Formulary Decisions and the Evolution of Psoriasis Treatment

Transcription

1 perspectives Formulary Decisions and the Evolution of Psoriasis Treatment William Malatestinic, PharmD, MBA; 1 David Amato, MD; 1 Steven R. Feldman, MD, PhD 2 affiliations: 1 Eli Lilly and Company, Indianapolis, IN 2 Wake Forest Baptist Medical, Winston- Salem, NC address correspondence to: William Malatestinic, PharmD, MBA Eli Lilly USA, LLC Indianapolis, IN Phone: malatestinic_bill@lilly.com abstract: Psoriasis is a common and significant illness characterized by systemic inflammation. In its mildest form, psoriasis can often be managed with relatively low-cost topical therapies; but for moderate-to-severe disease, which affects 20% of psoriasis patients, these solutions are neither very effective nor practical. Treatments that provide excellent outcomes for many patients with more severe disease are now available. The development of medications specifically targeting the inflammatory process associated with psoriasis has the potential to change the lives of patients with moderate-to-severe disease. However, access to medications can be challenging due to step-therapy protocols and limited formulary options. Specifically, formulary options for biologic use in psoriasis are often based on a product s market share across multiple indications and resulting rebates. This article provides a comprehensive review of psoriasis and of the practical obstacles encountered in optimizing care of patients with moderate-to-severe disease. Implementing psoriasis-centered coverage policies may give psoriasis patients better access to safer, more clinically effective, and possibly more cost-effective treatment options. key words: psoriasis, biologics, access, formulary, efficacy, safety. citation: Journal of Clinical Pathways. 2015;1(2): Received September 25, 2015; accepted November 16, Psoriasis is an often-debilitating, chronic condition characterized by systemic inflammation that causes thick, red, and scaly skin lesions. Psoriasis affects up to 125 million people worldwide, and its prevalence varies by geography. In the United States, psoriasis affects upwards of 3% of the population. A recent population-based study found that the incidence of psoriasis in the United States is rising and has doubled within the last several decades. Psoriasis often arises in patients between the ages of 15 years and 35 years, although it can occur at any age and affects infants and older adults as well. 1-3 Costs of psoriasis totaled $112 billion in 2013; 4 approximately half of costs were due to direct costs (medication, photo therapy, provider visits, etc), whereas half were due to indirect costs (co-morbid illness, societal productivity, etc). Genetics play an important and complex role in the etiology of psoriasis, with numerous genes identified as being associated with the presence of disease. 5,6 As an inflammatory disease, multiple cell types and cytokines are involved in the pathogenesis of psoriasis. Recent research has identified that activation of a particular T- helper cell, the T H 17 cell, is a key process in the development of psoriasis. 7,8 Specific cytokines, notably interleukin 23 (IL-23) and IL-17A, are essential components of this inflammatory cascade. 9 disclosures: Dr. Malatestinic is an employee and stockowner of Eli Lilly and Company. Dr. Amato is an employee and stockowner of Eli Lilly and Company. Dr. Feldman is a consultant for Novartis, Amgen, AbbVie, Celgene, Janssen, Galderma, and Eli Lilly and Company with research grants from Novartis, Amgen, AbbVie, Janssen, and Galderma. He is also a patent holder at Wake Forest University School of Medicine. acknowledgements: Appreciation is expressed to Tamara Ball, MD, for writing and editorial contributions. Dr. Ball is employed by inventiv Health Clinical, who contracted with Eli Lilly and Company for the technical writing of this manuscript. November/December 2015 Journal of Clinical Pathways 43

