Disparities in State Medicaid Coverage of Tretinoin for Pigmentary Disorders Compared to Acne Vulgaris.

BACKGROUND: Melasma and post-inflammatory hyperpigmentation (PIH) are common cosmetic dermatologic conditions that predominantly affect patients with skin phototypes III-VI. Comparing treatment coverage for these pigmentary disorders to treatment coverage for acne vulgaris may demonstrate disparities in insurance coverage for diseases that primarily affect patients of color. OBJECTIVE: Describe differences in Medicaid coverage for topical tretinoin for melasma and PIH vs. acne vulgaris in all 50 states and the District of Columbia. METHODS: This is a cross-sectional study of Medicaid insurance plans in all 50 states and the District of Columbia conducted between February 1 and 28, 2023. Data was collected from online publicly available preferred drug lists, prior authorization criteria, and email/telephone inquiries. Information was collected regarding coverage restrictions, including age restrictions, diagnostic restrictions, preferred drug status, and prior authorization requirements. RESULTS: Complete coverage data for all three clinical indications was retrieved from 30 (58.8%) states; partial coverage data for acne vulgaris was retrieved from 16 (31.4%) states; no coverage data was retrieved from 5 (9.8%) states. Of states reporting coverage data, topical tretinoin is covered in 45 (97.8%) states for acne vulgaris and 10 (33.3%) states for melasma and post-inflammatory hyperpigmentation. There was decreased Medicaid coverage of topical tretinoin for acne vulgaris compared to melasma and PIH (P<0.05).  Conclusion: There is differential Medicaid coverage for acne vulgaris compared to pigmentary disorders which disproportionately affect patients of color. Greater advocacy is required to ensure equal treatment for conditions that affect racial minority patients. J Drugs Dermatol. 2024;23(6):e151-e153.     doi:10.36849/JDD.8069e  .

A Non-Surgical and Cost-Effective Treatment Approach Employing Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Non-Melanoma Skin Cancers.

BACKGROUND: Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven. OBJECTIVE: We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers. METHODS: This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis. RESULTS: A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72). CONCLUSIONS: The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. J Drugs Dermatol. 2021;20(3):260-267. doi:10.36849/JDD.5427.

Two drugs facing key patent expirations and potential generic entry from July to August 2020.

A challenge in anticipating generic entry is elucidating which patents and regulatory protections constrain generic entry.

The economic research of arsenic trioxide for the treatment of newly diagnosed acute promyelocytic leukemia in China.

BACKGROUND: The objective of this study was to conduct the first systematic evaluation of the long-term economic impact of arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) for the treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) from the perspective of the Chinese health care system. METHODS: On the basis of clinical data from a randomized phase 3 trial, a time-dependent Markov model with 4 health states (complete remission, relapse or treatment failure, post-treatment failure, and death) was used to evaluate the incremental costs per quality-adjusted life-year (QALY) gained from the ATO plus ATRA regimen compared with the ATRA plus chemotherapy (CT) regimen over a 30-year period. All costs were adjusted to 2018 levels based on the Chinese Consumer Price Index. Both costs and health outcomes were discounted by 3% annually. One-way sensitivity analysis and probability sensitivity analysis were performed. RESULTS: Compared with the ATRA plus CT strategy, the ATO plus ATRA strategy was associated with 1.38 additional QALYs gained and $392.05 (estimated in 2018 US dollars) in incremental costs per patient over 30 years. Consequently, the incremental cost-effectiveness ratio was $284.02 per QALY gained, which was far below the Chinese willingness-to-pay threshold of $29,306 per QALY gained. Sensitivity analyses demonstrated the robustness of these results. CONCLUSIONS: From the perspective of the Chinese health care system, the ATO plus ATRA strategy is cost-effective for patients with newly diagnosed APL compared with the ATRA plus CT strategy. Therefore, the authors strongly suggest that China's health authorities choose the former strategy for these patients, whether for the elderly or for young people.

Efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment in the treatment of mild to moderate psoriasis vulgaris: A randomized, single-blind, multicenter clinical trial.

To assess the efficacy, safety, and cost-effectiveness of all-trans retinoic acid/Clobetasol Propionate Compound Ointment and calcipotriol/betamethasone dipropionate ointment in the treatment of mild-to-moderate patients with psoriasis vulgaris. This was a randomized, single-blind, multicenter clinical trial. A total of 240 patients were randomized to receive twice-daily all-trans retinoic acid/Clobetasol Propionate Compound Ointment (treatment group) or once-daily calcipotriol/betamethasone dipropionate ointment (control group) for 4 weeks. The efficacy, safety, and cost-effectiveness were assessed at Weeks 2 and 4. After 4 weeks, both groups showed a significant clinical improvement compared to baseline (88.33% vs. 89.83%, respectively, p = .7112). But PASI 75 response in the treatment group was superior to the control group (44.12% vs. 28.57%, respectively, p = .0200), at Week 4. SSRI improvement rate in the treatment group was also superior to control group (67.11% vs. 59.43%, respectively, p = .0119) at Week 4. All-trans retinoic acid/Clobetasol Propionate Compound Ointment showed a significant clinical improvement in erythema, infiltration, and scales of skin lesions and PASI score compared to baseline. 1.67% of patients (treatment group) reported adverse reactions compared to 2.50% (control group) with no statistical significance. In addition, the cost-effectiveness assessment showed a higher cost-effectiveness of the treatment group compared to the control group in 4 weeks (199.25 vs. 801.51). All-trans retinoic acid/Clobetasol Propionate Compound Ointment was effective and safe in the treatment of psoriasis vulgaris with similar efficacy as calcipotriol/betamethasone dipropionate ointment and lower treatment costs.

Cost-Effectiveness Analysis of Treating Acute Promyelocytic Leukemia Patients With Arsenic Trioxide and Retinoic Acid in the United States.

INTRODUCTION: This study estimated the cost-effectiveness of arsenic trioxide (ATO) added to all-trans retinoic acid (ATRA) when used in first-line acute promyelocytic leukemia (APL) treatment. MATERIALS AND METHODS: A Markov cohort model was developed with 3 states: stable disease (during first- or second-line treatment), disease event, and death. Newly diagnosed patients with low- to intermediate-risk APL were included and each month could remain in their current health state or move to another. Treatment consisted of ATO + ATRA, ATRA + idarubicin (IDA), or ATRA + cytarabine (AraC) + additional chemotherapy. After an initial disease event, patients discontinued first-line therapy and switched to a second-line ATO regimen. Efficacy and safety data were obtained from published trials; quality of life/utility estimates were obtained from the literature; costs were obtained from US data sources. Costs and outcomes over time were used to calculate incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Compared to ATRA + AraC + additional chemotherapy, ATRA + IDA treatment had ICERs of $2933 per life-year (LY) saved and $3122 per quality-adjusted life-year (QALY) gained. Compared to the ATRA + IDA regimen, first-line ATO + ATRA treatment had ICERs of $4512 per LY saved and $5614 per QALY gained. Results were sensitive to changes in pharmacy costs of the ATO + ATRA regimen during consolidation. CONCLUSION: The ATO + ATRA regimen is highly cost-effective compared to ATRA + AraC + additional chemotherapy or ATRA + IDA in the treatment of newly diagnosed low- to intermediate-risk APL patients.

Reduced medical costs and hospital days when using oral arsenic plus ATRA as the first-line treatment of acute promyelocytic leukemia.

