- Email: [email protected]
Improving patient access to hepatitis C virus treatment
SCIENCE AND PRACTICE Journal of the American Pharmacists Association 58 (2018) 109e112
Contents lists available at ScienceDirect
Journal of the American Pharmacists Association journal homepage: www.japha.org
COMMENTARY
Improving patient access to hepatitis C virus treatment Milena M. McLaughlin*, Kevin T. Marx, Colleen Terriff, on behalf of American Academy of HIV Medicine Pharmacists Committee a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 May 2017 Accepted 21 October 2017
Objectives: To discuss the current barriers to hepatitis C virus (HCV) treatment; to provide information and resources to assist health care providers with the prior authorization process; to provide resources for potential access to medications if a patient's third-party payer may not be an option; and to discuss the pharmacist's vital role as a patient advocate and considerations once medications are approved. Summary: Access to HCV medications is often restricted by third-party payers. Pharmacists are poised to fill an immediate need and assist with providing the necessary clinical evidence to gain access to HCV medications and advocate on the patient's behalf. Once approval for HCV treatment has been obtained, considerations must be given to procurement of therapy, refills, monitoring, and avoid interruptions in therapy. Conclusion: The assistance of a pharmacist should be sought to overcome barriers related to medication access. Once therapy has been obtained, the pharmacist can assist the entire patient care team to ensure timely refills, appropriate monitoring, tolerability of therapy, and continued medication access. © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Pharmacists provide a vital role in the initial and ongoing treatment of hepatitis C (HCV).1-3 This role includes providing patient education about the disease and complications of disease progression, assessment of patient readiness to start treatment, navigation of prescription insurance and prior authorizations, detailed consultations about HCV medications, and management of drugedrug interactions before initiation and throughout the course of therapy. Pharmacists are poised to provide recommendations for preferred treatments with the aid of national HCV guidance.4 Although several directacting antiviral agents are available and prices continue to decrease, there remains a clear issue with access to medications and third-party payer barriers. It has been suggested that pharmacists should fill the gap in patient access to HCV medications; however, not every patient currently has access to an HCV pharmacist specialist within an ambulatory clinic setting.5 Indeed, many health care providers are awaiting
Disclosure: All authors have no conflicts of interest (personal or financial) to disclose pertaining to the subject matter of this manuscript. * Correspondence: Milena M. McLaughlin, PharmD, MSc, Midwestern University Chicago College of Pharmacy, Department of Pharmacy Practice, 555 31st St., Downers Grove, IL 60515. E-mail address: [email protected] (M.M. McLaughlin).
additional resources or other support before beginning HCV treatment programs.6 The present article discusses the current barriers to HCV treatment, information, and resources to assist with the prior authorization process and suggests resources for potential access to medications if a patient's third-party payer is no longer an option. Resources for HCV general information, drugedrug interactions, and education are provided. In addition, the pharmacist's vital role as a patient advocate and considerations once medications are approved are discussed. Barriers to HCV medication access Because of the high cost of HCV treatments, third-party payers and patient assistance programs have placed many restrictions on therapy and requirements for coverage to limit the number of approvals and prioritize treatment of patients.7,8 Significantly less spending on sofosbuvir due to restrictions on the basis of drug or alcohol use was demonstrated with the use of fee-for-service utilization data.8 The California Association of Health Plans estimated that treating only 10% of patients with HCV in their state-funded programs would cost $2 billion.9 Common restrictions for HCV treatment coverage include early liver disease and active alcohol or injection drug use.10
https://doi.org/10.1016/j.japh.2017.10.013 1544-3191/© 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
SCIENCE AND PRACTICE M.M. McLaughlin et al. / Journal of the American Pharmacists Association 58 (2018) 109e112
Key Points Background: There are many third-party payer restrictions to hepatitis C virus (HCV) therapy because of the high cost of these medications. Health care providers may not have effective clinical resources to navigate access to HCV therapy. Findings: Pharmacists have the expertise required to provide patient-specific clinical information to gain access to guideline-based therapy, manage drugedrug interactions and adverse events, and provide patient counseling. After medication approval, pharmacists should continue to be involved with patient monitoring, refills, and assessment of adherence to avoid any interruptions in treatment.
Liver disease severity is often measured with the use of the Metavir score: F0 is associated with no liver fibrosis, whereas F4 is associated with cirrhosis.4 One study, published in 2015, indicated that among the 42 states with known Medicaid restriction criteria for sofosbuvir, 74% limited treatment to patients with the highest Metavir scores of F3 or F4.10 In an attempt to advocate for medication access for patients with HCV, the Centers for Medicare and Medicaid Services (CMS) issued a letter in November 2015 to State Medicaid Drug Rebate Programs to encourage fewer coverage restrictions (e.g., removal of limiting treatment to patients with Metavir fibrosis score F4).11 The letter further stated that although individual states may establish limitations and require prior authorizations, restrictions should not result in denial of medication access for clinically appropriate and medically necessary treatment for Food and Drug Administrationeapproved indications. Although the focus of the letter was medication access and affordability, CMS encouraged states to use expertise, guidelines, and supportive care programs to increase HCV treatment success rates. Pharmacists are able to work with health care providers to provide these supportive care programs to enhance adherence and positive patient outcomes.11 Some Medicaid programs have lifted restrictions, but many patients still do not have access to HCV therapy.12 Regarding restrictions related to substance abuse, of the 42 states with known Medicaid restriction criteria for sofosbuvir, 88% included drug or alcohol use exclusion criteria, 50% required a period of abstinence, and 64% required urine drug screening.10 National HCV guidance documents note that restriction of treatment for patients with a history of or active drug use should not be an exclusion for treatment.4 In addition, several articles have noted equivalent HCV therapy efficacy in patients with substance use disorders.13,14 However, a recent 2017 Morbidity and Mortality Weekly Report indicated that 24 states continue to have restrictive Medicaid treatment criteria (defined as any period of required sobriety from
110
substance abuse before approval of HCV therapy), and 16 states have permissive policies (defined as the need for substance use disorder screening only).15 Because of restrictions, there are reports in the literature of patients who are ultimately unable to receive approval for HCV therapy. A 2016 study of direct-acting antiviral prescriptions submitted to a specialty pharmacy found that 16.2% (377/2321) received an absolute denial (defined as ultimate lack of approval of prescription fill by the patient's insurer).16 A higher proportion of patients covered by Medicaid (n ¼ 233; 46.3%) received an absolute denial than those covered by Medicare (n ¼ 40; 5%; P < 0.001) or commercial insurance (n ¼ 104; 10.2%; P < 0.001). Furthermore, coverage with Medicaid (adjusted relative risk [RR], 4.14 [95% CI 3.38e5.08]) and absence of cirrhosis (1.96 [95% CI 1.53e2.50]) were statistically significantly associated with absolute denial. The authors concluded that there are clear disparities in access to HCV treatment, depending on patient insurance coverage.16 A 2017 study stated that only 33% of referred patients (129/388) were able to initiate treatment within a specific HCV program in New York City.17 After adjustment for significant variables found in the bivariate analyses, a multivariable model indicated that nonealcohol users (defined as not using alcohol at the time of initial assessment) and a high fibrosis score (defined as Metavir F3 or F4) were associated with treatment approval.
Pharmacist involvement with initial access to HCV therapy Most commonly, health care providers provide information about how patients meet treatment criteria or restrictions to third-party payers via prior authorization forms. Pharmacists possess the medication expertise required to assist with these forms. If a specific regimen is being prescribed, pharmacists can provide evidence for clinical necessity on the basis of patient-specific characteristics (e.g., liver disease severity, treatment experience, substance use disorder, etc.). For example, a patient with genotype 1 would have multiple options for treatment (e.g., elbasvir/grazoprevir, ledipasvir/ sofosbuvir, glecaprevir plus pibrentasvir, simeprevir plus sofosbuvir, sofosbuvir/velpatasvir). If a particular patient has chronic kidney disease, he or she would be an appropriate candidate for a regimen with treatment data in this patient population.4 If a third-party payer has a sofosbuvir-containing regimen as his or her preferred formulary medication, a request for an alternate treatment may be denied if evidence of chronic kidney disease is not included with the initial prior authorization. Specific information may be sent as evidence from national HCV guidance,4 primary literature, federal code, package inserts, or drug-interaction websites. This information may not be requested on a prior authorization form; however, if clinically relevant, it should be included. If the initial prior authorization is denied, other options to pursue access to medications include (but may not be limited to) appeal, external review, state fair hearing, and patient assistance programs. The first appeal may be submitted by the medication prescriber or his or her representative (i.e., the pharmacist), depending on the third-party payer. Details are usually found in the original denial letter, and a separate appeal form may be needed. Pharmacists may gather evidence-based
SCIENCE AND PRACTICE Accessing HCV treatment
literature to refute the specific reasons for initial prior authorization denial and address these in the appeal letter. For subsequent denials, the third-party payer may send the appeal to an external reviewer. The HIV Medicine Association and the Infectious Diseases Society of America have a joint website dedicated to HCV treatment access that includes template letters of appeal (http://hcvtreatmentaccess.org/drug-appeals/). Pharmacists should also advocate for patients to follow along with the appeal process, as extra forms may need to be signed or other important patient deadlines met (e.g., attendance at appeal hearings). If the patient is continually denied access to treatment through his or her third-party payer, patient assistance programs, usually offered by the medication manufacturers, may be an option. Each manufacturer has criteria for income limits, differing requirements for documents, and differing scenarios for which they will provide medications.18 This option should be considered a last resort; all options through the patient's primary insurance should be explored first (Supplemental Table 1). Many patient assistance programs limit access to those with no insurance. Therefore, if patients are denied through a thirdparty payer, they may be unable to access treatment.
Pharmacist involvement during HCV therapy The pharmacist's vital role continues after access to medication has been granted. Once a patient has been approved for HCV treatment, considerations must be given to procurement of therapy. Pharmacists should also assess the approval terms, including length of treatment. The length of treatment requested should match the length approved to avoid a gap in therapy. The patient's copayment or coinsurance also should be confirmed. If the patient is not able to afford the medications for the entire treatment period, copayment cards (for commercial third-party payers) or patient assistance networks (for government third-party payers) may be explored. It should be noted that there are maximum benefit amounts for copayment cards and that patient assistance networks may run out of funding. Copayment cards can often be obtained through the manufacturer's website (Supplemental Table 1). Not all community pharmacies are able to fulfill prescriptions for these medications; patients may need to use designated specialty pharmacies. Per the patient's third-party payer, he or she may need to fill his or her prescription through a specialty mail-service pharmacy. Issues with delivery may include lost or stolen medications or inappropriate storage. In some circumstances, health care providers may offer the option to have the medication(s) shipped to their office to avoid delivery or theft issues. The patient care team should also be aware that some mail-service pharmacies automatically request refills of HCV therapy or send new prior authorization forms even after the patient has completed treatment. Pharmacists should contact the patient to assess the amount of medication that the patient has actually received. It may be prudent to contact the specialty mail-service pharmacy to ask them to discontinue the prior authorization or refill requests as well as inform the patient that he or she has completed the treatment course. Pharmacists should also be involved in monitoring HCV treatment, including monitoring laboratory tests, conducting adherence checks, and assessing for adverse effects.
Laboratory monitoring should include comprehensive metabolic panel, complete blood count, HCV RNA, and any other pertinent laboratory tests based on patient-specific factors.4 During the treatment course, third-party payers may require a new prior authorization for the medication(s). This new prior authorization is often requested at week 4 or 12 of treatment, depending on treatment duration. The documentation usually requested for the reapproval consists of updated progress notes, including laboratory monitoring. Documentation in the medical record of patient adherence to therapy and monitoring appointments also may be needed. Although the reapproval process is streamlined, it can result in a delay in patients continuing their treatment. Pharmacists should also assist with the clinical and logistical pieces of follow-up to avoid any delays in processing of refills. Patients should be counseled to order refills well before they are out of medication to avoid potential delays with medication fulfillment and shipping from mail-service pharmacies. They will be unlikely to obtain an “emergency override” at a local retail pharmacy if they do not receive their mail-service supply in time because of the cost of the medication. Interruptions should be avoided once treatment is initiated. However, emergencies do arise, such as a patient's third-party payer coverage changing during treatment. Pharmacists can work with the patient to ensure that the remainder of therapy will be covered by the new third-party payer. Pharmacists should encourage patients to keep close track of these medications as part of their initial medication counseling. Replacement supplies due to lost or missing medications are often difficult to obtain. Patients should also be counseled to bring their HCV medications to the hospital if they are going to be admitted, as most institutions do not carry these medications because of their cost, and the patient will likely need to continue his or her regimen while admitted. Table 1 Hepatitis C resources Group or organization Clinical information American Association for the Study of Liver Diseases/ Infectious Diseases Society of America Clinical Care Options European Association for the Study of the Liver Infectious Diseases Society of America Medscape Toronto General Hospital University of Washington World Health Organization Patient information American Liver Foundation Center for Disease Control and Prevention HCV Advocate HEP Magazine Veterans Affairs Drugedrug interaction information University of Liverpool
Website www.hcvguidelines.org
http://www.clinicaloptions.com/ Hepatitis.aspx www.easl.eu/research/ourcontributions/clinical-practiceguidelines www.idsociety.org/Hepatitis_C emedicine.medscape.com www.hcvdruginfo.ca www.hepatitisc.uw.edu www.who.int/hiv/pub/hepatitis/ hepatitis-c-guidelines/en hepc.liverfoundation.org https://www.cdc.gov/hepatitis/ hcv/cfaq.htm www.hcvadvocate.org http://www.hepmag.com/index. shtml https://www.hepatitis.va.gov/ patient/index.asp www.hep-druginteractions.org
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SCIENCE AND PRACTICE M.M. McLaughlin et al. / Journal of the American Pharmacists Association 58 (2018) 109e112
HCV resources A list of HCV resources is provided in Table 1. The table is organized by websites providing clinical information, patient information, and drugedrug interaction information. Pharmacists are encouraged to check for new additions to these websites, as they are updated frequently (in particular, the latest HCV guidelines).4 The national HCV guidelines are an excellent source for up-to-date evidence to provide to thirdparty payers when drafting letters of medical necessity.4 Conclusion The assistance of a pharmacist should be sought to overcome barriers related to HCV medication access. Once therapy has been obtained, the pharmacist can assist the entire patient care team to ensure timely refills, appropriate monitoring, tolerability of therapy, and ongoing prior authorization approval if necessary. Acknowledgment The authors thank Gary F. Spinner, an HIV specialist who treats many patients with hepatitis C virus, for his thoughtful review of this manuscript. References 1. Deming P, Martin MT, Chan J, et al. Therapeutic advances in HCV genotype 1 infection: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2016;36:203e217. 2. Mohammad RA, Bulloch MN, Chan J, et al. Provision of clinical pharmacist services for individuals with chronic hepatitis C viral infection: joint opinion of the GI/Liver/Nutrition and Infectious Diseases Practice and Research Networks of the American College of Clinical Pharmacy. Pharmacotherapy. 2014;34:1341e1354. 3. Spooner LM. The expanding role of the pharmacist in the management of hepatitis C infection. J Manag Care Pharm. 2011;17:709e712. 4. American Association of the Study of Liver Diseases, Infectious Diseases Society of America, International Antiviral SocietydUSA. Recommendations for testing, managing, and treating hepatitis C. Available at: http:// www.hcvguidelines.org. Accessed October 20, 2017. 5. Wenzler E, Dickson W, Vibhakar S, et al. Hepatitis C management and the infectious diseases pharmacist. Clin Infect Dis. 2015;61:1201e1202.
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6. Chastain CA, Beekmann SE, Wallender EK, et al. Hepatitis C management and the infectious diseases physician: a survey of current and anticipated practice patterns. Clin Infect Dis. 2015;61:792e794. 7. Chhatwal J, Kanwal F, Roberts MS, et al. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med. 2015;162:397e406. 8. Liao JM, Fischer MA. Restrictions of hepatitis C treatment for substanceusing Medicaid patients: cost versus ethics. Am J Public Health. 2017;107: 893e899. 9. California Association of Health Plans. Hepatitis C drugs' costly impact on California. June 2015. Available at: http://www.calhealthplans.org/pdfs/ RunawayRx_%20Hep%20C_Infographic_FINAL063015.pdf. Accessed May 3, 2017. 10. Barua S, Greenwald R, Grebely J, et al. Restrictions for Medicaid reimbursement of sofosbuvir for the treatment of hepatitis C virus infection in the United States. Ann Intern Med. 2015;163:215e223. 11. Centers for Medicare and Medicaid Services. Assuring Medicaid beneficiaries access to hepatitis C (HCV) drugs. Medicaid Drug Rebate Program Notice release no. 172. November 5, 2015. Available at: http://www. natap.org/2015/HCV/110615_01.htm. Accessed May 3, 2017. 12. National Viral Hepatitis Roundtable Hepatitis C. The state of Medicaid access. November 14, 2016. Available at: http://www.chlpi.org/wpcontent/uploads/2013/12/HCV-Report-Card-National-Summary_FINAL. pdf. Accessed July 31, 2017. 13. Dore GJ, Altice F, Litwin AH, et al. Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy: a randomized trial. Ann Intern Med. 2016;165:625e634. 14. Talal AH, Thomas DL, Reynolds JL, et al. Toward optimal control of hepatitis C virus infection in persons with substance use disorders. Ann Intern Med. 2017;166:897e898. 15. Campbell CA, Canary L, Smith N, et al. State HCV incidence and policies related to HCV preventive and treatment services for persons who inject drugsdUnited States, 2015e2016. MMWR Morb Mortal Wkly Rep. 2017;66:465e469. 16. Lo Re 3rd V, Gowda C, Urick PN, et al. Disparities in absolute denial of modern hepatitis C therapy by type of insurance. Clin Gastroenterol Hepatol. 2016;14:1035e1043. 17. Ford MM, Johnson N, Desai P, et al. From care to cure: demonstrating a model of clinical patient navigation for hepatitis C care and treatment in high-need patients. Clin Infect Dis. 2017;64:685e691. 18. Silverman E. Gilead limits enrollment in its hep C patient program to pressure insurers. July 16, 2015. Available at: http://blogs.wsj.com/ pharmalot/2015/07/16/gilead-limits-enrollment-in-its-hep-c-patientprogram-to-pressure-insurers/. Accessed May 3, 2017. Milena M. McLaughlin, PharmD, MSc, BCPS-AQ ID, AAHIVP, Assistant Professor of Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, Downers Grove, IL; HIV/Infectious Diseases Clinical Pharmacist, Northwestern Memorial Hospital, Chicago, IL Kevin T. Marx, PharmD, AAHIVP, HIV Clinical Pharmacist, Jeffrey Goodman Special Care Clinic and Pharmacy, Los Angeles, CA Colleen Terriff, PharmD, MPH, AAHIVP, Infectious Diseases Clinical Pharmacist, Deaconess Hospital and Rockwood Health-Systems, Spokane, WA
SCIENCE AND PRACTICE Accessing HCV treatment
Appendix Supplemental Table 1 Patient assistance program websites Pharmaceutical company programs Company
Medication
Program
Contact info
Abbvie
Mavyret Technivie Viekira XR
Abbvie Patient Assistance Foundation
Bristol-Myers Squibb (BMS)
Daklinza
BMS Patient Support Connect
Genentech
Copegus Pegasys Pegasys ProClick Epclusa Harvoni Sovaldi Vosevi Olysio
Genentech Rx Assist Access to Care Gilead Support Path
www.abbviepaf.org 1-800-222-6885 https://www.viekira.com/patient-support 1-844-277-6233 (2PROCEED) www.patientsupportconnect.bmscustomerconnect.com 1-844-442-6663 (44CONNECT) www.rxassist.org/patients 1-888-941-3331 www.mysupportpath.com 1-855-769-7284 (7MYPATH)
Janssen Prescription Assistance
Ribasphere Ribapak Zepatier
Kadmon Enabling Your Success (KEYS) Program Merck Access & Support Services
www.janssenprescriptionassistance.com 1-800-652-6227 www.pparx.org (search Kadmon) 1-888-868-3393 https://www.merckaccessprogram.com
Medication
Program
Contact info
Gilead Sciences
Janssen/Johnson & Johnson Kadmon Pharmaceuticals Merck & Co. Nonprofit organizations Company Needy Meds Partnership for Prescription Assistance (PPA) Service Patient Access Network Foundation
www.needymeds.org/index.htm 1-800-503-6897 www.pparx.org www.panfoundation.org 1-866-316-7263
112.e1
Contents lists available at ScienceDirect
Journal of the American Pharmacists Association journal homepage: www.japha.org
COMMENTARY
Improving patient access to hepatitis C virus treatment Milena M. McLaughlin*, Kevin T. Marx, Colleen Terriff, on behalf of American Academy of HIV Medicine Pharmacists Committee a r t i c l e i n f o
a b s t r a c t
Article history: Received 3 May 2017 Accepted 21 October 2017
Objectives: To discuss the current barriers to hepatitis C virus (HCV) treatment; to provide information and resources to assist health care providers with the prior authorization process; to provide resources for potential access to medications if a patient's third-party payer may not be an option; and to discuss the pharmacist's vital role as a patient advocate and considerations once medications are approved. Summary: Access to HCV medications is often restricted by third-party payers. Pharmacists are poised to fill an immediate need and assist with providing the necessary clinical evidence to gain access to HCV medications and advocate on the patient's behalf. Once approval for HCV treatment has been obtained, considerations must be given to procurement of therapy, refills, monitoring, and avoid interruptions in therapy. Conclusion: The assistance of a pharmacist should be sought to overcome barriers related to medication access. Once therapy has been obtained, the pharmacist can assist the entire patient care team to ensure timely refills, appropriate monitoring, tolerability of therapy, and continued medication access. © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Pharmacists provide a vital role in the initial and ongoing treatment of hepatitis C (HCV).1-3 This role includes providing patient education about the disease and complications of disease progression, assessment of patient readiness to start treatment, navigation of prescription insurance and prior authorizations, detailed consultations about HCV medications, and management of drugedrug interactions before initiation and throughout the course of therapy. Pharmacists are poised to provide recommendations for preferred treatments with the aid of national HCV guidance.4 Although several directacting antiviral agents are available and prices continue to decrease, there remains a clear issue with access to medications and third-party payer barriers. It has been suggested that pharmacists should fill the gap in patient access to HCV medications; however, not every patient currently has access to an HCV pharmacist specialist within an ambulatory clinic setting.5 Indeed, many health care providers are awaiting
Disclosure: All authors have no conflicts of interest (personal or financial) to disclose pertaining to the subject matter of this manuscript. * Correspondence: Milena M. McLaughlin, PharmD, MSc, Midwestern University Chicago College of Pharmacy, Department of Pharmacy Practice, 555 31st St., Downers Grove, IL 60515. E-mail address: [email protected] (M.M. McLaughlin).
additional resources or other support before beginning HCV treatment programs.6 The present article discusses the current barriers to HCV treatment, information, and resources to assist with the prior authorization process and suggests resources for potential access to medications if a patient's third-party payer is no longer an option. Resources for HCV general information, drugedrug interactions, and education are provided. In addition, the pharmacist's vital role as a patient advocate and considerations once medications are approved are discussed. Barriers to HCV medication access Because of the high cost of HCV treatments, third-party payers and patient assistance programs have placed many restrictions on therapy and requirements for coverage to limit the number of approvals and prioritize treatment of patients.7,8 Significantly less spending on sofosbuvir due to restrictions on the basis of drug or alcohol use was demonstrated with the use of fee-for-service utilization data.8 The California Association of Health Plans estimated that treating only 10% of patients with HCV in their state-funded programs would cost $2 billion.9 Common restrictions for HCV treatment coverage include early liver disease and active alcohol or injection drug use.10
https://doi.org/10.1016/j.japh.2017.10.013 1544-3191/© 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
SCIENCE AND PRACTICE M.M. McLaughlin et al. / Journal of the American Pharmacists Association 58 (2018) 109e112
Key Points Background: There are many third-party payer restrictions to hepatitis C virus (HCV) therapy because of the high cost of these medications. Health care providers may not have effective clinical resources to navigate access to HCV therapy. Findings: Pharmacists have the expertise required to provide patient-specific clinical information to gain access to guideline-based therapy, manage drugedrug interactions and adverse events, and provide patient counseling. After medication approval, pharmacists should continue to be involved with patient monitoring, refills, and assessment of adherence to avoid any interruptions in treatment.
Liver disease severity is often measured with the use of the Metavir score: F0 is associated with no liver fibrosis, whereas F4 is associated with cirrhosis.4 One study, published in 2015, indicated that among the 42 states with known Medicaid restriction criteria for sofosbuvir, 74% limited treatment to patients with the highest Metavir scores of F3 or F4.10 In an attempt to advocate for medication access for patients with HCV, the Centers for Medicare and Medicaid Services (CMS) issued a letter in November 2015 to State Medicaid Drug Rebate Programs to encourage fewer coverage restrictions (e.g., removal of limiting treatment to patients with Metavir fibrosis score F4).11 The letter further stated that although individual states may establish limitations and require prior authorizations, restrictions should not result in denial of medication access for clinically appropriate and medically necessary treatment for Food and Drug Administrationeapproved indications. Although the focus of the letter was medication access and affordability, CMS encouraged states to use expertise, guidelines, and supportive care programs to increase HCV treatment success rates. Pharmacists are able to work with health care providers to provide these supportive care programs to enhance adherence and positive patient outcomes.11 Some Medicaid programs have lifted restrictions, but many patients still do not have access to HCV therapy.12 Regarding restrictions related to substance abuse, of the 42 states with known Medicaid restriction criteria for sofosbuvir, 88% included drug or alcohol use exclusion criteria, 50% required a period of abstinence, and 64% required urine drug screening.10 National HCV guidance documents note that restriction of treatment for patients with a history of or active drug use should not be an exclusion for treatment.4 In addition, several articles have noted equivalent HCV therapy efficacy in patients with substance use disorders.13,14 However, a recent 2017 Morbidity and Mortality Weekly Report indicated that 24 states continue to have restrictive Medicaid treatment criteria (defined as any period of required sobriety from
110
substance abuse before approval of HCV therapy), and 16 states have permissive policies (defined as the need for substance use disorder screening only).15 Because of restrictions, there are reports in the literature of patients who are ultimately unable to receive approval for HCV therapy. A 2016 study of direct-acting antiviral prescriptions submitted to a specialty pharmacy found that 16.2% (377/2321) received an absolute denial (defined as ultimate lack of approval of prescription fill by the patient's insurer).16 A higher proportion of patients covered by Medicaid (n ¼ 233; 46.3%) received an absolute denial than those covered by Medicare (n ¼ 40; 5%; P < 0.001) or commercial insurance (n ¼ 104; 10.2%; P < 0.001). Furthermore, coverage with Medicaid (adjusted relative risk [RR], 4.14 [95% CI 3.38e5.08]) and absence of cirrhosis (1.96 [95% CI 1.53e2.50]) were statistically significantly associated with absolute denial. The authors concluded that there are clear disparities in access to HCV treatment, depending on patient insurance coverage.16 A 2017 study stated that only 33% of referred patients (129/388) were able to initiate treatment within a specific HCV program in New York City.17 After adjustment for significant variables found in the bivariate analyses, a multivariable model indicated that nonealcohol users (defined as not using alcohol at the time of initial assessment) and a high fibrosis score (defined as Metavir F3 or F4) were associated with treatment approval.
Pharmacist involvement with initial access to HCV therapy Most commonly, health care providers provide information about how patients meet treatment criteria or restrictions to third-party payers via prior authorization forms. Pharmacists possess the medication expertise required to assist with these forms. If a specific regimen is being prescribed, pharmacists can provide evidence for clinical necessity on the basis of patient-specific characteristics (e.g., liver disease severity, treatment experience, substance use disorder, etc.). For example, a patient with genotype 1 would have multiple options for treatment (e.g., elbasvir/grazoprevir, ledipasvir/ sofosbuvir, glecaprevir plus pibrentasvir, simeprevir plus sofosbuvir, sofosbuvir/velpatasvir). If a particular patient has chronic kidney disease, he or she would be an appropriate candidate for a regimen with treatment data in this patient population.4 If a third-party payer has a sofosbuvir-containing regimen as his or her preferred formulary medication, a request for an alternate treatment may be denied if evidence of chronic kidney disease is not included with the initial prior authorization. Specific information may be sent as evidence from national HCV guidance,4 primary literature, federal code, package inserts, or drug-interaction websites. This information may not be requested on a prior authorization form; however, if clinically relevant, it should be included. If the initial prior authorization is denied, other options to pursue access to medications include (but may not be limited to) appeal, external review, state fair hearing, and patient assistance programs. The first appeal may be submitted by the medication prescriber or his or her representative (i.e., the pharmacist), depending on the third-party payer. Details are usually found in the original denial letter, and a separate appeal form may be needed. Pharmacists may gather evidence-based
SCIENCE AND PRACTICE Accessing HCV treatment
literature to refute the specific reasons for initial prior authorization denial and address these in the appeal letter. For subsequent denials, the third-party payer may send the appeal to an external reviewer. The HIV Medicine Association and the Infectious Diseases Society of America have a joint website dedicated to HCV treatment access that includes template letters of appeal (http://hcvtreatmentaccess.org/drug-appeals/). Pharmacists should also advocate for patients to follow along with the appeal process, as extra forms may need to be signed or other important patient deadlines met (e.g., attendance at appeal hearings). If the patient is continually denied access to treatment through his or her third-party payer, patient assistance programs, usually offered by the medication manufacturers, may be an option. Each manufacturer has criteria for income limits, differing requirements for documents, and differing scenarios for which they will provide medications.18 This option should be considered a last resort; all options through the patient's primary insurance should be explored first (Supplemental Table 1). Many patient assistance programs limit access to those with no insurance. Therefore, if patients are denied through a thirdparty payer, they may be unable to access treatment.
