Baru Psoriasis

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S Y S T E M A T I C R E V I E W

BJDBritish Journal of Dermatology

Topical therapies for the treatment of plaque psoriasis:

systematic review and network meta-analysesE.J. Samarasekera,1 L. Sawyer,2 D. Wonderling,1 R. Tucker3 and C.H. Smith4

1National Clinical Guideline Centre, Royal College of Physicians of London, 11 St Andrews Place, London NW1 4LE, U.K.2Symmetron Ltd, Kinetic Centre, Theobald St, Borehamwood WD6 4PJ, U.K.3Faculty of Health and Social Care, University of Hull, Hull HU6 7RX, U.K.4Division of Medicine and Molecular Genetics, St John’s Institute of Dermatology, Guy’s Hospital, London SE1 9RT, U.K.

Correspondence

Catherine H. Smith.

E-mail: [email protected]

Accepted for publication

10 February 2013

Funding sourcesNational Institute for Health and Clinical Excel-

lence, and National Institute for Health Research.

Conflicts of interest

All authors were members of the NICE Psoriasis

Guideline Development Group (C.H.S chaired the

group, E.S was the research fellow, L.S and O.W

were the health economists, and R.T was the phar-

macist). After completing the guideline analysis

but before its publication, L.S joined Symmetron

Limited.

DOI 10.1111/bjd.12276

Summary

The majority of people with psoriasis have localized disease, where topical ther-apy forms the cornerstone of treatment. We set out to summarize evidence onthe relative efficacy, safety and tolerability of different topical treatments used inplaque psoriasis. We undertook a systematic review and meta-analyses of ran-domized trial data of U.K.-licensed topical therapies. The primary outcome wasclear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp.

Network meta-analyses allowed ranking of treatment efficacy. In total, 48 stud-ies were available for trunk and limb psoriasis, and 17 for scalp psoriasis(22 028 patients in total); the majority included people with at least moderateseverity psoriasis. Strategies containing potent corticosteroids (alone or in com-bination with a vitamin D analogue) or very potent corticosteroids dominatedthe treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and reti-noids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice- and once-daily appli-cation of the same intervention or between any of the following: combinedvitamin D analogue and potent corticosteroid (applied separately or in a singleproduct), very potent corticosteroids, or potent corticosteroids (applied twice

daily). Investigator and patient assessment of response differed significantly forsome interventions (response rates to very potent corticosteroids: 78% and 39%,respectively). No significant differences were noted for tolerability or steroidatrophy, but data were limited. In conclusion, corticosteroids are highly effec-tive in psoriasis when used continuously for up to 8 weeks and intermittentlyfor up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lackof long-term efficacy and safety data available on topical interventions used forpsoriasis.

Psoriasis is a common chronic inflammatory skin condition

and, although generally not life threatening, it can have a pro-found impact on physical, psychological and social well-being.1 While recent advances and investment in high-costbiological therapies have revolutionized outcomes for peoplewith severe disease, comparatively little attention has beenpaid to topical therapy, which forms the cornerstone of man-agement for the majority of people with psoriasis.2 Further-more, the degree of disability does not necessarily correlatewith objective measures of disease extent or severity,3 andpeople with minimal involvement (less than the equivalent of three palm areas) state that psoriasis has a major effect on

their life,4 underscoring the importance of effective treatment

in this group.Corticosteroids, vitamin D3 and its analogues, calcineurin

inhibitors, retinoids, tar, dithranol and keratolytic agents suchas salicylic acid and urea are all used,5 and come in a vastarray of formulations, combinations and potencies. Choice of treatment is tailored to the needs of the patient and includesconsideration of the nature of the psoriasis (type, site, extent)and practical aspects such as cosmetic acceptability and timeavailable for application. How these factors, as well aspatients’ mood, beliefs and perceptions about psoriasis, mightimpact on treatment adherence is also relevant.6 However, in

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the context of these considerations, prescribers need reliableevidence on the relative efficacy, tolerability and safety of theavailable topical agents in order to devise a management strat-egy that delivers the best chance of achieving a satisfactoryoutcome. The aim of this analysis is therefore twofold: (i) tosummarize the evidence on topical treatments in chronicplaque psoriasis (stratified for trunk and limbs, and scalp) toallow comparison of their efficacy, tolerability and safety; and

(ii) to synthesize data on efficacy to inform original cost-effectiveness modelling.7 Data arising from this work wereused to inform recommendations on the use of topical therapyfor the National Institute for Health and Clinical Excellenceguideline on Assessment and Management of Psoriasis.8

Materials and methods

Search strategy and selection criteria

A systematic literature search was conducted according to apredefined protocol for randomized, placebo-controlled or

head-to-head trials of U.K.-licensed topical therapies for plaquepsoriasis. Outcomes for the scalp were considered separatelyfrom those of the trunk and limbs because the scalp is consid-ered a high need, difficult-to-treat site due to difficulties withapplication of topical therapies, differences in formulations,and acceptable frequencies of application. Comprehensivesearches of Medline, Embase, Cinahl and The Cochrane Librarywere conducted and last updated on 8 March 2012, restrictedto articles published in English (see Table S1, Supporting Infor-mation, for full search strategy). Abstracts were screened, andarticles that appeared to meet the inclusion criteria wereassessed further. Studies were excluded if they were not pub-lished as full reports, due to high risk of bias. Reference lists of relevant articles were scrutinized to identify additional reports.

Eligible studies were required to have at least 25 people ineach study arm and to report induction or maintenance of remission. The unit of randomization could be the individualpatient or one side of the body. Interventions included were:vitamin D and vitamin D analogues (henceforth referred to asvitamin D analogues), potent or very potent corticosteroids,combined application of vitamin D analogue and potent corti-costeroid either as a two-compound formulation (TCF) prod-uct (DovobetTM; LEO Pharma, Princes Risborough, U.K.) orapplied separately, one in the morning and one in the evening[two-compound application; TCA (am/pm)], tar, dithranol

and retinoids. The included comparisons for the pairwise anal-yses for trunk and limb psoriasis were (i) any of the topicalmonotherapies compared with vitamin D analogues or withplacebo or vehicle; and (ii) combined vitamin D analogue andpotent corticosteroid [TCF or TCA (am/pm)] compared withthe constituent monotherapies. For scalp psoriasis all compari-sons were included in the pairwise analysis.

The primary outcome was the proportion of patientsachieving clear or nearly clear status on either the Investiga-tor’s Assessment of Overall Global Improvement (IAGI) ordynamic Physician’s Global Assessment (PGA), or the static

PGA. The secondary outcome was clear or nearly clear statusas assessed by either the Patient’s Assessment of Overall GlobalImprovement (PAGI) or the static patient’s global assessment.Consistent data extraction for the outcome of clear or nearlyclear across the different scales was achieved by aligning thedescriptors as follows: ‘clear’, ‘nearly clear’, ‘75% improve-ment’, ‘excellent improvement’, ‘marked improvement’ or‘minimal’ for dynamic scales; and ‘minimal’ or ‘very mild’ for

static scales. Other outcomes were duration of remission ortime to relapse, skin atrophy and withdrawal due to adverseevents (as a marker of tolerability).

Data extraction and quality assessment

Data were extracted according to a standard template. Assess-ment of methodological quality and methods of analysis arereported elsewhere.8

Statistical analysis

Data were stratified according to the site of psoriasis: (i) trunkand limbs; and (ii) scalp. Given the number of different inter-ventions, data on all agents within a drug class were pooledinto one analysis; however, once- and twice-daily applicationswere kept as separate comparators for the network meta-anal-ysis (NMA). Additionally, although it was not possible toadjust data from within-patient comparison trials for thecorrelation coefficient relating to the comparison of paireddata, within- and between-patient data were pooled. Thisprovided a conservative estimate, accepting that it may resultin underweighting of the within-patient studies.