2 Figure 1. Skin Lesions of Plaque Psoriasis. Psoriasis can be local in distribution, commonly affecting elbows, knees, or scalp, but it can appear in any location (Figure 1). A Psoriasis Area and Severity Index (PASI) score 10 is a commonly used tool to measure the severity and extent of psoriasis in clinical trials. PASI combines an assessment of the severity of lesions (redness, thickness, scaling) and the percentage of affected area into a single score in the range of 0 (no disease) to 72 (maximal disease). Psoriasis causes itch and pain, with up to 90% of patients experiencing itch 10 and up to 43% of patients experiencing pain. 12 Mild disease (less than 3% of body surface area [BSA] affected) occurs in approximately 80% of patients, while moderate (3 10% BSA) to severe (>10% BSA) disease is present in 20% of patients. 1 Psoriasis impacts quality of life, physical, psychological, and social functioning, regardless of the extent of involvement Prevalence Ratio for Patients with Psoriasis Rheumatoid Arthritis Metabolic syndrome Crohn s Disease Diabetes Mellitus Ulcerative Colitis Ischemic Heart Disease Disease State Hyperlipidemia Arterial Hypertension Obesity All Comorbidities Figure 2. Prevalence Ratios for Disease States in Patients With Psoriasis (N=13,981) versus in Patients Without Psoriasis (N=1,310,090) Journal of Clinical Pathways November/December

3 Psoriasis is associated with an increased prevalence of comorbidities affecting different organ systems (Figure 2), resulting in a decline in overall health and increased risk of early mortality. 17 Aside from cutaneous lesions and associated comorbidities, psoriasis has a significant impact on patients mental health and quality of life. Patients with psoriasis suffer a higher prevalence of depression, anxiety, and thoughts of suicide compared with patients in a general medical population. 15 If complete resolution of psoriasis is achieved, improvements in selfconsciousness, perceived quality of life measures, social activity, relationships, and sexual function occur. 18 In a Phase 3 trial, patients who achieved 90% and 100% improvement in their PASI scores (PASI 90 and PASI 100, respectively) had improvements in quality of life measures that exceeded those of patients with 75 89% or less improvement in their PASI scores. 19 the evolution of psoriasis treatment Dermatologists provide the majority of patient treatment for psoriasis, with rheumatologists providing some overlapping treatment to patients with psoriatic arthropathy. For many years, providers treated patients with more severe disease with systemic drugs, such as cyclosporine and methotrexate, which had significant side effects and only partial, and often variable, efficacy. 20 Advances in psoriasis therapy began with the approval of the tumor necrosis factor (TNF) inhibitor etanercept in Several TNF inhibitors were subsequently approved for moderate-to-severe disease, and initial treatment guidelines were published to assist the practitioner in management of the disease. Advances in therapy have been associated with an increase in the ability to achieve complete clearance of psoriasis in patients (Figure 3). When methotrexate was the gold standard of treatment, achieving an improvement in baseline PASI of 50% (PASI 50) was considered clinically meaningful, and a 25% response (PASI 25) was considered minimal. 22 With the approved use of TNF inhibitors for the treatment of moderateto-severe psoriasis, the primary clinical study objective was to achieve a 75% improvement from baseline PASI score (PASI 75). PASI 75 became the benchmark for adequate response in most studies More recently, molecules that directly target the key cytokines IL-23 and IL-17A have been approved. These more specific, targeted therapies are associated with higher rates of near complete or complete skin clearance (PASI 90, PASI 100) than was previously possible with methotrexate. 26,27 This has led to ongoing consideration of what the benchmark level of response should be (Figure 4). Before the 1990s, the primary unmet need for patients with psoriasis (especially in patients with moderate-to-severe disease) was developing drugs potent and safe enough to control patients disease. Now that more potent drugs with favorable safety profiles are available, these medications must be made available to patients in order to provide the best quality of care. Guidelines for therapy selection are available from organizations such as the American Academy of Dermatology (Figure 5). 28 In its mildest form, psoriasis can be managed with relatively low-cost therapies. Often, dermatologists treat patients with A B C Figure 3. PASI Improvement Scores and Corresponding Disease Severity. A, baseline. B, PASI 75. C, PASI 100. limited psoriasis with topical agents or phototherapy. However, for moderate-to-severe disease, which affects 20% of psoriasis patients, these solutions are neither very effective nor practical. Those with more extensive disease may receive phototherapy, systemic agents, or biologics. 29 paying for psoriasis treatment The development of medications specifically targeting the inflammatory process associated with psoriasis has the potential to change the lives of patients with moderate-to-severe disease. However, cost remains an impediment for patients and the insurance companies that support them. Unfortunately, it is not always easy to obtain medications that can lead to better outcomes. Payers currently utilize a number of strategies to encourage health care providers to select drugs that provide the best outcomes while minimizing the overall costs of treatment. These strategies include the application of evidence-based guidelines, increasing patient cost-sharing, requiring prior authorization, incorporating step-therapy protocols, and excluding some medications from coverage plans. 30 When incorporating these strategies, the need to assure optimal treatment outcomes in a timely manner has not been a primary consideration. A recent review of patient surveys from the National Psoriasis Foundation over an 8-year period found that the inability to obtain adequate insurance coverage was among the top reasons for under-treatment and patient dissatisfaction for those with moderate-to-severe disease. 31 As signs point to a future of health care in the United States in which treatment value is based on an emerging pool of high-quality evidence, 32 present strategies will need to be reassessed for value. Such reassessments will likely reveal that higher initial treatment cost results in lower global costs in the long-term. Given the associated comorbidities and the multi-faceted November/December 2015 Journal of Clinical Pathways 45

