About the Author
Maxwell B. Sauder, MD, FRCPC, FAAD, FCDA
Dr. Sauder is currently an assistant professor in the division of dermatology at the University of Toronto. He is an onco-dermatologist at Princess Margaret Cancer Centre as well as the research director at Toronto Research Centre. He earned his Doctor of Medicine degree at McMaster University, completed a residency in dermatology at The University of Ottawa and completed fellowship training in Cutaneous Oncology at Harvard Medical School.
Special Supplement, Canadian Dermatology Today, February, 2022
Itching For Relief: The Evidence Of Fixed Dose Calcipotriol Plus Betamethasone Dipropionate Foam For Psoriasis
Psoriasis is a chronic immune-mediated skin disease with a variety of morphological presentations, distribution patterns and severities. Psoriasis can have a profound impact on health-related quality of life (HRQoL), almost equal to that seen in patients suffering from cardiovascular disease and cancer.1 In Canada, it is estimated that approximately 3% of the population suffers from psoriasis, equating to over 1 million people.2 The most common presentation is ‘mild-to-moderate’ plaque psoriasis characterized by well-defined silver scaly plaques on extensor surfaces.3 However, classifying severity can be challenging. In 2020, the International Psoriasis Council recommended classifying psoriasis severity with a dichotomous definition: either candidates for topical therapy or candidates for systemic therapy.4 Regardless of severity, all patients living with psoriasis will need a topical agent as part of their treatment regimen throughout the clinical course of their disease.
Topical treatments used to treat psoriasis in Canada include steroids, vitamin D analogues, retinoids, tar, keratolytic agents and fixed dose combination products. In 2001, the fixed dose combination of calcipotriol (Cal) 50 μg/g plus betamethasone dipropionate (BD) 0.5 mg/g was approved by Health Canada in ointment form, followed by a gel in 2012 and an aerosol ointment-based foam (Cal/BD foam) in 2016. Other combination products for psoriasis include topical steroids combined with either tazarotene or salicylic acid.
Fixed dose combination products have several advantages versus topical monotherapy agents including ease of use, increased efficacy, improved adherence, and potentially fewer adverse events.5 Specifically for Cal/BD, Cal has been shown to reduce atrophy associated with BD; whereas, BD has been shown to reduce the irritation associated with Cal.6
The aim of this article is to review the evidence with regards to efficacy, onset of action, itch relief and patient-reported outcomes for Cal/BD foam.
Cal/BD foam is approved in Canada for the topical treatment of psoriasis vulgaris in adult and adolescent patients 12 years or older for up to 4 weeks.8 All studies to be discussed hereafter include subjects with mild-to-severe disease severity. Head-to-head studies comparing Cal/BD foam to ointment9 and gel10 have demonstrated superiority of the foam in achieving physician global assessment as ‘‘clear’’ or ‘‘almost clear’’ (Figure 1) with at least a two-point improvement (PGA success), as well as superiority in the proportion of patients achieving at least a 75% reduction in modified psoriasis area severity index (mPASI75) (Figure 2). The PSO-LONG study also demonstrated ongoing proactive twice weekly use beyond the initial daily 4 weeks resulted in patients in the proactive group having an additional 41 days in remission compared with the reactive group over a 1 year period (P < .001).11 While there are no head-to-head studies comparing Cal/BD foam to the newer fixed dose combination of halobetasol plus tazarotene lotion (HP/TAZ lotion), an anchor-based, matching adjusted indirect comparison of the two products was performed. The indirect comparison found that 4 weeks of Cal/BD foam produced greater PGA success than 8 weeks of HP/TAZ lotion (Figure 3) (51.4 vs. 30.7%, p < .001).12
Onset of Action
