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

BJD T H E R A P E U T I CS British Journal of Dermatology 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 P.C.M. van de Kerkhof, V. Hoffmann,* A. Anstey, L. Barnes,à C. Bolduc,§ K. Reich,– S. Saari,** S. Segaert and L. Vaillantàà Department of Dermatology, University Hospital Nijmegen, Centrum St Radboud, Postbus 9101, 6525 GL Nijmegen, The Netherlands *LEO Pharma A ⁄S, Ballerup, Denmark Royal Gwent Hospital, Newport, U.K. àSt James’s Hospital, Dublin, Ireland §Innovaderm Research Inc., Quebec, Canada –Department of Dermatology, University of Göttingen, Göttingen, Germany **Polyclinic of Dermatology, Medical Reception Centre, Pulssi (Lääkärisema Pulssi), Turku, Finland University Hospital St Rafaël, Leuven, Belgium ààService de Dermatologie, Hôpital Trousseau, Tours, France Summary Correspondence Peter van de Kerkhof. E-mail: vandekerkhof@derma.azn.nl Accepted for publication 6 September 2008 Key words calcipotriol plus betamethasone dipropionate, clinical, psoriasis, randomized controlled trial, scalp, treatment Conflicts of interest P.C.M.v.d.K. with Abbott, Allmiral, Barrier, Cellgene, Centocor, Galderma, LEO Pharma, Pfizer, Serono, UCB Pharma and Wyeth. V.H. is an employee of LEO Pharma. This study was sponsored by LEO Pharma. Data collection took place at all the above institutions. A list of participating investigators is provided at the end of this article. DOI 10.1111/j.1365-2133.2008.08927.x Background There is a need for new treatments for scalp psoriasis, as many topical treatments are cosmetically unacceptable and difficult to apply, resulting in poor compliance. Objectives To compare the efficacy and safety of a new, once-daily, two-compound scalp formulation (Xamiol; LEO Pharma A ⁄S, Ballerup, Denmark) containing calcipotriol 50 lg g)1 plus betamethasone 0Æ5 mg g)1 (as dipropionate), with the active ingredients as single compounds in the same vehicle. Methods This 8-week, multicentre, double-blind, parallel-group study, randomized adult patients with scalp psoriasis involving > 10% of the scalp to the twocompound scalp formulation (n = 568), betamethasone dipropionate 0Æ5 mg g)1 (n = 563), or calcipotriol 50 lg g)1 (n = 286). The primary efficacy measure was the proportion of patients with ‘absence of disease’ or ‘very mild disease’ according to investigators’ assessments at week 8. Results The proportion of patients with ‘absence of disease’ or ‘very mild disease’ at week 8 was significantly higher in the two-compound group (68Æ4%) than the betamethasone dipropionate (61Æ0%, P = 0Æ0079) or calcipotriol (43Æ4%, P < 0Æ0001) groups. The proportion of patients rating their scalp psoriasis as ‘clear’ or ‘almost clear’ was significantly higher for the two-compound scalp formulation (69Æ6%) than for betamethasone dipropionate (59Æ9%, P = 0Æ0006) or calcipotriol (44Æ7%, P < 0Æ0001). The incidence of lesional ⁄perilesional adverse events was lower in the two-compound and betamethasone dipropionate groups than the calcipotriol group. Conclusions The two-compound scalp formulation was well tolerated and more effective in the treatment of scalp psoriasis than either of its individual components in the same vehicle. Approximately 50–80% of patients with psoriasis are reported to have scalp psoriasis.1–5 Scalp psoriasis often interferes with everyday activities, affecting the patient psychologically and socially, and reducing quality of life.5,6 Treatment of scalp psoriasis can be a major therapeutic challenge, as many topical treatments are messy and difficult to apply, resulting in poor compliance.7 Calcipotriol, a synthetic vitamin D3 analogue, has become an established  2008 The Authors 170 Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp170–176 Calcipotriol plus betamethasone in