BJD THERAPEUTICS British Journal of Dermatology Efficacy and safety of calcipotriol plus betamethasone dipropionate scalp formulation compared with calcipotriol scalp solution in the treatment of scalp psoriasis: a randomized controlled trial K. Kragballe, V. Hoffmann,* J.P. Ortonne, J. Tan,à P. Nordin§ and S. Segaert– Department of Dermatology, Marselisborg Center, Aarhus University Hospital, 8000 Aarhus, Denmark *Clinical Operations, LEO Pharma A ⁄S, Ballerup, Denmark Service de Dermatologie, Hôpital L’Archet 2, Nice cedex 3, France àUniversity of Western Ontario, London, ON, Canada §Dermatology Clinic, Läkarhuset, Gothenburg, Sweden –Department of Dermatology, Katholieke Universiteit, Leuven, Belgium Summary Correspondence Knud Kragballe. E-mail: ovl12kkr@as.aaa.dk Accepted for publication 12 December 2008 Key words calcipotriol plus betamethasone dipropionate, randomized controlled trial, scalp psoriasis, topical Conflicts of interest LEO Pharma A ⁄ S, Ballerup, Denmark, sponsored this study and provided financial support for manuscript preparation. K.K. has served as a speaker and ⁄ or consultant for LEO Pharma, Abbott, Merck-Serono, Schering-Plough and Wyeth. V.H. is a salaried employee of LEO Pharma. J.P.O. has served as a paid speaker and consultant for LEO Pharma. J.T. served as a speaker and advisory board member for LEO Pharma and received honoraria from LEO Pharma for these activities. P.N. served as a paid investigator for LEO Pharma in the clinical trial. S.S. has served as a paid speaker, clinical investigator and consultant for LEO Pharma. DOI 10.1111/j.1365-2133.2009.09116.x Background Current topical therapies for scalp psoriasis are difficult or unpleasant to apply, resulting in decreased adherence and efficacy. Objectives To compare the efficacy and safety of once-daily treatment with a combination of calcipotriol 50 lg g)1 plus betamethasone 0Æ5 mg g)1 (as dipropionate) (Xamiol; LEO Pharma A ⁄S, Ballerup, Denmark) and twice-daily calcipotriol 50 lg mL)1 scalp solution in patients with scalp psoriasis. Methods This 8-week, multicentre, randomized, investigator-blind, parallel-group study compared two-compound calcipotriol ⁄betamethasone scalp formulation with calcipotriol scalp solution in patients with moderately severe scalp psoriasis. Primary efficacy outcome was the proportion of patients who achieved ‘clear’ or ‘minimal’ disease severity according to investigator’s global assessment of disease severity at week 8. Secondary efficacy outcomes and adverse events were also evaluated. Relapse and rebound were assessed in an 8-week, post-treatment observation phase. Results In total, 207 patients received the two-compound scalp formulation and 105 patients received calcipotriol scalp solution. The proportion of patients with ‘clear’ or ‘minimal’ disease at week 8 was significantly greater in the twocompound scalp formulation group (68Æ6%) than in the calcipotriol scalp solution group (31Æ4%; P < 0Æ001). Improvement was more rapid with the twocompound scalp formulation than with calcipotriol scalp solution. Further evidence of the superiority of the two-compound scalp formulation over the scalp solution was demonstrated through greater improvements in clinical signs and fewer adverse events. Conclusions A once-daily combination of calcipotriol plus betamethasone dipropionate was significantly more effective and better tolerated than twice-daily calcipotriol scalp solution in the treatment of scalp psoriasis. Psoriasis vulgaris, one of the most common chronic skin diseases, affects 1–3% of the world’s population,1,2 with the scalp being one of the most frequent sites of disease involvement.3,4 Scalp psoriasis can severely impair patient quality of life, restricting lifestyle and daily functioning. Furthermore, it is embarrassing in social settings, and associated with psychological distress in many patients.5 Topical corticosteroids are established treatments for psoriasis of the scalp, with a rapid onset of action.6 However, concerns about long-term cutaneous adverse effects and safety have constrained their use.7 Corticosteroids are often combined with other topical agents in order to achieve additive efficacy due to different modes of action and a potential for corticosteroid-sparing therapy. The vitamin D3 analogue  2009 The Authors Journal Compilation  2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp159–166 159 160 Calcipotriol plus betamethasone in scalp psoriasis, K. Kragballe et al. calcipotriol is effective and well tolerated for the treatment of scalp