Received Date : 04-Apr-2016

Revised Date : 18-May-2016

Accepted Date : 20-May-2016
Article type : Review Article
Accepted Article
Topical treatments for scalp psoriasis – summary of a Cochrane Systematic Review

Authors:

J.G. Schlager1, S. Rosumeck1, R.N. Werner1, A. Jacobs1, J. Schmitt2, C. Schlager1, A.

Nast1

Institution:

1Division of Evidence Based Medicine (dEBM), Department of Dermatology,

Charité - Universitätsmedizin Berlin, Germany

2Zentrum für evidenzbasierte Gesundheitsversorgung (ZEGV)

Medical Faculty Carl Gustav Carus, Technischen Universität Dresden, Germany

Corresponding author:

Justin Gabriel Schlager

Division of Evidence Based Medicine (dEBM) / Department of Dermatology

Charité - Universitätsmedizin Berlin

Charitéplatz 1; 10117 Berlin

Tel.: + 49 30 450 518 373

Fax: + 49 30 450 518 977

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/bjd.14811
This article is protected by copyright. All rights reserved.
 justin-gabriel.schlager@charite.de
Accepted Article
Funding: This work was not funded.

Conflict of interests:
A Nast has received honoraria as a speaker in educational activities with direct or
indirect sponsoring from Bayer; Pfizer, Novartis, Abbot, Biogen Idec. This has been
in the last three years and is limited to the companies with an interest in psoriasis
treatment.
The dEBM has received research grants from Pfizer, Biogen Idec, GSK and Merz.
J Schmitt received funding for investigator-initiated research from Novartis, MSD,
Pfizer, Alk, and Sanofi.

What’s already known about this topic?

 Patients with chronic plaque psoriasis often have lesions of the scalp that are difficult to treat.

 There are various effective topical treatment options such as corticosteroids (e.g.

 betamethasone dipropionate), vitamin D (e.g. calcipotriol) and their combination therapy.

 Detailed Grading of Recommendations Assessment, Development and Evaluation

(GRADE) Working Group assessment of the effect of these treatments has not been done so

far.

What does this study add?

 Overall moderate quality of evidence that the two-compound combination is only of small

benefit over the corticosteroid alone and vitamin D monotherapy and that both therapies are

similarly safe (short-term therapy).

 Overall moderate quality of evidence that the two-compound combination and corticosteroid

monotherapy are more effective and safer than vitamin D alone (short-term therapy).

 Firm conclusions for other topical treatments cannot be drawn due to limited data.

This article is protected by copyright. All rights reserved.

 Abstract

People with chronic plaque psoriasis often have lesions on the scalp that are difficult to treat. This is a summary
of a Cochrane review on efficacy and safety of topical treatments for scalp psoriasis. For quality of evidence
Accepted Article
assessment, we used the Grading of Recommendations Assessment, Development and Evaluation (GRADE)
Working Group approach. Only randomised controlled trials (RCTs) were eligible for inclusion.
We searched the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, EMBASE and LILACS,
ongoing trials, index of included studies and screened abstracts of six psoriasis-specific conferences up to
August 2015.
We included 59 RCTs, with overall 11,561 participants. Most findings were limited to short-term treatments (<
six months). According to the clinician and patients’ self-assessment a corticosteroid/vitamin D combination
(e.g. betamethasone dipropionate plus calcipotriol) and corticosteroids of high and very high potency were
better than vitamin D. The two-compound combination was superior to the corticosteroid alone, but the
additional benefit was small. Reporting of quality of life data was insufficient. The two-compound combination
and corticosteroids caused fewer withdrawals due to adverse events (AEs) than vitamin D. There was no
difference between the two-compound combination and corticosteroid monotherapy concerning this outcome.
Overall evidence was of moderate quality. Evaluation of other topical treatments was limited.
Given the comparable safety profile and only slim benefit of the two-compound combination over the
corticosteroid alone, monotherapy with generic topical corticosteroids of high and very high potency may be
fully acceptable for short-term therapy. More quality of life data and long-term assessments are needed.

Background

This is a summary of a Cochrane Systematic Review1.

Psoriasis is a common, chronic immune-mediated disease. There are different types including pustular, guttate,
inverse, erythrodermic or chronic plaque psoriasis (psoriasis vulgaris) with the latter accounting for 90% of the
cases2. Clinical signs are characterised by well-demarcated reddish (erythematous) plaques of thickened skin
and silvery white scaling. Typically the plaques are distributed symmetrically on knees and elbows, the trunk or
the sacral region. Regardless of the type of psoriasis, up to 79% of people with the condition present with scalp
involvement which has frequently been the first site to show symptoms of the disease 3. The lesions are typically
located behind the ear (retro-auricular) and neck, but may appear anywhere on the scalp. The extent varies from
fine scaling to thick erythematous crusted plaques on the entire scalp, typically crossing the hair line and
affecting a small area of the adjacent facial skin. Compared to sites of the body that can easily be covered by
clothes, people with psoriasis on the scalp or face are often troubled, because lesions are difficult to hide.
Together with pruritus, this has been shown to be one of the most distressing symptoms4. Our objective was to
summarize the evidence on the efficacy and safety of topical treatments for patients of every age with scalp
psoriasis.

Material and methods

This review is based on a pre-specified protocol5.

Inclusion criteria

RCTs evaluating any type of topical treatment for scalp psoriasis.