scalp psoriasis, P.C.M. van de Kerkhof et al. 171 treatment for psoriasis, with several studies demonstrating its effectiveness in psoriasis of the trunk and limbs for up to 1 year of use.8–14 Calcipotriol scalp solution is effective and has good tolerability in the long-term treatment of scalp psoriasis.15–17 Betamethasone dipropionate has been used for many years in the treatment of various dermatological disorders, including psoriasis. Calcipotriol and betamethasone dipropionate have been combined in a formulation that has demonstrated efficacy and long-term safety in psoriasis of the trunk and limbs.18,19 A new two-compound product (Xamiol; LEO Pharma A ⁄S, Ballerup, Denmark) combining calcipotriol 50 lg g)1 and betamethasone 0Æ5 mg g)1 (as dipropionate) in a scalp formulation has been developed for once-daily treatment of scalp psoriasis. A phase II study showed the scalp formulation to have good efficacy and safety in the treatment of scalp psoriasis.20 To confirm these findings in a larger phase III study, we compared the clinical efficacy and safety of the once-daily two-compound scalp formulation with those of betamethasone dipropionate and calcipotriol individually in the same vehicle in patients with scalp psoriasis over a treatment period of 8 weeks. Materials and methods Patients Eligible patients were aged ‡ 18 years and had scalp psoriasis involving > 10% of the total scalp area that was amenable to topical treatment with a maximum of 100 g of medication per week. Patients also had clinical signs, or a previous diagnosis, of psoriasis vulgaris on the trunk and ⁄or limbs. One or more of the clinical signs (erythema, thickness and scaliness) had to be rated as at least ‘moderate’, while other clinical signs had to be rated as at least ‘slight’ and the overall disease severity on the scalp had to be graded from ‘mild’ to ‘very severe’ according to the Investigator’s Global Assessment (IGA) of disease severity. Exclusion criteria included any topical treatment of the scalp (except for medicated shampoos and emollients), topical treatment of the face, trunk or limbs with very potent (World Health Organization group IV) corticosteroids or ultraviolet B therapy, all within 2 weeks of randomization. Also excluded were patients who had psoralen and ultraviolet A or Grenz ray therapy, planned exposure to the sun that may affect scalp psoriasis, or systemic treatment with any other therapy with a possible effect on scalp psoriasis, within 4 weeks of randomization. Patients who planned initiation of, or changes to, concomitant medication that could affect scalp psoriasis, or who had systemic treatment with biological therapies with a possible effect on scalp psoriasis within 6 months of randomization, were also excluded. A current diagnosis of erythrodermic, exfoliative or pustular psoriasis, presence of viral lesions, fungal or bacterial skin infections, parasitic infections or atrophic skin on the scalp, known or suspected abnormality of calcium homeostasis associated with clinically significant hypercalcaemia, severe renal insufficiency or severe hepatic disorders were also criteria for exclusion. Study design This was an 8-week, international, multicentre, prospective, randomized, double-blind, three-arm, parallel-group study. If required, patients entered a washout phase prior to randomization, during which antipsoriatic treatments and other relevant medications were discontinued, as per the exclusion criteria. The duration of the washout period varied from 2 weeks to 1 month depending on the type of previous therapy. Patients were then randomized according to a computer-generated schedule in a 2 : 2 : 1 ratio to one of the following three treatment groups: the two-compound scalp formulation [calcipotriol 50 lg g)1 plus betamethasone 0Æ5 mg