The PSO-FAST study involving 426 subjects looked at the efficacy and safety of Cal/BD foam versus vehicle. At 4 weeks, 53.3% of subjects achieved PGA success in the Cal/BD foam group versus 4.8% in the vehicle group (OR 30.3, 95% CI 9.7,94.3; P < .001). Similarly, 52.9% of subjects achieved a mPASI75 in the Cal/BD foam group versus 8.2% on placebo (OR 14.9; 95% CI 6.5, 34.0; P < .001). Equally important, no major safety signals were identified. Incidence of adverse events were similar between active and placebo arms with most events rated as mild or moderate in severity. Adverse drug reactions were reported in ten Cal/BD foam patients (3.1%) and two vehicle patients (1.9%).13 Due to the fast onset of action of Cal/BD foam, the PSO-ABLE study was designed based on the hypothesis that 4 weeks of Cal/BD foam was superior in efficacy to 8 weeks of Cal/BD gel, which was demonstrated (Figure 4).10
Itch is a significant driver of health-related quality of life (HRQoL) deterioration related to psoriasis. As such, rapid and sustained improvement in itch is a valuable outcome for today’s therapeutic treatments. A pooled analysis from three phase III studies examined the following outcomes: itch visual analogue scale (VAS) reduction >40 (Figure 5a), ≥70% improvement in itch (Itch70) (Figure 5b) or itch-related sleep loss, mPASI75 (excluding head) and Dermatology Life Quality Index (DLQI) scores 0/1 through 4 weeks. The results demonstrated that 57.5% of Cal/BD foam subjects achieved an itch VAS reduction of >40 from day 5 onwards versus 40.2% in the vehicle group (P < 0.05) and by week 4 this increased to 83% in the Cal/BD arm vs 45.8% in the vehicle arm (P < 0.001). A statistically significant difference in those achieving ≥70% improvement in itch was demonstrated in the Cal/BD foam group vs the vehicle group as early as day 3 (34.2% vs 22.5%, P < 0.05) and by week 4 this increased to 79.3% vs 38.1% (P < 0.001).14
The PSO-ABLE study also examined HRQoL wholistically in addition to itch specifically. Subjects enrolled in the study completed the Dermatology Life Quality Index (DLQI), EuroQoL-5D-5L-PSO (EQ-5D), and Psoriasis QoL (PQoL-12) questionnaires at baseline, Weeks 4, 8 and 12. At the 4-week study time point Cal/BD foam demonstrated meaningful improvement in HRQoL measures. Significantly more Cal/BD foam patients achieved DLQI scores of 0/1 at Weeks 4 (45.7% vs 32.4%; p = 0.013) and 12 (60.5% vs 44.1%; p = 0.003) than Cal/BD gel patients (Figure 6). Cal/BD foam significantly improved EQ-5D utility index (0.09 vs 0.03; p<0.001) and PQoL-12 scores (-2.23 vs -2.07; p = 0.029) from baseline to Week 4 versus Cal/BD gel. Itch, itch-related sleep loss, and work impairment improved more with Cal/BD foam than gel.15
Psoriasis is a chronic, relapsing, and unpredictable inflammatory disease. All patients can benefit from a safe, effective, and fast treatment whether they are candidates for topical treatments only or if they are also candidates for systemic therapies. The use of Cal/BD foam has demonstrated efficacy, quick onset of action, itch relief and overall improvement in HRQoL measures in various peer-reviewed studies of mild-to-severe plaque psoriasis. Thus, Cal/BD foam should be considered a valuable therapeutic tool for clinicians to use with psoriasis patients across all disease severities.
- Møller AH, Erntoft S, Vinding GR, Jemec GB. A systematic literature review to compare quality of life in psoriasis with other chronic diseases using EQ-5D-derived utility values. Patient Relat Outcome Meas 2015; 6: 167–177.
- Papp KA, Gniadecki R, Beecker J, Dutz J, Gooderham MJ, Hong CH, Kirchhof MG, Lynde CW, Maari C, Poulin Y, Vender RB. Psoriasis Prevalence and Severity by Expert Elicitation. Dermatol Ther (Heidelb). 2021 Jun;11(3):1053-1064. doi: 10.1007/s13555-021-00518-8. Epub 2021 Apr 22. PMID: 33886086; PMCID: PMC8163919.
- Langley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis. 2005 Mar;64 Suppl 2(Suppl 2):ii18-23; discussion ii24-5. doi: 10.1136/ard.2004.033217. PMID: 15708928; PMCID: PMC1766861.