psoriasis, with proven superiority over the vehicle.8–10 Skin irritation, however, can be a disadvantage.7 Since 2001, the combination of calcipotriol with the potent corticosteroid betamethasone dipropionate in an ointment formulation has become a well-established treatment for psoriasis vulgaris of the trunk and limbs.11–15 Betamethasone dipropionate provides rapid symptom relief and counteracts the local skin irritation associated with calcipotriol, while the amount of corticosteroid required to obtain a favourable response may be reduced by the addition of calcipotriol. A calcipotriol ⁄betamethasone dipropionate two-compound scalp formulation has been developed specifically for once-daily treatment of scalp psoriasis. This two-compound formulation was shown to be effective in large-scale clinical studies of patients with scalp psoriasis.16–18 The objective of this study was to evaluate the clinical efficacy and safety of 8 weeks of treatment with the once-daily, two-compound scalp formulation compared with the currently marketed calcipotriol scalp solution (Daivonex ⁄Dovonex; LEO Pharma A ⁄S, Ballerup, Denmark), which is applied twice daily. Additionally, post-treatment relapse and rebound over an 8-week observation period after the end of treatment was investigated in patients who had responded well to treatment. Patients and methods Patients Patients were ‡ 18 years old, with a clinical diagnosis of scalp psoriasis amenable to topical treatment with a maximum of 100 g of the two-compound scalp formulation [a nonaqueous viscous formulation with calcipotriol (hydrate) 50 lg g)1 plus betamethasone 0Æ5 mg g)1 (as dipropionate); Xamiol, LEO Pharma A ⁄S] or 60 mL calcipotriol scalp solution (50 lg mL)1) per week. All patients had clinical signs, or prior diagnosis, of psoriasis vulgaris on the trunk and ⁄or limbs. At inclusion, psoriasis of the scalp had to involve ‡ 10% of the total scalp area and clinical signs (redness, thickness, scaliness) had to be scored by the investigator as at least ‘moderate’ on one sign and at least ‘slight’ on each of the other two signs. The investigator’s global assessment of disease severity (IGA) on the scalp using a six-point scale (see Assessments) had to be at least ‘moderate’. The main exclusion criteria were psoralen and ultraviolet A or Grenz ray therapy within 4 weeks of randomization and ultraviolet B therapy within 2 weeks of randomization. Patients were excluded if they had received a systemic therapy that may affect scalp psoriasis: for biological therapies this had to be within 6 months of randomization; for other systemic therapies this was within 4 weeks of randomization. Patients who had received topical treatments on the scalp, or very potent (WHO group IV) corticosteroids elsewhere on the body within 2 weeks of randomization could not enter the study. Other exclusion criteria included current diagnosis of unstable forms of psoriasis or other skin diseases confounding psoriasis assessment, skin infections, infestations or atrophy of the scalp, abnormalities in calcium homeostasis, severe renal or hepatic disorders, and concomitant use of medications with a possible effect on scalp psoriasis. Pregnant or breast feeding women were also excluded. The study was approved by the Institutional Review Boards or Independent Ethics Committees of the participating centres, and conducted in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice. All patients received written and verbal information concerning the trial, and each patient’s signed and dated informed consent was obtained before any trial-related procedure. Study design The study was an international, multicentre, prospective, randomized, investigator-blind, two-arm, parallel-group study conducted over 8 weeks in 17 centres in Belgium, Canada, Denmark, France and Sweden. Following a 2- to 4-week washout period, a computer-generated schedule randomized patients 2 : 1 to treatment with the two-compound scalp formulation once daily or calcipotriol scalp solution twice daily. No other topical treatments or emollients were allowed. If patients were washing their hair around the time of application, they were requested to apply study medication after hair washing. Only nonmedicated shampoo without conditioner was allowed during the study. Each patient was assigned an exclusive randomization code in ascending order. Patients whose scalp psoriasis cleared before the end of the 8-week treatment period stopped treatment, but remained in the study. These patients were allowed to restart treatment