A series of pairwise meta-analyses for the primary and sec-ondary outcomes for induction of remission produced 12direct comparisons for trunk and limb psoriasis and 10 forscalp psoriasis. To synthesize all data (both direct and indirectcomparisons) into a single, coherent set of effect sizes, a hier-archical Bayesian NMA was performed.9 This produced oddsratios (and 95% confidence intervals) for each treatment com-pared with all the others. We then derived relative risks andabsolute risks for each treatment from these odds ratios usingthe absolute risk from data on twice-daily vehicle or placebo.

The analysis was performed in WinBUGS 19 (Medical ResearchCouncil, Cambridge, U.K.) using a multi-arm, random-effectslogistic regression model, with parameters estimated by Markovchain Monte Carlo Simulation (Appendices S1 and S2; see

Supporting Information). The model used the assumption thatthe between-trial heterogeneity was equal across all comparisons.For each analysis, 20 000 burn-in simulations were run forconvergence followed by a further 40 000 simulations toproduce the outputs. Full details of the analysis methods havebeen published elsewhere.8 Inconsistency in the direct evidencewas assessed using Bucher’s method,10 comparing the odds ratiosfrom the pairwise meta-analysis wherever a loop of directevidence was available. We also compared estimates of effectfrom the pairwise meta-analyses and NMAs. No significant incon-sistency was identified.

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Results

Search results and study characteristics

Of 2619 abstracts retrieved, 48 studies11 – 59 were included fortrunk and limb psoriasis and 1760 – 76 for scalp psoriasis (seeFig. 1 for full selection process). Details of the included stud-ies for trunk and limb psoriasis and scalp psoriasis are summa-rized in Tables S2 and S3, respectively (see SupportingInformation). There was variation in methodology and report-ing between the studies, for example in treatment duration(range: 2 – 12 weeks for trunk and limbs; 2 – 8 weeks for scalp;maintenance studies up to 52 weeks). Evidence quality variedbetween outcomes and comparisons (range: very low tohigh); common limitations were unclear allocation conceal-ment and blinding, and imprecise estimates for safety or toler-ability measures. There were also differences in the baselinedisease severity. For trunk and limb psoriasis approximatelyhalf of the studies included populations with moderate-to-severe psoriasis assessed by PASI, PGA or body surface area

(BSA), while others included either mild-to-moderate psoria-sis, any disease severity or did not specify severity as aninclusion criterion. Therefore, there would have been arange from limited to more widespread disease among thestudies included. For scalp psoriasis, the majority of

studies60,62,63,65,68,70 – 73 included those with moderate-to-severe scalp involvement, with three64,67,69 stipulatingmild-to-moderate scalp disease and three61,66,74 allowing anyseverity to be included.

Achievement of clear or nearly clear

Pairwise results (investigator and patient assessments)

Tables 1 and 2 summarize the individual study results; theoutputs of the direct pairwise meta-analysis that were used asinputs for the NMA are available in Figures S1 and S2 (seeSupporting Information) for psoriasis of the trunk and limbs,and scalp, respectively. Time to remission varied among theinterventions (Table S4; see Supporting Information), andvariations in study length and frequency of application madedirect comparisons difficult. Overall, the most rapid improve-ment in response occurred during the first 2 – 4 weeks forcorticosteroids, and the first 4 weeks for vitamin D analogue-containing interventions, dithranol and coal tar. Data from

long-term or ‘maintenance’ studies were not included in theNMA (see Tables 3 and 4), and a separate NMA for long-termdata was not possible as only two studies were available foreach of trunk and limb57 – 59 and scalp75,76 psoriasis, and oneof these76 did not report the primary outcome.

SCALPTRUNK & LIMBS

101 Full-text articles excluded

30 Insufficient sample size

19 Incorrect outcomes

22 Incorrect comparison

22 Incorrect study/article type

4 Inadequate reporting

4 Not English language

48 Studies included inquantitative synthesis

33 Full-text articles assessed

for eligibility

149 Full-text articles

assessed for eligibility

2619 Records identified

2586 Records excluded

17 Studies included inquantitative synthesis

9 Excluded from NMA

Did not report primary or

secondary outcomes, or long-

term maintenance studies

39 Studies included in NMA

4 Excluded from NMA

Did not report primary

outcome, or long-term

maintenance studies

13 Studies included in NMA

2470 Records excluded

16 Full-text articles excluded

10 Incorrect outcomes

2 Incorrect comparison

2 Incorrect population

2 Incorrect study/article type

(a) (b)

Fig 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow chart for selection of studies; (a) for trunk and limb psoriasis and

(b) for scalp psoriasis. NMA, network meta-analysis.

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Table 1 Trunk and limb psoriasis – Investigator’s Assessment of Overall Global Improvement (IAGI), Physician’s Global Assessment (PGA) and

Patient’s Assessment of Overall Global Improvement (PAGI) efficacy data for induction of remission

Study Topical Dose

IAGI or PGA ‘clear/nearly clear’

PAGI ‘clear/nearlyclear’

r n % r n %

Barker 199911 Placebo OD 1 26 3.8Vitamin D OD 13 28 46.4

Perez 199612 Placebo OD 0 84 0.0Vitamin D OD 37 84 44.0

Fleming 201013 Placebo OD 0 40 0.0Vitamin D OD 9 79 11.4Potent corticosteroid OD 14 83 16.9Combined vitamin D and potent corticosteroid OD 44 162 272

Kaufmann 200214 Placebo OD 16 157 102 15 157 96Vitamin D OD 107 480 223 137 480 285Potent corticosteroid OD 176 476 370 216 476 454Combined vitamin D and potent corticosteroid OD 276 490 563 316 490 645

Langley 201115 Placebo OD 5 91 5.5 14 64 21.9Vitamin D OD 33 184 179 35 163 215Combined vitamin D and potent corticosteroid OD 73 183 399 69 171 404

Medansky 198716 Placebo OD 7 45 15.6

Potent corticosteroid OD 18 50 36.0Decroix 200417 Placebo OD 5 33 15.2

Very potent corticosteroid OD 144 189 762Weinstein study A 200318 Placebo OD 7 229 31

Retinoid OD 24 439 55Weinstein study B 200318 Placebo OD 2 214 09

Retinoid OD 26 421 62Langner 199219 Placebo BD 9 29 31.0

Vitamin D BD 21 29 72.4Langner 199320 Placebo BD 13 32 40.6

Vitamin D BD 24 32 75.0Highton 199521 Placebo BD 23 123 187

Vitamin D BD 87 124 702Dubertret 199222 Placebo BD 11 62 17.7

Vitamin D BD 46 62 74.2Harrington 199623 Placebo BD 13 71 18.3

Vitamin D BD 148 291 509Oranje 199747,a Placebo BD 15 43 34.9 16 34 47.1

Vitamin D BD 26 43 60.5 21 43 48.8

Papp 200324,b Placebo BD 8 107 75 13 107 121Vitamin D BD 103 308 334 99 308 321Potent corticosteroid BD 174 312 558 195 312 625Combined vitamin D and potent corticosteroid BDc 229 301 761 223 301 741

Guenther 200225 Placebo BD 19 206 92 26 206 126Vitamin D BD 115 227 507 117 227 515Combined vitamin D and potent corticosteroid OD 95 150 633 98 150 653Combined vitamin D and potent corticosteroid BDc 172 234 735 164 234 701

Wortzel 197526 Placebo BD 4 37 10.8

Potent corticosteroid BD 15 39 38.5Sears 199727 Placebo BD 1 83 1.2 2 83 2.4Potent corticosteroid BD 12 78 15.4 12 78 15.4

