P. Oh, Aditya K. Gupta, T. Einarson
Jul 1, 1997
Citations
1
Influential Citations
7
Citations
Quality indicators
Journal
Journal of Cutaneous Medicine and Surgery
Abstract
Sommaire Background: Calcipotriol (calcipotriene) is a vitamin-D. analogue that has recently become available in North America for the treatment of psoriasis. Objective: To perform a pharmacoeconomic analysis to determine the cost-effectiveness from a government payer perspective of calcipotriol compared with mediumto highpotency steroids in the management of plaque-type psoriasis of limited severity. Methods: A stepwise analysis was performed. Relevant clinical algorithms were developed after a thorough literature review and input from a clinical panel. A meta-analysis of 31 clinical trials was performed to determine efficacy rates. Costs and resource estimates were obtained from formularies, physician responses, and the literature. Utility values (ratings of health states) were obtained through interviews with 30 patients. Three different decision analytic models reflecting different clinical scenarios in psoriasis management were developed. Total expected costs of therapy including drugs, physician visits, and treatment of failures, and the total Quality Adjusted Life Years (QALYs) for each strategy were calculated. Extensive sensitivity analyses were carried out to explore uncertainty in the parameter estimates entered into the models. Results: In the comparison of drug acquisition cost and efficacy, the incremental cost per cure was $414 using a 6-week course of calcipotriol compared with betamethasone valerate. The cost-utility analyses demonstrated that when calcipotriol was used as a second-line therapy to betamethasone valerate, it was as cost-effective as, if not more cost-effective than, clobetasol propionate used for 4 to 6 weeks. Also, when calcipotriol was used as a primary therapy in patients who had failed prior therapies, it was an attractive alternate compared to betamethasone dipropionate and fluocinonide. Conclusion: Calcipotriol is a relatively new addition to the topical therapies available to treat psoriasis. In general, tolerability and efficacy are similar to those of topical corticosteroids. In the treatment of psoriatic patients with limited plaque disease, calcipotriol, as a second-line treatment to betamethasone valerate, is a cost-effectivealternative to mediumto high-potency corticosteroids. Received 8/22/96. Accepted for publication 2/28/97. "Divisions of Clinical Pharmacology and "Derrnatology, Department of Medicine, Sunnybrook Health Science Centre, The University of Toronto Toronto Ontario; tFaculty of Pharmacy and Department of Health Administr~tion,The University of Toronto, Toronto, Ontario Supported by a grant from Leo Laboratories Canada Ltd. Reprint requests: Paul I. Oh, MD, FRCPC, Sunnybrook He~lth Science Centre, 2075 Bayview Ave., Rm. E-240, Toronto, Ontario, Canada M4N 3M5 7 Antecedents: Le ca1cipotriol (calcipotriene] est un analogue de la vitamine D3, maintenant offert en Amerique du Nord pour le traitement du psoriasis. Objectif: Effectuer une analyse pharmaco-economique pour determiner la rentabilite du ca1cipotriol par rapport aux steroides de puissance moyenne a forte dans le traitement d'un psoriasis en plaques de gravite moyenne, dans l'optique des gouvernements payeurs. Methodes: L'analyse a ete graduelle. Des algorithmes cliniques pertinents ont ete elabores apres examen approfondi de la litterature et consultation de cliniciens. Le taux d'efficacite a ete mesure par l'analyse de 31 essais cliniques. L'estimation des coiits et des ressources a ete tiree des formulaires, de communications avec des medecins, et de la litterature, Des entrevues avec 30 patients ont permis de connaitre l'utilite du medicament (classification des etats de sante). Trois modeles de decision analytiques refletant les differents scenarios cliniques observables dans le traitement du psoriasis ont ete elabores, Le coiit total prevu de la therapie, y compris les medicaments, les consultations, et l'echec des traitements a ere calcule pour chaque strategic, tout comme les annees-personnes sans invalidite. Des analyses de sensibilite approfondies ont ete menees pour etudier l'incertitude entourant l'evaluation des parametres composant les modeles, Resultats : Au bout de six semaines d'une etude sur l'application du ca1cipotriol et du valerate de betamethasone visant acomparer Ie cofit de l'acquisition des medicaments et l'efficacite de ces derniers, il apparait que Ie cofit differentiel est de 414$. L'analyse coiit-utilite montre que le ca1cipotriol, utilise comme traitement secondaire