g)1 (as dipropionate)], betamethasone 0Æ5 mg g)1 (as dipropionate) in the vehicle, or calcipotriol 50 lg g)1 in the vehicle. Study treatments were used once daily for up to 8 weeks. There were six clinic visits during treatment, at baseline and at weeks 1, 2, 4, 6 and 8. Patients graded to have ‘absence of disease’ according to the IGA at weeks 1–8 could stop treatment with study medication at the investigator’s discretion, but were required to remain in the study and attend all clinic visits. Patients were instructed to restart treatment if required, based on the patients’ own judgement. At the last on-treatment visit, any patient with an ongoing adverse event that was classified as possibly or probably related to the study medication, or not assessable in relation to the study medication, was followed up for 14 days after this visit. Assessments At each clinic visit, the investigator performed a global assessment of the severity of scalp psoriasis according to a six-point scale (‘absence of disease’ ‘very mild disease’, ‘mild disease’, ‘moderate disease’, ‘severe disease’, ‘very severe disease’). The investigator also separately evaluated three clinical signs, erythema, thickness and scaliness, using a five-point score for each sign. The sum of the scores constituted the total sign score (TSS). At all on-treatment clinic visits, the patients made an assessment of the overall response to therapy compared with the condition at baseline, using a seven-point scale (‘worse’, ‘unchanged’, ‘slight improvement’, ‘moderate improvement’, ‘marked improvement’, ‘almost clear’, ‘clear’) taking into account both the extent and the severity of scalp psoriasis. At all on-treatment visits, patients were asked if they had used the medication as prescribed, and, if not, the extent and type of noncompliance were further assessed. Drug consumption was measured by weighing the bottles of medication before and at the end of treatment. The occurrence of adverse events was recorded at all clinic visits. Blood samples were taken at baseline, week 1 and week 4 for the analysis of serum levels of calcium and albumin.  2008 The Authors Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp170–176 172 Calcipotriol plus betamethasone in scalp psoriasis, P.C.M. van de Kerkhof et al. Statistical analysis Ethics The primary efficacy endpoint was the proportion of patients with ‘absence of disease’ or ‘very mild disease’ in the twocompound scalp formulation group compared with each of the other two groups, according to the IGA at week 8. Major secondary endpoints were the IGA at weeks 2 and 4, TSS at week 8, and the proportion of patients who were ‘almost clear’ or ‘clear’ according to the patient’s assessment at week 8. All randomized patients were included in the full analysis set and were analysed for efficacy parameters, and all patients who had received any trial medication and from whom the presence or confirmed absence of adverse events was available were included in the safety analysis set. The proportion of patients in the full analysis set who achieved ‘absence of disease’ or ‘very mild disease’ at week 8 was compared between treatment groups using last observation carried forward (LOCF) and the Cochran–Mantel–Haenszel (CMH) test adjusting for the effect of centre. The proportion of patients who were ‘clear’ or ‘almost clear’ according to the Patient’s Overall Assessment of treatment response was also compared between treatment groups using the CMH test adjusting for the effect of centre. The percentage change in TSS from baseline to week 8 was compared between treatments by analysis of variance with the factors of treatment group and centre. The proportion of patients with adverse events was compared between treatment groups by v2 test. The study was approved by the Institutional