We have demonstrated that oral arsenic (Realgar-Indigo naturalis formula, RIF) plus all-trans retinoic acid (ATRA) is not inferior to intravenous arsenic trioxide (ATO) plus ATRA as the first-line treatment of acute promyelocytic leukemia (APL). To compare the cost-effectiveness of oral and intravenous arsenic, we analyzed the results of 30 patients in each group involved in a randomized controlled trial at our center. The median total medical costs were $13,183.49 in the RIF group compared with $24136.98 in the ATO group (p<0.0001). This difference primarily resulted from the different costs of induction therapy (p=0.016) and maintenance treatment (p<0.0001). The length of hospitalization for the RIF group was significantly lower than that for the ATO group (24 vs. 31 days, p<0.0001) during induction therapy. During maintenance treatment, the estimated medical costs were $2047.14 for each patient in the RIF group treated at home compared with $11273.81 for each patient in the ATO group treated in an outpatient setting (p<0.0001). We conclude that oral RIF plus ATRA significantly reduced the medical costs and length of hospital stay during induction and remission therapy compared with ATO plus ATRA in APL patients.

Cost-effectiveness of oral alitretinoin in patients with severe chronic hand eczema--a long-term analysis from a Swiss perspective.

BACKGROUND: The impact on patients suffering from chronic hand eczema (CHE) is enormous, as no licensed systemic treatment option with proven efficacy for CHE is available. Alitretinoin is a novel agent which showed high clinical efficacy in patients with severe, refractory CHE. We assessed the cost-effectiveness of alitretinoin for CHE patient treatment from a Swiss third party payer perspective. A further objective of this study was to determine the burden of disease in Switzerland. METHODS: A long-term Markov cohort simulation model was used to estimate direct medical costs (euro) and clinical effectiveness (quality adjusted life years, QALYs) of treating severe CHE patients with alitretinoin. Comparison was against the standard treatment of supportive care (optimised emollient therapy). Information on response rates were derived from a randomized controlled clinical trial. Costs were considered from the perspective of the Swiss health system. Swiss epidemiological data was derived from official Swiss Statistic institutions. RESULTS: Annual costs of alitretinoin treatment accounted for 2'212 euro. After a time horizon of 22.4 years, average remaining long-term costs accounted for 42'208 euro or 38'795 euro in the alitretinoin and the standard treatment arm, respectively. Compared with the standard therapy, the addition of alitretinoin yielded an average gain of 0.230 QALYs at the end of the simulation. Accordingly, the incremental cost-effectiveness ratio resulted in 14'816 euro/QALY gained. These results were robust to changes in key model assumptions. CONCLUSION: The therapy for CHE patients is currently insufficient. In our long-term model we identified the treatment with alitretinoin as a cost-effective alternative for the therapy of CHE patients in Switzerland.

Alitretinoin for the treatment of severe chronic hand eczema.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below 20,000. pounds When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to 22,312 pounds per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of 12,931 pounds per QALY gained versus supportive care (placebo). However, the model underestimates the costs of treatment associated with alitretinoin. The manufacturer assumed that patients receiving alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturer's model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to 30,000 pounds per QALY gained for alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of alitretinoin. NICE recommended the use of alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

