JEADV ORIGINAL ARTICLE. Abstract

Similar documents
75th AAD Annual Meeting

Catherine Queille-Roussel Martin Olesen John Villumsen Jean-Philippe Lacour

Calcipotriol Plus Betamethasone Dipropionate Aerosol Foam in Patients with Moderate-to-Severe Psoriasis: Sub-Group Analysis of the PSO-ABLE Study

Patient Preferences for Topical Psoriasis Treatments are Diverse and Difficult to Predict

Month/Year of Review: January 2015 Date of Last Review: January 2010

Clinical Trial Report Synopsis. Patient insights following use of LEO aerosol foam and Daivobet gel in subjects with psoriasis vulgaris

Psoriasis is a lifelong condition, with onset

Pooled safety analysis of calcipotriol plus betamethasone dipropionate gel for the treatment of psoriasis on the body and scalp

Original Article % 88 74% >50 40 (1) (2) (3) Hong Kong J. Dermatol. Venereol. (2016) 24,

Expert recommendations: the use of the fixed combination calcipotriol and betamethasone dipropionate gel for the topical treatment of psoriasis

Location of study report in Regulatory Dossier for authorities

Adherence to Topical Therapies for the Treatment of Psoriasis: Surveys of Physicians and Patients

UnitedHealthcare Pharmacy Clinical Pharmacy Programs

Using Your ESP* in Pharmacy: How to Improve Treatment Adherence and Patient Outcomes in Psoriasis (*Expanded Scope of Practice)

Summer AAD Summer AAD Support provided by LEO Pharma A/S. Poster nº

Clinical Trial Report Synopsis

Clinical Trial Report Synopsis

COMPARATIVE STUDY OF THE EFFICACY OF VARIOUS TOPICAL TREATMENT MODALITIES AND PHOTOTHERAPY FOR PSORIASIS VULGARIS: A REVIEW

Clinical Policy: Brodalumab (Siliq) Reference Number: CP.PHAR.375 Effective Date: Last Review Date: 05.18

See Important Reminder at the end of this policy for important regulatory and legal information.

A study of treatment modalities in psoriasis in dermatology outpatient department of a tertiary care teaching hospital

Comparative Efficacy of Topical Calcipotriol (0.005%) Versus Topical Corticosteroid (Betamethasone 0.1%) in Treating Plaque Type Psoriasis

Literature Scan: Topical Corticosteroids. Month/Year of Review: March 2015 Date of Last Review: March 2013 Source Document: OSU College of Pharmacy

Clinical Policy: Ixekizumab (Taltz) Reference Number: ERX.SPA.122 Effective Date:

Approximately 3% of the US adult population,

Body Region Involvement and Quality of Life in Psoriasis: Analysis of a Randomized Controlled Trial of Adalimumab

Clinical Policy: Secukinumab (Cosentyx) Reference Number: ERX.SPA.165 Effective Date:

PUVA: Shall we still use it for psoriasis in 2019?

Clinical Policy: Secukinumab (Cosentyx) Reference Number: ERX.SPA.165 Effective Date:

This PDF is available for free download from a site hosted by Medknow Publications

Clinical Policy: Secukinumab (Cosentyx) Reference Number: CP.PHAR.261 Effective Date: 08/16 Last Review Date: 08/17

Patient reported outcomes in chronic skin diseases: ehealth applications for clinical practice van Cranenburgh, O.D.

A systematic review of treatments for severe psoriasis Griffiths C E, Clark C M, Chalmers R J, Li Wan Po A, Williams H C

The reliability of three psoriasis assessment tools: Psoriasis area and severity index, body surface area and physician global assessment

Clinical Policy: Ixekizumab (Taltz) Reference Number: CP.PHAR.257 Effective Date: Last Review Date: 05.18

ADHERENCE TO prescribed medication regimens. Assessing adherence to dermatology treatments: a review of self-report and electronic measures

Apprehension of the disease by patients suffering from psoriasis

EXAMINING THE CRUCIAL COALITION BETWEEN DERMATOLOGY AND RHEUMATOLOGY IN PSORIATIC ARTHRITIS

Enstilar , Version 3 PUBLIC SUMMARY OF RISK MANAGEMENT PLAN

The Natural History of Psoriasis and Treatment Goals

Evaluating Psoriasis: Patient Reported Outcomes and Impact of Disease

Drug Class Literature Scan: Topical Antipsoriatics

The Prevalence of Psoriasis and Vitiligo in a Rural Area in Turkey

Psoriasis in Jordan: a single center experience

Guselkumab for treating moderate to severe plaque psoriasis [ID1075]

A Pilot Study. Name of investigational product:

Corporate Medical Policy

Pharmacy Medical Necessity Guidelines: Stelara (ustekinumab)

PSORIASIS BEST PRACTICE IN MANAGEMENT

To order reprints or e-prints of JDD articles please contact JDD

QUALITY OF LIFE AMONG ADULT PATIENTS WITH PSORIASIS

5 European S3-Guidelines on the Systemic Treatment of Psoriasis Vulgaris

Clinical Policy: Apremilast (Otezla) Reference Number: CP.PHAR.245 Effective Date: 08/16 Last Review Date 08/17

Keywords: Psoriasis vulgaris Zinc pyrithione Betamethasone dipropionate

The Treatment Toolbox for Severe Pediatric Psoriasis

Etanercept: a new option in paediatric plaque psoriasis

Calcipotriene/betamethasone Combo Improves QOL.(PSORIASIS): An Article From: Skin & Allergy News [HTML] [Digital] By Heidi Splete READ ONLINE

Is Apremilast (Otezla) Effective in Reducing Pruritus in Adults over 18 Years Old with Plaque Psoriasis?