Review Boards or Independent Ethics Committees of the participating centres. The trial was 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 prior to any trial-related procedure. Results Patients In total, 1418 patients were enrolled and randomized into treatment groups with similar baseline characteristics (Table 1, Fig. 1). Withdrawals due to unacceptable efficacy of treatment and unacceptable adverse events occurred with a lower frequency in the two-compound group [n = 7 (1Æ2%) and n = 4 (0Æ7%), respectively] compared with the betamethasone dipropionate [n = 9 (1Æ6%) and n = 7 (1Æ2%), respectively] and calcipotriol groups [n = 8 (2Æ8%) and n = 8 (2Æ8%), respectively]. The full analysis set included 1415 patients (twocompound group n = 567, betamethasone group n = 562, calcipotriol group n = 286). The safety analysis set included 1401 patients (two-compound group n = 563, betamethasone group n = 556, calcipotriol group n = 282). Compliance was similar across the treatment groups. Among patients in the two-compound group who had compliance Table 1 Patient and disease characteristics at baseline (randomized patients) Age (years), mean ± SD (range) Female, n (%) Race, caucasian, n (%) Duration of scalp psoriasis (years), mean ± SD Extent of scalp psoriasis,a n (%) < 10% 10–29% 30–49% 50–69% 70–89% 90–100% Disease severity,c n (%) Mild Moderate Severe Very severe Total sign score, mean ± SD Two-compound scalp formulation (n = 568) Betamethasone dipropionate (n = 563) Calcipotriol (n = 286) 48Æ5 ± 16Æ4 (18–92) 330 (58Æ1) 559 (98Æ4) 15Æ7 ± 13Æ3 47Æ9 ± 16Æ4 (18–85) 303 (53Æ8) 545 (96Æ8) 16Æ1 ± 13Æ7 48Æ7 ± 16Æ2 (18–88) 149 (52Æ1) 274 (95Æ8) 15Æ8 ± 12Æ9 1 207 158 86 64 52 (0Æ2)b (36Æ4) (27Æ8) (15Æ1) (11Æ3) (9Æ2) 56 (9Æ9) 311 (54Æ8) 170 (29Æ9) 31 (5Æ5) 6Æ8 ± 1Æ9 0 188 155 89 69 61 (33Æ5) (27Æ6) (15Æ8) (12Æ3) (10Æ9) 45 (8Æ0) 302 (53Æ6) 189 (33Æ6) 27 (4Æ8) 6Æ9 ± 1Æ8 0 95 83 53 32 23 (33Æ2) (29Æ0) (18Æ5) (11Æ2) (8Æ0) 35 (12Æ2) 147 (51Æ4) 94 (32Æ9) 10 (3Æ5) 6Æ8 ± 1Æ8 a Baseline data missing for one patient in the betamethasone group. This patient withdrew voluntarily from the study at the first visit. bThis patient did not meet the inclusion criteria and was randomized in error, but did not receive study medication and is not included in the full analysis set. cAssessed using the Investigator’s Global Assessment of disease severity.  2008 The Authors Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp170–176 Calcipotriol plus betamethasone in scalp psoriasis, P.C.M. van de Kerkhof et al. 173 Fig 1. Patient disposition. *One randomized patient was subsequently excluded. †Completed: patients who completed the full 8-week study period or left the study due to ‘absence of disease’. Fig 2. Patients achieving ‘absence of disease’ or ‘very mild disease’ at weeks 2, 4 and 8 (last observation carried forward; full analysis set). Fig 3. Investigator’s Global Assessment of disease severity at week 8 (last observation carried forward; full analysis set). data recorded, 287 patients (50Æ5%) used the medication as instructed at all postrandomization visits; 149 (26Æ2%) patients had ‘absence of disease’ recorded for at least one visit and Fig 4. Mean total sign score over time (full analysis set). Fig 5. Patients rated as ‘clear’ or ‘almost clear’ according to the Patient’s Overall Assessment of treatment response at week 8 (last observation carried forward; full analysis set). were allowed to discontinue applications. The corresponding numbers for the betamethasone group were 275 (48Æ8%) and 123 (21Æ8%), respectively, and for the calcipotriol group were 147 (51Æ4%) and 34 (11Æ9%), respectively.  