Search strategies

We searched the following databases up to August 2015: the Cochrane Skin Group Specialised Register,
CENTRAL in The Cochrane Library (2015, Issue 1), MEDLINE (from 1946), Embase (from 1974), and
LILACS (from 1982). We also searched the following five trials registers: the metaRegister of Controlled Trials
(www.controlled-trials.com), the US National Institutes of Health Ongoing Trials Register
(www.clinicaltrials.gov), the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), the World
Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch/), the EU Clinical
Trials Register (https://www.clinicaltrialsregister.eu/). In addition, we hand-searched the following psoriasis
specific conferences of the past 12 years up to September 2015 for relevant RCTs presented as abstracts: the
American Academy of Dermatology (AAD), the European Academy of Dermatology and Venerology (EADV)

This article is protected by copyright. All rights reserved.

 the „Deutsche Dermatologische Gesellschaft“(DDG), the Psoriasis - From Gene to Clinic, the Psoriasis
International Network – Paris and the International Federation of Psoriasis Associations (IFPA) - Stockholm.
We also checked the bibliography of included studies for further references to relevant RCTs. No restrictions
with regard to language or publication status were made. Two authors (JGS and SR) independently carried out
Accepted Article
study selection.

Types of outcome measures

We assessed the quality of evidence for the following four outcomes: 1. Reduction in clinician-assessed disease
severity as measured by the number of patients achieving treatment response or clearance from scalp lesions
according to the Investigators' Global Assessment (IGA) 2. Improvement in quality of life. 3. Number of
participants withdrawing due to adverse events (AEs). 4. Patients’ self-assessment of reduction in disease
severity as measured by the number of participants achieving treatment response according to the Patients'
Global Assessment (PGA). We analysed outcomes according to short-term (≤ six months) and long-term (> six
months) evaluations. For more detailed information on all primary and secondary outcomes of the Cochrane
review, please refer to the full version1.

Data extraction and synthesis

Two authors (JGS and SR) independently extracted data from the included studies using Microsoft Office Excel
2003 and Review Manager. We assessed the risk of bias using the criteria described in the Cochrane Handbook
for Systematic Reviews of Interventions6. We attempted to obtain unpublished or missing data via
correspondence with trial authors and sponsors.
We expressed the results as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and
mean differences (MD) and 95% CI for continuous outcomes. If heterogeneity according to I 2 statistics was
<60%, we meta-analysed the effect estimates of the individual studies. If the RR was statistically significant, we
expressed the results as number needed to treat to benefit (NNTB) with 95% confidence intervals. We used
GRADEpro software to rate the quality of evidence.

Results

We included 59 RCTs, reported by 75 references, with a total of 11,561 participants. From 299 references that
were retrieved by the literature search, we excluded 176 based on titles or abstracts. We further excluded 28
references for reasons such as not being RCTs or not providing distinct data for scalp psoriasis. Fourteen studies
were classified as awaiting classification and 6 as ongoing trials. For further description of our screening
process, see the study flow diagram (Figure 1).

[Fig. 1]

The mean age of study participants was 45 years and both genders were represented equally. Most studies
included patients with moderate scalp psoriasis and had a median duration of four weeks. Our findings are
mainly limited to short-term treatments, as only one trial assessed long-term therapy (12 months). We
categorized the interventions of the included studies into 15 main comparisons: 1. Coricosteroid: once vs twice
daily use. 2. Corticosteroid vs vehicle. 3. Vitamin D vs vehicle. 4. Corticosteroid/vitamin D combination vs
vehicle. 5. Steroid versus steroid: very high versus high potency. 6. Corticosteroid versus coricosteroid: high
versus moderate potency. 7. Corticosteroid versus coricosteroid: both of high potency. 8. Corticosteroid versus
vitamin D. 10. Corticosteroid plus vitamin D versus corticosteroid. 11. Corticosteroid plus vitamin D versus
vitamin D. 12. Tar and dithranol. 13. Corticosteroid: vehicle comparisons. 14. Other corticosteroid and salicylic
acid containing comparisons. 15. Antifungals versus vehicle.

We classified vehicles into two main groups: rinse-offs (including shampoos) and leave-ons. The latter was
further divided in two subgroups: hydrophilic (including alcoholic solutions, foams, lotion, hydrogels, oil in
water emulsions) and lipophilic leave-ons (ointments, oleo gels, oils, creams, water in oil formulation). In
addition, we distinguished occlusive and non-occlusive dressings. We classified corticosteroid potency
according to the German steroid classification system7 as mild, moderate, high and very high.

This article is protected by copyright. All rights reserved.

 Risk of bias in included studies

The risk of bias for the included studies was considerably heterogeneous. For instance, most authors did not
state the randomisation method and few addressed allocation concealment. An overview of the risk of bias
Accepted Article
assessment is provided in Figure 2.

[Fig.2]

Effect of Interventions

We found a wide variety of different interventions. However, we limited the assessment of the quality of
evidence to three comparisons of clinical important interest: corticosteroid of high (e.g. betamethasone
dipropionate) or very high potency (e.g. clobetasol propionate) versus vitamin D (e.g. calcipotriol), two-
compound combination of a corticosteroid of high potency and vitamin D (e.g. betamethasone dipropionate plus
calcipotriol) versus the corticosteroid or vitamin D alone.

Corticosteroid versus vitamin D (Table 1)

Four studies8-11 addressed data on IGA ‘clearance’ and three 9,10,12 on IGA ‘response’. According to both
clinician-assessed outcomes corticosteroids of high and very high potency were more effective than vitamin D.
The quality of evidence was moderate for IGA ‘clearance’ and high for IGA ‘response’. No study assessed the
improvement in quality of life. Meta-analysis of four studies8-10,12 showed that the corticosteroids caused fewer
withdrawals due to AEs than vitamin D (moderate quality of evidence). However, none of the studies reported
the sort of AEs that actually led to withdrawal. There were no withdrawals due to adverse events in two
studies11,13. Data on PGA ‘response’ were reported in three studies9,10,12. The results of the patients’ self-
assessment confirmed the superiority of the corticosteroids over vitamin D (moderate quality of evidence).

