- patients for segment B was reached; the number of random-
phylaxis). Based on pilot studies, response rates of 55% were ized patients per center ranged from 3 to 12. Patients were ran-
assumed for ciclopirox and 35% for vehicle. The power of a 2-sided domized in 3 equal groups to receive the 3 treatments for seg-
comparison “active vs vehicle” at an adjusted ␣ level of 2.5% (to ment B (application once weekly, application once every 2 weeks,
maintain the global 5% level) was between 97% and 98%, and and vehicle).
the 95% CI for the response rate of an active treatment arm ranged
from 50% to 60%, while that of the vehicle ranged from 28% to STATISTICAL ANALYSIS
43%. The sample size for segment B was calculated to provide
sufficient power assuming relapse rates of 22% for ciclopirox once Statistical analyses were carried out using SAS software, ver-
a week, 32% for ciclopirox every 2 weeks, and 55% for vehicle. sion 6.12 (SAS Institute, Cary, NC) according to a detailed sta-
The power of the 2-sided comparison ciclopirox once every 2 tistical analysis plan prepared prior to unblinding. Results for
weeks vs vehicle at an ␣ level of 5% is 90%; for ciclopirox once segments A and B were analyzed separately. The analysis of seg-
a week vs vehicle, the power is 99.8%. ment A started after its completion and while segment B was
No interim analyses were performed. Segment A was ana- still ongoing. No results of segment A were disclosed to the in-
lyzed immediately after its completion, ie, before the database vestigators of segment B before the entire study was finished.
for segment B was closed. The results for segment A were kept The 2 response rates of the once-weekly and twice-weekly ap-
confidential until the database for segment B was closed. plications of 1% ciclopirox were compared sequentially to the
response rate of the vehicle group according to the Holm-
RANDOMIZATION AND/OR Bonferroni procedure.
SEQUENCE GENERATION For statistical analysis, the following populations were iden-
tified separately for both segments before unblinding. The safety
Segment A responders were randomized for segment B into 1 population comprised all randomized patients who received at
of the 3 different treatment arms at a ratio of 1:1:1 with the ob- least 1 dose of randomized study medication. The ITT popu-
jective to obtain 3⫻105=315 evaluable cases. lation comprised all randomized patients who received at least
1 dose of study medication and had a subsequent rating of the
primary efficacy variable or nonresponders who dropped out
Allocation Concealment
owing to lack of efficacy.
For segment B, the primary statistical analyses of efficacy
The investigator received a set of sealed envelopes, 1 for each were performed on the ITT population. A supplementary sta-
patient number. The research organization and the sponsor held tistical analysis of efficacy was provided for the valid cases and
an identical set of sealed envelopes. The randomization enve- for the all-randomized population. The analyses for the all-
lopes were not opened until the end of the study. randomized population (with a last-observation-carried-
forward for segment A and a worst-case approach for segment
Patient Identification B) was introduced after unblinding. This population was used
and Randomization to assess any potential bias that might have been introduced
by the requirement of at least 1 postbaseline efficacy reading
On enrollment at the center, each patient was assigned a 5-digit in the ITT population. The results for the all-randomized
screening number that allowed unambiguous identification. En- population were virtually identical to those of the ITT popula-
rolled patients who dropped out of the study before their first tion, confirming that no bias had been introduced by this
randomization retained their screening number without re- requirement.
ceiving a randomization number. The next patient enrolled was By definition, the all-randomized population was identical
given the next screening number. Patients who dropped out to the safety population; for the efficacy analyses, it was only
or were withdrawn from the study after their first randomiza- used for the primary response criterion effectively treated and
tion were not replaced. Patients in segment A and segment B for the variable cleared. Safety variables were analyzed within
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©2005 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 04/10/2020Table. Distribution of Seborrheic Dermatitis Severity Before Cleared Effectively Treated Relapse Rate
Treatment and Sumscores After Treatment in the 3 Groups*
80 Segment A Segment B
1% Ciclopirox 1% Ciclopirox
70
Twice Weekly Once Weekly Vehicle
Evaluation (n = 376) (n = 376) (n = 190)
60
Severity at Baseline, No. (%) of Patients
Response Rate, %
Mild 46 (12) 56 (15) 28 (15) 50
Moderate 195 (52) 195 (52) 86 (45)
40
Pronounced 121 (32) 113 (30) 63 (33) 35 35
Severe 14 (4) 12 (3) 13 (7) 30 29
23 22 22
Mean ± SD Sumscore
20 17
Baseline 9.2 ± 2.2 9.0 ± 2.2 9.4 ± 2.3 15
Week 2 5.0 ± 3.0 5.7 ± 3.2 6.7 ± 3.3 10
10
Week 4 2.9 ± 3.1 3.7 ± 3.3 5.1 ± 3.8
0
Twice Once Vehicle Once Every 2 Vehicle
*Intention-to-treat population, n=942. Weekly Weekly Weekly Weeks
Figure. Response and relapse rates with 1% ciclopirox and vehicle.