Pharmacist involvement during HCV therapy The pharmacist's vital role continues after access to medication has been granted. Once a patient has been approved for HCV treatment, considerations must be given to procurement of therapy. Pharmacists should also assess the approval terms, including length of treatment. The length of treatment requested should match the length approved to avoid a gap in therapy. The patient's copayment or coinsurance also should be confirmed. If the patient is not able to afford the medications for the entire treatment period, copayment cards (for commercial third-party payers) or patient assistance networks (for government third-party payers) may be explored. It should be noted that there are maximum benefit amounts for copayment cards and that patient assistance networks may run out of funding. Copayment cards can often be obtained through the manufacturer's website (Supplemental Table 1). Not all community pharmacies are able to fulfill prescriptions for these medications; patients may need to use designated specialty pharmacies. Per the patient's third-party payer, he or she may need to fill his or her prescription through a specialty mail-service pharmacy. Issues with delivery may include lost or stolen medications or inappropriate storage. In some circumstances, health care providers may offer the option to have the medication(s) shipped to their office to avoid delivery or theft issues. The patient care team should also be aware that some mail-service pharmacies automatically request refills of HCV therapy or send new prior authorization forms even after the patient has completed treatment. Pharmacists should contact the patient to assess the amount of medication that the patient has actually received. It may be prudent to contact the specialty mail-service pharmacy to ask them to discontinue the prior authorization or refill requests as well as inform the patient that he or she has completed the treatment course. Pharmacists should also be involved in monitoring HCV treatment, including monitoring laboratory tests, conducting adherence checks, and assessing for adverse effects.
Laboratory monitoring should include comprehensive metabolic panel, complete blood count, HCV RNA, and any other pertinent laboratory tests based on patient-specific factors.4 During the treatment course, third-party payers may require a new prior authorization for the medication(s). This new prior authorization is often requested at week 4 or 12 of treatment, depending on treatment duration. The documentation usually requested for the reapproval consists of updated progress notes, including laboratory monitoring. Documentation in the medical record of patient adherence to therapy and monitoring appointments also may be needed. Although the reapproval process is streamlined, it can result in a delay in patients continuing their treatment. Pharmacists should also assist with the clinical and logistical pieces of follow-up to avoid any delays in processing of refills. Patients should be counseled to order refills well before they are out of medication to avoid potential delays with medication fulfillment and shipping from mail-service pharmacies. They will be unlikely to obtain an “emergency override” at a local retail pharmacy if they do not receive their mail-service supply in time because of the cost of the medication. Interruptions should be avoided once treatment is initiated. However, emergencies do arise, such as a patient's third-party payer coverage changing during treatment. Pharmacists can work with the patient to ensure that the remainder of therapy will be covered by the new third-party payer. Pharmacists should encourage patients to keep close track of these medications as part of their initial medication counseling. Replacement supplies due to lost or missing medications are often difficult to obtain. Patients should also be counseled to bring their HCV medications to the hospital if they are going to be admitted, as most institutions do not carry these medications because of their cost, and the patient will likely need to continue his or her regimen while admitted. Table 1 Hepatitis C resources Group or organization Clinical information American Association for the Study of Liver Diseases/ Infectious Diseases Society of America Clinical Care Options European Association for the Study of the Liver Infectious Diseases Society of America Medscape Toronto General Hospital University of Washington World Health Organization Patient information American Liver Foundation Center for Disease Control and Prevention HCV Advocate HEP Magazine Veterans Affairs Drugedrug interaction information University of Liverpool
Website www.hcvguidelines.org
http://www.clinicaloptions.com/ Hepatitis.aspx www.easl.eu/research/ourcontributions/clinical-practiceguidelines www.idsociety.org/Hepatitis_C emedicine.medscape.com www.hcvdruginfo.ca www.hepatitisc.uw.edu www.who.int/hiv/pub/hepatitis/ hepatitis-c-guidelines/en hepc.liverfoundation.org https://www.cdc.gov/hepatitis/ hcv/cfaq.htm www.hcvadvocate.org http://www.hepmag.com/index. shtml https://www.hepatitis.va.gov/ patient/index.asp www.hep-druginteractions.org
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HCV resources A list of HCV resources is provided in Table 1. The table is organized by websites providing clinical information, patient information, and drugedrug interaction information. Pharmacists are encouraged to check for new additions to these websites, as they are updated frequently (in particular, the latest HCV guidelines).4 The national HCV guidelines are an excellent source for up-to-date evidence to provide to thirdparty payers when drafting letters of medical necessity.4 Conclusion The assistance of a pharmacist should be sought to overcome barriers related to HCV medication access. Once therapy has been obtained, the pharmacist can assist the entire patient care team to ensure timely refills, appropriate monitoring, tolerability of therapy, and ongoing prior authorization approval if necessary. Acknowledgment The authors thank Gary F. Spinner, an HIV specialist who treats many patients with hepatitis C virus, for his thoughtful review of this manuscript. References 1. Deming P, Martin MT, Chan J, et al. Therapeutic advances in HCV genotype 1 infection: insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2016;36:203e217. 2. Mohammad RA, Bulloch MN, Chan J, et al. Provision of clinical pharmacist services for individuals with chronic hepatitis C viral infection: joint opinion of the GI/Liver/Nutrition and Infectious Diseases Practice and Research Networks of the American College of Clinical Pharmacy. Pharmacotherapy. 2014;34:1341e1354. 3. Spooner LM. The expanding role of the pharmacist in the management of hepatitis C infection. J Manag Care Pharm. 2011;17:709e712. 4. American Association of the Study of Liver Diseases, Infectious Diseases Society of America, International Antiviral SocietydUSA. Recommendations for testing, managing, and treating hepatitis C. Available at: http:// www.hcvguidelines.org. Accessed October 20, 2017. 5. Wenzler E, Dickson W, Vibhakar S, et al. Hepatitis C management and the infectious diseases pharmacist. Clin Infect Dis. 2015;61:1201e1202.