Lowe 200528 Placebo BD 0 29 0.0Very potent corticosteroid BD 84 162 519

Gottlieb 200329 Placebo BD 27 125 216 36 140 257Very potent corticosteroid BD 85 120 708 79 139 568

Lebwohl 200230 Placebo BD 1 20 5.0 1 20 5.0Very potent corticosteroid BD 10 61 16.4 8 61 13.1

Jarratt 200631 Placebo BD 2 60 3.3Very potent corticosteroid BD 47 60 78.3

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Network meta-analysis results for trunk and limb psoriasis

Investigator’s assessment of response Thirty four stidues11 – 35,38 – 46

were available for the base-case network for the primary out-come of investigator’s assessment of achieving clear or nearlyclear status, including 11 604 patients randomized to 14interventions. Seventeen of these studies included people withat least moderate disease severity, most commonly measuredby having over 10% BSA coverage. There was a notable

absence of trials comparing the TCF product with TCA (am/pm) (see Fig. S3, Supporting Information, showing directcomparisons forming the network). All active interventionswere significantly more effective than placebo twice daily,except coal tar used once daily and retinoids (Fig. 2). Verypotent steroids were the most effective treatment option (cal-culated response rate of 782% when applied twice daily). Forother active interventions, response rates ranged from 122%for once-daily coal tar to 709% for once-daily TCF product

Table 1 (Continued)

Study Topical Dose



r n % r n %

Kragballe 199832 Vitamin D OD 49 172 285 46 172 267Vitamin D BD 69 172 401 69 172 401Concurrent vitamin D and potent corticosteroid 73 172 424 89 174 511

Ortonne 200433

Vitamin D OD 43 252 171 44 252 175Combined vitamin D and potent corticosteroid OD 143 249 574 135 249 542

Camarasa 200334 Vitamin D BD 67 128 523Potent corticosteroid BD 81 130 623

Molin 199735 Vitamin D BD 119 205 580Potent corticosteroid BD 116 207 560

Kragballe 199136 Vitamin D BD 281 342 822Potent corticosteroid BD 237 342 693

Cunliffe 199237 Vitamin D BD 123 201 612Potent corticosteroid BD 101 200 505

Douglas 200238 Vitamin D BD 142 365 389 140 365 384Potent corticosteroid BD 169 363 466 183 363 504Combined vitamin D and potent corticosteroid BDc 251 369 680 248 369 672

Ruzicka 199839 Vitamin D BD 22 49 44.9

Concurrent vitamin D and potent corticosteroid 27 39 69.2Tham 199440 Vitamin D BD 13 27 48.1Coal tar OD 3 27 11.1

Alora-Palli 201041 Vitamin D BD 6 28 21.4Coal tar BD 14 27 51.9

Pinheiro 199742 Vitamin D BD 47 65 72.3Coal tar BD 28 57 49.1

Hutchinson 200043 Vitamin D BD 23 60 38.3Dithranol OD 24 54 44.4

Wall 199844 Vitamin D BD 92 153 601 93 153 608Dithranol OD 67 131 511 65 131 496

Berth-Jones 199245 Vitamin D BD 180 231 779 180 231 779Dithranol OD 116 227 511 123 227 542

Christensen 199946 Vitamin D BD 6 89 6.7

Dithranol OD 4 77 5.2Thawornchaisit 200749,d Potent corticosteroid BD 23 30 76.7Coal tar BD 7 28 25.0

Menter 200948,e Very potent corticosteroid BD 32 44 72.7Combined v ita min D a nd pot ent corticos teroid OD 32 49 65 .3

OD, once daily; BD, twice daily. Bold text denotes data included only in the sensitivity analysis of the network meta-analysis. aOranje 1997

evaluated treatments in a paediatric population. bData from Papp 2003 for IAGI/PGA were included in the base case, but only PAGI data

were included in the sensitivity analysis because they were excluded from the clinical review of direct evidence, given that in the paper they

were reported graphically. cTwice-daily combined vitamin D and potent corticosteroid was included only as a comparator in the sensitivity

analysis given that it is currently unlicensed in the U.K. at this dose. dThe protocol for the clinical review of direct evidence included only

comparisons of single topical therapies with either placebo/vehicle or vitamin D; therefore, the comparison of potent corticosteroid and coal

tar was included only in the sensitivity analysis. eThe protocol for the clinical review of direct evidence included only comparisons of combi-

nation therapies with either vitamin D or potent corticosteroid; therefore, the comparison of combined vitamin D and potent corticosteroid

and very potent corticosteroid was included only in the sensitivity analysis.

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(Fig. 3 and Table S5; see Supporting Information). The proba-bility distributions for the rank order of each interventionwithin the treatment hierarchy are shown in Figure S4 (seeSupporting Information).

When comparing the odds of response between differentactive interventions, for the majority of comparisons therewere no significant differences, including between TCF prod-

uct and TCA (am/pm) (Fig. S1; see Supporting Information).However, the TCF product was significantly more effectivethan once-daily application of vitamin D analogues, potentcorticosteroids, retinoids or coal tar. There was a trend to sug-gest that twice-daily application of any given intervention wasmore effective than once-daily application (especially for coaltar), but any differences were not statistically significant whencomparing odds of response.

A sensitivity analysis investigating the impact of includingthree studies excluded from the base case (one paediatricstudy47 and two studies48,49 with comparisons that did not

match the protocol) did not alter the overall findings, withtwice-daily application of a very potent steroid still being themost effective treatment compared with vehicle twice daily[relative risk (RR) 610 in base case vs. 573 in sensitivityanalysis]. The only notable difference was that the estimatedefficacy of twice-daily coal tar was reduced markedly by theinclusion of a study with shorter duration (6 weeks vs.

8 –

12 weeks in base-case studies); see also Reference 8 for fulldetails of this analysis.

Patient’s assessment of response For the secondary outcome of patientassessment of response, 14 studies were available( n = 7644),14,15,23,25,27,29,30,32,33,36 – 38,44 – 46 substantially fewerthan for investigator assessment (Fig. S5; see Supporting Infor-mation). Regarding the hierarchy of efficacy, notable differ-ences from the outcomes based on the investigators’assessment included very potent corticosteroid twice dailybeing ranked much lower by the patient assessment (sixth vs.

Table 2 Scalp psoriasis – Investigator’s Assessment of Overall Global Improvement (IAGI), Physician’s Global Assessment (PGA) and Patient’s

Assessment of Overall Global Improvement (PAGI) efficacy data for induction of remission

Study Topical Dose



r n % r n %

Buckley 200861 Potent corticosteroid OD 91 110 827Combined vitamin D and potent corticosteroid OD 100 108 926

Franz 199962 Placebo BD 12 57 21.1 10 57 17.5Potent corticosteroid BD 68 115 591 71 115 617

Franz 200063 Placebo BD 5 63 7.9 4 63 6.3Very potent corticosteroid BD 86 125 688 77 125 616

Green 199464 Placebo OD 4 24 16.7Vitamin D OD 15 25 60.0

Jarratt 200465 Placebo OD 1 47 2.1Very potent corticosteroid OD 40 95 42.1

Jemec 200866 Placebo OD 31 136 228 28 136 206Vitamin D OD 100 272 368 104 272 382Potent corticosteroid OD 356 556 640 348 556 626Combined vitamin D and potent corticosteroid OD 385 541 712 371 541 686

Klaber 199467 Vitamin D BD 138 236 585 136 236 576Potent corticosteroid BD 175 232 754 171 232 737

Kragballe 200968 Vitamin D BD 33 105 314Combined vitamin D and potent corticosteroid OD 142 207 686

McKinnon 200069 Vitamin D BD 120 210 571Coal tar polytherapy OD 79 213 371

Olsen 199170 Placebo BD 16 189 85Very potent corticosteroid BD 129 188 686

Reygagne 200571 Vitamin D BD 21 75 28.0 23 75 30.7Very potent corticosteroid OD 38 76 50.0 36 76 47.4

Sofen 201172 Placebo BD 5 40 12.5Very potent corticosteroid BD 35 41 85.4

Tyring 201073 Placebo OD 17 42 40.5 15 42 35.7Combined vitamin D and potent corticosteroid OD 97 135 719 84 135 622

van de Kerkhof 200974 Vitamin D OD 124 286 434 128 286 448Potent corticosteroid OD 343 562 610 227 562 404

Combined vitamin D and potent corticosteroid OD 388 567 684 395 567 697

OD, once daily; BD, twice daily. Bold text denotes data not included in the network meta-analysis.