associe au valerate de betamethasone est aussi voire plus rentable que le propionate de clobetasol, utilise pendant 4 a 6 semaines. Par ailleurs, utilise comme traitement primaire chez des patients pour qui d'autres medicaments se sont reveles inoperants, le ca1cipotriol se degage comme une interessante solution de rechange si on le compare au dipropionate de betamethasone et au fluocinonide. Conclusion: Le ca1cipotriol est un ajout relativement recent aux medicaments topiques contre le psoriasis. En general, la tolerabilite et I'efficacite sont identiques a celles des corticosteroides topiques. Comme traitement secondaire associe au valerate de betamethasone, le ca1cipotriol est une solution de rechange rentable aux corticosteroides de puissance moyenne aforte pour Ie traitement des patients presentant un psoriasis en plaques modere, Psoriasis is a common and chronic condition affecting 1 to 2% of the general population.' In a recent review, psoriasis was described as a "disabling, though rarely lifethreatening, disease with a social and economic impact that is underestimated by physicians and health care providers."? A large proportion of patients may be able to control their psoriasis with topical corticosteroids, tar, anthralin, and 8 Journal of Cutaneous Medicine and Surgery I Volume 2, Number 1, 1997 keratolytics.l-' For more extensive and resistant psoriasis, ultraviolet light B (UVB), psora len plus ultraviolet A (PlNA), or systemic therapies such as methotrexate, retinoids, or cyclosporine may become necessary. Topical corticosteroids remain the most commonly employed initial therapy,' but their long-term use may be associated with local and/or systemic adverse effects such as cutaneous atrophy, development of telangiectasias, striae, tachyphylaxis, and hypothalamic-pituitary-adrenal suppression." Tars and anthralins are used less commonly in North America due to the staining, irritation, and inconvenience associated with their use. Calcipotriol (MC 903, calcipotriene)(CAL) is a vitamin-D, analogue that has recently become available in the USA; it has been in use for several years in Europe and Canada.":" Topical CAL is believed to inhibit keratinocyte proliferation and induce terminal differentiation of keratinocytes.' Several trials have demonstrated the shortterm and long-term efficacy and tolerability of CAL in the management of psoriasis.Y" In Canada, the drug acquisition price per gram of CAL is similar to the most potent topical corticosteroids, but greater than generic betamethasone-17-valerate, 0.1 %, the most commonly employed corticosteroid. We performed an economic evaluation to assess the relative cost-effectiveness of CAL in comparison to mediumand high-potency corticosteroids for the management of psoriasis of limited extent that had previously been treated with betamethasone-17-valerate, 0.1 %. Methods Step 2: Perspective The government payer perspective was adopted for the analysis. Total direct health care costs were therefore included and disaggregated into the Ontario Drug Benefit Formulary (ODBF) and the Ontario Health Insurance Plan (OHIP) components. Step 3: Time Horizon A 1-year time horizon was chosen for analysis to allow a sufficient period of time to capture important clinical events such as treatment success, failure, and relapse. This window was felt to be clinically relevant and representative of the lifetime pattern of disease in a patient with psoriasis because the condition does not necessarily worsen with time, but rather relapses and remits. In most clinical trials, the efficacy data on topical corticosteroids have been limited to 6 to 12 weeks; in contrast, long-term efficacy data were available for CAL. The short-term success rates for the corticosteroids were extrapolated to a longer time-horizon that may have inflated their estimates for success. Discounting was not used due to the short time-horizon for the analysis. Step 4: Clinical Management Algorithms Input from the expert panel of dermatologists and a thorough literature review helped us to define the clinical algorithms used in treating psoriasis and the probabilities of success, failure, and adverse effects. The pathways involved treatment sequences and combinations with CAL, either as firstor second-line therapy (Figs. 1, 2 and 3). The basic structures consisted of the following scheme: after choosing an initial drug, possible downstream events included initial "success" versus "failure" (Fig. 2, Model 2), and late The pharmacoeconomic analysis was conducted by an independent group of academic researchers following the rigorous framework outlined below. Calcipotriene Success