Psoriasis SEPTEMBER 2018

Ustekinumab for severe treatment-resistant psoriasis: a 24-week pilot study in Hong Kong Chinese

Clinical Policy: Ixekizumab (Taltz) Reference Number: CP.PHAR.257 Effective Date: Last Review Date: 11.18

COS DERM. Do Not Copy

Clinical Policy: Ustekinumab (Stelara) Reference Number: ERX.SPMN.167

P4081 Secukinumab skin clearance is associated with greater improvements in patient-reported pain, itching, and scaling

Psoriasis. Jessica Kaffenberger, M.D. Assistant Professor of Dermatology Division of Dermatology The Ohio State University Wexner Medical Center

EFFICACY AND SAFETY OF CLOBETASOL PROPIONATE SHAMPOO IN THERAPY OF PSORIASIS OF THE SCALP

Trial ID: LP May-2016 Page 2 of 5

Insights from the Kaiser Permanente database

Details of UNCOVER-2 and UNCOVER-3 Study Results Published in The Lancet

Location of study report in Regulatory Dossier for authorities. Vohune: Page:

Brodalumab for treating moderate to severe plaque psoriasis [ID878]

Horizon Scanning Centre January Apremilast for psoriasis SUMMARY NIHR HSC ID: 2652

Review Article. Psoriasis and quality of life. Introduction. D Butler, R Gupta, E Levin, M Huynh, A Leon, J Koo

Pharmacy Medical Necessity Guidelines: Stelara (ustekinumab)

Clinical Policy: Acitretin (Soriatane) Reference Number: CP.PMN.40. Line of Business: Medicaid

Clinical Policy: Apremilast (Otezla) Reference Number: CP.PHAR.245 Effective Date: Last Review Date: Line of Business: HIM, Medicaid

Individual Study Table Referring to Part of the Dossier. Volume: Page:

Clinical Study Report Synopsis. Effect of LEO on the HPA axis and Calcium Metabolism in Subjects with Extensive Psoriasis Vulgaris

Psoriasis Disease Severity Affects Patient Satisfaction With Therapy

Topical Therapies for Psoriasis: Improving Management Strategies and Patient Adherence

Original Policy Date

USTEKINUMAB Generic Brand HICL GCN Exception/Other USTEKINUMAB STELARA GUIDELINES FOR USE

Effect of etanercept therapy on psoriasis symptoms in patients from Latin America, Central Europe, and Asia: a subset analysis of the PRISTINE trial

Change/Insert Date & Location via >Insert >Header & Footer To view drawing guides

Developments in Psoriasis Management Celgene Corporation 07/14 USII-CELG140030

Breakthrough Drugs in Dermatology. Mark Lebwohl, MD

Comparative study of oral methotrexate and acitretin in the treatment of palmoplantar psoriasis

Clinical Policy: Etanercept (Enbrel) Reference Number: PA.CP.PHAR.250 Effective Date: 01/18 Last Review Date: 08/17 Line of Business: Medicaid

Mark G. Lebwohl 1 Arthur Kavanaugh

The role of the practice nurse in managing psoriasis in primary care

Clinical Policy: Ustekinumab (Stelara) Reference Number: CP.PHAR.264

Horizon Scanning Centre March Tildrakizumab for moderate to severe plaque psoriasis SUMMARY NIHR HSC ID: 6798

Psoriasis. Dr. Pablo de la Cueva Hospital Universitario Infanta Leonor Madrid

Clinical Policy: Secukinumab (Cosentyx) Reference Number: CP.PHAR.261 Effective Date: Last Review Date: Line of Business: HIM, Medicaid

What is Cosentyx (secukinumab)?

See Important Reminder at the end of this policy for important regulatory and legal information.

