Cost-effectiveness of Topical Therapies for Plaque Psoriasis
We performed a cost-effectiveness analysis of potential treatment sequences for psoriasis of the trunk, limbs and scalp. This model was adapted from published analyses evaluating a more limited range of comparators. Our results indicate that the various topical therapies produce similar health benefits, but they differ substantially in terms of cost.
Based on the costs and benefits of 118 compared sequences for the treatment of trunk and limb psoriasis, the results showed potent corticosteroids to be highly cost-effective, although there is some uncertainty regarding what frequency of application offers the best value for money. Twice-daily application was more cost-effective than once-daily use in the base case, but this was reversed when patient-assessed response outcomes were modelled (Table S2; see Supporting Information). The model also does not capture potential AEs of potent steroids (e.g. skin atrophy, rapid relapse) due to a lack of data. Therefore, even if application twice daily is more effective at inducing a response than once-daily use, the risks of a higher dose are likely to outweigh the potential benefits.
Separate application of vitamin D and potent corticosteroids [TCA (am/pm)] represents the most cost-effective first-line option for trunk and limb psoriasis if twice-daily corticosteroids are deemed too aggressive. Once-daily TCF product was more effective than TCA (am/pm); however, the slight additional benefit (equivalent to 0·40 quality-adjusted days) would come at a cost of nearly £200 more per patient, a difference explained almost entirely by its high cost relative to separate vitamin D and corticosteroid products (two to four times more costly). We explicitly considered whether the practicality of a once-daily combined product might make it cost-effective given the problems that many patients have adhering to twice-daily regimens. A sensitivity analysis wherein 40% of patients prescribed a twice-daily regimen were assumed to apply their topical only once daily showed that the benefits of a once-daily TCF product were still too small to justify the extra cost. This cost, multiplied across the numerous patients using topical therapies to manage their psoriasis, would represent a huge NHS expenditure, with insufficient evidence that it would dramatically improve outcomes. The most efficient placement of TCF product would therefore be after both potent corticosteroids (once and twice daily) and TCA (am/pm) have failed to bring about the desired response.
After comparing 169 sequences of scalp treatments, results suggest that initial treatment with once-daily very potent corticosteroids is likely to offer the best value for NHS resource; however, there is concern that very potent corticosteroids are an aggressive strategy and carry greater risk of steroid-related AEs, which the model did not capture. The second-most cost-effective first-line treatment was once-daily potent corticosteroids. TCF product was dominated by very potent corticosteroids and was not cost-effective compared with potent corticosteroids or vitamin D analogues; the very modest additional benefits compared with these agents (equivalent to 0·24–0·75 quality-adjusted days) might be considered cost-effective only if WTP thresholds were substantially higher than NICE's £20 000. These conclusions were robust to changes in key assumptions including adherence, efficacy, cost and time horizon.
Across both populations, vitamin D is optimal when looking to avoid continuous use of corticosteroids. In scalp psoriasis particularly, the additional benefits of twice-daily compared with once-daily vitamin D are negligible; therefore, other considerations such as convenience and cosmetic acceptability should have greater influence on treatment decisions. Indeed, such considerations are important across all agents, as the added benefits of a second daily application quickly wane if adherence is adversely affected.
Short-contact dithranol, coal tar and coal-tar shampoo performed less well compared with alternatives. For example, the majority of patients offered only coal-tar shampoo failed treatment and were referred onward, making the true costs of coal-tar shampoo much higher than its acquisition cost alone. It should be reserved for less severe scalp psoriasis or combined with other more effective topical agents.
Although these analyses provide the most complete evaluation of licensed topical therapies to date, the results should be considered in light of several limitations related to gaps in the clinical and economic evidence base. Firstly, costs and consequences of treatment-related AEs were not captured. Longer-term, good-quality data on the safety of topical therapies is lacking, but it is generally accepted that long-term use of corticosteroids carries risks of local AEs and, in those with extensive disease, potential systemic AEs. Had these AEs been included, the expected benefits of corticosteroids, particularly in higher doses, may have been outweighed by their risks. Secondly, the model focused on the induction of disease clearance, not on the maintenance of clearance. Maintenance trials were limited and, where available, inadequately reported for use in the economic model. The model takes a relatively short time horizon considering that psoriasis is a chronic, long-term condition for which patients may take up treatment intermittently for many years. Longer time horizons of up to 10 years were explored in sensitivity analyses and conclusions were insensitive to these extensions. Frequency and severity of relapse, selection for and speed of onward referral, adherence, methods of self-management and long-term safety are all inadequately addressed by the published literature, and future clinical studies should be designed to address these gaps to improve the value, validity and interpretability of health economic conclusions. Finally, evidence assessing the impact of localized psoriasis on quality of life is limited and quite uncertain. Future studies measuring patients' quality of life using preference-based tools or mapping algorithms from disease-specific measures will help to quantify the disease's impact and the gains associated with effective treatment.