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first) and once-daily application of potent corticosteroid or

placebo appearing to be more effective than twice-daily appli-cation of the same agent (Fig. 4). There was also a trendacross the majority of interventions showing that the patientassessment of response produced a lower estimate of the pro-portion responding than the investigator’s assessment (TableS5; see Supporting Information). This difference was mostpronounced for twice-daily application of potent corticoste-roid and once-daily dithranol.

Sensitivity analysis showed that including two studies ini-tially excluded from the protocol for direct comparisons, onein a paediatric population47 and one because the results werepresented only graphically,24 did not alter the overall findings,with the TCF product still being the most effective compared

with vehicle twice daily (RR 463 in the base case vs. 428 insensitivity analysis). See also Reference 8 for full details of thisanalysis.

Network meta-analysis results for scalp psoriasis

Investigator’s assessment of response Thirteen studies62 – 74 were avail-able in the base-case network for the primary outcome of investigator’s assessment of achieving clear or nearly clear sta-tus, including 5640 patients randomized to 10 different inter-ventions (Fig. S6, see Supporting Information, showing directcomparisons forming the network). Ten of the studies

reported on scalp psoriasis of at least moderate severity.All active interventions were more efficacious than placebo

applied twice daily, although there was uncertainty about thisfor coal-tar shampoo and vitamin D analogues used once daily(see Fig. 5 for relative risks and Fig. 6 for absolute risks of each intervention compared with the baseline risk of response). As with psoriasis of the trunk and limbs, verypotent steroids were the most effective treatment option(response rates 7835% for twice-daily and 6926% for once-daily applications). Twice-daily coal-tar shampoo was no bet-ter than placebo (1892% and 1809%, respectively). The

probability distribution of being ranked in a certain position

in the treatment hierarchy for each intervention is shown inFigure S7 (see Supporting Information).Considering comparisons between different active inter-

ventions, very few demonstrated a statistically significantdifference (Fig. S2). Exceptions were that once-daily applica-tion of potent corticosteroid or the TCF product was signifi-cantly more effective than vitamin D analogues once daily,and very potent corticosteroids were significantly better thanvitamin D analogues regardless of frequency of application.Additionally, very potent corticosteroids and the TCF prod-uct were significantly more effective than coal-tar shampooonce daily. Unlike the results for trunk and limb psoriasis,across all interventions there was no consistent trend that

increasing treatment frequency was linked to improved effi-cacy.

It was not possible to analyse the patient-assessed outcomesas no single connected network could be formed based onpublished comparisons.

Duration of remission

Clear evidence regarding the duration of remission was lack-ing, with only seven studies, three for trunk and limbs57,67,68

and four for scalp,15,34,46,75 reporting this outcome (Table 4).One study for scalp68 and one for trunk and limb34 psoriasis

suggested that the relapse rate was greater for interventionscontaining steroids compared with vitamin D analogues. Theproportion relapsing following treatment withdrawal across allinterventions ranged from 20% to 80% in the short term, upto 88% after 6 months, with no consistent evidence for supe-riority of any one intervention.

Tolerability and adverse effects

Withdrawals from trials due to toxicity (as a proxy marker of tol-erability) and reported cases of skin atrophy (as the principal local

Table 3 Long-term maintenance of remission

Study Topical Dose Duration of follow-up


r n %*

Trunk and limbsKragballe 200658,a Combined vitamin D and potent corticosteroid OD 52 weeks 80 104 769

Combined vitamin D and potent corticosteroid

(4 weeks) then vitamin D (48 weeks)

OD 52 weeks 62 89 69.7

Alternating 4-week periods of combined vitaminD and potent corticosteroid, and vitamin D

OD 52 weeks 78 104 75

Katz 199157,b Potent corticosteroid – 6 months 27 46 58.7Placebo – 6 months 7 44 15.9

IAGI, Investigator’s Assessment of Overall Global Improvement; PGA, Physician’s Global Assessment; OD, once daily. aThis maintenance study

enrolled patients with plaque psoriasis of at least moderate severity and allowed treatment once daily according to the randomized interven-

tion schedule for up to 52 weeks for application when required. bThis maintenance study included participants who achieved remission after

3 – 4 weeks’ treatment with betamethasone dipropionate. The maintenance regimen was intermittent betamethasone dipropionate applied to

the site of the healed lesion (three consecutive applications 12 h apart, once a week for a maximum treatment period of 6 months).

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adverse effect associated with corticosteroids) across all compari-sons and both populations showed low event rates, even in thelong term and in maintenance studies up to 52 weeks. The rela-tive estimates were very imprecise, but in absolute terms demon-strated precise evidence of no clinically relevant differencesbetween the interventions because the numbers involved were solow. There was no statistically significant increased risk of steroidatrophy with corticosteroid use compared with other interven-tions, although the majority of cases of steroid atrophy reported

did occur in people who received corticosteroids, andgreater numbers of withdrawals due to adverse effects were seenwith twice-daily potent corticosteroid compared with once-dailyuse. See also Reference 8 for full details of these outcomes.

Discussion

Overall, the NMA hierarchy of effectiveness for topical therapyfor trunk and limb psoriasis indicated that, discounting very

Table 4 Duration of remission and relapse rates

Study Definitions Intervention Relapse rate Time to relapse

Trunk and limbsLangley 201115 Remission: clear/nearly clear on IAGA.

Relapse: reduction in PASI improvementfrom baseline

Dovobetc OD 8 weeks post-treatment:28/67 responders (42%)

Median: 63 days

Tacalcitol OD 8 weeks post-treatment:7/31 responders (23%)

Median: 61 days

Placebo 8 weeks post-treatment:3/5 responders (60%) Median: 61 days

Camarasa 200334 Remission: clear/nearly clear.Relapse: requiring retreatment(not maintaining clear/nearly clear)

Calcitriol BD 8 weeks post-treatment:30/58 responders (52%)

Mean: 234 days

Betamethasonedipropionate BD

8 weeks post-treatment:55/73 responders (75%)

Mean: 253 days

Christensen 199946 Remission: at least 50% improvement.Relapse: requiring retreatment(loss of response)

Calcipotriol BD 8 weeks post-treatment:50/62 responders (81%)

Median: 29 days

Dithranol OD 8 weeks post treatment:19/33 responders (58%)

Median: 56 days

Katz 199157,a Remission: clear or slight on a 4-point scale(clear, slight, moderate, severe).Relapse: moderate or severe diseaseor TSS 25 at two consecutive visits

Intermittentbetamethasonedipropionate

During 24-weekmaintenance: 16/46(35%)

Hazard ratio037 (95%CI 021 – 067)

Placebo During 24-weekmaintenance: 35/44(80%)

ScalpKlaber 199467 Remission: not applicable – no relapse among

responders only.Relapse: increase in the total sign score toat least 50% of the score at the start of double-blind treatment

Calcipotriol BD 4 weeks post-treatment:75/99 (76%)

–

Betamethasonevalerate BD

4 weeks post-treatment:102/129 (791%)

