- Email: [email protected]
A pharmacist-run anabolic osteoporosis clinic: An abaloparatide descriptive report
SCIENCE AND PRACTICE Journal of the American Pharmacists Association 59 (2019) 593e597
Contents lists available at ScienceDirect
Journal of the American Pharmacists Association journal homepage: www.japha.org
ADVANCES IN PHARMACY PRACTICE
A pharmacist-run anabolic osteoporosis clinic: An abaloparatide descriptive report Jenna L. McGreevy, Michael P. Kane*, Robert S. Busch, Gary Bakst, Samer ElDeiry a r t i c l e i n f o
a b s t r a c t
Article history: Received 27 January 2019 Accepted 26 March 2019 Available online 14 May 2019
Objectives: To review the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. Setting: This ambulatory-care health system endocrinology practice consists of 10 boardcertified endocrinologists and 6 nurse practitioners and physician assistants. Approximately 1200 patients are seen weekly. The practice is affiliated with the Albany College of Pharmacy and Health Sciences and hosts 2 clinical pharmacy faculty members and a PGY-2 endocrinology pharmacy resident. A pharmacist-run teriparatide clinic was implemented in 2002. In 2017, the clinic was expanded to accept referrals for abaloparatide. No description of a pharmacist-run abaloparatide clinic has yet been reported. Practice description: Patients are referred to a clinical pharmacist for initiation and education of anabolic osteoporosis therapy. The pharmacist is responsible for assessing for contraindications to anabolic therapy, securing managed care coverage of an anabolic agent, and providing medication counseling. This pharmacist is available as a resource to patients throughout their course of anabolic osteoporosis therapy. Practice innovation: This is the first description of a pharmacist-run abaloparatide clinic. Evaluation: Not applicable. Results: During its first year of availability, 52 patients were referred for abaloparatide therapy. Of these, 31 patients (59.6%) initiated treatment. The population predominately consisted of postmenopausal white women. Approximately two-thirds of patients had a history of an osteoporosis-related fracture, and half of patients had previously received antiresorptive therapy for osteoporosis. Mean baseline T-scores for the lumbar spine and femoral neck were 2.41 and 2.57, respectively. Twenty-one patients did not initiate abaloparatide therapy owing to cost (9), concerns of therapy (8), or contraindication to therapy (4). An additional 5 patients discontinued abaloparatide therapy owing to adverse effects. Conclusion: This paper reviews the first-year experience of abaloparatide use in a pharmacistrun anabolic osteoporosis clinic. The fact that only 60% of referred patients initiated therapy indicates that significant barriers (e.g., high patient cost and safety concerns) remain. © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Osteoporosis is the most common bone disorder in the United States.1 Ten million Americans older than 50 years are diagnosed with osteoporosis, and approximately 1.5 million fractures occur annually.1 Osteoporotic fractures are associated with increased morbidity and mortality and are a strong Disclosure: The authors declare no relevant conflicts of interest or financial relationships. * Correspondence: Michael P. Kane, PharmD, FCCP, BCPS, BCACP, Professor, Clinical Pharmacy Specialist, Albany College of Pharmacy and Health Sciences, Albany Medical Center Division of Community Endocrinology, 106 New Scotland Avenue, Albany, NY 12208. E-mail address: [email protected] (M.P. Kane).
predictor of recurrent fracture risk.2,3 Unfortunately, fewer than 25% of women over 65 years of age with an osteoporosisrelated fracture undergo bone density measurements or initiate treatment for osteoporosis.4 Available treatment options for osteoporosis include antiresorptive agents (bisphosphonates, denosumab, hormonal therapies, and calcitonin) and anabolic agents.2 Patients in whom anabolic therapy is indicated include men and postmenopausal women at high risk of an osteoporotic fracture.3 The Food and Drug Administration (FDA) defines high risk of fracture as having a history of fragility fracture, multiple risk factors for fracture, or failure to respond to drug therapy.5
https://doi.org/10.1016/j.japh.2019.03.017 1544-3191/© 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
SCIENCE AND PRACTICE J.L. McGreevy et al. / Journal of the American Pharmacists Association 59 (2019) 593e597
Key Points Background: Abaloparatide (TymloseRadius Health) was approved in 2017 as an anabolic agent for treatment of postmenopausal women with osteoporosis at high risk of fracture. To ensure safe and effective use of anabolic therapy, a pharmacist-run anabolic clinic was developed at our practice in 2002. In 2017, the clinic was expanded to accept referrals for abaloparatide. Findings: Only 60% of referred patients in this pharmacist-run anabolic osteoporosis clinic initiated abaloparatide therapy. The most common barriers to therapy initiation were cost and medication safety concerns. The typical patient initiating abaloparatide therapy was a postmenopausal white woman; two-thirds of patients had a history of osteoporotic fracture.