Follow this and additional works at: Part of the Medicine and Health Sciences Commons

2 SYNOPSIS. Study code : MC 9308 FR.

First Real-World Insights on Apremilast Therapy for Patients With Plaque Psoriasis From the LAPIS-PSO Study: An Interim Analysis

Transcription:

DOI: 1.1111/jdv.1323 JEADV ORIGINAL ARTICLE Real-life effectiveness of once-daily calcipotriol and betamethasone dipropionate gel vs. ointment formulations in psoriasis vulgaris: final analysis of the 52-week PRO-long study J. Lambert, 1, * C.W. Hol, 2 J. Vink 3 1 Department of Dermatology, Ghent University Hospital, Ghent, Belgium 2 LEO Pharma BV, Amsterdam, Netherlands 3 Department of Dermatology, Medical Centrum Haaglanden, Westeinde Hospital, The Hague, Netherlands *Correspondence: J. Lambert. E-mail: jo.lambert@uzgent.be Abstract Background Topical therapies are the mainstay of treatment for psoriasis vulgaris. The fixed combination of calcipotriol (Cal) 5 lg/g plus betamethasone.5 mg/g (as dipropionate; BD) is a first-line topical treatment and available as a gel or ointment. The use of these fixed combination products was compared in PRO-long, a long-term noninterventional study, for which interim results (4 and 12 weeks) have previously been reported. Objective To describe and compare patients perspectives on the fixed combination gel and ointment formulations; to include efficacy, adherence behaviour, treatment satisfaction and health-related quality of life (HRQoL) aspects during long-term real-life psoriasis management. Methods PRO-long was a multicentre, prospective, observational, 52-week study of patients prescribed fixed combination Cal/BD gel or ointment in clinical practice. For final analysis the following were assessed at weeks 24, 36 and 52: differences in the proportion of patients with mild / very mild disease according to patient s global assessment of disease severity, adherence behaviour, treatment satisfaction (nine-item treatment satisfaction questionnaire for medication) and HRQoL (Skindex-29). Results Patients (n = 328) were prescribed once-daily Cal/BD gel (n = 152) or ointment (n = 176). At week 52, a higher proportion of patients reported that the severity of their psoriasis was mild / very mild vs. baseline (gel: 6.2 vs. 47.1%; ointment: 58.8 vs. 42.4%), with greater treatment satisfaction reported in patients using gel vs. those using ointment. A higher proportion of patients found the gel easy to use compared with the ointment (66.7 vs. 45.2%). Daily application of treatment took 5 min for 86.1% of patients using gel and 71.% of patients using ointment. Conclusion This real-life study has demonstrated similar effectiveness between the Cal/BD formulations. However, over a 52-week treatment period, patients reported greater treatment satisfaction with the gel, which was considered easier to use, faster to apply and overall a more convenient product. Received: 18 March 215; Accepted: 22 May 215 Conflicts of interest C.W. Hol is an employee of LEO Pharma BV. J. Lambert and J. Vink have no conflicts of interest to declare. Funding sources This research was funded by LEO Pharma BV. Introduction Psoriasis is a chronic skin disorder with inflammatory involvement 1 with a global incidence of 1 3%. 1 3 Psoriasis vulgaris, the Previous presentations and publications: Poster presentation of interim analysis at EADV 213; Poster presentation of final analysis at EADV 214; Interim analysis original article in JEADV 214. 19 most common form of psoriasis, manifests in sharply demarcated, scaly plaques, usually present on the scalp, limbs and trunk. 4 These plaques are the result of epidermal hyperplasia with abnormal keratinocyte differentiation; infiltration of inflammatory cells into the epidermis and dermis; and increased dermal vascularity. 5,6 Psoriasis is associated with a number of comorbidities and psychological disorders, 4 and impacts the JEADV 215, 29, 2349 2355 215 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