Kragballe 200968 Remission: ‘clear’ or ‘minimal’ diseaseaccording to PGA.Relapse: recurrence of at least moderate diseaseaccording to PGA

Xamiolc OD 8 weeks post-treatment:73/135 responders(541%)

Median: 35 days

Calcipotriol BD 8 weeks post-treatment:10/29 responders (34%)

Median: 58 days

Poulin 201075,b Remission: at least mild on PGA.Relapse: PGA > 2 (moderate, severe or

very severe scalp psoriasis)

Clobetasolpropionate

twice weekly

Number still in remissionafter 6 months of

maintenance: 27/67(40%)

Median: 141days

Placebo Number still in remissionafter 6 months of maintenance: 8/69 (12%)

Median: 305days

IAGA, Investigator’s Assessment of Overall Global Improvement; PASI, Psoriasis Area and Severity Index; OD, once daily; BD, twice daily; TSS,

total severity score; CI, confidence interval; PGA, Physician’s Global Assessment. aThis was a maintenance study that included participants who

achieved remission after 3 – 4 weeks’ treatment with betamethasone dipropionate. The maintenance regimen was intermittent betamethasone di-

propionate applied to the site of the healed lesion (three consecutive applications 12 h apart, once a week for a maximum treatment period of

6 months). bThis was a maintenance study with treatment for up to 6 months among those who had achieved clear, very mild or mild disease

during a 4-week induction phase with once-daily clobetasol propionate. During the maintenance phase clobetasol propionate was used twice

weekly (3 days apart), but once-daily dosing was permitted for up to 4 weeks if relapse occurred. cLeo Pharma, Princes Risborough, U.K.

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potent steroids (which many dermatologists would notconsider a suitable option for most patients based on clinicalexperience of local adverse effects), the combination of potent

corticosteroid and vitamin D analogue, either applied oncedaily in a single TCF product or applied separately, was themost effective intervention, with no significant difference

0·1 1·1 2·1 3·1 4·1

Risk Ratio

5·1 6·1 7·1 8·1

Placebo OD: 0·78 (0·21–2·29)

Coal tar OD: 0·98 (0·12–4·18)

Retinoid OD: 2·17 (0·43–5·57)

Dithranol OD: 3·38 (1·71–5·34)

Vitamin D OD: 3·44 (1·56–5·63)

Potent corticosteroid OD: 3 ·78 (1·46–6·14)

Vitamin D BD: 4·26 (3·06–5·42)

Coal tar BD: 4·23 (1·90–6·49)

Potent corticosteroid BD: 4·90 (3·40–6·14)

TCA (am/pm): 5·12 (2·87–6·78)

Very potent corticosteroid OD: 5·31 (1·44–7·38)

TCF OD: 5·55 (3·49–6·88)

Very potent corticosteroid BD: 6·10 (4·48–7·14)

Fig 2. Summary of relative risk of response for all interventions compared with twice-daily placebo for trunk and limb psoriasis based on

investigator’s assessment of response. BD, twice daily; TCF, two-compound formulation product containing potent corticosteroid and vitamin D

analogue; OD, once daily; TCA (am/pm), two-compound application of potent corticosteroid and vitamin D analogue, one in the morning and

one in the evening.

9·70%

27·30%

42·80%

12·20%

43·50%

47·90%

70·90%67·90%

12·50%

54·90% 54·20%

62·40%65·40%

78·20%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Vehicle Tazarotene Dithranol Coal tar Vitamin D Potentcorticosteroid

TCA (am/pm) TCF product Very potentcorticosteroid

Once daily

Twice daily

P r o b a b i l i t y

o f r e s p o n s e

Fig 3. Absolute response rates for trunk and limb psoriasis based on investigator’s assessment of response. TCF, two-compound formulation

product containing potent corticosteroid and vitamin D analogue; TCA (am/pm), two-compound application of potent corticosteroid and vitamin

D analogue, one in the morning and one in the evening.

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between these application methods. No important differencesin terms of tolerability or toxicity were evident between thesetreatment options. The rank order of efficacy (confined to

investigator’s assessment) was similar for the scalp; however,perhaps not surprisingly given difficulties with application,there was a lack of any consistent trend linking frequency of

0·1 2·1

Risk Ratio

4·1 6·1

Placebo OD: 1·54 (0·45–3·80)

Dithranol OD: 2·29 (0·83–4·43)

Vitamin D OD: 2·45 (0·99–4·43)



Vitamin D BD: 3·56 (2·16–4·92)

Potent corticosteroid OD: 3·85 (1·50–5·82)

TCA (am/pm): 4·22 (1·85–5·92)

TCF OD: 4·63 (2·86–5·86)

Fig 4. Summary of relative risk of response for all interventions compared with twice-daily placebo for trunk and limb psoriasis based on patient’s

assessment of response. TCF, two-compound formulation product containing potent corticosteroid and vitamin D analogue; OD, once daily; TCA

(am/pm), two-compound application of potent corticosteroid and vitamin D analogue, one in the morning and one in the evening; BD, twice

daily.

0·1 1·1 2·1

Risk Ratio

3·1 4·1 5·1 6·1 7·1 8·1 9·1

Coal tar polytherapy OD: 1·68 (0·42–5·29)

Placebo OD: 1·74 (0·37–4·89)

Vitamin D OD 3·07 (0·71–6·59)

Vitamin D BD: 3·10 (1·31–5·94)


Potent corticosteroid OD: 5·04 (1·61–7·79)

TCF OD: 5·71 (2·35–7·95)

Very potent corticosteroid OD: 6·15 (2·99–8·31)


Fig 5. Summary of relative risk of response for all interventions compared with twice-daily placebo for scalp psoriasis based on investigator’s

assessment of response. BD, twice daily; OD, once daily; TCF, two-compound formulation product containing potent corticosteroid and vitamin D

analogue.

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application to improved efficacy. Very potent steroids werethe most effective treatment and vitamin D analogues andcoal-tar shampoo were the least effective overall, with coal-tarshampoo showing similar response rates to placebo. Thiseffect estimate was based on just one study for coal tar69 andmay be unreliable, but the absence of evidence for efficacy isimportant to note given that coal-tar shampoo is commonlyprescribed in primary care.77,78

For trunk and limb psoriasis, some discordance was evidentbetween results for physician- and patient-assessed outcomes,which may be caused by the relative paucity of evidence toinform the effect estimates for the patient-assessed outcome.

However, for most interventions, patients were less positive intheir evaluation of response than investigators, particularly fortwice-daily application of potent corticosteroid and once-dailydithranol. This may indicate differences between patients’ andphysicians’ perception of ‘clear or nearly clear’ and highlightsthe importance of including both outcomes when evaluatingtopical interventions. Similarly, the nonsignificant trendtowards twice-daily applications being more effective thanonce-daily application was not seen in the patient-assesseddata, which might reflect the preference of patients for once-daily applications to reduce the burden of treatment.

Strengths of this study include the additional power affor-

ded by synthesizing all of the available data in one coherentnetwork. Additionally, the assumption that between-trialheterogeneity is equal across all comparisons may allow heter-ogeneity to be more accurately estimated for comparisonswith few studies. For example, for the comparison of TCF vs.vitamin D twice daily the confidence interval from the directevidence (based on only two trials) was narrower than thatbased on the NMA. In this case the NMA estimate is moreconservative than the direct evidence, but if more trials wereconducted we might find that the existing direct evidence isunderestimating heterogeneity.

A recognized limitation of this analysis is that for themajority of trunk and limb studies included, the severity of psoriasis was recorded as moderate to severe. Consequently,our results may not be wholly generalizable to patients withmild-to-moderate disease for which topical therapy is themainstay of treatment. Nevertheless, our analysis did include12 studies with mild-to-moderate disease, which representsthe majority of patients for whom topical therapy is appropri-ate. Additionally, generalizability may be further limited bythe common risk of recruitment bias, meaning that the clinicaltrial participants may not be representative of those in clinicalpractice, owing to the restrictions on those included, although

in the majority of studies the exclusion criteria were notexcessively stringent.