Corticosteroid plus vitamin D combination versus corticosteroid monotherapy (Table 2)

Four studies9-11,14 reported data on IGA ‘clearance’ and three9,10,14 on IGA ‘response’. According to both
clinician-assessed outcomes the two-compound combination was more effective than the corticosteroid alone,
but the benefit was small (moderate quality of evidence). No study reported data on the improvement in quality
of life. Meta-analysis of three studies9,10,14 showed that the number of withdrawals due to AEs was not different
between the treatments (moderate quality of evidence). No study reported the sort of AEs that actually caused
withdrawal. In one trial11 no withdrawals occurred. PGA ‘response’ data were reported in two studies9,10.
According to the patient self-assessment, the two-compound combination was more effective than the
corticosteroid alone, but the benefit may not be clinically relevant (high quality of evidence).

Corticosteroid plus vitamin D combination versus vitamin D monotherapy (Table 3)

Four studies addressed data on IGA ‘clearance’ 9-11,15 and on IGA ‘response’ 9,10,15,16, respectively. According to
both clinician-assessed outcomes the two-compound combination was more effective than vitamin D alone. The
quality of evidence was high for IGA ‘clearance’ and moderate for IGA ‘response’. According to one study 17,
the two-compound combination led to a better improvement in quality of life than vitamin D alone. However,
reporting of the data was insufficient to calculate an effect estimate and the evaluation of the quality of evidence
was not feasible. Four studies9,10,15,16 reported the number of withdrawals due to AEs, but none stated which
specific AE caused withdrawal from the study. The two-compound combination led to significantly fewer
withdrawals due to AEs than vitamin D alone (high quality of evidence). This finding was also found in one
large well-conducted study18 that assessed both treatments over 12 months. However, we did not include this
long-term result in our quality of evidence evaluation. According to patients’ self-assessment of treatment
response, which was reported by four studies9,10,15,16, the two-compound combination was more effective than
the vitamin alone (moderate quality of evidence).

Common AEs with these three treatments were local irritation, skin pain and folliculitis. They were mostly
limited to the site of application. Systemic adverse events were particularly rare and most likely not drug-
related, as judged by the study authors. However, most studies poorly reported the nature of AEs which
occurred.

This article is protected by copyright. All rights reserved.

 [Tables 1,2,3]

Other findings
Accepted Article
Numerous studies compared the two-compound combination9,19, corticosteroids9,20-30 or vitamin D9,31-34
monotherapy with the vehicle (which did not contain the active agent). All three treatments were significantly
more effective. Other findings are restricted to results of individual studies with heterogeneous risk of bias. For
instance, corticosteroids of moderate, high and very high potency tended to be similarly effective and well
tolerated35-44. One small study45 showed that there is probably no difference if a corticosteroid is applied once or
twice daily. Two individual studies showed that a corticosteroid within foam was more effective than within
lotion24, but not if applied within solution25. Due to few and mostly unreliable data, the evaluation of other
corticosteroid vehicles-preparations28,46-49, salicylic acid50-54, antifungals55, tar or dithranol56-64 containing
treatments was limited.

Discussion

This review summarises the evidence of the efficacy and safety of topical treatments for scalp psoriasis. The 59
included studies combined numerous different interventions. Only few studies assessed the improvement in
quality of life. However, no study reported the quality of life data in a form in which we were able to evaluate
the quality of evidence. Our analyses were mainly restricted to short-term treatments.

Clinicians and participants rated the efficacy of the individual treatments similarly. With regard to our safety
outcomes, it should be considered that the particular risk of specific adverse events (e.g. skin irritation, skin
atrophy) for individual treatments was not evaluated in this review.

The overall quality of evidence for our three major comparisons was moderate. According to our efficacy and
safety measures, corticosteroids of high and very high potency were superior to vitamin D. The two-compound
combination of a corticosteroid and vitamin D was statistically more effective than corticosteroids as
monotherapy. However, the additional benefit might not be clinically relevant. Furthermore, both treatments
were similarly safe. The two-compound combination was more effective than vitamin D alone. In addition, in
was shown to be safer for short- and long-term treatment.
One study found that the two-compound combination improved quality of life better than vitamin D alone. The
study was well designed and well conducted and the findings appear reliable. However, we could not assess the
quality of evidence, because the authors did not provide suitable data to calculate an estimate of effect.

Numerous studies, of which some were well conducted and well designed, showed that corticosteroids, vitamin
D and their two-compound combination were more effective than the vehicle. The interpretation of other
findings was limited, as they are mainly based on limited data of individual studies with heterogeneous risk of
bias. For this reason we could not draw firm conclusions for other treatment options.

For quality of evidence assessment, we followed the GRADE approach65. In three instances we downgraded the
quality of evidence for risk of bias and in three cases we downgraded because of heterogeneity among the trial
results. We lowered the quality of evidence in two instances because of serious imprecision. In both cases the
confidence interval crossed the minimal important difference (MID) thresholds.