Available anabolic agents for osteoporosis include teriparatide (ForteoeEli Lilly and Company) and abaloparatide (TymloseRadius Health). Table 1 lists key differences between these medications. Teriparatide was approved in 2002 and contains the biologically active 34 N-terminal amino acids of human parathyroid hormone (PTH).6 Abaloparatide gained approval in 2017 and is a synthetic analogue of human PTH-related protein.7 Changes in the amino acid sequence of abaloparatide affect conformational binding at the PTH receptor to increase anabolic activity compared to PTH. The structural modifications also increase the stability of abaloparatide, allowing for storage of the drug at room temperature once in use.8 Intermittent exposure to either agent with oncedaily dosing preferentially stimulates osteoblast activity and promotes bone formation. Bone architecture is improved because of this increase in bone formation and microstructural repair.9 Both agents carry a boxed warning regarding the risk of osteosarcoma.6,7 Anabolic therapy reduces the 2-year risk of vertebral fractures by 65% to 85% and nonvertebral fragility fractures by approximately 50%.10,11 In the ACTIVE (Abaloparatide Comparator Trial in Vertebral Endpoints) trial, 2463 women with osteoporosis were randomized to receive either blinded abaloparatide, placebo, or open-label teriparatide for 18 months. The risks of new vertebral fractures in the abaloparatide and teriparatide groups were reduced 86% and 80%, respectively, compared with placebo (P < 0.001 for both).11 The risk of nonvertebral fractures was significantly reduced by 43% in the abaloparatide group compared with placebo (P ¼ 0.049), whereas the 28% reduction in the teriparatide group was not statistically significant (P ¼ 0.22).11 Nonvertebral fracture risk reduction was seen earlier in patients treated with abaloparatide therapy compared with teriparatide therapy.11 Although anabolic therapy is recommended for patients with osteoporosis at high risk of fracture, its use presents with challenges. First, use of a daily subcutaneous injection requires
594
both patient acceptance and training on injection technique. Second, potential candidates must not be at an increased risk of developing osteosarcoma before initiation of anabolic therapy. Patients at higher risk of osteosarcoma, and in whom anabolic therapy is contraindicated, include those with Paget disease, history of bone metastases or skeletal malignancies, unexplained elevations in alkaline phosphatase, previous skeletal radiation, and children with open epiphyseal plates. Finally, because the use of anabolic therapy is expensive, completion of medication prior authorizations and detailed communication with insurance companies is essential for medication access. Teriparatide is estimated to cost $1866 per 28-day supply, and abaloparatide is estimated to cost $1186 per 30-day supply.12 Objective To overcome challenges and ensure safe and effective use of anabolic therapy, a pharmacist-run teriparatide clinic was implemented at this practice in 2002. In 2017, the clinic was expanded to accept referrals for abaloparatide. No description of a pharmacist-run abaloparatide clinic has yet been reported. The objective of this report was to review the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. Setting The Albany Medical Center Division of Community Endocrinology (formerly The Endocrine Group) is in Albany, NY, and consists of 10 board-certified endocrinologists and 6 nurse practitioners and physician assistants. Approximately 1200 patients are seen weekly. The practice is affiliated with the Albany College of Pharmacy and Health Sciences and hosts 2 clinical pharmacy faculty members and a PGY-2 endocrinology pharmacy resident. With the approval of teriparatide in 2002, providers of the practice asked clinical pharmacy staff to develop a referral process to identify and train potential candidates for anabolic therapy. Since clinic establishment in late 2002, approximately 50 patients have been referred annually for teriparatide therapy. A description of this clinic and effects of teriparatide therapy on bone mineral density and fracture risk have previously been described.13,14 In 2017, the clinic was expanded to accept referrals for abaloparatide. This descriptive report was approved by the Institutional Review Board of the Albany College of Pharmacy and Health Sciences. A data collection form was used to collect the following patient information from abaloparatide referrals: baseline demographic information (sex, race, age, height, weight), contraindications to anabolic therapy (if applicable), duration of osteoporosis, history of osteoporosis-related fracture, previous osteoporosis medication use, and dual energy X-ray absorptiometry (DXA) results (bone mineral density and T-scores). A descriptive report of the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic follows. Practice description Patients are referred to the anabolic clinic by providers via electronic, verbal, and written orders. Typical patients include
SCIENCE AND PRACTICE Pharmacist-run abaloparatide clinic
Table 1 Key differences between anabolic therapy agents Teriparatide (Forteo)
Abaloparatide (Tymlos)
Recombinant human parathyroid hormone Indicated for:a Postmenopausal women with osteoporosis Increase in bone mass in men with primary or hypogonadal osteoporosis Treatment of men or women with glucocorticoid-induced osteoporosis Typical treatment duration of 24 months Dose: 20 mcg subcutaneously once daily Administer in abdomen or upper thigh Refrigeration for storage, may be at room temperature for maximum 36 hours 1 pen provides 28-day supply Estimated cost per pen of $1866 a
Synthetic analogue human parathyroid hormoneerelated protein Indicated for:a Postmenopausal women with osteoporosis
Typical treatment duration of 18 months Dose: 80 mcg subcutaneously once daily Administer in abdomen Store up to 30 days at room temperature after first use 1 pen provides 30-day supply Estimated cost per pen of $1186
All subgroups also at high risk of fracture.
those with a history of previous osteoporotic fracture, intolerance to antiresorptive therapies, or worsening bone mineral density or fracture while receiving antiresorptive therapy. Following referral, a clinical pharmacist reviews the patient’s electronic medical record to rule out contraindications to anabolic therapy and to ensure that a work-up for secondary causes of osteoporosis (e.g., hyperparathyroidism, hyperthyroidism, Cushing disease, vitamin D deficiency, multiple myeloma, drug-induced) has been performed. Relative contraindications to anabolic therapy include preexisting hypercalcemia or hypercalciuria. Candidates for anabolic therapy are contacted by the pharmacist via telephone to provide an introduction and preliminary medication education. The clinical pharmacist also obtains managed care approval of the anabolic agent. Selection of the anabolic agent is traditionally driven by the patient’s managed care company, but if the provider prefers a particular agent, the preferred therapy is pursued. For example, providers may prefer use of abaloparatide in patients anticipated to use a shorter course of anabolic therapy, owing to its earlier effects on reducing nonvertebral fracture risk. Pharmacist time and effort to obtain managed care approval can vary significantly (e.g., from an hour to several days) per patient. Anabolic therapy is generally approved in patients who have a history of osteoporotic fracture, those at high risk for having a future fracture, or those with clinical failure or intolerance to antiresorptive therapies. Once approval for an anabolic agent is obtained, the patient is scheduled for an hour-long education session with a clinical pharmacist. During this visit, the patient is counseled on nonpharmacologic management of osteoporosis, fall risk reduction, common medication adverse effects, warnings specific to anabolic therapy (including the osteosarcoma boxed warning), and injection technique. Patient education is provided by means of the teach-back method. The patient is also given a starter kit supplied by the manufacturer consisting of a carrying case, pen needles, and written instructions for use. Approximately 1 week after the clinic visit, the clinical pharmacist contacts the patient to answer additional questions or address any concerns. The clinical pharmacist serves as a resource to the patient throughout the course of his or her anabolic therapy. Traditionally, follow-up is performed via telephone but may include future office visits at the patient’s request. The patient continues to follow-up with his or her endocrinologist for osteoporosis management and for
transition to antiresorptive therapy after completion of anabolic therapy. Currently, pharmacists are not practicing under a collaborative drug therapy management protocol and are therefore unable to prescribe or change drug therapy. In addition, pharmacists do not bill for services owing to the institution’s policy on incident-to-physician billing. Results Over the first year of its availability, 52 patients were referred to our anabolic osteoporosis clinic for abaloparatide therapy, which constituted two-thirds of all anabolic drug referrals. Of these 52 patients, 31 patients (59.6%) initiated treatment with abaloparatide. Table 2 presents baseline characteristics of this population, which predominately consisted of elderly white women. One male patient was initiated on therapy, which is considered to be off-label use. Approximately two-thirds of patients had a history of an osteoporosisrelated fracture, and approximately one-half of patients had previously received antiresorptive therapy for osteoporosis. One patient was switched to abaloparatide after experiencing adverse effects with teriparatide. Table 3 presents baseline bone mineral density of the cohort. Twenty-one of the 52 referred patients did not initiate therapy, primarily because of cost (9 patients) and safety
Table 2 Baseline characteristics Characteristic (n ¼ 31) Age, mean ± SD (years) Female White Previous osteoporosis drug use Previous osteoporosis drug therapya Bisphosphonates Denosumab Raloxifene Calcitonin Teriparatide History of osteoporosis-related fracture Total number of fractures Type of osteoporotic fracture Hip Vertebral Wrist Other a
Value 65 30 31 15
± 7.09 (96.8%) (100%) (48.4%)
11 6 1 1 1 21 (67.7%) 28 3 (10.7%) 8 (28.6%) 5 (17.8%) 12 (42.9%)
Five patients received more than 1 previous therapy.
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SCIENCE AND PRACTICE J.L. McGreevy et al. / Journal of the American Pharmacists Association 59 (2019) 593e597
Table 3 Baseline bone mineral density Variable Lumbar spine BMD (g/cm2) (n ¼ T-score (n ¼ 30) Total hip BMD (g/cm2) (n ¼ T-score (n ¼ 28) Femoral neck BMD (g/cm2) (n ¼ T-score (n ¼ 27) Wrist BMD (g/cm2) (n ¼ T-score (n ¼ 9)
Value 27)
0.793 ± 0.136 2.41 ± 1.14
25)
0.719 ± 0.112 ¡1.90 ± 0.948
26)
0.582 ± 0.10 2.57 ± 0.710
9)
0.548 ± 0.082 2.42 ± 1.37
Abbreviation used: BMD, bone mineral density.
concerns (8 patients). Abaloparatide therapy was found to be contraindicated in 4 patients. The contraindications to therapy included hypercalcemia (1 patient), unexplained elevations in alkaline phosphatase (1 patient), abnormal serum protein electrophoresis results (1 patient), and osteoporosis secondary to hyperparathyroidism (1 patient). After initiation of therapy, 5 patients discontinued abaloparatide, including 4 patients who discontinued therapy because of adverse effects. Reported adverse effects included palpitations (2 patients) and nausea (2 patients). Other reported adverse effects included headache and dizziness (1 patient) and hip pain, weight gain, and fatigue (1 patient). One patient died while receiving abaloparatide therapy. That patient was a 62-year-old man with presumed pituitary Cushing disease awaiting inferior petrosal sinus sampling who had received care at our practice for approximately 3 months before his death. The presumed cause of death was myocardial infarction, and use of abaloparatide was not thought to be associated with the patient’s death. Discussion This paper reviews the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. Most patients referred for abaloparatide treatment either had a history of fracture or had received previous treatment with antiresorptive therapies. In addition, only 60% of referred patients were able to initiate abaloparatide therapy. Barriers to initiation of abaloparatide therapy were identified as high patient cost and concerns about medication safety. Pharmacist involvement in the treatment and management of chronic conditions such as diabetes, hypertension, and hyperlipidemia has been extensively described. Pharmacist involvement in treatment of osteoporosis also has increased. In a study of 686 patients treated in a family medicine clinic, clinical pharmacists were available to review DXA scans and provide treatment recommendations to providers. Two-thirds of patients managed by a collaborative pharmacistephysician team initiated or continued antifracture therapy compared with only one-third of patients managed by physicians.15 However, only a single patient in each group was treated with anabolic therapy.15 Similarly, an interprofessional osteoporosis clinic of a physician and geriatric pharmacist was developed at a retirement community. Of 29 patients referred
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to the clinic, all but 4 patients were appropriately treated for osteoporosis or osteopenia with the use of bisphosphonate therapy.16 Likewise, recommendations made by pharmacists for calcium and vitamin D supplementation were accepted 90% and 86% of the time, respectively.16 Our pharmacist-run anabolic osteoporosis clinic is unique from these previous studies in multiple ways. First, our pharmacist-run clinic is embedded within a large endocrinology practice. Patients referred to an endocrinologist for osteoporosis management are often more complex and require advanced therapy. Second, a limited number of patients in the previous trials were treated with anabolic therapy. To our knowledge, our pharmacist-run clinic is the only one of its type for the management of anabolic osteoporosis therapy. Finally, pharmacist intervention in this report occurred outside of a collaborative drug therapy management protocol. This is different from typical pharmacist intervention in other types of chronic disease state management, and it serves as a future goal to aspire to. The role of our pharmacist-run anabolic clinic will likely grow in the future to include additional therapies. In January 2019, the FDA Bone, Reproductive, and Urologic Drugs Advisory Committee voted in favor of approving romosozumab (EvenityeAmgen) for treatment of osteoporosis in postmenopausal women at high risk of osteoporotic fracture.17 Romosozumab is a fully humanized monoclonal antibody to sclerostin that exhibits both anabolic and antiresorptive properties. In a study of 4093 postmenopausal women with histories of fragility fracture, romosozumab was associated with a 48% relative risk reduction in vertebral fracture at 24 months.18 Serious cardiovascular events occurred more commonly with romosozumab compared with placebo, driven primarily by cardiac ischemic and cerebrovascular events.18 Future integration of this medication into the anabolic osteoporosis clinic will be essential to ensure its safe and effective use. In the clinic’s first year of experience with abaloparatide, barriers to treatment were identified. High patient cost was the most commonly cited barrier to therapy initiation. Copay assistance of up to $600 per month is available through the manufacturer for commercially insured patients, but no such assistance is available for patients receiving prescription benefits through Medicare or Medicaid. The average age of patients initiated on therapy in this descriptive report was 65 years, the age at which most Americans become eligible for Medicare. All 9 patients in this report who refused to start abaloparatide because of cost were Medicare patients, who cited monthly copays of $500 to $600. Access to anabolic therapy may be increased in the future due to impending biosimilar competition.19 The second most common barrier to therapy initiation in our clinic was patient medication concerns, including fear of osteosarcoma and unwillingness to perform a daily injection. Regardless of extensive boxed warning counseling, screening for predisposing risk factors, and limited duration of therapy, some patients remained hesitant to initiate therapy. Eight years of registry data for teriparatide are now available and indicate that there is no increased risk of osteosarcoma compared with the general population.20 Unfortunately, comparable data are not yet available for abaloparatide. In addition, abaloparatide use may have been hampered owing to fears of discomfort or inconvenience of a daily injection, although similar apprehension is occasionally seen in patients referred for teriparatide.