- Strober B, Ryan C, van de Kerkhof P, van der Walt J, Kimball AB, Barker J, Blauvelt A; International Psoriasis Council Board Members and Councilors. Recategorization of psoriasis severity: Delphi consensus from the International Psoriasis Council. J Am Acad Dermatol. 2020 Jan;82(1):117-122. doi: 10.1016/j. jaad.2019.08.026. Epub 2019 Aug 16. PMID: 31425723.
- Stein Gold LF, Kircik LH, Pariser DM. Understanding topical therapies for psoriasis. Cutis. 2019 Apr;103(4S):S8-S12. PMID: 31116805.
- Norsgaard H, Kurdykowski S, Descargues P, Gonzalez T, Marstrand T, Dünstl G, Røpke M. Calcipotriol counteracts betamethasone-induced decrease in extracellular matrix components related to skin atrophy. Arch Dermatol Res. 2014 Oct;306(8):719-29. doi: 10.1007/ s00403-014-1485-3. Epub 2014 Jul 16. PMID: 25027750; PMCID: PMC4168021.
- Vakirlis E, Kastanis A, Ioannides D. Calcipotriol/betamethasone dipropionate in the treatment of psoriasis vulgaris. Ther Clin Risk Manag. 2008;4(1):141-148. doi:10.2147/tcrm.s1478.
- Shttps://health-products. canada.ca/dpd-bdpp/info. do?lang=en&code=94445.
- Koo J, Tyring S, Werschler WP, Bruce S, Olesen M, Villumsen J, Bagel J. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris–A randomized phase II study. J Dermatolog Treat. 2016;27(2):120-7. doi: 10.3109/09546634.2015.1083935. Epub 2015 Oct 7. PMID: 26444907; PMCID: PMC4772687.
- Paul C, Stein Gold L, Cambazard F, Kalb RE, Lowson D, Bang B, Griffiths CE. Calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled PSO-ABLE study. J Eur Acad Dermatol Venereol. 2017 Jan;31(1):119-126. doi: 10.1111/ jdv.13859. Epub 2016 Aug 17. PMID: 27531752; PMCID: PMC6207928.
- Lebwohl M, Kircik L, Lacour JP, Liljedahl M, Lynde C, Mørch MH, Papp KA, Perrot JL, Gold LS, Takhar A, Thaçi D, Warren RB, Wollenberg A. Twice-weekly topical calcipotriene/ betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial). J Am Acad Dermatol. 2021 May;84(5):1269-1277. doi: 10.1016/j.jaad.2020.09.037. Epub 2020 Sep 18. PMID: 32950546.
- Wu JJ, Hansen JB, Patel DS, Nyholm N, Veverka KA, Swensen AR. Effectiveness comparison and incremental cost-per-responder analysis of calcipotriene 0.005%/ betamethasone dipropionate 0.064% foam vs. halobetasol 0.01%/ tazarotene 0.045% lotion for plaque psoriasis: a matching-adjusted indirect comparative analysis. J Med Econ. 2020 Jun;23(6):641-649. doi: 10.1080/13696998.2020.1722139. Epub 2020 Mar 2. PMID: 31985301.
- Leonardi C, Bagel J, Yamauchi P, Pariser D, Xu Z, Olesen M, Østerdal ML, Stein Gold L. Efficacy and Safety of Calcipotriene Plus Betamethasone Dipropionate Aerosol Foam in Patients With Psoriasis Vulgaris–a Randomized Phase III Study (PSO-FAST). J Drugs Dermatol. 2015 Dec;14(12):1468-77. PMID: 26659941.
- Jalili A, Lebwohl M, Stein Gold L et al. Itch relief in patients with psoria-sis: effectiveness of calcipotriol plus betamethasone dipropionate foam. J Eur Acad Dermatol Venereol 2019; 33: 709–717.
- Griffiths CE, Stein Gold L, Cambazard F, Kalb RE, Lowson D, Møller A, Paul C. Greater improvement in quality of life outcomes in patients using fixed-combination calcipotriol plus betamethasone dipropionate aerosol foam versus gel: results from the PSO-ABLE study. Eur J Dermatol. 2018 Jun 1;28(3):356-363. doi: 10.1684/ejd.2018.3302. PMID: 29952297.