4 Goal PASI 50 Clinically Meaningful PASI 75 Significant PASI 90 Nearcomplete PASI 100 Complete Resolution Year Before and beyond Available Therapies MTX TNF IL-12/IL-23 IL-17 Figure 4. Historical View of Anticipated PASI Improvement over Time. 20,21,25 ways psoriasis impacts every aspect of a patient s life, it is inappropriate to categorize this unique, debilitating condition beneath the larger rubric of inflammatory disease. Presently, biologic formularies and step-therapy decisions are often made based on market share, meaning that those agents with a greater number of indications, regardless of efficacy within a specific disease state, are the primary agents of choice. 33 Hence, the needs of patients with psoriasis may not be met by policies and incentives that are largely derived from the care of disease states other than psoriasis (eg, rheumatoid arthritis). Such policies are unlikely to give patients with psoriasis optimal outcomes. Recent studies have demonstrated improved outcomes with newer, more targeted agents compared to a first generation TNF alpha antagonist. 27,34,35 alternative pricing models for psoriasis medications Formulary decision-makers, employers, and patients may benefit from consideration of pricing models beyond drug cost that include total cost for disease treatment, direct and indirect Psoriasis ± Psoriatic Arthritis Yes No Anti-TNF ± MTX Limited Disease Topicals/Targeted Phototherapy Extensive Disease UVB/PUVA Systemic Biologic Lack of Effect Figure 5. Algorithm for Treating Psoriasis Journal of Clinical Pathways November/December

5 (additional provider visits, follow-up labs, quality of life, decreased work productivity, etc). As an example, a recent study considered the cost per patient to achieve PASI 75 and a minimally important difference in quality of life after 12 weeks of treatment. The authors utilized models that included medication dosage, route of administration, laboratory monitoring, and clinical visits per manufacturing guidelines. Non-medical costs and indirect costs to patients were not incorporated into the model. Prices were based on the wholesale price of the drug in 2010, and all FDA-approved biologics for psoriasis at that time were considered. 36 With near-complete resolution (PASI 90) as an accepted improvement goal, 37 the cost to achieve that goal using earlier biologics versus newer agents that specifically target psoriasis will need to be explored. The final cost to achieve a specific outcome is dependent on the number needed to treat (NNT) with an agent to achieve one such outcome. One pharmacoeconomic study examined the NNT to achieve PASI improvements of 75%, 90%, and 100% using four FDA-approved biologics. Though the study was limited by lack of PASI 100 data, there was a consistent increase in price to achieve greater levels of clearance using those agents. 38 Understanding pharmacoeconomic implications of more effective treatments, including the relationship between cost and NNT, may be valuable as an alternative method of evaluation for medications used in psoriasis. conclusion Significant breakthroughs in our understanding of psoriasis have led to a new generation of highly effective therapies. Treatments now exist to provide excellent outcomes, including complete clearance, for many patients with more severe disease. Given the high direct physical, mental, and social costs of this illness and given the potential indirect costs from co-morbid illness, psoriasis treatment decisions should not be made based primarily on disease states other than psoriasis. 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