Our findings on the efficacy and safety of topical corticosteroids, vitamin D and their combination therapy
support the current European, American and Asian consensus recommendations 66-68. As part of a Cochrane
review on topical treatments for chronic plaque psoriasis, Mason et al. 69 compared treatments for scalp psoriasis
with the focus on vehicle-controlled trials and active comparisons with vitamin D preparations. With regard to
these treatments, our results correspond closely. Contrary to Mason et al., we did not make restrictions with
regard to other topical treatments. Our findings concerning topical corticosteroids, vitamin D analogues, tar
preparations and application frequency are in accordance with the results of a systematic review from
Samarasekera et al.70. However, the authors did not find the marginal benefit of the two-compound combination
over corticosteroid monotherapy. This may be due to two reasons: in their meta-analysis of the outcome IGA
response, the authors did not include one trial14, which found a small benefit of the two-compound combination
with respect to IGA and PGA. In addition, the authors did not meta-analyse data from the participants’ self-
assessment of treatment efficacy. Both aspects would have emphasised the small, but statistically significant
benefit of the combination product. In contrast to both systematic reviews, we graded the quality of evidence

This article is protected by copyright. All rights reserved.

 based on the GRADE working-group recommendations.

We aimed to minimise potential biases during the review process. However, for 14 studies we were unable to
obtain the full text or our requests for unpublished data was not successful. The fact that these studies have not
Accepted Article
yet been incorporated may be a source of potential bias. As none of these studies evaluated any of our major
three comparisons, this aspect does not affect our quality of evidence assessment.

In conclusion, the corticosteroid/vitamin D combination as well as monotherapy with a corticosteroid of high or

very high potency were more effective and safer than vitamin D alone. Given the similar safety profile and only
slim benefit of the two-compound combination over the corticosteroid alone, monotherapy with generic topical
corticosteroids of high and very high potency may be fully acceptable for short-term therapy. Future RCTs
should investigate how specific therapies improve the participants’ quality of life. Furthermore, long-term
assessments are needed (i.e. 6 to 12 months).

Acknowledgements

We would like to thank the Cochrane Skin Group for their support during all stages of this review. We further
thank Dr.Regina Dantas Jales of the Department of Dermatology, Universidade Federal de São Paulo, São
Paulo, Brazil for writing the protocol on which this review is founded.

1. Schlager JG, Rosumeck S, Werner RN, et al. Topical treatments for scalp psoriasis.
Cochrane Database Syst Rev. 2016;2:CD009687.
2. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. Jul
21 2007;370(9583):263-271.
3. van de Kerkhof PC, Steegers-Theunissen RP, Kuipers MV. Evaluation of topical
drug treatment in psoriasis. Dermatology. 1998;197(1):31-36.
4. van de Kerkhof PC, de Hoop D, de Korte J, Kuipers MV. Scalp psoriasis, clinical
presentations and therapeutic management. Dermatology. 1998;197(4):326-334.
5. Jales RD NA, Saconato H, Atallah ÁN, Hirata SH. Topical treatments for scalp
psoriasis. Cochrane Database of Systematic Reviews. . 2012(4).
6. Higgins JPT GS. Cochrane Handbook for Systematic Reviews of Interventions
Version 5.1.0. The Cochrane Collaboration. 2011;Available from www.cochrane-
handbook.org
7. Niedner R. Glucocorticosteroids in dermatology. Dt Ärzteblatt.
1996;93(44):A2868-A2872.
8. Klaber MR, Hutchinson PE, Pedvis-Leftick A, et al. Comparative effects of
calcipotriol solution (50 micrograms/ml) and betamethasone 17-valerate
solution (1 mg/ml) in the treatment of scalp psoriasis. Br J Dermatol.
1994;131(5):678-683.
9. Jemec GB, Ganslandt C, Ortonne JP, et al. A new scalp formulation of calcipotriene
plus betamethasone compared with its active ingredients and the vehicle in the
treatment of scalp psoriasis: a randomized, double-blind, controlled trial. J Am
Acad Dermatol. 2008;59(3):455-463.
10. van de Kerkhof PC, Hoffmann V, Anstey A, et al. A new scalp formulation of
calcipotriol plus betamethasone dipropionate compared with each of its active
ingredients in the same vehicle for the treatment of scalp psoriasis: a
randomized, double-blind, controlled trial. Br J Dermatol. 2009;160(1):170-176.
11. Yilmaz H, Aydin F, Senturk N, Canturk T, Turanli AY. A comparison between the
effects of calcipotriol lotion, momethasone furoate lotion and their combinations
for the treatment of scalp psoriasis. Turkderm Deri Hastaliklari ve Frengi Arsivi.
2005;39(2):109-114.
12. Reygagne P, Mrowietz U, Decroix J, et al. Clobetasol propionate shampoo 0.05%
and calcipotriol solution 0.005%: a randomized comparison of efficacy and

This article is protected by copyright. All rights reserved.