2008 The Authors Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp170–176 174 Calcipotriol plus betamethasone in scalp psoriasis, P.C.M. van de Kerkhof et al. Efficacy results The proportion of patients who achieved an IGA of ‘absence of disease’ or ‘very mild disease’ at week 8 (LOCF) was significantly greater in the two-compound scalp formulation group (68Æ4%) compared with the betamethasone dipropionate group [61Æ0%; odds ratio (OR) 1Æ41; 95% confidence interval (CI) 1Æ09–1Æ81; P = 0Æ0079] and the calcipotriol group (43Æ4%; OR 3Æ13; 95% CI 2Æ29–4Æ28; P < 0Æ0001) (Fig. 2). Already by week 2, the two-compound scalp formulation was significantly more effective than both betamethasone dipropionate (P = 0Æ0001) and calcipotriol (P < 0Æ0001). At week 4, it was significantly more effective than calcipotriol (P < 0Æ0001). Two-compound scalp formulation (n = 563) General disorders, administration site Application site pain 0 Secretion discharge 0 Swelling 0 Immune system disorders Hypersensitivity 1 Infections ⁄ infestations Folliculitis 3 Pustular rash 1 Nervous system disorders Burning sensation 0 Hyperaesthesia 1 Paraesthesia 0 Skin ⁄ subcutaneous tissue disorders Acne 1 Alopecia 2 Dermatitis 1 Acneiform dermatitis 0 Exfoliative dermatitis 1 Dry skin 1 Erythema 0 Hair disorder 0 Abnormal hair texture 1 Hyperhidrosis 0 Hypotrichosis 1 Localized skin reaction 1 Skin pain 3 Pruritus 12 1 Psoriasisb Rash 0 Burning sensation of skin 1 Hypertrophy of skin 1 Inflammation of skin 0 Irritation of skin 3 Skin lesion 0 Tightness of skin 1 Total number of patientsc 35 Betamethasone dipropionate (n = 556) Compared with the IGA at baseline, more patients had ‘absence of disease’ at week 8 (LOCF) in the two-compound group than in the betamethasone dipropionate and the calcipotriol groups (Fig. 3). Although patients in all groups improved according to mean TSS (Fig. 4) at week 8 (LOCF), the percentage improvement from baseline in mean TSS was significantly larger for the two-compound scalp formulation ()74Æ4%) than for betamethasone dipropionate ()67Æ9%; mean difference )6Æ4%; P = 0Æ0002) and calcipotriol in the same vehicle ()56Æ6%; mean difference )17Æ8%; P < 0Æ0001). Significantly more patients treated with the two-compound scalp formulation (69Æ6%) compared with those treated with betamethasone dipropionate (59Æ9%; OR 1Æ55; 99Æ3% CI Table 2 Lesional ⁄ perilesional adverse events on the scalp (safety set) Calcipotriol (n = 282) conditionsa 1 (0Æ2%) 0 0 0 1 (0Æ4%) 1 (0Æ4%) (0Æ2%) 0 0 (0Æ5%) (0Æ2%) 5 (0Æ9%) 0 0 0 (0Æ2%) 3 (0Æ5%) 0 2 (0Æ4%) 3 (1Æ1%) 0 2 (0Æ7%) (0Æ2%) (0Æ4%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ5%) (2Æ1%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ5%) (0Æ2%) (6Æ2%) 1 2 0 1 0 1 0 1 0 1 0 0 1 7 1 1 1 0 1 2 1 0 32 (0Æ2%) (0Æ4%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ2%) (1Æ3%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ2%) (0Æ4%) (0Æ2%) (5Æ8%) 0 2 0 0 0 1 2 0 0 0 0 0 1 25 1 0 0 0 0 6 0 0 36 (0Æ7%) (0Æ4%) (0Æ7%) (0Æ4%) (8Æ9%) (0Æ4%) (2Æ1%) (12Æ8%) a Classification according to MedDRA version 6.1. bA recurrence or exacerbation of psoriasis that appeared on the scalp £ 2 cm from the lesional site was considered a lesional ⁄ perilesional adverse event. cA single patient may have experienced more than one event.  2008 The Authors Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp170–176 Calcipotriol plus betamethasone in scalp psoriasis, P.C.M. van de Kerkhof et al. 175 1Æ10–2Æ20; P = 0Æ0006) or calcipotriol (44Æ7%; OR 3Æ00; 99Æ3% CI 1Æ97–4Æ58; P < 0Æ0001) rated their scalp psoriasis as ‘clear’ or ‘almost clear’ at week 8 (LOCF) (Fig. 5). Safety results The mean weight of study medication used for the whole study period was 163Æ8 g for the two-compound scalp formulation, 177Æ2 g for betamethasone dipropionate and 192Æ3 g for calcipotriol. The mean weight of study medication used in each of the three arms ranged from 20 to 25 g per week. The proportion of patients with at least one