at any time during the study period if their psoriasis returned. Patients whose scalp psoriasis was graded as ‘clear’ or ‘minimal’ at the end of treatment entered an 8-week observation period to assess post-treatment relapse and rebound. Due to differences in the dosing frequency and formulation between the investigational products, it was not possible to undertake a double-blind study. The packaging and labels for the medications were identical, however, and they were dispensed by a designated independent nonassessor, to maintain blinding of investigators performing the assessments. Patients were instructed not to reveal the formulation or dosing frequency of their medication to their assessor. Assessments Patients were assessed on the day of inclusion into the study (baseline, day 0) and after 1, 2, 4, 6 and 8 weeks of treatment. Follow-up visits during the observation period took place 4 and 8 weeks after the end of treatment, at weeks 12 and 16. Adverse events (AEs) were assessed at all postbaseline visits. Patients with an ongoing AE that could be related to study treatment were followed up 12–16 days after their last on-treatment visit.  2009 The Authors Journal Compilation  2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp159–166 Calcipotriol plus betamethasone in scalp psoriasis, K. Kragballe et al. 161 The severity of scalp psoriasis was evaluated by the six-point IGA scale (‘clear’, ‘minimal’, ‘mild’, ‘moderate’, ‘severe’, ‘very severe’). Clinical signs of redness, scaliness and thickness were assessed using a five-point scale for each sign (0, none; 1, slight; 2, moderate; 3, severe; 4, very severe). The sum of the scores for the three signs constituted the Total Sign Score (TSS), which ranged from 0 to 12. Patient’s global assessment of disease severity was recorded using a five-point scale (‘clear’, ‘very mild’, ‘mild’, ‘moderate’, ‘severe’). Patients also assessed the degree of itching of the scalp (‘none’, ‘mild’, ‘moderate’, ‘severe’). Relapse of psoriasis was defined as a recurrence of at least ‘moderate’ disease according to IGA. Rebound was defined as a one-category increase in IGA from baseline. The time to relapse was the number of days from the last application of medication to relapse. Compliance with treatment was evaluated at all scheduled on-treatment visits by asking each patient if their study medication had been applied as instructed and whether unnecessary or additional applications had been made. Study medication was weighed at each visit. Quality of life assessments were also performed and will be published separately. The severity and possibility of causal relationship to study medication were recorded for all AEs. confidence interval (CIs) and P-values were calculated. The Breslow–Day test for homogeneity of the OR across centres was calculated using a 0Æ10 level of significance. Secondary efficacy criteria assessed during the 8 weeks of treatment were compared between the two groups using the Cochran–Mantel–Haenszel test with adjustment for centre, and the ORs, 99Æ3% CIs and P-values were calculated. The level of significance was set at 0Æ007, using Bonferroni correction for multiple comparisons. The TSS was dichotomized to a score of £ 1 or ‡ 2. Scores for each clinical sign of scalp psoriasis were dichotomized to scores of 0 or ‡ 1. Descriptive statistics were presented for relapse and rebound data during the 8-week observation period, as this was a selected population of patients. The proportions of patients reporting AEs were compared between treatment groups using v2 tests. Results Patients The primary efficacy endpoint was the proportion of patients with ‘clear’ or ‘minimal’ disease according to IGA at week 8. Secondary response criteria included the proportion of patients with ‘clear’ or ‘minimal’ disease according to IGA at weeks 2 and 4, a TSS ‡ 1 at week 8, a score of 0 (absence) for each clinical sign at week 8, ‘clear’ or ‘very mild’ disease according to the patient’s global assessment at week 8, relapse of psoriasis, rebound, and time to relapse. AEs were also recorded. The study was carried out between September 2005 and May 2006. In total, 312 patients were randomized to receive the two-compound scalp formulation (n = 207) or calcipotriol scalp solution (n = 105). Two patients withdrew from the study voluntarily after visit 1 and did not provide any efficacy or safety data thereafter; the safety set thus included 310 patients. Figure 1 shows the patient disposition throughout the study. In total, 272 of 312 randomized patients (87Æ2%) completed the treatment phase, 190 of 207 (91Æ8%) in the two-compound scalp formulation group and 82 of 105 (78Æ1%) in the calcipotriol scalp solution group. At baseline, the treatment groups were well balanced for age, sex, ethnic origin, extent of disease, disease severity according to IGA, TSS and mean duration of psoriasis (Table 1). Statistical analysis Efficacy An estimated sample size of 160–185 patients in the twocompound scalp formulation group and 80–93 patients in the calcipotriol scalp solution group was required for a v2 test to have 90% power to reject the null hypothesis. Therefore, a sample size of 200 patients in the two-compound scalp formulation group and 100 patients in the calcipotriol scalp solution group was planned. The intent-to-treat (ITT) population comprised all patients randomized to study medication, and was used for analysis of all efficacy endpoints. The safety population comprised all patients who received any treatment with study medication and for whom the presence or confirmed absence of AEs was available. A last observation carried forward (LOCF) approach accounted for missing data. The primary outcome measure (proportion of patients with ‘clear’ or ‘minimal’ disease according to IGA at week 8) was compared between treatment groups using the Cochran–Mantel–Haenszel test, adjusting for the effect of centre, and the associated odds ratios (ORs), 95% At week 8 LOCF, the proportion of patients with ‘clear’ or ‘minimal’ disease according to IGA (primary efficacy endpoint) was significantly greater in the two-compound scalp formulation group (142 of 207, 68Æ6%) than in the calcipotriol scalp solution group (33 of 105, 31Æ4%; OR 5Æ4, 95% CI 3Æ1–9Æ4; P < 0Æ001) (Fig. 2). An example of this improvement in psoriasis between baseline and week 8 is shown in Figure 3. Significant differences were also observed between the groups at weeks 2 (OR 14Æ3, 99Æ3% CI 5Æ3–39Æ1; P < 0Æ001) and 4 (OR 5Æ8, 99Æ3% CI 2Æ6–13Æ0; P < 0Æ001). At week 8, there was a greater overall improvement in the distribution of disease severity in the two-compound scalp formulation group than in the calcipotriol scalp solution group, compared with baseline (Fig. 4). At week 8, a significantly greater proportion of patients in the two-compound scalp formulation group had a TSS £ 1 compared with the calcipotriol scalp solution group (80 of 207, 38Æ6% vs. 11 of 105, 10Æ5%; P < 0Æ001). Compared Outcomes  2009 The Authors Journal Compilation  2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp159–166 162 Calcipotriol plus betamethasone in scalp psoriasis, K. Kragballe et al. Fig 1. Patient disposition. Age (years), mean ± SD (range) Males, n (%) Caucasian, n (%) Duration of psoriasis (years), mean ± SD (range) IGA, n (%) Moderate Severe Very severe TSS, mean ± SD Two-compound scalp formulation (n = 207) Calcipotriol scalp solution (n = 105) 50Æ8 ± 15Æ3 (18–91) 90 (43Æ5) 205 (99Æ0) 18Æ4 ± 13Æ8 (0–62) 51Æ4 ± 15Æ6 (24–85) 44 (41Æ9) 104 (99Æ0) 19Æ3 ± 16Æ0 (1–70) 113 (54Æ6) 78 (37Æ7) 16 (7Æ7) 7Æ4 ± 1Æ7 Table 1 Demographics and baseline characteristics (all randomized patients) 64 (61Æ0) 34 (32Æ4) 7 (6Æ7) 7Æ1 ± 1Æ8 IGA, investigator’s global assessment of disease severity; TSS, Total Sign Score. with baseline, the mean percentage change in TSS at week 8 was )68Æ2% in the two-compound scalp formulation group and )37Æ3% in the calcipotriol scalp solution group. Over the first 2 weeks of treatment, the mean TSS for the twocompound scalp formulation decreased more rapidly than for the calcipotriol scalp solution and remained below that of the calcipotriol scalp solution throughout the treatment period to week 8 LOCF (Fig. 5). Significantly more patients in the twocompound scalp formulation group than in the calcipotriol scalp solution group had complete absence of the individual signs at week 8: redness, 67 of 207 (32Æ4%) vs. 11 of 105 (10Æ5%); thickness, 124 of 207 (59Æ9%) vs. 29 of 105 (27Æ6%); and scaliness, 76 of 207 (36Æ7%) vs. 10 of 105 (9Æ5%), respectively (P < 0Æ001 for all signs). The patient’s global assessment of disease severity showed that the proportion of patients with ‘clear’ or ‘very mild’ disease was significantly higher in the two-compound scalp formulation group (170 of 207, 82Æ1%) than in the calcipotriol scalp solution group (36 of 105, 34Æ3%) at week 8 LOCF (OR 9Æ4, 99Æ3% CI 4Æ3–20Æ3; P < 0Æ001) (Fig. 6). Significantly more patients in the two-compound scalp formulation group than in the calcipotriol scalp solution group reported no itching at week 8 (119 of 207, 57Æ5% vs. 28 of 105, 26Æ7%; P < 0Æ001). Tolerability and safety The frequency of AEs during the treatment phase (including all medical events regardless of whether related to study drug)  2009 The Authors Journal Compilation  2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp159–166 Calcipotriol plus betamethasone in scalp psoriasis, K. Kragballe et al. 163 (a) Fig 2. Patients rated as ‘clear’ or with ‘minimal’ disease according to the investigator’s global assessment of disease severity by visit (full analysis set, last observation carried forward). ***P < 0Æ001. was significantly lower in the two-compound scalp formulation group compared with the calcipotriol scalp solution group (71 of 206, 34Æ5% vs. 59 of 104, 56Æ7%, respectively; P < 0Æ001). The proportion of patients with at least one adverse drug reaction (AEs rated as possibly or probably drugrelated by the investigator) was significantly lower in the twocompound scalp formulation group than in the calcipotriol scalp solution group (7 of 206, 3Æ4% vs. 28 of 104, 26Æ9%, respectively; P < 0Æ001). The proportion of patients with at least one lesional ⁄perilesional AE on the scalp was significantly lower in the two-compound scalp formulation group than in the calcipotriol scalp solution group (7 of 206, 3Æ4% vs. 20 of 104, 19Æ2%, respectively; P < 0Æ001) (Table 2). AEs included pruritus, skin irritation and application-site burning, and erythema of the face; all occurred at a higher incidence in the calcipotriol scalp solution group than in the twocompound scalp formulation group. There were no reports of atrophy or systemic adverse drug reactions. Fewer patients in the two-compound scalp formulation group than in the calcipotriol scalp solution group withdrew due to AEs in the treatment phase (2 of 207, 1Æ0% vs. 9 of 105, 8Æ6%, respectively; ITT population). (b) Fig 3. Appearance of scalp psoriasis (a) before (baseline) and (b) after (week 8) treatment with the two-compound scalp formulation once daily. Courtesy of Dr Marc Bourcier, Clinique de Dermatologie, Moncton, Canada. Compliance Compliance with study medication was similar between treatment groups: 170 of 206 patients (82Æ5%) in the twocompound scalp formulation group and 82 of 102 patients (80Æ4%) in the calcipotriol scalp solution group were fully compliant or missed £ 10% of the applications. Compliance data were not available for all patients. The mean weight of study medication used over the total treatment period was similar in both groups (17Æ5 g per week in the two-compound scalp formulation group and 19Æ0 g per week in the calcipotriol scalp solution group). Patients who cleared before week 8 could use the treatment as needed until the end of the treatment period. Observation phase At week 8, 164 patients had ‘clear’ or ‘minimal’ disease according to IGA (two-compound scalp formulation n = 135, calcipotriol scalp solution n = 29) and entered into the 8-week observation phase. In the two-compound scalp formulation group, relapse was observed in 73 of 135 patients (54Æ1%) with a median time to relapse of 35 days. Two patients (1Æ5%) in this group met the criteria for rebound of scalp psoriasis, with ‘moderate’ disease at baseline, ‘clear’ or ‘minimal’ disease severity at week 8, and ‘severe’ disease approximately 4 weeks later. In the calcipotriol scalp solution  2009 The Authors Journal Compilation  2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp159–166 164 Calcipotriol plus betamethasone in scalp psoriasis, K. Kragballe et al. Table 2 Lesional ⁄ perilesional adverse events on the scalp recorded during the treatment period (weeks 1–8; safety population) Adverse event Fig 4. Investigator’s global assessment of disease severity at baseline and week 8 (full analysis set, last observation carried forward). Application-site burning Pruritus Skin irritation Skin burning sensation Application-site warmth Skin laceration Burning sensation Contact dermatitis Skin injury Dry skin Psoriasis Total number of lesional ⁄ perilesional adverse eventsa Total number of patients Two-compound scalp formulation (n = 206), n (%) Calcipotriol scalp solution (n = 104), n (%) 1 1 0 0 0 0 2 0 1 1 1 7 5 5 4 2 1 1 1 1 0 0 0 20 (0Æ5) (0Æ5) (1Æ0) (0Æ5) (0Æ5) (0Æ5) 7 (3Æ4) (4Æ8) (4Æ8) (3Æ8) (1Æ9) (1Æ0) (1Æ0) (1Æ0) (1Æ0) 20 (19Æ2) a Multiple adverse events within the same preferred term in the same patient have been counted as 1. Discussion Fig 5. Mean Total Sign Score (TSS) over time (full analysis set, last observation carried forward). Fig 6. Patients with ‘clear’ or ‘very mild’ disease according to the patient’s global assessment of disease severity by visit (full analysis set, observed case for weeks 0–6, last observation carried forward for week 8). group, relapse was observed in 10 of 29 patients (34Æ5%) with a median time to relapse of 58 days. None of these patients experienced rebound. The once-daily, two-compound scalp formulation, which combines calcipotriol with betamethasone dipropionate, was significantly more effective than twice-daily calcipotriol scalp solution in the management of scalp psoriasis. We found significant improvements in achieving clearance or minimal disease at week 8 with the two-compound scalp formulation compared with calcipotriol scalp solution (primary efficacy endpoint); this improvement had a rapid onset and was noted as early as week 2. Likewise, more patients in the twocompound scalp formulation group showed improvement in individual clinical signs and TSS, with improvement noted earlier than in patients treated with calcipotriol scalp solution. Both investigator and patient assessments of treatment confirmed these results. The efficacy results found in this study confirm earlier findings from clinical studies, in which the two-compound scalp formulation improved scalp psoriasis more effectively than calcipotriol alone.16–18 The two-compound scalp formulation was effective in relieving itching, one of the most distressing symptoms of scalp psoriasis.4 The relief from itching reported by patients may partly explain the high number who reported ‘clear’ or ‘very mild’ disease at the end of treatment. The two-compound scalp formulation was better tolerated than calcipotriol scalp solution, with significantly fewer AEs and adverse drug reactions over 8 weeks of treatment. In particular, the two-compound scalp formulation was associated with fewer of the AEs frequently associated with calcipotriol, such as erythema, pruritus and skin irritation, which may be irritating or painful for patients, and can lead to compliance  2009 The Authors Journal Compilation  2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp159–166 Calcipotriol plus betamethasone in scalp psoriasis, K. Kragballe et al. 165 issues or even premature discontinuation of treatment. The low rate of withdrawals due to unacceptable AEs with the two-compound scalp formulation (1Æ0%) underlines its tolerability advantage over calcipotriol scalp solution. Although the two-compound scalp formulation is a highly efficacious and fast-acting therapy for psoriasis, it is not a cure and relapse may be expected. The time to relapse was shorter with the two-compound scalp formulation compared with calcipotriol scalp solution. This may be expected in a treatment containing a steroid that has a characteristically rapid onset of action. While two cases of rebound were observed in the follow-up period with the two-compound scalp formulation, this may reflect a natural fluctuation of disease severity with relapse. Furthermore, the definition of severity by IGA explicitly excludes area of involvement—thus increase in lesional severity does not necessarily mean an increased surface area involvement. Statistical analyses were not performed on relapse and rebound as only a subset of the patients entered the observation phase. These groups were not randomized and the group sizes differed considerably. Maintenance therapy with the two-compound scalp formulation may keep disease activity at a stable level.19 This is supported by a recent 1-year study of the two-compound ointment for body psoriasis, which stabilized disease activity while providing an acceptable safety profile when used as required.20,21 Calcipotriol scalp solution was chosen as comparator for this study as it is a commonly used treatment for scalp psoriasis with well-documented efficacy. However, potent steroids are generally considered more effective in scalp psoriasis, for example betamethasone 17-valerate solution has been shown to be more effective than calcipotriol scalp solution,22 so the results from the current study were not unexpected. In previous studies, the two-compound scalp formulation was consistently superior to betamethasone dipropionate applied once daily in the same scalp formulation.16–18 This superior effect was achieved although significantly less medication (steroid) was applied compared with betamethasone dipropionate alone.17 As most plain steroids are licensed for twice-daily use, the difference in steroid exposure might be even higher with this regimen compared with the once-daily application of