In conclusion, this study demonstrates the likely cost-effectiveness of corticosteroids for patients with chronic plaque psoriasis. Potent corticosteroids, used alone or in combination with vitamin D for patients with trunk or limbs psoriasis, are likely to offer the best value for money, while potent or very potent corticosteroids are likely to be best for patients with scalp psoriasis
Discussion
We performed a cost-effectiveness analysis of potential treatment sequences for psoriasis of the trunk, limbs and scalp. This model was adapted from published analyses evaluating a more limited range of comparators. Our results indicate that the various topical therapies produce similar health benefits, but they differ substantially in terms of cost.
Based on the costs and benefits of 118 compared sequences for the treatment of trunk and limb psoriasis, the results showed potent corticosteroids to be highly cost-effective, although there is some uncertainty regarding what frequency of application offers the best value for money. Twice-daily application was more cost-effective than once-daily use in the base case, but this was reversed when patient-assessed response outcomes were modelled (Table S2; see Supporting Information). The model also does not capture potential AEs of potent steroids (e.g. skin atrophy, rapid relapse) due to a lack of data. Therefore, even if application twice daily is more effective at inducing a response than once-daily use, the risks of a higher dose are likely to outweigh the potential benefits.
Separate application of vitamin D and potent corticosteroids [TCA (am/pm)] represents the most cost-effective first-line option for trunk and limb psoriasis if twice-daily corticosteroids are deemed too aggressive. Once-daily TCF product was more effective than TCA (am/pm); however, the slight additional benefit (equivalent to 0·40 quality-adjusted days) would come at a cost of nearly £200 more per patient, a difference explained almost entirely by its high cost relative to separate vitamin D and corticosteroid products (two to four times more costly). We explicitly considered whether the practicality of a once-daily combined product might make it cost-effective given the problems that many patients have adhering to twice-daily regimens. A sensitivity analysis wherein 40% of patients prescribed a twice-daily regimen were assumed to apply their topical only once daily showed that the benefits of a once-daily TCF product were still too small to justify the extra cost. This cost, multiplied across the numerous patients using topical therapies to manage their psoriasis, would represent a huge NHS expenditure, with insufficient evidence that it would dramatically improve outcomes. The most efficient placement of TCF product would therefore be after both potent corticosteroids (once and twice daily) and TCA (am/pm) have failed to bring about the desired response.
After comparing 169 sequences of scalp treatments, results suggest that initial treatment with once-daily very potent corticosteroids is likely to offer the best value for NHS resource; however, there is concern that very potent corticosteroids are an aggressive strategy and carry greater risk of steroid-related AEs, which the model did not capture. The second-most cost-effective first-line treatment was once-daily potent corticosteroids. TCF product was dominated by very potent corticosteroids and was not cost-effective compared with potent corticosteroids or vitamin D analogues; the very modest additional benefits compared with these agents (equivalent to 0·24–0·75 quality-adjusted days) might be considered cost-effective only if WTP thresholds were substantially higher than NICE's £20 000. These conclusions were robust to changes in key assumptions including adherence, efficacy, cost and time horizon.
Across both populations, vitamin D is optimal when looking to avoid continuous use of corticosteroids. In scalp psoriasis particularly, the additional benefits of twice-daily compared with once-daily vitamin D are negligible; therefore, other considerations such as convenience and cosmetic acceptability should have greater influence on treatment decisions. Indeed, such considerations are important across all agents, as the added benefits of a second daily application quickly wane if adherence is adversely affected.
Short-contact dithranol, coal tar and coal-tar shampoo performed less well compared with alternatives. For example, the majority of patients offered only coal-tar shampoo failed treatment and were referred onward, making the true costs of coal-tar shampoo much higher than its acquisition cost alone. It should be reserved for less severe scalp psoriasis or combined with other more effective topical agents.
Although these analyses provide the most complete evaluation of licensed topical therapies to date, the results should be considered in light of several limitations related to gaps in the clinical and economic evidence base. Firstly, costs and consequences of treatment-related AEs were not captured. Longer-term, good-quality data on the safety of topical therapies is lacking, but it is generally accepted that long-term use of corticosteroids carries risks of local AEs and, in those with extensive disease, potential systemic AEs. Had these AEs been included, the expected benefits of corticosteroids, particularly in higher doses, may have been outweighed by their risks. Secondly, the model focused on the induction of disease clearance, not on the maintenance of clearance. Maintenance trials were limited and, where available, inadequately reported for use in the economic model. The model takes a relatively short time horizon considering that psoriasis is a chronic, long-term condition for which patients may take up treatment intermittently for many years. Longer time horizons of up to 10 years were explored in sensitivity analyses and conclusions were insensitive to these extensions. Frequency and severity of relapse, selection for and speed of onward referral, adherence, methods of self-management and long-term safety are all inadequately addressed by the published literature, and future clinical studies should be designed to address these gaps to improve the value, validity and interpretability of health economic conclusions. Finally, evidence assessing the impact of localized psoriasis on quality of life is limited and quite uncertain. Future studies measuring patients' quality of life using preference-based tools or mapping algorithms from disease-specific measures will help to quantify the disease's impact and the gains associated with effective treatment.
In conclusion, this study demonstrates the likely cost-effectiveness of corticosteroids for patients with chronic plaque psoriasis. Potent corticosteroids, used alone or in combination with vitamin D for patients with trunk or limbs psoriasis, are likely to offer the best value for money, while potent or very potent corticosteroids are likely to be best for patients with scalp psoriasis
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