adverse event in the two-compound scalp formulation group (218 patients, 38Æ7%) was similar to that in the betamethasone dipropionate group (228 patients, 41Æ0%), while the proportion of patients with adverse events in the calcipotriol group (130 patients, 46Æ1%) was significantly higher than that in the twocompound scalp formulation group (P = 0Æ04). Most of the adverse events were rated as ‘not related’ to study treatment. More lesional or perilesional adverse events were reported in the calcipotriol group than in any other group (Table 2). There were no changes of clinical concern in albumincorrected serum calcium measures. Discussion This study demonstrates that the two-compound scalp formulation was significantly more effective in the treatment of scalp psoriasis, with evidence of a more rapid onset of action, than betamethasone dipropionate or calcipotriol alone in the same vehicle. Compared with patients using the individual components, a higher proportion of patients treating their scalp psoriasis with the two-compound scalp formulation achieved ‘absence of disease’ or ‘very mild disease’, and a greater number of patients showed reduced clinical signs of redness, thickness and scaliness. The results of the current study using calcipotriol plus betamethasone dipropionate combined in a scalp formulation are in accordance with the results of previous studies, where a combination of both compounds was more effective than the individual compounds in the treatment of psoriasis on the trunk and limbs.21–23 In these studies, there was also evidence that the combination product produced a more rapid onset of action than the individual components.21–23 In the current study, the proportion of patients experiencing at least one adverse event was similar in the twocompound and betamethasone dipropionate groups, but was significantly greater in the calcipotriol group. The adverse event profiles seen in this study are consistent with the adverse event profiles seen in previous studies using the twocompound scalp formulation.21,23 It is likely that using calcipotriol plus betamethasone dipropionate in combination on the scalp creates an additive or synergistic effect comparable with that observed in the treatment of psoriasis on the trunk and limbs.21–24 By combining the two active components in one formulation, it is assumed that betamethasone dipropionate helps to counteract the local skin irritation that calcipotriol can cause in some patients. Alternatively, calcipotriol may allow the use of a lower dose, or fewer applications, of corticosteroid and thus reduce the risk of steroid-related adverse effects.25 In the current study, the incidence of lesional or perilesional pruritus, skin irritation and burning sensation was lower in the group using the two-compound scalp formulation than in the group using calcipotriol alone. In a 52-week safety study, an ointment formulation containing calcipotriol plus betamethasone dipropionate was well tolerated when used either on its own, as required, or alternating every 4 weeks with the calcipotriolonly formulation.18 These data support the high tolerability and safety of the two-compound products. Psoriasis of the scalp often represents a significant therapeutic problem. The combination of calcipotriol and a topical corticosteroid to optimize efficacy and tolerability has previously been recommended by several authors.26–28 Using the two products separately, however, has the disadvantage of inconvenience and low practicability that will reduce the patients’ adherence to treatment. A previous study showed that while twice-daily treatment was advised in 50% of the patients, this treatment frequency was followed in only 33% of the patients.4 The chemical properties of the two compounds prevent simultaneous application of