the two-compound scalp formulation. However, the twocompound scalp formulation appears to compare favourably with corticosteroid monotherapy considering risks and benefits. In conclusion, once-daily application of the two-compound scalp formulation containing calcipotriol plus betamethasone dipropionate is a more effective and better tolerated treatment than twice-daily application of calcipotriol scalp solution for patients with moderate-to-severe psoriasis of the scalp. Acknowledgments The study was sponsored by LEO Pharma A ⁄S, Ballerup, Denmark. Statistical analysis was conducted by Merle Kurvits (LEO Pharma A ⁄S, Denmark), and Caudex Medical, UK (supported by LEO Pharma A ⁄S) assisted with manuscript preparation. The authors also thank the following participating investigators: Belgium: E. Suys, R. Geerts; Canada: M. Bourcier, L. Guenther, W. Gulliver, N. Wasel, D. Wexler, J. Amiss, A. Brassard; Denmark: T. Karlsmark; France: J.-M. Bressieux, F. Truchetet; Sweden: I. Popova. References 1 Gelfand JM, Weinstein R, Porter SB et al. Prevalence and treatment of psoriasis in the United Kingdom: a population-based study. Arch Dermatol 2005; 141:1537–41. 2 Schafer T. Epidemiology of psoriasis. Review and the German perspective. Dermatology 2006; 212:327–37. 3 Farber EM, Nall ML. The natural history of psoriasis in 5600 patients. Dermatologica 1974; 148:1–18. 4 van de Kerkhof PCM, de Hoop D, de Korte J et al. Scalp psoriasis, clinical presentations and therapeutic management. Dermatology 1998; 197:326–34. 5 Poyner TF, Fell PJ. A survey of patients with plaque psoriasis who had not consulted their doctor in the past year. Br J Clin Res 1995; 6:201–7. 6 van de Kerkhof PCM, Franssen ME. Psoriasis of the scalp. Diagnosis and management. Am J Clin Dermatol 2001; 2:159–65. 7 van der Vleuten CJ, van de Kerkhof PCM. Management of scalp psoriasis: guidelines for corticosteroid use in combination treatment. Drugs 2001; 61:1593–8. 8 Barnes L, Altmeyer P, Forstrom L et al. Long-term treatment of psoriasis with calcipotriol scalp solution and cream. Eur J Dermatol 2000; 10:199–204. 9 Thaci D, Daiber W, Boehncke WH et al. Calcipotriol solution for the treatment of scalp psoriasis: evaluation of efficacy, safety and acceptance in 3396 patients. Dermatology 2001; 203:153–6. 10 Green C, Ganpule M, Harris D et al. Comparative effects of calcipotriol (MC903) solution and placebo (vehicle of MC903) in the treatment of psoriasis of the scalp. Br J Dermatol 1994; 130:483–7. 11 Douglas WS, Poulin Y, Decroix J et al. A new calcipotriol ⁄ betamethasone formulation with rapid onset of action was superior to monotherapy with betamethasone dipropionate or calcipotriol in psoriasis vulgaris. Acta Derm Venereol (Stockh) 2002; 82:131–5. 12 Guenther L, van de Kerkhof PCM, Snellman E et al. Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, doubleblind, vehicle-controlled clinical trial. Br J Dermatol 2002; 147:316– 23. 13 Kaufmann R, Bibby AJ, Bissonnette R et al. A new calcipotriol ⁄ betamethasone dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis vulgaris. 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A new scalp formulation of calcipotriene plus betamethasone in the treatment of scalp psoriasis: a randomized, double-blind, controlled trial. J Am Acad Dermatol 2008; 59:455–63. 18 van de Kerkhof PCM, Hoffmann V, Anstey A et al. A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial. Br J Dermatol 2009; 160:170–6. 19 Luger TA, Cambazard F, Larsen FG. A study of the safety and efficacy of calcipotriol and betamethasone dipropionate scalp formulation in the long-term management of scalp psoriasis. Dermatology 2008; 217:321–8. 20 Kragballe K, Austad J, Barnes L et al. A 52-week randomized safety study of a calcipotriol ⁄ betamethasone dipropionate two-compound product (Dovobet ⁄ Daivobet ⁄ Taclonex) in the treatment of psoriasis vulgaris. Br J Dermatol 2006; 154:1155–60. 21 Kragballe K, Austad J, Barnes L et al. Efficacy results of a 52-week randomised, double-blind, safety study of a calcipotriol ⁄ betamethasone dipropionate two-compound product (Daivobet ⁄ Dovobet ⁄ Taclonex) in the treatment of psoriasis vulgaris. Dermatology 2006; 213:319–26. 22 Klaber MR, Hutchinson PE, Pedvis-Leftick A et al. Comparative effects of calcipotriol solution (50 lg ⁄ ml) and betamethasone 17-valerate solution (1 mg ⁄ ml) in the treatment of scalp psoriasis. Br J Dermatol 1994; 131:678–83.  2009 The Authors Journal Compilation  2009 British Association of Dermatologists • British Journal of Dermatology 2009 161, pp159–166