235 Lambert et al. patient s ability to perform daily activities and form social relationships. 7 Psoriasis has been reported to reduce patient healthrelated quality of life (HRQoL) to an extent comparable with diseases, such as depression and cancer. 8 Treatment nonadherence is a universal medical issue, particularly in chronic disorders. For patients prescribed topical treatment, nonadherence is further exacerbated by the requirement of application, which can be time-consuming and cumbersome. This is a challenge in psoriasis as topicals are the mainstay of treatment for mild-to-moderate disease. 9 A real-life study showed that 46% of psoriasis patients were not fully adherent to their prescribed topical therapy, applying treatment only when they felt it necessary. 1 The choice of vehicle is one of the key factors affecting patient adherence to topical psoriasis treatment. A number of formulations are available, including creams, gels and ointments, although some are perceived as less convenient and more difficult to apply than others; 11,12 patients generally prefer a gel, for example, to an ointment. 13,14 Treatment nonadherence impacts the real-life effectiveness of a drug (defined as a function of drug efficacy [determined by randomized clinical trial results] and patient safety and compliance ). 15 Clinical trials provide a stringent environment in which to determine drug efficacy and tolerability, but do not accurately reflect real-life conditions 16 and evidence of patient use from daily clinical practice is limited. Fixed combination calcipotriol (5 lg/g) plus betamethasone (.5 mg/g; as dipropionate), available in gel and ointment formulations, is a recommended first-line treatment for mild-tomoderate psoriasis vulgaris. 9,17,18 PRO-long (Patient-Reported Outcomes in a long-term study) was the first direct real-life study to compare patients perspectives on the gel to that of the ointment formulation of this fixed combination, for up to 52 weeks of treatment. From interim analysis (4 and 12 weeks), patients found the gel more convenient, easier and faster to apply than the ointment. 19 Here, we report the final analysis of this noninterventional study, including assessments at 24, 36 and 52 weeks after initiation of treatment. Materials and methods Full details of the methods have previously been reported with the interim analysis. 19 In brief, psoriasis patients aged 18 years and eligible for topical treatment were prescribed fixed combination calcipotriol (5 lg/g) plus betamethasone (.5 mg/g; as dipropionate) gel or ointment once daily, for up to 52 weeks. Baseline disease severity was evaluated using the physician s global assessment of disease severity (PGA; 5-point scale: very mild, mild, moderate, severe, very severe), and extent of body surface area affected with psoriasis. Assessments conducted for interim analysis (4 and 12 weeks) were also conducted at weeks 24, 36 and 52. Efficacy was evaluated according to patient s global assessment of disease severity (PaGA; same 5-point scale as PGA). Adherence behaviour was assessed using a study-specific questionnaire. 19 Treatment satisfaction was assessed using the nine-item treatment satisfaction questionnaire for medication (TSQM-9), 2 consisting of three domains: effectiveness, convenience and overall satisfaction (overall satisfaction questions were completed at week 52 only). HRQoL was assessed using the Skindex-29 questionnaire, consisting of three domains: emotions, symptoms and functioning. 21 Statistical analysis was performed as for the interim analysis. 19 The chi-squared test was used to compare the proportion of patients with controlled disease between treatments and McNemar s test was used to confirm the statistical significance of changes in the proportion of patients with controlled disease from baseline. 19 For patients who had not completed week-52 questionnaires, PaGA was imputed using the last observation carried forward method. No imputation was applied to the other parameters assessed; missing data were treated as missing completely at random and not replaced. Final analysis endpoints The primary endpoint was the difference in the proportion of patients with controlled disease (defined as mild or very mild according to PaGA) between the gel and ointment at week 52. Secondary endpoints included patients perspectives on adherence behaviour, treatment satisfaction and HRQoL at weeks 24, 36 and 52, compared with baseline, as well as differences in the proportion of patients with controlled disease between the gel and the ointment at weeks 24 and 36. Results Patients In total, 328 patients (gel, n = 152; ointment, n = 176) were included in this study. Patient baseline characteristics across treatment groups were generally well-balanced (Table 1). In this 52-week, noninterventional study, noncompletion was observed for a large proportion of patients (73%; Fig. 1); post-hoc analysis revealed that baseline characteristics were similar for completers and noncompleters (Table 2). Efficacy A significant increase in the proportion of patients with controlled disease ( mild or very mild compared with baseline, according to PaGA) was seen with the gel (increase: 13.1%; P =.9) and the ointment (increase: 16.4%; P =.3) at week 52 (Fig. 2a,b). This significant increase was also seen at earlier time points (week 24: 16. [gel] and 14.7% [ointment]; P =.9 and P =.7; week 36: 12.3 and 18.1%; P =.164 and P <.1; Fig. 2c). There were no statistically significant differences in the proportion of patients with controlled disease between treatment groups at any time point (Fig. 2c). JEADV 215, 29, 2349 2355 215 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd

Final results from the PRO-long study 2351 Table 1 Patient demographics and baseline clinical characteristics (by treatment) Patients using gel (n = 152) Patients using ointment (n = 176) All patients (n = 328) Gender, n (%) Male 91 (59.9) 98 (55.7) 189 (57.6) Female 61 (4.1) 78 (44.3) 139 (42.4) Median age, years (range) 47 (11 77) 42 (17 73) 44 (11 77) Study site, n (%) Belgium 2 (1.3) 78 (44.3) 8 (24.4) Netherlands 119 (78.3) 4 (22.7) 159 (48.5) Years suffering from psoriasis, n (%) <1 1 (6.6) 2 (11.4) 3 (9.1) 1 5 39 (25.7) 47 (26.7) 86 (26.2) 6 1 29 (19.1) 33 (18.8) 62 (18.9) 11 15 18 (11.8) 23 (13.1) 41 (12.5) 16 2 15 (9.9) 15 (8.5) 3 (9.1) >2 41 (27.) 38 (21.6) 79 (24.1) Percentage body surface area affected by psoriasis, n (%) 1 5 42 (27.6) 8 (45.5) 122 (37.2) 6 1 46 (3.3) 43 (24.4) 89 (27.1) 11 15 16 (1.5) 23 (13.1) 39 (11.9) 16 2 14 (9.2) 14 (8.) 28 (8.5) 21 3 24 (15.8) 9 (5.1) 33 (1.1) 31 4 8 (5.3) 4 (2.3) 12 (3.7) >4 2 (1.3) 2 (1.1) 4 (1.2) PGA disease severity, n (%) Very mild 18 (11.8) 24 (13.6) 42 (12.8) Mild 58 (38.2) 63 (35.8) 121 (36.9) Moderate 66 (43.4) 75 (42.6) 141 (43.) Severe 1 (6.6) 14 (8.) 24 (7.3) Very severe Comorbidity, n (%) Hypertension 23 (15.1) 3 (17.) 53 (16.2) Diabetes 1 (6.6) 8 (4.5) 18 (5.5) Dyslipidaemia 11 (7.2) 21 (11.9) 32 (9.8) None of the above 125 (82.2) 135 (76.7) 26 (79.3) Topicals used during the last year for psoriasis on the body Fixed combination calcipotriol plus betamethasone dipropionate, n (%) 4 (26.3) 55 (31.3) 95 (29.) Vitamin D analogues, n (%) 14 (9.2) 19 (1.8) 33 (1.1) Steroids, n (%) 6 (39.5) 66 (37.5) 126 (38.4) Combination of steroids and vitamin D analogues, n (%) 2 (1.3) 13 (7.4) 15 (4.6) Other, n (%) 7 (4.6) 1 (5.7) 17 (5.2) Prescribed systemic treatment at baseline Methotrexate, n (%) 16 (1.5) 12 (6.8) 28 (8.5) Cyclosporine, n (%) 1 (.7) 4 (2.3) 5 (1.5) Acitretin, n (%) 4 (2.6) 6 (3.4) 1 (3.) Fumaric acid, n (%) 12 (7.9) 1 (.6) 13 (4.) Biologicals, n (%) 9 (5.9) 8 (4.5) 17 (5.2) Other, n (%) 2 (1.3) 1 (.6) 3 (.9) Adherence behaviour Patient adherence to treatment was assessed using a study-specific questionnaire. 19 At week 52, a large proportion of patients (gel: 86.1%; ointment: 67.8%) reported that application of treatment was never or rarely too great a burden. No patients using gel reported that the burden of application was often or always too great compared with 16.1% of patients using ointment (Fig. 3a). Daily application of treatment took 5 min or less for 86.1% of patients using gel and 71.% of patients using ointment at 52 weeks (Fig. 3b). Treatment satisfaction Treatment satisfaction was assessed using TSQM-9 (comprising convenience, effectiveness and overall satisfaction [at week 52 only] domains). At week 52, patients found that the gel was significantly more convenient (P =.33) and effective (P =.3) than the ointment (Fig. 4a). At weeks 24 and 36, significant differences in convenience between the gel and ointment were also seen (P =.27 and P <.1, respectively). At week 52, a greater proportion of patients using the gel compared with those using ointment found it easy to use (66.7 vs. 45.2%), easy to plan treatment (61.1 vs. 38.7%), or easy to apply (72.2 vs. 45.2%), although this led to a significant difference in TSQM-9 mean scores for ease of application only (P =.19; Fig. 4b). Significantly favourable responses to the gel over ointment were seen in all TSQM-9 components for effectiveness at week 52 (Fig. 4c) and patient responses to application time were also significantly more positive for the gel compared with ointment at weeks 24 and 36 (P =.9 and P =.26, respectively). For week-52 overall satisfaction, patients rated the gel significantly greater at providing benefit than the ointment (P =.31; Fig. 4d) and were in favour of the gel, although not significantly so, when asked whether the positives of their treatment outweighed the negatives (P =.296). However, a numerical difference in favour of ointment was observed when patients evaluated their global satisfaction with treatment (P =.726), although the TSQM-9 mean overall satisfaction domain score was similar for both treatments (P =.192; Fig. 4a). HRQoL According to Skindex-29 assessment of HRQoL, improvements from baseline in mean scores at week 52 were greater for patients treated with the gel vs. ointment (Fig. 5), although these differences did not reach significance. Discussion This 52-week, noninterventional study compared patients perspectives on the use of calcipotriol (5 lg/g) plus betamethasone (.5 mg/g; as dipropionate) gel with ointment for the management of psoriasis vulgaris. Patients who completed this study reported greater treatment satisfaction with the gel compared JEADV 215, 29, 2349 2355 215 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd

2352 Lambert et al. ENROLMENT Prescribed treatment (n = 328) FOLLOW-UP Cal/BD gel (n = 152) Treatment use at Week 4 (n = 82) Gel only, n = 44 Gel plus other treatment, n = 32 Not necessary as clear/minimal disease, n = Treatment use at Week 12 (n = 76) Gel only, n = 38 Gel plus other treatment, n = 3 Not necessary as clear/minimal disease, n = 2 Treatment use at Week 24 (n = 61) Gel only, n = 28 Gel plus other treatment, n = 2 Not necessary as clear/minimal disease, n = 4 Treatment use at Week 36 (n = 49) Gel only, n = 24 Gel plus other treatment, n = 16 Not necessary as clear/minimal disease, n = 3 Treatment use at Week 52 (n = 45) Gel only, n = 21 Gel plus other treatment, n = 15 Not necessary as clear/minimal disease, n = 3 Cal/BD ointment (n = 176) Treatment use at Week 4 (n = 74) Ointment only, n = 32 Ointment plus other treatment, n = 36 Not necessary as clear/minimal disease, n = 1 Treatment use at Week 12 (n = 62) Ointment only, n = 27 Ointment plus other treatment, n = 26 Not necessary as clear/minimal disease, n = 6 Treatment use at Week 24 (n = 54) Ointment only, n = 29 Ointment plus other treatment, n = 13 Not necessary as clear/minimal disease, n = 7 Treatment use at Week 36 (n = 49) Ointment only, n = 24 Ointment plus other treatment, n = 15 Not necessary as clear/minimal disease, n = 4 Treatment use at Week 52 (n = 42) Ointment only, n = 2 Ointment plus other treatment, n = 11 Not necessary as clear/minimal disease, n = 3 Figure 1 Patient disposition. with ointment: it was considered easier to use, faster to apply and overall more convenient than the ointment. This supports the findings of the interim analysis, where a difference in convenience was observed in favour of the gel by the first assessment (week 4). 19 Treatment adherence in chronic diseases remains a challenge and adherence rates to topical treatments are low, with over a third of patients not using their medication as prescribed. 13 Even for short-term topical psoriasis treatment (up to 8 weeks) in clinical trials, patient adherence is still poor, ranging between 51 and 58%. 22 24 Furthermore, in a 52-week, randomized study, the withdrawal rate of patients using the fixed combination gel was 21.4 and 39.8% of those using calcipotriol gel. 25 For PROlong, being a 52-week, noninterventional study, high rates of noncompletion were expected; this was found to be the case, regardless of the overall preference for the gel; however, post-hoc analysis indicated that patient demographics and baseline characteristics were generally similar for completers compared to noncompleters and a sensitivity analysis supported the final analysis. Cosmetically elegant products, such as gels and creams, are generally considered less greasy, taking less time to apply than ointments. 13,26 As such, patients perceive gels and creams to be more acceptable than ointments for topical treatment. 11 PROlong supports the difference in application time between topical preparations, as more patients using the gel (86.1%) compared with the ointment (71.%) could apply their treatment within 5 min. Treatment effectiveness is a key aspect of adherence, as patients are more likely to continue with treatments that they judge to be beneficial. 27 In our study, there were patients using the ointment who reported good treatment satisfaction and completed the study. This finding is in agreement with previously reported incidental evidence that some patients like using the ointment and do not notice a cosmetic difference between formulations. 26 Furthermore, this finding demonstrates that resolving treatment adherence is not as simple as developing a more cosmetically elegant vehicle. Each patient has a different experience of previous treatments and their own expectations of the current course of treatment, and involving patients in treatment decisions may increase rates of adherence. 26 A recent expert review of the management of topical psoriasis treatment, using the fixed combination calcipotriol plus betamethasone dipropionate gel as a working example, highlighted the importance of tailoring treatment to the needs of each patient. 26 On the basis of our findings, as well as the recommendations presented within the recent expert review, 26 we suggest that patients are given a choice between gel and ointment formulations. A noninterventional study design is important to gain insight into real-life effectiveness, although this design has its limitations. Patients were prescribed gel or ointment at the dermatologists discretion and therefore bias may have been introduced during the selection process. This bias may have been augmented JEADV 215, 29, 2349 2355 215 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd

Final results from the PRO-long study 2353 Table 2 Patient demographics and baseline clinical characteristics (completers vs. noncompleters) Completers (n = 87) Noncompleters (n = 241) Gender, n (%) Male 53 (6.9) 136 (56.4) Female 34 (39.1) 15 (43.6) Median age, years (range) 52 (11 77) 42 (17 77) Study site, n (%) Belgium 32 (36.8) 48 (19.9) Netherlands 55 (63.2) 14 (43.2) Years suffering from psoriasis, n (%) <1 11 (12.6) 19 (7.9) 1 5 19 (21.8) 67 (27.8) 6 1 17 (19.5) 45 (18.7) 11 15 8 (9.2) 33 (13.7) 16 2 6 (6.9) 24 (1.) >2 26 (29.9) 53 (22.) Percentage body surface area affected by psoriasis, n (%) 1 5 33 (37.9) 89 (36.9) 6 1 26 (29.9) 63 (26.1) 11 15 14 (16.1) 25 (1.4) 16 2 5 (5.7) 23 (9.5) 21 3 7 (8.) 26 (1.8) 31 4 2 (2.3) 1 (4.1) >4 4 (1.7) PGA disease severity, n (%) Very mild 11 (12.6) 31 (12.9) Mild 4 (46.) 81 (33.6) Moderate 34 (39.1) 17 (44.4) Severe 2 (2.3) 22 (9.1) Very severe Comorbidity, n (%) Hypertension 15 (17.2) 38 (15.8) Diabetes 4 (4.6) 14 (5.8) Dyslipidaemia 5 (5.7) 27 (11.2) None of the above 7 (8.5) 19 (78.8) Topicals used for psoriasis of the body during the year prior to start of treatment Fixed combination calcipotriol plus betamethasone dipropionate, n (%) 29 (33.3) 66 (27.4) Vitamin D analogues, n (%) 7 (8.) 26 (1.8) Steroids, n (%) 35 (4.2) 91 (37.8) Combination of steroids 7 (8.) 8 (3.3) and vitamin D analogues, n (%) Other, n (%) 5 (5.7) 12 (5.) Prescribed systemic treatment at baseline Methotrexate, n (%) 5 (5.7) 23 (9.5) Cyclosporine, n (%) 1 (1.1) 4 (1.7) Acitretin, n (%) 3 (3.4) 7 (2.9) Fumaric acid, n (%) 3 (3.4) 1 (4.1) Biologicals, n (%) 7 (8.) 1 (4.1) Other, n (%) 3 (1.2) (a) % of patients with controlled (mild or very mild) disease 1 8 6 4 2 (c) Gel (n = 121) % of patients with controlled (mild or very mild) disease P =.9 47.1 6.2 1 8 6 4 2 Baseline Week 52 (b) Gel (n = 121) Ointment (n = 118) 47.1 42.4 % of patients with controlled (mild or very mild) disease 1 8 6 4 2 Baseline Wk 24 Wk 36 Wk 52 Ointment (n = 118) P =.3 Baseline Week 52 by the limited availability of the gel formulation in Belgium. Furthermore, incomplete follow-up is common in noninterventional studies and limits the power of these studies for 42.4 P =.34 P =.85 P =.83 63.1 6.5 6.2 ** 57.1 59.4 58.8 ** * *** * ** Figure 2 Proportion of patients with controlled disease (PaGA) (a) using gel, week 52 compared with baseline; (b) using ointment, week 52 compared with baseline and (c) using gel or ointment, weeks 24, 36 and 52 compared with baseline. *P <.5; **P <.1; ***P <.1 vs. baseline. BD, betamethasone.5 mg/g (as dipropionate); Cal, calcipotriol 5 lg/g. (a) (b) % of patients who reported not applying treatment because it was too great a burden % of patients who reported applying treatment for an average time per day of... 1 8 6 4 2 1 8 6 4 2 86.1 67.8 Never or rarely 86.1 71. Sometimes 58.8 Gel (n = 36) Ointment (n = 31) 13.9 16.1 16.1. Often or always 25.8 11.1 2.8 3.2 5 6 1 >1 Time (minutes) Figure 3 Patient adherence to treatment at week 52 (a) patientreported burden of treatment (b) patient-reported application time. JEADV 215, 29, 2349 2355 215 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd

2354 Lambert et al. (a) TSQM-9 mean domain score (c) TSQM-9 mean individual question score 1 8 6 4 2 Gel (n = 36) Ointment (n = 31) P =.33 P =.3 P =.192 88.58 77.24 8.9 62.9 Convenience 7 6 5 4 3 2 1 Effectiveness 57.64 51.39 Overall satisfaction 6.11 5.75 5.56 4.87 4.68 4.77 (b) TSQM-9 mean individual question score (d) P =.15 P =.2 P <.1 Treatment ability Symptom relief Application time TSQM-9 mean individual question score 7 6 5 4 comparator analysis. However, as previously discussed, post-hoc analysis showed no difference in baseline characteristics between completers and noncompleters, and the sample sizes for both 3 2 1 P =.78 P =.58 P =.19 6.31 6.19 6.44 5.71 5.52 5.68 Ease of use 5 4 3 2 1 Planning Ease of application P =.31 P =.296 P =.726 4.11 3.58 3.72 3.48 3.4 3.52 Provides benefit Positive outweighs negative Global satisfaction Figure 4 Treatment satisfaction at week 52 (a) total convenience, effectiveness, and overall satisfaction domain scores (b) individual convenience scores (c) individual effectiveness scores (d) individual overall satisfaction scores. TSQM-9, nine-item treatment satisfaction questionnaire for medication. Gel (n = 45) Ointment (n = 42) Mean change from baseline in Skindex-29 score -2-4 -6-8 7. Emotions 5.6 5.4 Symptoms 3.6 4.4 Functioning 1.4 5.6 P =.72 P =.618 P =.315 P =.372 Composite score Figure 5 Patient-reported quality of life, week 52 compared with baseline. 3.4 groups were similar at week 52, indicating similar rates of noncompletion for both treatments. This study has drawn on the perspectives of patients managing their psoriasis with the use of topical therapy, over a long treatment period. It provides a valuable insight into the behaviour of psoriasis patients and their perspectives on the fixed combination gel and ointment formulations. Patients found the gel to be more convenient than the ointment, as it was easier to use, faster to apply and had similar efficacy. Both formulations are effective in daily clinical practice and decisions on which formulation to prescribe should be made on a per-patient basis. Acknowledgements This study was sponsored by LEO Pharma. We would like to thank Mirjam Griekspoor and Patricia Dockx (LEO Pharma), who facilitated the conduct of the study. Additionally, writing assistance was provided by Carly Hayes, PhD, from Mudskipper Business Ltd, funded by LEO Pharma. References 1 Sch on MP, Boehncke W-H. Psoriasis. N Engl J Med 25; 352: 1899 1912. 2 Gelfand JM, Weinstein R, Porter SB, Neimann AL, Berlin JA, Margolis DJ. Prevalence and treatment of psoriasis in the United Kingdom: a population-based study. Arch Dermatol 25; 141: 1537 1541. 3 Sch afer T. Epidemiology of psoriasis. Review and the German perspective. Dermatology 26; 212: 327 337. 4 Menter A, Gottlieb A, Feldman SR et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 28; 58: 826 85. 5 Elder JT, Bruce AT, Gudjonsson JE et al. Molecular dissection of psoriasis: integrating genetics and biology. J Invest Dermatol 21; 13: 1213 1226. 6 Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet 27; 37: 263 271. 7 Kimball AB, Jacobson C, Weiss S, Vreeland MG, Wu Y. The psychosocial burden of psoriasis. Am J Clin Dermatol 25; 6: 383 392. 8 Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol 1999; 41: 41 47. 9 Menter A, Korman NJ, Elmets CA et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 29; 6: 643 659. 1 Bewley A, Burrage DM, Ersser SJ, Hansen M, Ward C. Identifying individual psychosocial and adherence support needs in patients with psoriasis: a multinational two-stage qualitative and quantitative study. J Eur Acad Dermatol Venereol 213; 28: 763 77. 11 Hol K. Patient preference for topical psoriasis formulations. Poster presented at the EADV Congress, Gothenburg, Sweden, 6 1 October 21; abst: P572. 12 Housman TS, Mellen BG, Rapp SR, Fleischer AB Jr, Feldman SR. Patients with psoriasis prefer solution and foam vehicles: a quantitative assessment of vehicle preference. Cutis 22; 7: 327 332. 13 Bewley A, Page B. Maximizing patient adherence for optimal outcomes in psoriasis. J Eur Acad Dermatol Venereol 211; 25(Suppl. 4): 9 14. JEADV 215, 29, 2349 2355 215 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd

Final results from the PRO-long study 2355 14 Sandoval LF, Huang KE, Harrison J, Clark A, Feldman SR. Calcipotriene.5%-betamethasone dipropionate.64% ointment versus topical suspension in the treatment of plaque psoriasis: a randomized pilot study of patient preference. Cutis 214; 94: 34 39. 15 Stein Gold L, Corvari L. The roles of safety and compliance in determining effectiveness of topical therapy for psoriasis. Cutis 27; 79: 32 38. 16 Devaux S, Castela A, Archier E et al. Adherence to topical treatment in psoriasis: a systematic literature review. J Eur Acad Dermatol Venereol 212; 26(Suppl. 3): 61 67. 17 Murphy G, Reich K. In touch with psoriasis: topical treatments and current guidelines. J Eur Acad Dermatol Venereol 211; 25(Suppl. 4): 3 8. 18 Paul C, Gallini A, Archier E et al. Evidence-based recommendations on topical treatment and phototherapy of psoriasis: systematic review and expert opinion of a panel of dermatologists. J Eur Acad Dermatol Venereol 212; 26(Suppl. 3): 1 1. 19 Lambert J, Hol CW, Vink J. Real-life effectiveness of once-daily calcipotriol and betamethasone dipropionate gel vs. ointment formulations in psoriasis vulgaris: 4- and 12-week interim results from the PRO-long study. J Eur Acad Dermatol Venereol 214; 28: 1723 1731. 2 Bharmal M, Payne K, Atkinson MJ, Desrosiers M-P, Morisky DE, Gemmen E. Validation of an abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) among patients on antihypertensive medications. Health Qual Life Outcomes 29; 7: 36. 21 Chren MM, Lasek RJ, Flocke SA, Zyzanski SJ. Improved discriminative and evaluative capability of a refined version of Skindex, a quality-of-life instrument for patients with skin diseases. Arch Dermatol 1997; 133: 1433 144. 22 Carroll CL, Feldman SR, Camacho FT, Balkrishnan R. Better medication adherence results in greater improvement in severity of psoriasis. Br J Dermatol 24; 151: 895 897. 23 Carroll CL, Feldman SR, Camacho FT, Manuel JC, Balkrishnan R. Adherence to topical therapy decreases during the course of an 8-week psoriasis clinical trial: commonly used methods of measuring adherence to topical therapy overestimate actual use. J Am Acad Dermatol 24; 51: 212 216. 24 Feldman SR, Camacho FT, Krejci-Manwaring J, Carroll CL, Balkrishnan R. Adherence to topical therapy increases around the time of office visits. J Am Acad Dermatol 27; 57:81 83. 25 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 28; 217: 321 328. 26 Dauden E, Bewley A, Lambert J, Girolomoni G, Cambazard F, Reich K. Expert recommendations: the use of the fixed combination calcipotriol and betamethasone dipropionate gel for the topical treatment of psoriasis. J Eur Acad Dermatol Venereol 214; 28(Suppl. 2): 22 32. 27 Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 25; 353: 487 497. JEADV 215, 29, 2349 2355 215 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd