Shopping Cart

Introduction

A decision to begin therapy with a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor does not equate to patient accessibility. Their use in clinical practice is frequently offset by medication cost, insurance restrictions, and prescriber unfamiliarity (Table 1).^1,2 Additionally, health insurance approval does not ensure affordable copayments or patient adherence. Barriers to PCSK9 inhibitor therapy have recently been described in the literature.^1,2 Pharmacy claims data from Symphony Health Solutions was reviewed for factors contributing to diminished patient access to PCSK9 inhibitor therapy. During a 12-month period, 45,029 patients were prescribed a PCSK9 inhibitor and over 75% of claims were initially rejected. Ultimately, 45% of those patients receiving an initial rejection received approval of a PCSK9 inhibitor. Interestingly, low-density lipoprotein (LDL) values and therapy with a high-intensity statin did not impact approval rates; however, therapy with ezetimibe increased the likelihood of PCSK9 inhibitor approval. Prescriptions from a cardiologist and those filled at a specialty pharmacy also had a high success rate for approval. Lastly, the authors reported findings for patients with insurance approval, but abandoned prescriptions (e.g., filled and never picked up). Patients with $0 copays had a > 90% pick-up rate, whereas pick-up rates decreased to 20%-25% in those with ≥ $350 copays. A careful review of this data suggests thoughtful screening for appropriateness of PCSK9 inhibitor therapy, detailed completion of prior authorization paperwork, and affordable copayment amounts may lead to higher utilization of PCSK9 inhibitor therapy. The challenges identified by this analysis present a well-constructed role for pharmacists and specialty pharmacies, and will be discussed below in this article.

Table 1: Barriers to PCSK9 inhibitor therapy1,2

Medication cost Prior authorization process Patient selection criteria Patient copay Prescriber comfort with PCSK9 inhibitor therapy

The Role of the Pharmacist in Obtaining Prior Authorizations

Despite the known LDL reduction and cardiovascular benefits of PCSK9 inhibitors, the aforementioned rejection rate may discourage providers from attempting therapy in their patients. In 2017, the National Lipid Association (NLA) surveyed providers to assess the barriers to PCSK9 inhibitor use.² A variety of providers responded to the survey, with the majority being self-identified lipid specialists. Survey responders primarily utilized NLA treatment recommendations and targeted a specific LDL goal with utilization of high-intensity statins as first-line therapy. Use of PCSK9 inhibitors was reported in 2 primary patient groups: 1) those necessitating additional nonstatin therapy to achieve the desired LDL target and 2) those unwilling or unable to utilize statin therapy (due to adverse drug effects or patient refusal). Interestingly, the majority of respondents identified the presence of readily available resources to assist in the approval process for PCSK9 inhibitors. Even with reported resources, 1 in 6 providers never attempted to prescribe a PCSK9 inhibitor. Medication cost and paperwork required were listed as the primary reasons for prescription avoidance.

Pharmacists remain the frontline mediator between prescribers, patients, and payer sources. The high cost of PCSK9 inhibitor therapy has resulted in implementation of detailed criteria for use and routine prior authorization requirements. A clear understanding of the optimal steps to securing insurance approval of alirocumab or evolocumab can make for a seamless transition between prescription attainment and drug dispensing (Figure 1).³ To maximize successful attainment of insurance coverage, clear documentation of statin intolerance or treatment failure at maximal doses is mandatory. Additionally, some insurance companies may require documentation of statin intolerance or failure with multiple separate statin therapies and specific LDL level requirements. Clear adherence to the FDA-approved indications (familial hypercholesterolemia [FH] and clinical atherosclerotic cardiovascular disease [ASCVD]) and the corresponding NLA⁴ and ACC⁵ guidelines will also increase the likelihood of successful payer approval.

Figure 1: PCSK9 inhibitor prescribing checklist

Clinical ASCVD or FH present Document statin intolerance or allergy (if applicable) Utilization of maximally tolerated statin dose Document current LDL and goal LDL Complete the prior authorization form Prescription sent to a specialty pharmacy

All of these findings strengthen the role of pharmacists in providing prescription drug management for PCSK9 inhibitor eligible patients. Pharmacists are positioned to screen eligible patients for therapy, assist in the prior authorization process, educate patients on PCSK9 inhibitor use, and monitor and adjust therapy for optimal outcomes. Although limited data is published, many pharmacists and specialty pharmacies are filling this gap in care. Atanda et al has described one successful PCSK9 inhibitor program created at the University of Illinois Hospital and Health Sciences System (UIH).⁶ The pharmacy team identified a unique opportunity to link together outpatient clinical pharmacy services with specialty pharmacy management of PCSK9 inhibitors. An electronic pathway was created to encourage pharmacy consultation in patients prescribers thought eligible for PCSK9 inhibitor therapy. Pharmacists conducted a clinical screen of each patient to determine if PCSK9 inhibitor or alternative therapy was warranted. Patients appropriate for a PCSK9 inhibitor had thorough documentation in the medical record, including description of statin or ezetimibe history, pertinent laboratory values, and PCSK9 inhibitor indication. Finally, collaboration between clinic prescribing and the UIH specialty pharmacy allowed for facilitation of prior authorizations, detailed patient education, medication monitoring, and adherence management. Implementation of a consultative service similar to UIH may facilitate transitions in care between prescription generation and patient adherence.

Overcoming Barriers to Optimal Adherence

Once approved, patient education, adherence, and comfort with PCSK9 inhibitor therapy are essential. Use of a specialty pharmacy is often mandatory by payers, although use of a traditional retail pharmacy may be allowed. Specialty pharmacies are more likely to have the prescribed PCSK9 inhibitor in stock and have experience in navigating the prior authorization approval process. Specialty pharmacists are also equipped to provide education, adherence support, and improve patient comfort with PCSK9 inhibitor injections. Each PCSK9 inhibitor has detailed administration instructions via an online tutorial and provided in print within the packaging.^7,8 Alirocumab and evolocumab are both available in pre-filled pens for administration, while evolocumab is also supplied as a single use on-body infuser pump and as a pre-filled manual syringe. A thorough understanding of the different administration options and technique nuances is best demonstrated by specialty pharmacists routinely dispensing this class of medications. Use of a traditional retail pharmacy may lead to treatment delays or incomplete education, in part due to product availability and pharmacist workload.

In addition to detailed instructions regarding administration and use, patients also require education about the potential adverse effects of PCSK9 inhibitor therapy. Adverse effects for both PCSK9 inhibitors were similar to placebo and include injection site reactions, nasopharyngitis, upper respiratory infections (including influenza), and musculoskeletal pain.^9,10 The degree of LDL lowering seen with PCSK9 inhibitors and corresponding risk for decreased neurocognitive function came into question during preliminary trials, culminating in a request from the FDA for ongoing assessment in later trials.¹¹ The EBBINGHAUS trial was designed to assess differences in memory, cognition, reaction time, and attention in patients receiving add-on therapy with evolocumab or placebo for ASCVD. Although not fully published, preliminary data suggests no difference between evolocumab and placebo on memory.¹²

The LDL lowering seen in clinical trials with PCSK9 inhibitors has undoubtable potential to revolutionize hyperlipidemia treatment. However, the lifetime cost effectiveness of PCSK9 inhibitors continues to raise concerns.^13-16 Resources are currently available to aid prior authorizations, improve access, and optimize adherence to therapy (Table 2).^7,8 Interestingly, Amgen has publicly announced an opportunity for payers to pursue a money-back guarantee with evolocumab. Insurance providers have begun negotiating with Amgen for a full refund if patients are hospitalized with a myocardial infarction or stroke while receiving evolocumab.¹⁷ While stipulations apply for this guarantee, this remains new territory for providers, payers, and patients. Pharmacists are ideally positioned to navigate optimal use of PCSK9 inhibitors, ensure patient affordability and adherence, and monitor for long-term effects.