Alitretinoin for severe chronic hand eczema: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of alitretinoin (Basilea Pharmaceuticals Ltd, Basel, Switzerland) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with severe chronic hand eczema (CHE), as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE's subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer's decision analytic model to examine the impact of altering some of the key assumptions. The main clinical effectiveness data were derived from a single-placebo randomized controlled trial (RCT) of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe CHE unresponsive to topical corticosteroids. A significantly greater proportion of patients achieved 'clear' or 'almost clear' hands by week 24 with alitretinoin than those using placebo: 48% with alitretinoin 30 mg (p < 0.001); 28% with alitretinoin 10 mg (p < 0.005); 17% with placebo. Most patients who responded remained in remission during the 24-week follow-up period. The most commonly reported adverse event was dose-dependent headache, with rates of 20% in the alitretinoin 30 mg group and 11% in the alitretinoin 10 mg group, respectively. Serious adverse events were rare, although alitretinoin was associated with increases in both total cholesterol and triglycerides. No direct or indirect comparisons of alitretinoin with any of the relevant treatment comparators (psoralen + UVA [PUVA], ciclosporin or azathioprine) were available. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were pound8614 per QALY versus ciclosporin, - pound469 per QALY versus PUVA (with alitretinoin dominant) and pound10 612 per QALY versus azathioprine (year 2007-8 values). In response to a request from the ERG, the manufacturers provided a revised model that compared alitretinoin only with placebo, for which the ICER was reported to be pound12 931. However, the omission of adverse events entirely from this revised model, in combination with a number of other factors, led the ERG to conclude that the model underestimated the costs of treatment associated with alitretinoin. Estimates of health-related quality of life (HR-QOL) were the primary source of uncertainty, with the use of values from an alternative source producing ICERs of around pound30 000 per QALY gained. The ERG concluded that, although the evidence presented indicates that alitretinoin is efficacious in the treatment of severe CHE, it gives little indication of alitretinoin's efficacy relative to likely alternative treatment options or its efficacy and safety in the longer term. Although the ICERs estimated by the manufacturer suggested that alitretinoin may be cost effective for use in the UK NHS, utilizing the alternative HR-QOL estimates resulted in a 2-fold increase in the ICER. Thus, there was considerable uncertainty as to the true ICER of alitretinoin versus the relevant treatment comparators. The Appraisal Committee recommended that alitretinoin be provided to those patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. They recommended that treatment be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

Cost-effectiveness of a hydroquinone/tretinoin/fluocinolone acetonide cream combination in treating melasma in the United States.

BACKGROUND: Melasma, a disorder of facial hyperpigmentation, presents a treatment obstacle to many physicians. Combination therapy with hydroquinone, tretinoin, and fluocinolone acetonide has proven effective, but it is generally more expensive than other treatments. OBJECTIVE: To assess the cost-effectiveness of daily triple combination therapy (TCT) compared with daily use of each possible pair of agents (dyads) and twice daily use of hydroquinone (HQ) alone from a payer's perspective. METHODS: Efficacy data were obtained from two clinical trials with the primary endpoint being complete clearance at 8 weeks. For all treatments, total cost per successful treatment was calculated. The incremental cost-effectiveness ratio (ICER) was calculated for each dyad and for HQ monotherapy in comparison with TCT. Sensitivity analyses for efficacy and number of office visits were similarly performed. RESULTS AND CONCLUSION: TCT consistently had the lowest cost per primary success in all the analyses performed. Furthermore, ICERs were low, indicating that TCT's superior efficacy is attained at marginal cost increases. Our results indicate that TCT is the most cost-effective treatment when compared with any of its dyads or with hydroquinone alone.

Cost-effectiveness of a fixed combination of hydroquinone/tretinoin/fluocinolone cream compared with hydroquinone alone in the treatment of melasma.

BACKGROUND: A once-daily fixed combination of hydroquinone, tretinoin, and fluocinolone acetonide (Tri-luma) is a newly available treatment for melasma. OBJECTIVE: To assess cost-effectiveness of triple combination therapy (TCT) applied once daily and hydroquinone alone applied twice daily in the U.S., Argentina, Brazil, Chile, and Colombia from a payer's perspective. METHODS: Clinical data and utilization of key health resources (medication only) were assessed within an 8-week clinical trial conducted in Brazil. Total cost per primary success (complete clearing) was used to compare each treatment with not treating and incremental cost effectiveness ratios were used to compare between treatments. RESULTS AND CONCLUSION: TCT had a 30% better rate of complete clearing than hydroquinone with a lower cost in the U.S. and an incremental cost in other countries. In every country, cost per primary success was lower for TCT than for hydroquinone. Results were robust to varying assumptions of success rates and quantity used.

Management of acne.

Precise classification methods are used to define acne according to type (comedonal, papulopustular, or nodular) and severity. The relative effectiveness of several topical and systemic agents has been established in clinical trials, making possible an algorithm of specific treatment decisions based on acne classification.