 safety in subjects with scalp psoriasis. Journal of Dermatological Treatment.
2005;16(1):31-36.
13. Kose O. Calcipotriol ointment vs clobetasol solution in scalp psoriasis. Journal of
Dermatological Treatment. 1997;8(4):287.
Accepted Article
14. Buckley C, Hoffmann V, Shapiro J, Saari S, Cambazard F, Milsgaard M. Calcipotriol
plus betamethasone dipropionate scalp formulation is effective and well
tolerated in the treatment of scalp psoriasis: a phase II study. Dermatology
(Basel, Switzerland). 2008;217(2):107-113.
15. Kragballe K, Hoffmann V, Ortonne JP, Tan J, Nordin P, Segaert S. Efficacy and
safety of calcipotriol plus betamethasone dipropionate scalp formulation
compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a
randomized controlled trial. Br J Dermatol. 2009;161(1):159-166.
16. NCT01195831. Efficacy and Safety of Xamiol® Gel Compared to Calcipotriol
Scalp Solution in Patients With Scalp Psoriasis. clinicaltrials.gov + who.
2013(NCT01195831).
17. Ortonne JP, Ganslandt C, Tan J, Nordin P, Kragballe K, Segaert S. Quality of life in
patients with scalp psoriasis treated with calcipotriol/betamethasone
dipropionate scalp formulation: a randomized controlled trial. Journal of the
European Academy of Dermatology and Venereology : JEADV. 2009;23(8):919-
926.
18. Luger TA, Cambazard F, Larsen FG, et al. A study of the safety and efficacy of
calcipotriol and betamethasone dipropionate scalp formulation in the long-term
management of scalp psoriasis. Dermatology (Basel, Switzerland).
2008;217(4):321-328.
19. Tyring S, Mendoza N, Appell M, et al. A calcipotriene/betamethasone
dipropionate two-compound scalp formulation in the treatment of scalp
psoriasis in Hispanic/Latino and Black/African American patients: results of the
randomized, 8-week, double-blind phase of a clinical trial. Int J Dermatol.
2010;49(11):1328-1333.
20. Ellis C, Horwitz S, Menter A. Amcinonide lotion 0.1% in the treatment of patients
with psoriasis of the scalp. Curr Ther Res Clin Exp. 1988;44(2):315-324.
21. Medansky RS, Handler RM. Treating psoriasis of the scalp with a new
corticosteroid lotion. Ill Med J. 1974;145(6):503-504.
22. Sofen H, Hudson CP, Cook-Bolden FE, et al. Clobetasol propionate 0.05% spray
for the management of moderate-to-severe plaque psoriasis of the scalp: results
from a randomized controlled trial. Journal of Drugs in Dermatology: JDD.
2011;10(8):885-892.
23. Olsen EA, Cram DL, Ellis CN, et al. A double-blind, vehicle-controlled study of
clobetasol propionate 0.05% (Temovate) scalp application in the treatment of
moderate to severe scalp psoriasis. J Am Acad Dermatol. 1991;24(3):443-447.
24. Franz TJ, Parsell DA, Halualani RM, Hannigan JF, Kalbach JP, Harkonen WS.
Betamethasone valerate foam 0.12%: a novel vehicle with enhanced delivery and
efficacy. Int J Dermatol. 1999;38(8):628-632.
25. Franz TJ, Parsell DA, Myers JA, Hannigan JF. Clobetasol propionate foam 0.05%: a
novel vehicle with enhanced delivery. Int J Dermatol. 2000;39(7):535-538.
26. Harris JJ. A national double-blind clinical trial of a new corticosteroid lotion: a
12-investigator cooperative analysis. Curr Ther Res Clin Exp. 1972;14(9):638-
646.

This article is protected by copyright. All rights reserved.

 27. Jarratt M, Breneman D, Gottlieb AB, Poulin Y, Liu Y, Foley V. Clobetasol
propionate shampoo 0.05%: a new option to treat patients with moderate to
severe scalp psoriasis. Journal of Drugs in Dermatology. 2004;3(4):367-373.
28. Reygagne P. Efficacy and safety comparison of clobetasol propionate shampoo,
Accepted Article
gel and vehicle in scalp psoriasis Abstract. 11th Congress of the European
Academy of Dermatology & Venereology Prague October 2nd-6th, 2002. 2002:27-
29.
29. Pauporte M, Maibach H, Lowe N, et al. Fluocinolone acetonide topical oil for scalp
psoriasis. Journal of Dermatological Treatment. 2004;15(6):360-364.
30. Lepaw MI. Double-blind comparison of halcinonide solution and placebo control
in treatment of psoriasis of the scalp. Cutis. 1978;21(4):571-573.
31. Green C, Ganpule M, Harris D, et al. Comparative effects of calcipotriol (MC903)
solution and placebo (vehicle of MC903) in the treatment of psoriasis of the
scalp. Br J Dermatol. 1994;130(4):483-487.
32. Feldman SR, Mills M, Brundage T, Eastman WJ. A multicenter, randomized,
double-blind study of the efficacy and safety of calcipotriene foam, 0.005%, vs
vehicle foam in the treatment of plaque-type psoriasis of the scalp. Journal of
Drugs in Dermatology: JDD. 2013;12(3):300-306.
33. Kiss I, McCreary HL, Siskin SB, Epinette WW. A Randomized, Double - Blind,
Parallel Group Dose Ranging Comparison of the Efficacy and Safety of
Calcipotriene Solution in the Treatment of Scalp Psoriasis. American Academy of
Dermatology. 54th annual meeting. Feb, 10-15. J Am Acad Dermatol. 1996:301.
34. Ruzicka T, Trompke C. [Treatment of scalp psoriasis. An effective and safe
tacalcitol emulsion]. Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und
verwandte Gebiete. 2004;55(2):165-170.
35. Katz HI, Lindholm JS, Weiss JS, et al. Efficacy and safety of twice-daily augmented
betamethasone dipropionate lotion versus clobetasol propionate solution in
patients with moderate-to-severe scalp psoriasis. Clin Ther. 1995;17(3):390-401.
36. Lassus A. Local treatment of psoriasis of the scalp with clobetasol propionate and
betamethasone-17,21-dipropionate: a double-blind comparison. Curr Med Res
Opin. 1976;4(5):365-367.
37. Jarratt M. Comparative studies of augmented betamethasone dipropionate lotion
0.05% and clobetasol propionate solution 0.05%: Correlation of the
vasoconstriction assay and clinical activity in scalp psoriasis. Adv Ther.
1991;8(2):103-111.
38. De Cuyper C, De Greef H, De La Brassinne M, et al. A randomized single-blind
study to compare hydrocortisone 17-butyrate 0.1% emulsion versus
betamethasone 17,21-dipropionate 0.05% lotion in the treatment of patients
suffering from psoriasis of the scalp. J Eur Acad Dermatol Venereol. 1995;5(Suppl
1):S.
39. Willis I. Multicenter study comparing 0.05% gel formulations of desoximetasone
and fluocinonide in patients with scalp psoriasis. Clin Ther. 1986;8(3):275-282.
40. Swinehart JM, Barkoff JR, Dvorkin D, Fisher G, Peets E. Mometasone furoate
lotion once daily versus triamcinolone acetonide lotion twice daily in psoriasis.
Int J Dermatol. 1989;28(10):680-681.
41. Gip L. Hydrocortisone 17-butyrate 0.1% cream and fluocinolone acetonide
0.025% cream: A double-blind comparison in patients suffering from psoriasis of
the scalp. Curr Ther Res Clin Exp. 1981;29(1 II):198-201.