the safety population. To avoid the effects of too small a
sample size in single centers, these were pooled before
ⱖ3) for status of seborrheic dermatitis of the scalp, scal-
unblinding.
ing, and inflammation as defined on the 6-point ordinal
scale (primary outcome measure). The secondary out-
RESULTS come measure cleared was defined as a score of 0 for
status, scaling, inflammation, and itching. The sum-
RECRUITMENT score of the clinical variables itching, scaling, and
inflammation were summarized by descriptive statistics
A total of 1000 patients were enrolled in the study, 949 for each visit and for the changes from baseline to each
of whom were randomized to receive 1 of the 2 ciclo- visit. The sumscores at baseline, week 2, and week 4,
pirox regimens or vehicle. The first patient was enrolled calculated as mean±SD, are summarized in the Table.
in April 1997, and the last visit of the last patient was in In both groups, ciclopirox was significantly superior
June 1998. The randomized population and the safety to vehicle at the primary efficacy end point. Twice- and
population were identical. The ITT population com- once-weekly shampooing produced response rates of 57.9%
prised 942 patients. A total of 40 patients (4%) dropped (220/380) (odds ratio [OR], 3.025; 95% CI, 2.096-4.366;
out prematurely, with the highest proportion in the ve- P⬍.001 compared with vehicle) and 45.4% (171/377) (OR,
hicle group (3% in each of the ciclopirox groups and 8% 1.826; 95% CI, 1.266-2.634; P⬍.001 compared with ve-
in the vehicle group). hicle), respectively. The response rate data are depicted
The disease severity at baseline was comparable in all in the Figure. In the ITT population, 58.5% (220/376)
treatment groups (Table). Of the randomized patients, 537 responded in the twice-weekly group (OR, 3.056; 95% CI,
(57%) of 949 were men, and 412 (43%) were women. Their 2.114-4.416; P⬍.001 compared with vehicle) and 45.5%
ages ranged from 18 to 88 years (median, 38 years) with- (171/376) in the once-weekly group (OR, 1.807; 95% CI,
out appreciable differences between the treatment groups. 1.252-2.609; P⬍.001 compared with vehicle).
About half of the patients (266/566) had a documented his- For the secondary efficacy end points, the ITT analy-
tory of the study disease for more than 2 years. There were sis of cleared showed higher response rates with active
no relevant group differences regarding history. treatment than with vehicle (ciclopirox twice weekly,
Previous treatment of the study disease was similar 23.1% [P⬍.001]; once weekly, 17.0% [P=.04]; vehicle,
in all treatment groups: 60% (557/949) had previously 10.0%). For all response categories, rates were mark-
received treatment. By far the highest proportion had used edly lower with vehicle than with active treatment (Table
topical antifungals; the next most common drug treat- and Figure).
ment was corticosteroids.
Concomitant diseases were recorded in all 3 treat- ADVERSE EVENTS
ment groups. The most common were erythematosqua-
mous dermatosis (5%-8%) and diseases of the seba- Segment A
ceous glands (5%-6%). Other diseases were recorded in
less than 6% of the patients. There were no differences In segment A, 146 adverse events were recorded in 120
in the incidences of concomitant diseases between the patients (12.6%), with an even distribution in all treat-
treatment groups. ment groups. Most were dermatologic, and the most
frequent were seborrhea (n=12) and rhinitis (n=9). No
EFFECTIVELY TREATED relevant group differences were observed. A total of 12
patients dropped out owing to adverse events, with the
Patients were effectively treated in segment A if they highest proportion of dropouts leaving the vehicle
achieved a score of 0 (or 1 if their baseline score was group (2%). Adverse events considered possibly related
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©2005 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 04/10/2020to the study drug were recorded in 19 patients. Most establish the efficacy, safety, local tolerance, and cos-
were dermatologic, and none of them were judged as metic acceptability of 1% ciclopirox shampoo for the treat-
serious. The distribution in the 3 treatment groups was ment and prophylaxis of seborrheic dermatitis of the scalp.
similar. Treatment-emergent serious adverse events After 4 weeks of treatment, the response rates for the ITT
were recorded in 3 patients (shock, anxiety, and skin population were significantly higher in both active treat-
ulcer); none of them was related to the study drug. Pre- ment groups than in the vehicle group (P⬍.001). The
defined abnormal laboratory changes were recorded in response rates were dose-dependent, ie, higher for the
41 cases; 33 of these were increases in liver enzyme lev- ciclopirox twice-weekly group (58.5%) than for the once-
els. This change occurred in only 4%, and a causal rela- weekly group (45.5%) or the vehicle group (31.6%).
tionship to the study treatment was ruled out. No seri- Ciclopirox shampoo was safe and well tolerated. Both
ous adverse event was judged to be causally related to investigators and patients rated local tolerance and cos-
the study medication. metic acceptability as high.15-21 Thus the therapeutic re-
The overall scores for local tolerance (investigator as- sponse, safety, and tolerance found with ciclopirox in the
sessment) and cosmetic acceptability and tolerance (pa- present study of a large cohort of patients extends and
tient assessment) during the treatment phase were cal- confirms the findings of smaller studies of ciclo-
culated. More than 85% of the patients who used pirox15-21 and shows that its therapeutic effect is compa-
ciclopirox shampoo rated local tolerance and cosmetic rable to that of topical ketoconazole.7,15,16,19,20
acceptability and tolerance at least good. After 12 weeks of treatment, the relapse rates for the
ITT population were significantly lower in both active
Segment B treatment groups than in the vehicle group (P⬍.001 for
the once-weekly prophylactic group; P=.02 for the pro-
In segment B, the prophylactic phase, 428 patients (me- phylactic group shampooing once every 2 weeks) indi-
dian age, 37 years) were randomized to 1 of the 3 treat- cating the superiority of ciclopirox over vehicle in the
ments. The ITT population comprised 421 patients, and prophylaxis of seborrheic dermatitis of the scalp. The
the randomized population and the safety population were relapse rates were lower with ciclopirox once a week
identical. A total of 43 patients (10.2%) dropped out pre- (14.7%) than with treatment every 2 weeks (22.1%), in
maturely (7% in the once-weekly treatment group; 13% keeping with the dose-dependent relationship found in
in the once-every-2-weeks treatment group; and 9% in the response to initial treatment. All other efficacy
the vehicle group). In the ITT population, relapses oc- parameters showed a smaller deterioration with active
curred in 14.7% of the patients (20/136) in the once- medication than with vehicle.
weekly group, 22.1% (32/145) in the group shampoo- Ciclopirox shampoo proved to be safe, well toler-
ing once every 2 weeks, and 35.5% (50/141) in the vehicle ated, and cosmetically acceptable during the 12-week pro-
group. Comparison of relapse between ciclopirox (both phylactic regimen of segment B, confirming and extend-
weekly and every 2 weeks) and vehicle showed a signifi- ing the findings of segment A. Despite the efficacy studies
cant difference (P⬍.001), as did the primary analysis. of preparations in current use for seborrheic dermatitis
Adverse events during segment B were recorded in 72 of the scalp, there is a paucity of data on prophylaxis.
(16.8%) of 428 patients, with a similar distribution in all The present study is the first to demonstrate the prophy-
treatment groups. Most were dermatologic; the most fre- lactic response to ciclopirox shampoo; similar findings
quent were seborrhea (n=7) and eczema (n=6), and there have likewise been published for ketoconazole.7
was no relevant group difference. A total of 10 patients were Ciclopirox is a synthetic, broad-spectrum antifungal
excluded owing to adverse events, with the highest pro- agent of the hydroxypyridone family that differs chemi-
portion in the group shampooing once every 2 weeks (4%). cally and mechanistically from other antifungals such as
Adverse events considered possibly related to the study the imidazoles and allylamines and, moreover, is with-
drug were recorded in 15 patients. Most were dermato- out effect on cell membrane lipid synthesis or drug and
logic, and none of them was judged as serious. No group hormone metabolism. Considering its efficacy, safety, and
differences were apparent. No relevant differences were acceptability profiles, we conclude that ciclopirox is a
seen in liver enzyme, creatinine, or hematologic param- worthwhile alternative to existing antipityrosporal thera-
eters between the treatment groups. No serious adverse pies for the treatment and prophylaxis of seborrheic der-
events were recorded. Abnormal laboratory changes were matitis and its minor component, dandruff.
recorded in 16 patients; 11 were increases in liver en-
zyme levels. A causal relationship to the study treat- Accepted for Publication: July 20, 2004.
ment was ruled out. Correspondence: Sam Shuster, MD, East Gables, 42
Local tolerance and cosmetic acceptability and toler- Double St, Framlingham, Suffolk, IP13 9BN, England (sam
ance during the prophylactic phase were rated at least @shuster42.freeserve.co.uk).
good in more than 85% of the patients in all treatment Funding/Support: This study was sponsored and con-
groups, including vehicle. ducted by Aventis Pharma, formerly Hoechst Aktienge-
sellschaft, Frankfurt, Germany.
Acknowledgment: We acknowledge the contribution of
COMMENT
all the investigators involved in this study and also wish
to thank Sabine Otto, MSc, for her tireless help in the or-
This vehicle-controlled, parallel-group, randomized, ganization of the study and Deborah Landry, BA, for her
double-blind, multicenter study fulfilled its objective to patient assistance in preparing this article.
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©2005 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ on 04/10/202012. Abrams BB, Hanel H, Hoehler T. Ciclopirox olamine: a hydroxypyridone antifun-
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