the individual products. Therefore, twice-daily application is unavoidable. In a study of compliance with topical treatments requiring two or more applications a day, the adherence rate was 44% compared with 82% for once-daily treatments.29 The formulation of calcipotriol and a steroid in a combination product therefore represents an important therapeutic advance. Combining the two compounds in a formulation with optimized qualities for use on the scalp might contribute towards improved compliance, resulting in a better treatment response.7 In conclusion, the two-compound scalp formulation containing calcipotriol plus betamethasone dipropionate was significantly more effective in the treatment of scalp psoriasis than either of the individual components in the same vehicle. Acknowledgments The authors thank Mikala Fiig Jarner, MSc Stat, LEO Pharma A ⁄S, Ballerup, Denmark, for the statistical analysis and Alexandra Lemonidis, Caudex Medical, U.K., for writing support. This study was sponsored by LEO Pharma A ⁄S, Ballerup, Denmark. This study has been registered with ClinicalTrials.gov. NCT 00216840. The following investigators participated in this study: Belgium: S. Segaert, A.-K. Minne, J. Porters, P.P. Roquet-Gravy, E. Suys, W. Broeckx, L. van Herpe, P. De Merlier, J.E. Snauwaert, H. Boonen, J.J. Stene; Canada: R. Vender, C. Bolduc, D.P. Toth, L.A. Rosoph, S. Sapra, W.D. Carey; Finland: H. Heikkila, T. Jarvinen, S. Saari, J. Saarinen, H. Majamaa, T. Puolakka, J. Juhela; France: L. Vaillant, J. Revuz, P. Humbert, J.-M. Bressieux, P. Bernard, L. Misery, B. Morlain; Germany: D. Thaçi, P. Elsner, B. Schwarz, K. Fritz, U.M. Niemczyk-Richter, B. Gerlach,  2008 The Authors Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp170–176 176 Calcipotriol plus betamethasone in scalp psoriasis, P.C.M. van de Kerkhof et al. T. Bieber, K. Reich, M. Friedrich, E. Glorer, J. Kloos, H. Uhlemann, H. Friedrich, G. Popp; Ireland: G. Murphy, L. Barnes, C. Buckley, B. Kirby; Netherlands: I.M.L. Majoie, P.C.M. van de Kerkhof, H.C.J. Liberton, R.J. Damstra, H.J.L. van Gerwen, E.P. Prens, M.J.M. de Rooij, H.J.M. van Baar; U.K.: J. Zachariah, T. Lee, B. King, A. Patel, M. Blagden, R. Charlton, N. Kerry, D. Howarth, J. Vernon, D. Burwood, S. Edwards, A. George, C. Murphy, S. Rowlands, S. Patel, B.F. Penney, A. Anstey, I. James, P. Eavis, T. Cahill, J.W. Murphy, R. Brownlie, J.A. Milne, L.M. Adler, W. Scullion, C. Strang, J. Calvert, B.D. Silvert, G. Chapman, I.S. Farmer, A. Graham, C.G. Langdon, F. Makhani, A. Takhar, A. Drummond, A. Mishra, M. Sommerville, M. Simpson, W. Young, B. Kilgallon, J. Ochoa. References 1 Brandrup F, Green A. The prevalence of psoriasis in Denmark. Acta Derm Venereol (Stockh) 1981; 61:344–6. 2 Farber EM, Nall ML. The natural history of psoriasis in 5,600 patients. Dermatologica 1974; 148:1–18. 3 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. 4 van de Kerkhof PCM, Steegers-Theunissen RPM, Kuipers MV. Evaluation of topical drug treatment in psoriasis. Dermatology 1998; 197:31–6. 5 Farber EM, Bright RD, Nall ML. Psoriasis. A questionnaire survey of 2,144 patients. Arch Dermatol 1968; 98:248–59. 6 van de Kerkhof PCM, de Hoop D, de Korte J, Kuipers MV. Scalp psoriasis, clinical presentations and therapeutic management. Dermatology 1998; 197:326–34. 7 Feldman SR, Housman TS. Patients’ vehicle preference for corticosteroid treatments of scalp psoriasis. Am J Clin Dermatol 2003; 4:221–4. 8 Berth-Jones J, Dodd WA, Ganpule M et al. A multi-centre, parallelgroup comparison of calcipotriol ointment and short-contact dithranol therapy in chronic plaque psoriasis. Br J Dermatol 1992; 127:266–71. 9 Tham SN, Lim KC, Cheong WK. A comparative study of calcipotriol ointment and tar in chronic plaque psoriasis. 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