This article is protected by copyright. All rights reserved.

 42. Housman TS, McMichael AJ, Mellen BG, Derrow E, McCarty MA, Feldman SR. Use
of 0.12% betamethasone valerate foam vs 0.01% fluocinolone acetonide topical
oil to treat scalp psoriasis: Quantitative assessment of patient preference and
treatment efficacy. Cosmetic Dermatology. 2002;15(11):27-30.
Accepted Article
43. Van der Ploeg DEC. Clinical trial in scalp psoriasis mometasone furoate lotion
0.1% apllied once daily vs betamethasone valerate lotion 0.1% applied twice
daily. Acta Ther. 1989;15(2):145-152.
44. Ellis C, Menter M. A randomized, blinded comparison of amcinonide lotion and
fluocinonide solution in patients with psoriasis of the scalp. Curr Ther Res Clin
Exp. 1989;46(3):471-477.
45. Feldman SR, Ravis SM, Fleischer AB, et al. Betamethasone valerate in foam
vehicle is effective with both daily and twice a day dosing: a single-blind, open-
label study in the treatment of scalp psoriasis. J Cutan Med Surg. 2001;5(5):386-
389.
46. Josse M, Mengeaud V, Khemis A, Ortonne JP. Efficacy of a new keratolytic
shampoo containing glycolic acid and ictyol for the treatment of scalp psoriasis -
results of a comparative study. Abstract P16.34. The 14th Congress of the
European Academy of Dermatology and Venereology, London,UK. 12-15th
October 2005. J Eur Acad Dermatol Venereol. 2005;19(Suppl 2):391.
47. Andres P, Poncet M, Farzaneh S, Soto P. Short-term safety assessment of
clobetasol propionate 0.05% shampoo: hypothalamic-pituitary-adrenal axis
suppression, atrophogenicity, and ocular safety in subjects with scalp psoriasis.
Journal of Drugs in Dermatology. Apr 2006;5(4):328-332.
48. Bergstrom KG, Arambula K, Kimball AB. Medication formulation affects quality of
life: a randomized single-blind study of clobetasol propionate foam 0.05%
compared with a combined program of clobetasol cream 0.05% and solution
0.05% for the treatment of psoriasis. Cutis. 2003;72(5):407-411.
49. Wilhem K, Ocker G, Tebbs V, Guilabert A. A new mometasone formulation
(LAS41002 emulsion with 36% water content) is effective, well tolerated and
cosmetically acceptable in the treatment of scalp psoriasis. Paper presented at:
European Academy of Dermatology and Venereology 2013; Istanbul.
50. Fredriksson T. A clinical comparison of 3 corticosteroid alcoholic solutions in the
treatment of psoriasis of the scalp. Pharmatherapeutica. 1976;1(4):252-256.
51. Hillstrom L, Pettersson L. Studies with betamethasone dipropionate lotion with
salicylic acid (Diprosalic) in psoriasis and seborrhoic eczema of the scalp.
Current Therapeutic Research Clinical and Experimental. 1978;24(1):46.
52. Hillstrom L, Pettersson L, Svensson L. Comparison of betamethasone
dipropionate lotion with salicylic acid (Diprosalic(TM)) and clobetasol
propionate lotion (Dermovate(TM)) in the treatment of psoriasis of the scalp. J
Int Med Res. 1982;10(6):419-422.
53. Hillstrom L. Comparison of topical treatment with desoxymethasone solution
0.25% with salicylic acid 1% and betamethasone valerate solution 0.1% in
patients with psoriasis of the scalp. J Int Med Res. 1984;12(3):170-173.
54. Curley RK, Vickers CF, Norris H. A comparative study of betamethasone
dipropionate with salicylic acid and betamethasone valerate for the treatment of
steriod-responsive dermatoses of the scalp. J DERMATOL TREAT. 1990;1(4):203-
206.
55. Shuttleworth D, Galloway DB, Boorman GC, Donald AE. A double-blind, placebo-
controlled study of the clinical efficacy of ciclopirox olamine (1.5%) shampoo for

This article is protected by copyright. All rights reserved.