This review highlights important gaps in the evidence.There were no direct comparisons between TCA (am/pm)and TCF products. More importantly, the majority of the trialsfocused on achievement of remission, with very limited dataon key outcomes of relevance to psoriasis such as relapserates, the optimal point at which to reinstate treatment onrelapse and strategies to maintain remission. The data do notsuggest any major risk associated with corticosteroid use, evenin the context of moderate or severe disease. While this isreassuring, these data should be interpreted with caution:

most of the studies were short term and may be inadequatelypowered to accurately determine true risk. Furthermore, pres-ence or absence of steroid atrophy was a key outcome in onlya minority of studies, and no study used validated objectivemeasures for assessment (e.g. skin ultrasound). Patients andclinicians should therefore remain vigilant for potential local(and systemic) sequelae associated with corticosteroids in pso-riasis. However, nonsteroid-based treatments such as retinoids,coal tar and vitamin D are less effective, and so a strategy forthe safe and effective long-term use of treatments for themaintenance of disease control in psoriasis is urgently needed.

18·09% 18·92%

34·59%

56·75%

64·24%

69·26%

11·26%

34·89%

49·31%

78·35%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

Vehicle Coal tar polytherapy Vitamin D Potent corticosteroid TCF product Very potent corticosteroid

P r o b a b i l i t y

o f r e s p o n s e

Once daily

Twice daily

Fig 6. Absolute response rates for scalp psoriasis based on investigator’s assessment of response. TCF, two-compound formulation product

containing potent corticosteroid and vitamin D analogue.

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Future studies should ensure that patients’ evaluations of treat-ment are included as outcomes.

What’s already known about this topic?

● Topical treatments are widely available and prescribedfor plaque-type psoriasis.

What does this study add?

● Explicit rank order of efficacy, showing that treatmentstrategies containing potent or very potent corticoster-oids are the most effective.

● Investigator and patient evaluation of efficacy may dif-fer.

● Twice-daily application of the same intervention offersno important benefit over once-daily application formost treatments.

Acknowledgments

This work was undertaken by the National Clinical GuidelineCentre, which received funding from the National Institute forHealth and Clinical Excellence. The views expressed in thispublication are those of the authors and not necessarily thoseof the Institute. No funding was received that directly influ-enced the preparation or decision to publish this review. Thisresearch was supported by the National Institute for HealthResearch Biomedical Research Centre at Guy’s and St Thomas’NHS Foundation Trust and King’s College London. The views

expressed are those of the authors and not necessarily those of the NHS, NIHR or the Department of Health.

References

1 Rapp SR, Feldman SR, Exum ML et al. Psoriasis causes as much dis-ability as other major medical diseases. J Am Acad Dermatol 1999;41:401 – 7.

2 Kurd SK, Gelfand JM. The prevalence of previously diagnosed andundiagnosed psoriasis in U.S. adults: results from NHANES 2003 – 2004. J Am Acad Dermatol 2009; 60:218 – 24.

3 Schmitt JM, Ford DE. Work limitations and productivity loss areassociated with health-related quality of life but not with clinicalseverity in patients with psoriasis. Dermatology 2006; 213:102 – 10.

4 Dubertret L, Mrowietz U, Ranki A et al. European patient perspec-tives on the impact of psoriasis: the EUROPSO patient membershipsurvey. Br J Dermatol 2006; 155:729 – 36.

5 Smith CH, Barker JN. Psoriasis and its management. BMJ 2006;333:380 – 4.

6 Bewley A, Page B. Maximizing patient adherence for optimal out-comes in psoriasis. J Eur Acad Dermatol Venereol 2011; 25 (Suppl.4):9 – 14.

7 Sawyer L, Samarasekera EJ, Wonderling D, Smith CH. Topical ther-apies for the treatment of localized plaque psoriasis in primarycare: a cost-effectiveness analysis. Br J Dermatol 2013; 168:1095 – 105.

8 National Clinical Guideline Centre. Psoriasis: Assessment and Manage-ment of Psoriasis. London: National Clinical Guideline Centre,2012.

9 Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ2005; 331:897 – 900.

10 Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta-analysis of ran-domized controlled trials. J Clin Epidemiol 1997; 50:683 – 91.

11 Barker JN, Griffiths CE. Combination therapy for psoriasis. DermatolTher 1999; 11:96 – 103.

12 Perez A, Chen TC, Turner A et al. Efficacy and safety of topical cal-citriol (1,25-dihydroxyvitamin D3) for the treatment of psoriasis.Br J Dermatol 1996; 134:238 – 46.

13 Fleming C, Ganslandt C, Guenther L et al. Calcipotriol plus beta-methasone dipropionate gel compared with its active componentsin the same vehicle and the vehicle alone in the treatment of pso-riasis vulgaris: a randomised, parallel group, double-blind, explor-atory study. Eur J Dermatol 2010; 20:465 – 71.

14 Kaufmann R, Bibby A, Bissonnette R et al. A new calcipotriol/beta-methasone dipropionate formulation (DaivobetTM) is an effectiveonce-daily treatment for psoriasis vulgaris. Dermatology 2002;205:389 – 93.

15 Langley RG, Gupta A, Papp K et al. Calcipotriol plus betamethasonedipropionate gel compared with tacalcitol ointment and the gelvehicle alone in patients with psoriasis vulgaris: a randomized,controlled clinical trial. Dermatology 2011; 222:148 – 56.

16 Medansky RS, Brody NI, Kanof NB et al. Clinical investigations of mometasone furoate – a novel nonfluorinated, topical corticoste-roid. Semin Dermatol 1987; 6:94 – 100.

17 Decroix J, Pres H, Tsankov N et al. Clobetasol propionate lotion inthe treatment of moderate to severe plaque-type psoriasis. Cutis2004; 74:201 – 6.

18 Weinstein GD, Koo JY, Krueger GG et al. Tazarotene cream in thetreatment of psoriasis: two multicenter, double-blind, randomized,vehicle-controlled studies of the safety and efficacy of tazarotenecreams 005% and 01% applied once daily for 12 weeks. J Am

Acad Dermatol 2003; 48:760 –

7.19 Langner A, Verjans H, Stapor V et al. 1-a, 25-Dihydroxyvitamin D3(calcitriol) ointment in psoriasis. J Dermatolog Treat 1992; 3:177 – 80.

20 Langner A, Verjans H, Stapor V et al. Topical calcitriol in thetreatment of chronic plaque psoriasis: a double-blind study. Br J Dermatol 1993; 128:566 – 71.

21 Highton A, Quell J. Calcipotriene ointment 0005% for psoriasis: asafety and efficacy study. Calcipotriene Study Group. J Am AcadDermatol 1995; 32:67 – 72.

22 Dubertret L, Wallach D, Souteyrand P et al. Efficacy and safety of calcipotriol (MC 903) ointment in psoriasis vulgaris. A random-ized, double-blind, right/left comparative, vehicle-controlledstudy. J Am Acad Dermatol 1992; 27:983 – 8.

23 Harrington CI, Goldin D, Lovell CR et al. Comparative effects of two different calcipotriol (MC 903) cream formulations versusplacebo in psoriasis vulgaris. A randomised, double-blind, pla-cebo-controlled, parallel group multi-centre study. J Eur Acad Derma-tol Venereol 1996; 6:152 – 8.

24 Papp KA, Guenther L, Boyden B et al. Early onset of action andefficacy of a combination of calcipotriene and betamethasonedipropionate in the treatment of psoriasis. J Am Acad Dermatol 2003;48:48 – 54.