Once-daily tazarotene 0.1 % gel versus once-daily tretinoin 0.1 % microsponge gel for the treatment of facial acne vulgaris: a double-blind randomized trial.

The efficacy and tolerability of tazarotene 0.1% gel and tretinoin 0.1% microsponge gel were evaluated in a multicenter, double-blind, randomized, parallel-group study in patients with mild-to-moderate inflammatory facial acne vulgaris. A total of 169 patients were randomized to once-daily applications of one of these topical retinoids for 12 weeks. Both agents were associated with significant reductions from baseline in the noninflammatory and inflammatory lesion counts. Tazarotene treatment was associated with a significantly greater incidence of treatment success (defined as > or = 50% global improvement [67% vs 49%; P=.03]) and significantly greater reductions in overall disease severity (36% vs 26%; P=.02) and noninflammatory lesion count (60% vs 38% at week 12; P=.02) than tretinoin microsponge treatment. Both drugs were well tolerated, with mean levels of dryness, burning, pruritus, erythema, and peeling generally being no more than trace throughout the study. There were no clinically significant between-group differences in these measures of tolerability. Two patients in each group (2%) discontinued because of treatment-related adverse events. The mean amount of medication applied by the patients was 0.28 g per application with tazarotene and 0.41 g per application with tretinoin microsponge, resulting in cost-effectiveness ratios of $81.45 per treatment success with tazarotene and $108.24 per treatment success with tretinoin microsponge. Tazarotene was observed to have greater efficacy and comparable tolerability and to be a cost-effective alternative to tretinoin 0.1% microsponge gel.

Is prior authorization of topical tretinoin for acne cost effective?

OBJECTIVE: To determine whether prior authorization of topical tretinoin for acne is in the best interest of health insurers and, if so, to determine the optimal prior authorization age for topical tretinoin. STUDY DESIGN: A retrospective, cross-sectional study of data from the National Ambulatory Medical Care Survey was performed. PATIENTS AND METHODS: We performed a sensitivity analysis using published data on the age distribution for topical tretinoin prescriptions for acne and nonacne indications to estimate the cost of topical tretinoin and the cost of performing prior authorizations as a function of the prior authorization age. RESULTS: A prior authorization age of 25 for topical tretinoin is not cost effective for health insurers. If prior authorization is required, an age threshold of 35 or older is most cost effective. The total cost of topical tretinoin (the sum of the drug costs plus the prior authorization costs) changes little with changes in the prior authorization age; if the prior authorization age is set too low, total costs increase (because the number of prior authorizations increase). CONCLUSIONS: Prior authorization for topical tretinoin is of no great benefit to insurers. As the prior authorization age decreases, the cost of requiring prior authorization increases. Eliminating prior authorization altogether would result in at most a small increase in costs and would be balanced by the benefits to both patients and physicians.

Kaposi's sarcoma: new topical treatment approved.

AIDS: Ligand Pharmaceuticals has received FDA approval for Panretin Gel (alitretinoin) for topical treatment of Kaposi's sarcoma. The company has also filed for approval in Europe and Canada. The gel is applied twice daily, and a 4- to 6-month course of therapy costs between $3,900 and $5,800. The main side effect is skin irritation; 7 percent of patients withdrew from trials because of skin toxicity. Panretin capsules have been tested in phase II clinical trials. Results of 2 trials with 402 patients were presented at the Retroviruses conference.^ieng

[All-trans retinoic acid (Tretinoin)].

Differentiation therapy with all-trans retinoic acid (ATRA, tretinoin) alone or in combination with chemotherapy induces around 90% complete remission in acute promyelocytic leukemia (APL). By giving non-cross resistant chemotherapy as postremission therapy, more than 50% of APL, especially more than 70% of APL patients of age less than 30, became curable. Since this active form of Vitamin A causes less toxicity and fewer complications compared with other cytotoxic drugs, the medical costs required are less. Therefore, ATRA therapy should be incorporated as a first-line therapy for APL.