 the control of scalp psoriasis. Journal of Dermatological Treatment.
1998;9(3):163-167.
56. van de Kerkhof PC, Green C, Hamberg KJ, et al. Safety and efficacy of combined
high-dose treatment with calcipotriol ointment and solution in patients with
Accepted Article
psoriasis. Dermatology. 2002;204(3):214-221.
57. He YL, Guo ZP. [Clinical efficacy of 0.1% tacrolimus ointment on plaque psoriasis
of scalp and face]. Journal of Clinical Dermatology. 2008;37(4):254-255.
58. Wright S, Mann RJ. Comparison of a cream containing 0.1% dithranol in a 17%
urea base (Psoradrate(TM)) with coal tar pomade in the treatment of scalp
psoriasis. Clin Exp Dermatol. 1985;10(4):375-378.
59. Griffiths CE, Finlay AY, Fleming CJ, Barker JN, Mizzi F, Arsonnaud S. A
randomized, investigator-masked clinical evaluation of the efficacy and safety of
clobetasol propionate 0.05% shampoo and tar blend 1% shampoo in the
treatment of moderate to severe scalp psoriasis. Journal of Dermatological
Treatment. 2006;17(2):90-95.
60. Klaber MR, McKinnon C. Calcipotriol (Dovonex©) scalp solution in the treatment
of scalp psoriasis: comparative efficacy with 1% coal tar/1% coconut oil/0.5%
salicylic acid (Capasal©) shampoo, and long-term experience. Journal of
Dermatological Treatment. 2000;11:21-28.
61. Wall A. Combined use of calcipotriol solution (50 ug/ml) and polytar liquid in
scalp psoriasis Abstract P-689 The 8th Congress of the European Academy of
Dermatology and Venereology. Amsterdam, The Netherlands 29thSept-3rd
October 1999. J Eur Acad Dermatol Venereol. 1999;12(Suppl 2):S337.
62. Monk B, Mason RBS, Munro CS, Darley CR. An open and single-blind comparative
assessment of unguentum cocois compound in the treatment of psoriasis of the
scalp. Journal of Dermatological Treatment. 1995;6(3):159-161.
63. Barrett C, Lowson D, Blades KJ. Limited benefit of combined use of tar-based
shampoo with 50 microg/ml calcipotriol solution in scalp psoriasis. Journal of
Dermatological Treatment. 2005;16(3):175.
64. Regana M, ,. Increased efficacy and acceptability of a nonecoal tar shampoo for
scalp psoriasis: Better efficacy and acceptability. J Am Acad Dermatol.
2009;Conference: 67th Annual Meeting of the American Academy of
Dermatology, AAD San Francisco, CA United States. Conference Start: 20090306
Conference End: 20090310. Conference Publication:(var.pagings).
65. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE
evidence profiles and summary of findings tables. J Clin Epidemiol. Apr
2011;64(4):383-394.
66. Chan CS, Van Voorhees AS, Lebwohl MG, et al. Treatment of severe scalp
psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am
Acad Dermatol. Jun 2009;60(6):962-971.
67. Frez ML, Asawanonda P, Gunasekara C, et al. Recommendations for a patient-
centered approach to the assessment and treatment of scalp psoriasis: a
consensus statement from the Asia Scalp Psoriasis Study Group. J Dermatolog
Treat. Feb 2014;25(1):38-45.
68. Ortonne J, Chimenti S, Luger T, Puig L, Reid F, Trueb RM. Scalp psoriasis:
European consensus on grading and treatment algorithm. J Eur Acad Dermatol
Venereol. Dec 2009;23(12):1435-1444.

This article is protected by copyright. All rights reserved.

 69. Mason AR, Mason JM, Cork MJ, Hancock H, Dooley G. Topical treatments for
chronic plaque psoriasis of the scalp: a systematic review. Br J Dermatol.
2013;169(3):519-527.
70. Samarasekera EJ. Topical therapies for the treatment of plaque psoriasis:
Accepted Article
systematic review and network meta-analyses. Br J Dermatol. 2013;168(5).

Footnote:

This article is based on a Cochrane Review published in the Cochrane Database of

Systematic Reviews (CDSR) 2016, Issue 2, DOI: 10.1002/14651858.CD009687.pub2 (see
www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as
new evidence emerges and in response to feedback, and the CDSR should be consulted for
the most recent version of the review.

Figure/Table legends:

Figure 1: study flow diagram

Figure 2: Risk of bias graph: review authors’ judgements about each risk of bias item
presented as percentages across all included studies.
Table 1: Summary of findings: corticosteroids compared to vitamin D for scalp psoriasis
Table 2: Summary of findings: corticosteroid plus vitamin D compared to corticosteroid for
scalp psoriasis.
Table 3: Summary of findings: corticosteroid plus vitamin D compared to vitamin D for scalp
psoriasis.

This article is protected by copyright. All rights reserved.

 Table 1: Summary of findings: corticosteroids compared to vitamin D for scalp
psoriasis

Summary of findings:
Accepted Article
Corticosteroid compared to vitamin D for scalp psoriasis

Patient or population: scalp psoriasis

Setting:
Intervention: corticosteroid
Comparison: vitamin D

Outcomes Anticipated absolute Relative № of Quality of the Comments

effects* (95% CI) effect participants evidence
(95% CI) (studies) (GRADE)
Risk with Risk with
vitamin D corticosteroid

Number of participants Study population RR 1.82 2180 ⨁⨁⨁◯

achieving 'clearance' (1.52 to (4 RCTs) MODERATE 1
by IGA 159 per 289 per 1000 2.18)
1000 (241 to 346)

Moderate

156 per 284 per 1000

1000 (237 to 340)

Number of participants Study population RR 2.09 1827 ⨁⨁⨁⨁

achieving 'response' (1.80 to (3 RCTs) HIGH
by IGA 251 per 525 per 1000 2.41)
1000 (452 to 605)

Moderate

259 per 541 per 1000

1000 (466 to 624)

Quality of life Study population not (0 studies) No study addressed this outcome.
estimable
0 per 0 per 1000
1000 (0 to 0)

Number of participants Study population RR 0.22 2291 ⨁⨁⨁◯ No study reported the sort of AE that caused
withdrawing due to (0.11 to (4 RCTs) MODERATE 2 withdrawal. In two small studies with high risk of
adverse events (AE) 53 per 12 per 1000 0.42) bias (Köse 1997, N = 43 subjects; Yilmaz 2005,
1000 (6 to 22) N = 30 subjects) no withdrawals occurred.

Moderate

60 per 13 per 1000

1000 (7 to 25)

Number of participants Study population RR 1.48 1827 ⨁⨁⨁◯

achieving 'response' (1.28 to (3 RCTs) MODERATE 3
by PGA 403 per 596 per 1000 1.72)
1000 (516 to 693)

Moderate

382 per 565 per 1000

1000 (489 to 657)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the
intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence

High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a
possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

This article is protected by copyright. All rights reserved.

 1. 3 out of 4 studies with unclear blinding of outcome assessment (Klaber 1994, van de Kerkhof 2009, Yilmaz 2005); all studies with unclear
allocation concealment
2. 2 out of 4 studies with unclear blinding of outcome assessment (Klaber 1994, van de Kerkhof 2009); all studies with unclear allocation
concealment
3. All 4 studies with unclear allocation concealment; 1 study with unclear risk of bias in selective reporting (Reygagne 2005); 1 study with unclear
Accepted Article
blinding of outcome assessment (van de Kerkhof 2009)

This article is protected by copyright. All rights reserved.

 Table 2: Summary of findings: corticosteroid plus vitamin D compared to corticosteroid
for scalp psoriasis.

Summary of findings:
Accepted Article
Corticosteroid plus vitamin D compared to corticosteroid for scalp psoriasis
Patient or population: scalp psoriasis
Setting:
Intervention: corticosteroid plus vitamin D
Comparison: corticosteroid

Outcomes Anticipated absolute effects* (95% Relative № of Quality of the Comments

CI) effect participants evidence
(95% CI) (studies) (GRADE)
Risk with Risk with
corticosteroid corticosteroid
plus vitamin D

Number of Study population RR 1.22 2474 ⨁⨁⨁◯

participants (1.08 to (4 RCTs)
MODERATE 1
achieving 'clearance' 350 per 1000 1.36)
287 per 1000
by IGA (310 to 391)

Number of Study population RR 1.15 2444 ⨁⨁⨁◯

participants (1.06 to (3 RCTs)
MODERATE 2
achieving 'response' 628 per 1000 1.25)
546 per 1000
by IGA (579 to 683)

Quality of life Study population not (0 studies) No study addressed this outcome.
estimable
0 per 1000
0 per 1000
(0 to 0)

Number of Study population RR 0.88 2433 ⨁⨁⨁◯ No study reported the sort of AE that
participants (0.42 to (3 RCTs) caused withdrawal. In one small study
MODERATE 3

withdrawing due to 11 per 1000 1.88) with high risk of bias (Yilmaz 2005, N
12 per 1000
(5 to 23) = 30 subjects) no withdrawals
adverse events (AE)
occured.
Moderate

11 per 1000
13 per 1000
(5 to 24)

Number of Study population RR 1.13 2226 ⨁⨁⨁⨁

participants (1.06 to (2 RCTs) HIGH
achieving 'response' 692 per 1000 1.20)
613 per 1000
by PGA (649 to 735)
Moderate

693 per 1000

613 per 1000
(650 to 736)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the
intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence

High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a
possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1. CI crosses line of MID thresholds: uncertain if statistically significant difference is clinically important
2. Moderate heterogeneity (I²=35%)
3. CI crosses line of MID thresholds: uncertain if statistically significant difference is clinically important

This article is protected by copyright. All rights reserved.

 Table 3: Summary of findings: corticosteroid plus vitamin D compared to vitamin D for
scalp psoriasis.
Accepted Article
Summary of findings:

Corticosteroid plus vitamin D compared to vitamin D for scalp psoriasis

Patient or population: scalp psoriasis
Setting:
Intervention: corticosteroid plus vitamin D
Comparison: vitamin D

Outcomes Anticipated absolute effects* Relative № of Quality of the Comments

(95% CI) effect participants evidence
(95% CI) (studies) (GRADE)
Risk with Risk with
vitamin D corticosteroid plus
vitamin D

Number of Study population RR 2.28 2008 ⨁⨁⨁⨁

participants achieving (1.87 to (4 RCTs) HIGH
'clearance' by IGA 145 per 330 per 1000 2.78)
1000 (270 to 402)

Number of Study population RR 2.31 2222 ⨁⨁⨁◯

participants achieving (1.75 to (4 RCTs)
MODERATE 1
'response' by IGA 280 per 646 per 1000 3.04)
1000 (489 to 850)

Quality of life Study population not (0 studies) Only one study (Ortonne et al. 2009)
estimable addressed this outcome, but did not
0 per 0 per 1000 provide sufficient information to allow
1000 (0 to 0) assessment of the quality of evidence.

Number of Study population RR 0.19 1970 ⨁⨁⨁⨁ No study reported the sort of AE that
participants (0.11 to (3 RCTs) HIGH caused withdrawal. In one small study with
withdrawing due to 56 per 11 per 1000 0.36) high risk of bias (Yilmaz 2005, N = 30
1000 (6 to 20) subjects) no withdrawals occured.
adverse events

Number of Study population RR 1.76 2222 ⨁⨁⨁◯

participants achieving (1.46 to (4 RCTs)
MODERATE 2
'response' by PGA 427 per 751 per 1000 2.12)
1000 (623 to 905)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the
intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence

High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a
possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1. Substantial to considerable heterogeneity (I²=81%), maybe due to different application frequency in studies (once versus twice daily)
2. Substantial heterogeneity (I²=77%), maybe due to different application frequency in studies (once versus twice daily)

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.

Accepted Article

This article is protected by copyright. All rights reserved.