25 Guenther L, van de Kerkhof PC, Snellman E et al. Efficacy andsafety of a new combination of calcipotriol and betamethasone di-propionate (once or twice daily) compared to calcipotriol (twicedaily) in the treatment of psoriasis vulgaris: a randomized, dou-

© 2013 The Authors





13/14

ble-blind, vehicle-controlled clinical trial. Br J Dermatol 2002;147:316 – 23.

26 Wortzel WH. A new corticosteroid for moderate/severe dermato-ses. Clin Med 1975; 82:23 – 6.

27 Sears HW. A double-blind, randomized, placebo-controlled evalua-tion of the efficacy and safety of hydrocortisone buteprate 0 1%cream in the treatment of psoriasis. Adv Ther 1997; 14:140 – 9.

28 Lowe N, Feldman SR, Sherer D et al. Clobetasol propionate lotion,an efficient and safe alternative to clobetasol propionate emollient

cream in subjects with moderate to severe plaque-type psoriasis. J Dermatolog Treat 2005; 16:158 – 64.

29 Gottlieb A, Chaudhari U, Baker D et al. The National PsoriasisFoundation Psoriasis Score (NPF-PS) system versus the PsoriasisArea Severity Index (PASI) and Physician’s Global Assessment(PGA): a comparison. J Drugs Dermatol 2003; 2:260 – 6.

30 Lebwohl M, Sherer D, Washenik K et al. A randomized, double-blind, placebo-controlled study of clobetasol propionate 005%foam in the treatment of nonscalp psoriasis. Int J Dermatol 2002;41:269 – 74.

31 Jarratt MT, Clark SD, Savin RC et al. Evaluation of the efficacy andsafety of clobetasol propionate spray in the treatment of plaque-type psoriasis. Cutis 2006; 78:348 – 54.

32 Kragballe K, Barnes L, Hamberg KJ et al. Calcipotriol cream with or

without concurrent topical corticosteroid in psoriasis: tolerabilityand efficacy. Br J Dermatol 1998; 139:649 – 54.

33 Ortonne P, Kaufmann R, Lecha M, Goodfield M. Efficacy of treat-ment with calcipotriol/betamethasone dipropionate followed bycalcipotriol alone compared with tacalcitol for the treatment of psoriasis vulgaris: a randomised, double-blind trial. Dermatology2004; 209:308 – 13.

34 Camarasa JM, Ortonne JP, Dubertret L. Calcitriol shows greaterpersistence of treatment effect than betamethasone dipropionate intopical psoriasis therapy. J Dermatolog Treat 2003; 14:8 – 13.

35 Molin L. Does addition of topical calcipotriol to UVB increase therisk of irritant reactions in psoriasis? The Calcipotriol-UVB studygroup Acta Derm Venereol 1997; 77:401 – 2.

36 Kragballe K, Gjertsen BT, de Hoop D et al. Double-blind, right/left

comparison of calcipotriol and betamethasone valerate in treatmentof psoriasis vulgaris. Lancet 1991; 337:193 – 6.37 Cunliffe WJ, Berth-Jones J, Claudy A et al. Comparative study of

calcipotriol (MC 903) ointment and betamethasone 17-valerateointment in patients with psoriasis vulgaris. J Am Acad Dermatol1992; 26:736 – 43.

38 Douglas WS, Poulin Y, Decroix J et al. A new calcipotriol/beta-methasone formulation with rapid onset of action was superior tomonotherapy with betamethasone dipropionate or calcipotriol inpsoriasis vulgaris. Acta Derm Venereol 2002; 82:131 – 5.

39 Ruzicka T, Lorenz B. Comparison of calcipotriol monotherapy anda combination of calcipotriol and betamethasone valerate after2 weeks’ treatment with calcipotriol in the topical therapy of psoriasis vulgaris: a multicentre, double-blind, randomized study.Br J Dermatol 1998; 138:254 – 8.

40 Tham SN, Lun KC, Cheong WK. A comparative study of calcipotri-ol ointment and tar in chronic plaque psoriasis. Br J Dermatol 1994;131:673 – 7.

41 Alora-Palli MB, Perkins AC, Van Cott A, Kimball AB. Efficacy andtolerability of a cosmetically acceptable coal tar solution in thetreatment of moderate plaque psoriasis: a controlled comparisonwith calcipotriene (calcipotriol) cream. Am J Clin Dermatol 2010;11:275 – 83.

42 Pinheiro N. Comparative effects of calcipotriol ointment (50 lg/g)and 5% coal tar/2% allantoin/05% hydrocortisone cream in treat-ing plaque psoriasis. Br J Clin Pract 1997; 51:16 – 19.

43 Hutchinson P, Marks R, White J. The efficacy, safety and toleranceof calcitriol 3 lg/g ointment in the treatment of plaque psoriasis:a comparison with short-contact dithranol. Dermatology 2000;201:139 – 45.

44 Wall AR, Poyner TF, Menday AP. A comparison of treatment withdithranol and calcipotriol on the clinical severity and quality of lifein patients with psoriasis. Br J Dermatol 1998; 139:1005 – 11.

45 Berth-Jones J, Chu AC, Dodd WA et al. A multicentre, parallel-group comparison of calcipotriol ointment and short-contact dithr-

anol therapy in chronic plaque psoriasis. Br J Dermatol 1992;127:266 – 71.

46 Christensen OB, Mork N-J, Ashton R et al. Comparison of a treat-ment phase and a follow-up phase of short-contact dithranol andcalcipotriol in outpatients with chronic plaque psoriasis. J DermatologTreat 1999; 10:261 – 5.

47 Oranje AP, Marcoux D, Svensson A et al. Topical calcipotriol inchildhood psoriasis. J Am Acad Dermatol 1997; 36:203 – 8.

48 Menter A, Abramovits W, Colon LE et al. Comparing clobetasolpropionate 005% spray to calcipotriene 0005% betamethasonedipropionate 0064% ointment for the treatment of moderate tosevere plaque psoriasis. J Drugs Dermatol 2009; 8:52 – 7.

49 Thawornchaisit P, Harncharoen K. A comparative study of tar andbetamethasone valerate in chronic plaque psoriasis: a study in

Thailand. J Med Assoc Thai 2007; 90:1997 –

2002.50 Beutner K, Chakrabarty A, Lemke S, Yu K. An intra-individual ran-

domized safety and efficacy comparison of clobetasol propionate005% spray and its vehicle in the treatment of plaque psoriasis. J Drugs Dermatol 2006; 5:357 – 60.

51 Bruce S, Epinette WW, Funicella T et al. Comparative study of cal-cipotriene (MC 903) ointment and fluocinonide ointment in thetreatment of psoriasis. J Am Acad Dermatol 1994; 31:755 – 9.

52 Jorizzo JL, Magee K, Stewart DM et al. Clobetasol propionate emol-lient 0.05 percent: hypothalamic-pituitary-adrenal-axis safety andfour-week clinical efficacy results in plaque-type psoriasis. Cutis1997; 60:55 – 60.

53 Kragballe K, Noerrelund KL, Lui H et al. Efficacy of once-dailytreatment regimens with calcipotriol/betamethasone dipropionate

ointment and calcipotriol ointment in psoriasis vulgaris. Br J Derma-tol 2004; 150:1167 – 73.54 Salmhofer W, Maier H, Soyer HP et al. Double-blind, placebo-con-

trolled, randomized, right-left study comparing calcipotriol mono-therapy with a combined treatment of calcipotriol anddiflucortolone valerate in chronic plaque psoriasis. Acta Derm VenereolSuppl (Stockh) 2000; 211:5 – 8.