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6. Chastain CA, Beekmann SE, Wallender EK, et al. Hepatitis C management and the infectious diseases physician: a survey of current and anticipated practice patterns. Clin Infect Dis. 2015;61:792e794. 7. Chhatwal J, Kanwal F, Roberts MS, et al. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States. Ann Intern Med. 2015;162:397e406. 8. Liao JM, Fischer MA. Restrictions of hepatitis C treatment for substanceusing Medicaid patients: cost versus ethics. Am J Public Health. 2017;107: 893e899. 9. California Association of Health Plans. Hepatitis C drugs' costly impact on California. June 2015. Available at: http://www.calhealthplans.org/pdfs/ RunawayRx_%20Hep%20C_Infographic_FINAL063015.pdf. Accessed May 3, 2017. 10. Barua S, Greenwald R, Grebely J, et al. Restrictions for Medicaid reimbursement of sofosbuvir for the treatment of hepatitis C virus infection in the United States. Ann Intern Med. 2015;163:215e223. 11. Centers for Medicare and Medicaid Services. Assuring Medicaid beneficiaries access to hepatitis C (HCV) drugs. Medicaid Drug Rebate Program Notice release no. 172. November 5, 2015. Available at: http://www. natap.org/2015/HCV/110615_01.htm. Accessed May 3, 2017. 12. National Viral Hepatitis Roundtable Hepatitis C. The state of Medicaid access. November 14, 2016. Available at: http://www.chlpi.org/wpcontent/uploads/2013/12/HCV-Report-Card-National-Summary_FINAL. pdf. Accessed July 31, 2017. 13. Dore GJ, Altice F, Litwin AH, et al. Elbasvir-grazoprevir to treat hepatitis C virus infection in persons receiving opioid agonist therapy: a randomized trial. Ann Intern Med. 2016;165:625e634. 14. Talal AH, Thomas DL, Reynolds JL, et al. Toward optimal control of hepatitis C virus infection in persons with substance use disorders. Ann Intern Med. 2017;166:897e898. 15. Campbell CA, Canary L, Smith N, et al. State HCV incidence and policies related to HCV preventive and treatment services for persons who inject drugsdUnited States, 2015e2016. MMWR Morb Mortal Wkly Rep. 2017;66:465e469. 16. Lo Re 3rd V, Gowda C, Urick PN, et al. Disparities in absolute denial of modern hepatitis C therapy by type of insurance. Clin Gastroenterol Hepatol. 2016;14:1035e1043. 17. Ford MM, Johnson N, Desai P, et al. From care to cure: demonstrating a model of clinical patient navigation for hepatitis C care and treatment in high-need patients. Clin Infect Dis. 2017;64:685e691. 18. Silverman E. Gilead limits enrollment in its hep C patient program to pressure insurers. July 16, 2015. Available at: http://blogs.wsj.com/ pharmalot/2015/07/16/gilead-limits-enrollment-in-its-hep-c-patientprogram-to-pressure-insurers/. Accessed May 3, 2017. Milena M. McLaughlin, PharmD, MSc, BCPS-AQ ID, AAHIVP, Assistant Professor of Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, Downers Grove, IL; HIV/Infectious Diseases Clinical Pharmacist, Northwestern Memorial Hospital, Chicago, IL Kevin T. Marx, PharmD, AAHIVP, HIV Clinical Pharmacist, Jeffrey Goodman Special Care Clinic and Pharmacy, Los Angeles, CA Colleen Terriff, PharmD, MPH, AAHIVP, Infectious Diseases Clinical Pharmacist, Deaconess Hospital and Rockwood Health-Systems, Spokane, WA
SCIENCE AND PRACTICE Accessing HCV treatment
Appendix Supplemental Table 1 Patient assistance program websites Pharmaceutical company programs Company
Medication
Program
Contact info
Abbvie
Mavyret Technivie Viekira XR
Abbvie Patient Assistance Foundation
Bristol-Myers Squibb (BMS)
Daklinza
BMS Patient Support Connect
Genentech
Copegus Pegasys Pegasys ProClick Epclusa Harvoni Sovaldi Vosevi Olysio
Genentech Rx Assist Access to Care Gilead Support Path
www.abbviepaf.org 1-800-222-6885 https://www.viekira.com/patient-support 1-844-277-6233 (2PROCEED) www.patientsupportconnect.bmscustomerconnect.com 1-844-442-6663 (44CONNECT) www.rxassist.org/patients 1-888-941-3331 www.mysupportpath.com 1-855-769-7284 (7MYPATH)
Janssen Prescription Assistance
Ribasphere Ribapak Zepatier
Kadmon Enabling Your Success (KEYS) Program Merck Access & Support Services
www.janssenprescriptionassistance.com 1-800-652-6227 www.pparx.org (search Kadmon) 1-888-868-3393 https://www.merckaccessprogram.com
Medication
Program
Contact info
Gilead Sciences
Janssen/Johnson & Johnson Kadmon Pharmaceuticals Merck & Co. Nonprofit organizations Company Needy Meds Partnership for Prescription Assistance (PPA) Service Patient Access Network Foundation
www.needymeds.org/index.htm 1-800-503-6897 www.pparx.org www.panfoundation.org 1-866-316-7263
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