SCIENCE AND PRACTICE Pharmacist-run abaloparatide clinic
There are multiple limitations of this descriptive report. Baseline bone mineral density and T-scores were not available for all patients initiated on abaloparatide therapy. Patients could have had baseline DXA scans performed at outside facilities that may not test all sites (e.g., wrist) or report both T-scores and bone mineral density results. Another limitation of this descriptive report includes a lack of outcome data regarding abaloparatide use. Currently, only a limited number of patients have completed a full 18-month treatment course of abaloparatide. Future research includes reporting bone mineral density and fracture data following treatment with abaloparatide. Conclusion This paper reviews the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. The fact that only 60% of referred patients initiated therapy is indicative that significant barriers to treatment (such as high patient cost and safety concerns) remain. References 1. Office of the Surgeon General. Bone health and osteoporosis: a report of the surgeon general. Available at: https://www.ncbi.nlm.nih.gov/ pubmed/20945569. Accessed January 15, 2019. 2. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25:2359e2381. ttir K, Harvey NC, et al. Imminent risk of fracture 3. Johansson H, Siggeirsdo after fracture. Osteoporos Int. 2017;28(3):775e780. 4. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2016. Endocr Pract. 2016;22(Suppl 4):1e42. 5. U.S. Food and Drug Administration. Available at: https://www.fda.gov/ downloads/drugs/newsevents/ucm470574.pdf. Accessed January 15, 2019. 6. Teriparatide [package insert]. Indianapolis, IN: Eli Lilly; 2017. 7. Abaloparatide [package insert]. Waltham, MA: Radius; 2017. 8. Tella SH, Kommalapati A, Correa R. Cureus. Profile of abaloparatide and its potential in the treatment of postmenopausal osteoporosis. Cureus. 2017;9(5):e1300. 9. Riggs BL, Parfitt AM. Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res. 2005;20(2):177e184.
10. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1e34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434e1441. 11. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):722e733. 12. Institute for Clinical and Economic Review. Anabolic therapies for osteoporosis in postmenopausal women: effectiveness and value: evidence report. Available at: https://icer-review.org/wp-content/uploads/2016/ 11/CTAF_Osteoporosis_Evidence_Report_061617.pdf. Accessed January 15, 2019. 13. Stroup J, Kane MP, Busch RS. Pharmacist-run teriparatide clinic. Am J Health Syst Pharm. 2003;60(21):2247e2249. 14. Stroup JS, Rivers SM, Abu-Baker AM, Kane MP. Two-year changes in bone mineral density and T scores in patients treated at a pharmacist-run teriparatide clinic. Pharmacotherapy. 2007;27(6):779e788. 15. Bowers BL, Drew AM, Verry C. Impact of pharmacist-physician collaboration on osteoporosis treatment. Ann Pharmacother. 2018;52(9): 876e883. 16. Masterson J, Woodall T, Wilson CG, et al. Interprofessional care for patients with osteoporosis in a continuing care retirement community. J Am Pharm Assoc (2003). 2016;56(2):184e188. 17. U.S. Food and Drug Administration. Available at: https://www.fda.gov/ downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ ReproductiveHealthDrugsAdvisoryCommittee/UCM629456.pdf. Accessed February 24, 2019. 18. Saag KG, Petersen J, Brandi ML, et al. Romososumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417e1427. 19. Davio K. Pfenex submits follow-on teriparatide for FDA review. Available at: https://www.centerforbiosimilars.com/news/pfenex-submits-follow on-teriparatide-for-fda-review. Accessed January 15, 2019. 20. Gilsenan A, Harding A, Kellier-Steele N, et al. The Forteo patient registry linkage to multiple state cancer registries: study design and results from the first 8 years. Osteoporos Int. 2018;29:2335e2343. Jenna L. McGreevy, PharmD, PGY-2 Endocrinology Resident, Albany College of Pharmacy and Health Sciences, Albany Medical Center Division of Community Endocrinology, Albany, NY Michael P. Kane, PharmD, FCCP, BCPS, BCACP, Professor, Clinical Pharmacy Specialist, Albany College of Pharmacy and Health Sciences, Albany Medical Center Division of Community Endocrinology, Albany, NY Robert S. Busch, MD, FACE, Endocrinologist, Albany Medical Center Division of Community Endocrinology, Albany, NY Gary Bakst, MD, FACE, Endocrinologist, Albany Medical Center Division of Community Endocrinology, Albany, NY Samer ElDeiry, MD, PhD, Endocrinologist, Albany Medical Center Division of Community Endocrinology, Albany, NY
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Contents lists available at ScienceDirect
Journal of the American Pharmacists Association journal homepage: www.japha.org
ADVANCES IN PHARMACY PRACTICE
A pharmacist-run anabolic osteoporosis clinic: An abaloparatide descriptive report Jenna L. McGreevy, Michael P. Kane*, Robert S. Busch, Gary Bakst, Samer ElDeiry a r t i c l e i n f o
a b s t r a c t
Article history: Received 27 January 2019 Accepted 26 March 2019 Available online 14 May 2019
Objectives: To review the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. Setting: This ambulatory-care health system endocrinology practice consists of 10 boardcertified endocrinologists and 6 nurse practitioners and physician assistants. Approximately 1200 patients are seen weekly. The practice is affiliated with the Albany College of Pharmacy and Health Sciences and hosts 2 clinical pharmacy faculty members and a PGY-2 endocrinology pharmacy resident. A pharmacist-run teriparatide clinic was implemented in 2002. In 2017, the clinic was expanded to accept referrals for abaloparatide. No description of a pharmacist-run abaloparatide clinic has yet been reported. Practice description: Patients are referred to a clinical pharmacist for initiation and education of anabolic osteoporosis therapy. The pharmacist is responsible for assessing for contraindications to anabolic therapy, securing managed care coverage of an anabolic agent, and providing medication counseling. This pharmacist is available as a resource to patients throughout their course of anabolic osteoporosis therapy. Practice innovation: This is the first description of a pharmacist-run abaloparatide clinic. Evaluation: Not applicable. Results: During its first year of availability, 52 patients were referred for abaloparatide therapy. Of these, 31 patients (59.6%) initiated treatment. The population predominately consisted of postmenopausal white women. Approximately two-thirds of patients had a history of an osteoporosis-related fracture, and half of patients had previously received antiresorptive therapy for osteoporosis. Mean baseline T-scores for the lumbar spine and femoral neck were 2.41 and 2.57, respectively. Twenty-one patients did not initiate abaloparatide therapy owing to cost (9), concerns of therapy (8), or contraindication to therapy (4). An additional 5 patients discontinued abaloparatide therapy owing to adverse effects. Conclusion: This paper reviews the first-year experience of abaloparatide use in a pharmacistrun anabolic osteoporosis clinic. The fact that only 60% of referred patients initiated therapy indicates that significant barriers (e.g., high patient cost and safety concerns) remain. © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Osteoporosis is the most common bone disorder in the United States.1 Ten million Americans older than 50 years are diagnosed with osteoporosis, and approximately 1.5 million fractures occur annually.1 Osteoporotic fractures are associated with increased morbidity and mortality and are a strong Disclosure: The authors declare no relevant conflicts of interest or financial relationships. * Correspondence: Michael P. Kane, PharmD, FCCP, BCPS, BCACP, Professor, Clinical Pharmacy Specialist, Albany College of Pharmacy and Health Sciences, Albany Medical Center Division of Community Endocrinology, 106 New Scotland Avenue, Albany, NY 12208. E-mail address: [email protected] (M.P. Kane).
predictor of recurrent fracture risk.2,3 Unfortunately, fewer than 25% of women over 65 years of age with an osteoporosisrelated fracture undergo bone density measurements or initiate treatment for osteoporosis.4 Available treatment options for osteoporosis include antiresorptive agents (bisphosphonates, denosumab, hormonal therapies, and calcitonin) and anabolic agents.2 Patients in whom anabolic therapy is indicated include men and postmenopausal women at high risk of an osteoporotic fracture.3 The Food and Drug Administration (FDA) defines high risk of fracture as having a history of fragility fracture, multiple risk factors for fracture, or failure to respond to drug therapy.5
https://doi.org/10.1016/j.japh.2019.03.017 1544-3191/© 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
SCIENCE AND PRACTICE J.L. McGreevy et al. / Journal of the American Pharmacists Association 59 (2019) 593e597
Key Points Background: Abaloparatide (TymloseRadius Health) was approved in 2017 as an anabolic agent for treatment of postmenopausal women with osteoporosis at high risk of fracture. To ensure safe and effective use of anabolic therapy, a pharmacist-run anabolic clinic was developed at our practice in 2002. In 2017, the clinic was expanded to accept referrals for abaloparatide. Findings: Only 60% of referred patients in this pharmacist-run anabolic osteoporosis clinic initiated abaloparatide therapy. The most common barriers to therapy initiation were cost and medication safety concerns. The typical patient initiating abaloparatide therapy was a postmenopausal white woman; two-thirds of patients had a history of osteoporotic fracture.
Available anabolic agents for osteoporosis include teriparatide (ForteoeEli Lilly and Company) and abaloparatide (TymloseRadius Health). Table 1 lists key differences between these medications. Teriparatide was approved in 2002 and contains the biologically active 34 N-terminal amino acids of human parathyroid hormone (PTH).6 Abaloparatide gained approval in 2017 and is a synthetic analogue of human PTH-related protein.7 Changes in the amino acid sequence of abaloparatide affect conformational binding at the PTH receptor to increase anabolic activity compared to PTH. The structural modifications also increase the stability of abaloparatide, allowing for storage of the drug at room temperature once in use.8 Intermittent exposure to either agent with oncedaily dosing preferentially stimulates osteoblast activity and promotes bone formation. Bone architecture is improved because of this increase in bone formation and microstructural repair.9 Both agents carry a boxed warning regarding the risk of osteosarcoma.6,7 Anabolic therapy reduces the 2-year risk of vertebral fractures by 65% to 85% and nonvertebral fragility fractures by approximately 50%.10,11 In the ACTIVE (Abaloparatide Comparator Trial in Vertebral Endpoints) trial, 2463 women with osteoporosis were randomized to receive either blinded abaloparatide, placebo, or open-label teriparatide for 18 months. The risks of new vertebral fractures in the abaloparatide and teriparatide groups were reduced 86% and 80%, respectively, compared with placebo (P < 0.001 for both).11 The risk of nonvertebral fractures was significantly reduced by 43% in the abaloparatide group compared with placebo (P ¼ 0.049), whereas the 28% reduction in the teriparatide group was not statistically significant (P ¼ 0.22).11 Nonvertebral fracture risk reduction was seen earlier in patients treated with abaloparatide therapy compared with teriparatide therapy.11 Although anabolic therapy is recommended for patients with osteoporosis at high risk of fracture, its use presents with challenges. First, use of a daily subcutaneous injection requires
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both patient acceptance and training on injection technique. Second, potential candidates must not be at an increased risk of developing osteosarcoma before initiation of anabolic therapy. Patients at higher risk of osteosarcoma, and in whom anabolic therapy is contraindicated, include those with Paget disease, history of bone metastases or skeletal malignancies, unexplained elevations in alkaline phosphatase, previous skeletal radiation, and children with open epiphyseal plates. Finally, because the use of anabolic therapy is expensive, completion of medication prior authorizations and detailed communication with insurance companies is essential for medication access. Teriparatide is estimated to cost $1866 per 28-day supply, and abaloparatide is estimated to cost $1186 per 30-day supply.12 Objective To overcome challenges and ensure safe and effective use of anabolic therapy, a pharmacist-run teriparatide clinic was implemented at this practice in 2002. In 2017, the clinic was expanded to accept referrals for abaloparatide. No description of a pharmacist-run abaloparatide clinic has yet been reported. The objective of this report was to review the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. Setting The Albany Medical Center Division of Community Endocrinology (formerly The Endocrine Group) is in Albany, NY, and consists of 10 board-certified endocrinologists and 6 nurse practitioners and physician assistants. Approximately 1200 patients are seen weekly. The practice is affiliated with the Albany College of Pharmacy and Health Sciences and hosts 2 clinical pharmacy faculty members and a PGY-2 endocrinology pharmacy resident. With the approval of teriparatide in 2002, providers of the practice asked clinical pharmacy staff to develop a referral process to identify and train potential candidates for anabolic therapy. Since clinic establishment in late 2002, approximately 50 patients have been referred annually for teriparatide therapy. A description of this clinic and effects of teriparatide therapy on bone mineral density and fracture risk have previously been described.13,14 In 2017, the clinic was expanded to accept referrals for abaloparatide. This descriptive report was approved by the Institutional Review Board of the Albany College of Pharmacy and Health Sciences. A data collection form was used to collect the following patient information from abaloparatide referrals: baseline demographic information (sex, race, age, height, weight), contraindications to anabolic therapy (if applicable), duration of osteoporosis, history of osteoporosis-related fracture, previous osteoporosis medication use, and dual energy X-ray absorptiometry (DXA) results (bone mineral density and T-scores). A descriptive report of the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic follows. Practice description Patients are referred to the anabolic clinic by providers via electronic, verbal, and written orders. Typical patients include
SCIENCE AND PRACTICE Pharmacist-run abaloparatide clinic
Table 1 Key differences between anabolic therapy agents Teriparatide (Forteo)
Abaloparatide (Tymlos)
Recombinant human parathyroid hormone Indicated for:a Postmenopausal women with osteoporosis Increase in bone mass in men with primary or hypogonadal osteoporosis Treatment of men or women with glucocorticoid-induced osteoporosis Typical treatment duration of 24 months Dose: 20 mcg subcutaneously once daily Administer in abdomen or upper thigh Refrigeration for storage, may be at room temperature for maximum 36 hours 1 pen provides 28-day supply Estimated cost per pen of $1866 a
Synthetic analogue human parathyroid hormoneerelated protein Indicated for:a Postmenopausal women with osteoporosis
Typical treatment duration of 18 months Dose: 80 mcg subcutaneously once daily Administer in abdomen Store up to 30 days at room temperature after first use 1 pen provides 30-day supply Estimated cost per pen of $1186
All subgroups also at high risk of fracture.
those with a history of previous osteoporotic fracture, intolerance to antiresorptive therapies, or worsening bone mineral density or fracture while receiving antiresorptive therapy. Following referral, a clinical pharmacist reviews the patient’s electronic medical record to rule out contraindications to anabolic therapy and to ensure that a work-up for secondary causes of osteoporosis (e.g., hyperparathyroidism, hyperthyroidism, Cushing disease, vitamin D deficiency, multiple myeloma, drug-induced) has been performed. Relative contraindications to anabolic therapy include preexisting hypercalcemia or hypercalciuria. Candidates for anabolic therapy are contacted by the pharmacist via telephone to provide an introduction and preliminary medication education. The clinical pharmacist also obtains managed care approval of the anabolic agent. Selection of the anabolic agent is traditionally driven by the patient’s managed care company, but if the provider prefers a particular agent, the preferred therapy is pursued. For example, providers may prefer use of abaloparatide in patients anticipated to use a shorter course of anabolic therapy, owing to its earlier effects on reducing nonvertebral fracture risk. Pharmacist time and effort to obtain managed care approval can vary significantly (e.g., from an hour to several days) per patient. Anabolic therapy is generally approved in patients who have a history of osteoporotic fracture, those at high risk for having a future fracture, or those with clinical failure or intolerance to antiresorptive therapies. Once approval for an anabolic agent is obtained, the patient is scheduled for an hour-long education session with a clinical pharmacist. During this visit, the patient is counseled on nonpharmacologic management of osteoporosis, fall risk reduction, common medication adverse effects, warnings specific to anabolic therapy (including the osteosarcoma boxed warning), and injection technique. Patient education is provided by means of the teach-back method. The patient is also given a starter kit supplied by the manufacturer consisting of a carrying case, pen needles, and written instructions for use. Approximately 1 week after the clinic visit, the clinical pharmacist contacts the patient to answer additional questions or address any concerns. The clinical pharmacist serves as a resource to the patient throughout the course of his or her anabolic therapy. Traditionally, follow-up is performed via telephone but may include future office visits at the patient’s request. The patient continues to follow-up with his or her endocrinologist for osteoporosis management and for
transition to antiresorptive therapy after completion of anabolic therapy. Currently, pharmacists are not practicing under a collaborative drug therapy management protocol and are therefore unable to prescribe or change drug therapy. In addition, pharmacists do not bill for services owing to the institution’s policy on incident-to-physician billing. Results Over the first year of its availability, 52 patients were referred to our anabolic osteoporosis clinic for abaloparatide therapy, which constituted two-thirds of all anabolic drug referrals. Of these 52 patients, 31 patients (59.6%) initiated treatment with abaloparatide. Table 2 presents baseline characteristics of this population, which predominately consisted of elderly white women. One male patient was initiated on therapy, which is considered to be off-label use. Approximately two-thirds of patients had a history of an osteoporosisrelated fracture, and approximately one-half of patients had previously received antiresorptive therapy for osteoporosis. One patient was switched to abaloparatide after experiencing adverse effects with teriparatide. Table 3 presents baseline bone mineral density of the cohort. Twenty-one of the 52 referred patients did not initiate therapy, primarily because of cost (9 patients) and safety
Table 2 Baseline characteristics Characteristic (n ¼ 31) Age, mean ± SD (years) Female White Previous osteoporosis drug use Previous osteoporosis drug therapya Bisphosphonates Denosumab Raloxifene Calcitonin Teriparatide History of osteoporosis-related fracture Total number of fractures Type of osteoporotic fracture Hip Vertebral Wrist Other a
Value 65 30 31 15
± 7.09 (96.8%) (100%) (48.4%)
11 6 1 1 1 21 (67.7%) 28 3 (10.7%) 8 (28.6%) 5 (17.8%) 12 (42.9%)
Five patients received more than 1 previous therapy.
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SCIENCE AND PRACTICE J.L. McGreevy et al. / Journal of the American Pharmacists Association 59 (2019) 593e597
Table 3 Baseline bone mineral density Variable Lumbar spine BMD (g/cm2) (n ¼ T-score (n ¼ 30) Total hip BMD (g/cm2) (n ¼ T-score (n ¼ 28) Femoral neck BMD (g/cm2) (n ¼ T-score (n ¼ 27) Wrist BMD (g/cm2) (n ¼ T-score (n ¼ 9)
Value 27)
0.793 ± 0.136 2.41 ± 1.14
25)
0.719 ± 0.112 ¡1.90 ± 0.948
26)
0.582 ± 0.10 2.57 ± 0.710
9)
0.548 ± 0.082 2.42 ± 1.37
Abbreviation used: BMD, bone mineral density.
concerns (8 patients). Abaloparatide therapy was found to be contraindicated in 4 patients. The contraindications to therapy included hypercalcemia (1 patient), unexplained elevations in alkaline phosphatase (1 patient), abnormal serum protein electrophoresis results (1 patient), and osteoporosis secondary to hyperparathyroidism (1 patient). After initiation of therapy, 5 patients discontinued abaloparatide, including 4 patients who discontinued therapy because of adverse effects. Reported adverse effects included palpitations (2 patients) and nausea (2 patients). Other reported adverse effects included headache and dizziness (1 patient) and hip pain, weight gain, and fatigue (1 patient). One patient died while receiving abaloparatide therapy. That patient was a 62-year-old man with presumed pituitary Cushing disease awaiting inferior petrosal sinus sampling who had received care at our practice for approximately 3 months before his death. The presumed cause of death was myocardial infarction, and use of abaloparatide was not thought to be associated with the patient’s death. Discussion This paper reviews the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. Most patients referred for abaloparatide treatment either had a history of fracture or had received previous treatment with antiresorptive therapies. In addition, only 60% of referred patients were able to initiate abaloparatide therapy. Barriers to initiation of abaloparatide therapy were identified as high patient cost and concerns about medication safety. Pharmacist involvement in the treatment and management of chronic conditions such as diabetes, hypertension, and hyperlipidemia has been extensively described. Pharmacist involvement in treatment of osteoporosis also has increased. In a study of 686 patients treated in a family medicine clinic, clinical pharmacists were available to review DXA scans and provide treatment recommendations to providers. Two-thirds of patients managed by a collaborative pharmacistephysician team initiated or continued antifracture therapy compared with only one-third of patients managed by physicians.15 However, only a single patient in each group was treated with anabolic therapy.15 Similarly, an interprofessional osteoporosis clinic of a physician and geriatric pharmacist was developed at a retirement community. Of 29 patients referred
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to the clinic, all but 4 patients were appropriately treated for osteoporosis or osteopenia with the use of bisphosphonate therapy.16 Likewise, recommendations made by pharmacists for calcium and vitamin D supplementation were accepted 90% and 86% of the time, respectively.16 Our pharmacist-run anabolic osteoporosis clinic is unique from these previous studies in multiple ways. First, our pharmacist-run clinic is embedded within a large endocrinology practice. Patients referred to an endocrinologist for osteoporosis management are often more complex and require advanced therapy. Second, a limited number of patients in the previous trials were treated with anabolic therapy. To our knowledge, our pharmacist-run clinic is the only one of its type for the management of anabolic osteoporosis therapy. Finally, pharmacist intervention in this report occurred outside of a collaborative drug therapy management protocol. This is different from typical pharmacist intervention in other types of chronic disease state management, and it serves as a future goal to aspire to. The role of our pharmacist-run anabolic clinic will likely grow in the future to include additional therapies. In January 2019, the FDA Bone, Reproductive, and Urologic Drugs Advisory Committee voted in favor of approving romosozumab (EvenityeAmgen) for treatment of osteoporosis in postmenopausal women at high risk of osteoporotic fracture.17 Romosozumab is a fully humanized monoclonal antibody to sclerostin that exhibits both anabolic and antiresorptive properties. In a study of 4093 postmenopausal women with histories of fragility fracture, romosozumab was associated with a 48% relative risk reduction in vertebral fracture at 24 months.18 Serious cardiovascular events occurred more commonly with romosozumab compared with placebo, driven primarily by cardiac ischemic and cerebrovascular events.18 Future integration of this medication into the anabolic osteoporosis clinic will be essential to ensure its safe and effective use. In the clinic’s first year of experience with abaloparatide, barriers to treatment were identified. High patient cost was the most commonly cited barrier to therapy initiation. Copay assistance of up to $600 per month is available through the manufacturer for commercially insured patients, but no such assistance is available for patients receiving prescription benefits through Medicare or Medicaid. The average age of patients initiated on therapy in this descriptive report was 65 years, the age at which most Americans become eligible for Medicare. All 9 patients in this report who refused to start abaloparatide because of cost were Medicare patients, who cited monthly copays of $500 to $600. Access to anabolic therapy may be increased in the future due to impending biosimilar competition.19 The second most common barrier to therapy initiation in our clinic was patient medication concerns, including fear of osteosarcoma and unwillingness to perform a daily injection. Regardless of extensive boxed warning counseling, screening for predisposing risk factors, and limited duration of therapy, some patients remained hesitant to initiate therapy. Eight years of registry data for teriparatide are now available and indicate that there is no increased risk of osteosarcoma compared with the general population.20 Unfortunately, comparable data are not yet available for abaloparatide. In addition, abaloparatide use may have been hampered owing to fears of discomfort or inconvenience of a daily injection, although similar apprehension is occasionally seen in patients referred for teriparatide.
SCIENCE AND PRACTICE Pharmacist-run abaloparatide clinic
There are multiple limitations of this descriptive report. Baseline bone mineral density and T-scores were not available for all patients initiated on abaloparatide therapy. Patients could have had baseline DXA scans performed at outside facilities that may not test all sites (e.g., wrist) or report both T-scores and bone mineral density results. Another limitation of this descriptive report includes a lack of outcome data regarding abaloparatide use. Currently, only a limited number of patients have completed a full 18-month treatment course of abaloparatide. Future research includes reporting bone mineral density and fracture data following treatment with abaloparatide. Conclusion This paper reviews the first-year experience of abaloparatide use in a pharmacist-run anabolic osteoporosis clinic. The fact that only 60% of referred patients initiated therapy is indicative that significant barriers to treatment (such as high patient cost and safety concerns) remain. References 1. Office of the Surgeon General. Bone health and osteoporosis: a report of the surgeon general. Available at: https://www.ncbi.nlm.nih.gov/ pubmed/20945569. Accessed January 15, 2019. 2. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25:2359e2381. ttir K, Harvey NC, et al. Imminent risk of fracture 3. Johansson H, Siggeirsdo after fracture. Osteoporos Int. 2017;28(3):775e780. 4. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2016. Endocr Pract. 2016;22(Suppl 4):1e42. 5. U.S. Food and Drug Administration. Available at: https://www.fda.gov/ downloads/drugs/newsevents/ucm470574.pdf. Accessed January 15, 2019. 6. Teriparatide [package insert]. Indianapolis, IN: Eli Lilly; 2017. 7. Abaloparatide [package insert]. Waltham, MA: Radius; 2017. 8. Tella SH, Kommalapati A, Correa R. Cureus. Profile of abaloparatide and its potential in the treatment of postmenopausal osteoporosis. Cureus. 2017;9(5):e1300. 9. Riggs BL, Parfitt AM. Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res. 2005;20(2):177e184.
10. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1e34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344:1434e1441. 11. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):722e733. 12. Institute for Clinical and Economic Review. Anabolic therapies for osteoporosis in postmenopausal women: effectiveness and value: evidence report. Available at: https://icer-review.org/wp-content/uploads/2016/ 11/CTAF_Osteoporosis_Evidence_Report_061617.pdf. Accessed January 15, 2019. 13. Stroup J, Kane MP, Busch RS. Pharmacist-run teriparatide clinic. Am J Health Syst Pharm. 2003;60(21):2247e2249. 14. Stroup JS, Rivers SM, Abu-Baker AM, Kane MP. Two-year changes in bone mineral density and T scores in patients treated at a pharmacist-run teriparatide clinic. Pharmacotherapy. 2007;27(6):779e788. 15. Bowers BL, Drew AM, Verry C. Impact of pharmacist-physician collaboration on osteoporosis treatment. Ann Pharmacother. 2018;52(9): 876e883. 16. Masterson J, Woodall T, Wilson CG, et al. Interprofessional care for patients with osteoporosis in a continuing care retirement community. J Am Pharm Assoc (2003). 2016;56(2):184e188. 17. U.S. Food and Drug Administration. Available at: https://www.fda.gov/ downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ ReproductiveHealthDrugsAdvisoryCommittee/UCM629456.pdf. Accessed February 24, 2019. 18. Saag KG, Petersen J, Brandi ML, et al. Romososumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417e1427. 19. Davio K. Pfenex submits follow-on teriparatide for FDA review. Available at: https://www.centerforbiosimilars.com/news/pfenex-submits-follow on-teriparatide-for-fda-review. Accessed January 15, 2019. 20. Gilsenan A, Harding A, Kellier-Steele N, et al. The Forteo patient registry linkage to multiple state cancer registries: study design and results from the first 8 years. Osteoporos Int. 2018;29:2335e2343. Jenna L. McGreevy, PharmD, PGY-2 Endocrinology Resident, Albany College of Pharmacy and Health Sciences, Albany Medical Center Division of Community Endocrinology, Albany, NY Michael P. Kane, PharmD, FCCP, BCPS, BCACP, Professor, Clinical Pharmacy Specialist, Albany College of Pharmacy and Health Sciences, Albany Medical Center Division of Community Endocrinology, Albany, NY Robert S. Busch, MD, FACE, Endocrinologist, Albany Medical Center Division of Community Endocrinology, Albany, NY Gary Bakst, MD, FACE, Endocrinologist, Albany Medical Center Division of Community Endocrinology, Albany, NY Samer ElDeiry, MD, PhD, Endocrinologist, Albany Medical Center Division of Community Endocrinology, Albany, NY
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