55 van de Kerkhof PC, van der Valk PG, Swinkels OQ et al. A compar-ison of twice-daily calcipotriol ointment with once-daily short-contact dithranol cream therapy: a randomized controlled trial of supervised treatment of psoriasis vulgaris in a day-care setting. Br JDermatol 2006; 155:800 – 7.

56 van de Kerkhof PC, Werfel T, Haustein UF et al. Tacalcitol oint-ment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety. Br J Dermatol1996; 135:758 – 65.

57 Katz HI, Prawer SE, Medansky RS et al. Intermittent corticosteroidmaintenance treatment of psoriasis: a double-blind multicentertrial of augmented betamethasone dipropionate ointment in apulse dose treatment regimen. Dermatologica 1991; 183:269 – 74.

58 Kragballe K, Austad J, Barnes L et al. A 52-week randomized safetystudy of a calcipotriol/betamethasone dipropionate two-compoundproduct (Dovobet/Daivobet/Taclonex) in the treatment of psoria-sis vulgaris. Br J Dermatol 2006; 154:1155 – 60.

59 Kragballe K, Austad J, Barnes L et al. Efficacy results of a 52-week,randomised, double-blind, safety study of a calcipotriol/betameth-

© 2013 The Authors





14/14

asone dipropionate two-compound product (Daivobet/Dovobet/Taclonex) in the treatment of psoriasis vulgaris. Dermatology 2006;213:319 – 26.

60 Griffiths CE, Finlay AY, Fleming CJ et al. A randomized, investiga-tor-masked clinical evaluation of the efficacy and safety of clobeta-sol propionate 005% shampoo and tar blend 1% shampoo in thetreatment of moderate to severe scalp psoriasis. J Dermatolog Treat2006; 17:90 – 5.

61 Buckley C, Hoffmann V, Shapiro J et al. Calcipotriol plus betameth-

asone dipropionate scalp formulation is effective and well toleratedin the treatment of scalp psoriasis: a phase II study. Dermatology2008; 217:107 – 13.

62 Franz TJ, Parsell DA, Halualani RM et al. Betamethasone valeratefoam 012%: a novel vehicle with enhanced delivery and efficacy.Int J Dermatol 1999; 38:628 – 32.

63 Franz TJ, Parsell DA, Myers JA, Hannigan JF. Clobetasol propionatefoam 005%: a novel vehicle with enhanced delivery. Int J Dermatol2000; 39:535 – 8.

64 Green C, Ganpule M, Harris D et al. Comparative effects of calci-potriol (MC903) solution and placebo (vehicle of MC903) in thetreatment of psoriasis of the scalp. Br J Dermatol 1994; 130:483 – 7.

65 Jarratt M, Breneman D, Gottlieb AB et al. Clobetasol propionateshampoo 005%: a new option to treat patients with moderate to

severe scalp psoriasis. J Drugs Dermatol 2004; 3:367 –

73.66 Jemec GB, Ganslandt C, Ortonne JP et al. A new scalp formulation

of calcipotriene plus betamethasone compared with its activeingredients and the vehicle in the treatment of scalp psoriasis: arandomized, double-blind, controlled trial. J Am Acad Dermatol2008; 59:455 – 63.

67 Klaber MR, Hutchinson PE, Pedvis-Leftick A et al. Comparativeeffects of calcipotriol solution (50 lg mL1) and betamethasone17-valerate solution (1 mg mL1) in the treatment of scalp psoria-sis. Br J Dermatol 1994; 131:678 – 83.

68 Kragballe K, Hoffmann V, Ortonne JP et al. Efficacy and safety of calcipotriol plus betamethasone dipropionate scalp formulationcompared with calcipotriol scalp solution in the treatment of scalppsoriasis: a randomized controlled trial. Br J Dermatol 2009;

161:159 –

66.69 McKinnon C, Klaber MR. Calcipotriol (Dovonex) scalp solution inthe treatment of scalp psoriasis: comparative efficacy with 1% coaltar/1% coconut oil/05% salicylic acid (Capasal) shampoo, andlong-term experience. J Dermatolog Treat 2000; 11:21 – 8.

70 Olsen EA, Cram DL, Ellis CN et al. A double-blind, vehicle-con-trolled study of clobetasol propionate 005% (Temovate) scalpapplication in the treatment of moderate to severe scalp psoriasis. J Am Acad Dermatol 1991; 24:443 – 7.

71 Reygagne P, Mrowietz U, Decroix J et al. Clobetasol propionateshampoo 005% and calcipotriol solution 0005%: a randomizedcomparison of efficacy and safety in subjects with scalp psoriasis. J Dermatolog Treat 2005; 16:31 – 6.

72 Sofen H, Hudson CP, Cook-Bolden FE et al. Clobetasol propionate005% spray for the management of moderate-to-severe plaquepsoriasis of the scalp: results from a randomized controlled trial. J Drugs Dermatol 2011; 10:885 – 92.

73 Tyring SK, Mendoza N, Appell M et al. A calcipotriene/betametha-sone dipropionate two-compound scalp formulation in the treat-ment of scalp psoriasis in Hispanic/Latino and Black/AfricanAmerican patients: results of the randomized, 8-week, double-blind phase of a clinical trial. Int J Dermatol 2010; 49:1328 – 33.

74 van de Kerkhof PC, Hoffmann V, Anstey A et al. A new scalpformulation of calcipotriol plus betamethasone dipropionatecompared with each of its active ingredients in the same vehi-cle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial. Br J Dermatol 2009; 160:170 – 6.

75 Poulin Y, Papp K, Bissonnette R et al. Clobetasol propionate sham-poo 0.05% is efficacious and safe for long-term control of moder-ate scalp psoriasis. J Dermatolog Treat 2010; 21:185 – 92.

76 Luger TA, Cambazard F, Larsen FG et al. A study of the safety and

efficacy of calcipotriol and betamethasone dipropionate scalp for-mulation in the long-term management of scalp psoriasis. Dermatol-ogy 2008; 217:321 – 8.

77 Smith DR, Bottomley JM, Auland M et al. Heterogeneity in thetreatment of moderately severe scalp psoriasis in Scotland – resultsof a survey of Scottish health professionals. Curr Med Res Opin 2011;27:239 – 49.

78 British Association of Dermatologists, Primary Care DermatologySociety. Recommendations for the Initial Management of Psoriasis. London:British Association of Dermatologists, 2010.

Supporting Information

Additional Supporting Information may be found in the onlineversion of this article at the publisher’s website:

Fig S1. Trunk and limb psoriasis – odds ratios for clear/nearly clear as measured by IAGI or PGA, results of conven-tional and network meta-analyses.

Fig S2. Scalp psoriasis – odds ratios for clear/nearly clear asmeasured by IAGI or PGA, results of conventional and net-work meta-analyses.

Fig S3. Network of evidence for investigator’s assessmentof clear or nearly clear status for trunk and limb psoriasis(base case).

Fig S4. Rank density plots for investigator assessed response – trunk and limb psoriasis.

Fig S5. Network of evidence for patient’s assessment of clearor nearly clear status for trunk and limb psoriasis (base case).

Fig S6. Network of evidence for investigator’s assessment of clear or nearly clear status for scalp psoriasis (base case).

Fig S7. Rank density plots for investigator assessed response – scalp psoriasis.

Table S1. Full search strategy (using Embase (OVID) as anexample).

Table S2. Included study characteristics – trunk and limbpsoriasis.

Table S3. Included study characteristics – scalp psoriasis.Table S4. Proportion achieving clear or nearly clear at differ-

ent time-points during the trials.Table S5. Absolute response rates for all interventions forpsoriasis of the trunk and limbs.

Appendix S1. WinBUGS code for investigator assessment of trunk and limb psoriasis.

Appendix S2. WinBUGS code for investigator assessment of scalp psoriasis.

© 2013 The Authors




Baru Psoriasis

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