Table 2: PCSK9 inhibitor resources7,8
	Alirocumab (Praluent®)	Evolocumab (Repatha®)
Prior authorizations	Specific insurance requirements and prior authorization forms available at: http://praluentcoverage.com/#search	Specific insurance requirements and prior authorization forms available at: https://www.repathahcp.com/resources/
Patient assistance	$0 copay available for eligible patients Commercial insurance only ≥ 18 years FDA-approved indication Maximum annual copay of $5,500	$5 copay available for eligible patients Commercial insurance only FDA-approved indication Maximum annual copay of $5,500
Adherence support program	MyPRALUENT® to assist with refill reminders, supplies, and nursing support	RepathaReady® to assist with refill reminders, supplies, and nursing support

REFERENCES

1. Navar AM, Taylor B, Mulder H, et al. Association of Prior Authorization and Out-of-pocket Costs With Patient Access to PCSK9 Inhibitor Therapy. JAMA Cardiol. 2017;2(11):1217-1225.
2. Cohen JD, Cziraky MJ, Jacobson TA, et al. Barriers to PCSK9 inhibitor prescriptions for patients with high cardiovascular risk: Results of a healthcare provider survey conducted by the National Lipid Association. J Clin Lipidol. 2017;11(4):891-900.
3. Stadler SL, Cook TJ. PCSK9 inhibitors and managing cost in the managed care setting. Am J Manag Care. 2017;23(9 Suppl):S149-S155.
4. Orringer CE, Jacobson TA, Saseen JJ, et al. Update on the use of PCSK9 inhibitors in adults: Recommendations from an Expert Panel of the National Lipid Association. J Clin Lipidol. 2017;11(4):880-890.
5. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70(14):1785-1822.
6. Atanda A, Shapiro NL, Stubbings J, et al. Implementation of a New Clinic-Based, Pharmacist-Managed PCSK9 Inhibitor Consultation Service. J Manag Care Spec Pharm. 2017;23(9):918-925.
7. Praluent^® (alirocumab) – For Healthcare Professionals. https://www.praluenthcp.com. Accessed November 2, 2017.
8. Repatha^® (evolocumab) – For Healthcare Professionals. https://www.repathahcp.com. Accessed November 2, 2017.
9. Praluent^® [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2017.
10. Repatha^® [package insert]. Thousand Oaks, CA: Amgen Inc; 2016.
11. Banach M, Rizzo M, Nikolic D, et al. Intensive LDL-cholesterol lowering therapy and neurocognitive function. Pharmacol Ther. 2017;170:181-191.
12. American College of Cardiology. Early Evidence Linking PCSK9 Inhibitors to Neurocognitive Adverse Events: Does Correlation Imply Causation? 2015; http://www.acc.org/latest-in-cardiology/articles/2015/06/01/12/36/early-evidence- linking-pcsk9-inhibitors-to-neurocognitive-adverse-events. Accessed November 1, 2017.
13. Hernandez I. Revisiting Outcomes-Based Pricing Propositions for the PCSK9 Inhibitor Evolocumab. JAMA Intern Med. 2017;177(9):1388-1390.
14. Kazi DS, Moran AE, Coxson PG, et al. Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease. JAMA. 2016;316(7):743-753.
15. Gandra SR, Villa G, Fonarow GC, et al. Cost-Effectiveness of LDL-C Lowering With Evolocumab in Patients With High Cardiovascular Risk in the United States. Clin Cardiol. 2016;39(6):313-320.
16. Korman M, Wisløff T. Modelling the cost-effectiveness PCSK9 inhibitors vs. ezetimibe through LDL-C reductions in a Norwegian setting. Eur Heart J Cardiovasc Pharmacother. 2017 Apr 21. [Epub ahead of print]
17. BioPharmaDIVE. 2017; http://www.biopharmadive.com/news/amgen-repatha- refund-contract-harvard-pilgrim/441777/. Accessed November 1, 2017.

Back to Top