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Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis

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Abstract

The objective of this study was to compare the changes on bone mineral density, and the effects on persistence and adverse events in patients treated for postmenopausal osteoporosis with generic alendronate or with branded alendronate (Fosamax®) or branded risedronate (Actonel®) once weekly. In this retrospective patient chart analysis, we reviewed the 1-year observational treatment results for 186 women (ITT population) with postmenopausal osteoporosis. Patients from our outpatient department, who had started with once-weekly bisphosphonate therapy between 36 and at least 12 months before this chart review, were included in this comparative three-arm study according to their treatment: A, Generic Alendonate 70 mg products; B, Branded Alendronate (Fosamax®) 70 mg once weekly and C, Branded Risedronate (Actonel®) 35 mg once weekly. All patients received basic therapy with 1,200 mg calcium and 800 IU vitamin D per day. Patient’s bone mineral density (BMD) at lumbar spine and total hip was below −2.5 T-score, and they were with or without prevalent vertebral and non-vertebral fractures. Data analysis regarding the 186 patients shows an average increase in LS-BMD after 12 months of 2.8, 5.2 and 4.8% for the groups A, B and C, respectively. The respective mean changes at total hip were 1.5, 2.9, and 3.1%. At both sites, the mean increases in BMD were not different between the two groups receiving branded bisphosphonates (B, C) but for both were significantly higher than for the group treated with generic alendronate (A). At 12 months, 68% of group A, 84% of group B and 94% of group C were still on bisphosphonate therapy. The persistence of patients treated with generic alendronate was significantly lower as compared to each of the two with branded bisphosphonate-treated groups. The total numbers of patients reporting gastrointestinal adverse events were 32, 15 and 9 for group A, group B, and group C, respectively. Significantly lower increases of lumbar spine and total hip BMD with generic alendronate once weekly as compared to the two branded bisphosphonate originals (Fosamax®, Actonel®) were observed. The reasons for the 40–50% lower BMD increase rates when using the generic compounds are not known yet. At least in part the lower efficacy can be explained by a significantly lower degree of persistence with generic alendronate, which could be related to a higher incidence of gastrointestinal adverse events. Other reasons could be lower bioavailability or potency of generic alendronate.

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References

  1. Dachverband Deutschsprachiger Wissenschaftlicher Gesellschaften für Osteologie (2006) DVO-guideline for prevention, clinical assesssment and treatment of osteoporosis for women after menopause, for men after age 60. http://www.lutherhaus.de/osteo/leitlinien-dvo/index.php

  2. Pfeilschifter J (2006) DVO-guideline for prevention, diagnosis, and therapy of osteoporosis for women after menopause, for men after age 60. Executive summary guidelines. Exp Clin Endocrinol Diabetes 114:611–622

    CAS  PubMed  Google Scholar 

  3. Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733. doi:10.1007/s00198-006-0172-4

    Article  CAS  PubMed  Google Scholar 

  4. DeSantis A, Buchman A (2002) 2002 current and emerging therapies in osteoporosis. Expert Opin Pharmacother 3:835–843. doi:10.1517/14656566.3.7.835

    Article  CAS  PubMed  Google Scholar 

  5. Kobayashi K, Shimoyama K, Nakamura K, Murata K (2005) Percutaneous vertebroplasty immediately relieves pain of osteoporotic vertebral compression fractures and prevents prolonged immobilization of patients. Eur Radiol 15:360–367. doi:10.1007/s00330-004-2549-0

    Article  PubMed  Google Scholar 

  6. Theodorou DJ, Theodorou SJ, Sartoris DJ (2002) Treatment of osteoporosis: current status and recent advances. Compr Ther 28:109–122. doi:10.1007/s12019-002-0048-2

    Article  PubMed  Google Scholar 

  7. Liberman UA, Weiss SR, Broll J et al (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333:1437–1443. doi:10.1056/NEJM199511303332201

    Article  CAS  PubMed  Google Scholar 

  8. Black DM, Cummings SR, Karpf DB et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541. doi:10.1016/S0140-6736(96)07088-2

    Article  CAS  PubMed  Google Scholar 

  9. Cummings SR, Black DM, Thompson DE et al (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the fracture intervention trial. JAMA 280:2077–2082. doi:10.1001/jama.280.24.2077

    Article  CAS  PubMed  Google Scholar 

  10. Harris ST, Watts NB, Genant HK et al (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. JAMA 282:1344–1352. doi:10.1001/jama.282.14.1344

    Article  CAS  PubMed  Google Scholar 

  11. Reginster J, Minne HW, Sorensen OH et al (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis.Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83–91. doi:10.1007/s001980050010

    Article  CAS  PubMed  Google Scholar 

  12. Ringe JD, Faber H, Farahmand P et al (2006) Efficacy of risedronate in men with primary and secondary osteoporosis. Results of a 1-year study. Rheumatol Int 26:427–431. doi:10.1007/s00296-005-0004-4

    Article  CAS  PubMed  Google Scholar 

  13. Chesnut CHIII, Skag A, Christiansen C et al (2004) Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 19:1241–1249. doi:10.1359/JBMR.040325

    Article  CAS  Google Scholar 

  14. Ringe JD, Dorst A, Faber H et al (2003) Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative trial. Osteoporos Int 14:801–807. doi:10.1007/s00198-003-1425-0

    Article  CAS  PubMed  Google Scholar 

  15. McClung MR, Geusens P, Miller PD et al (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med 344:333–340. doi:10.1056/NEJM200102013440503

    Article  CAS  PubMed  Google Scholar 

  16. Black DM, Delmas PD, Eastell R et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822. doi:10.1056/NEJMoa067312

    Article  CAS  PubMed  Google Scholar 

  17. SEIOMM. http://www.seiomm.org/

  18. Nuova Nota 79 relativa all’osteoporosi. http://www.amiciitalia.org/nuovo_nota_79.htm

  19. Ebetino FH, Barnett BL, Russell RGG (2005) A computational model delineates differences in hydroxyapatite binding affinities of bisphosphonates in clinical use. J Bone Miner Res 20(suppl 1):S259

    Google Scholar 

  20. Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH (2007) Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 1117:209–257. doi:10.1196/annals.1402.089

    Article  CAS  PubMed  Google Scholar 

  21. Actonel® 5 mg Filmtabletten Fachinformation

  22. Roux C, Seeman E, Eastell R, Adachi J, Jackson RD, Felsenberg D, Songcharoen S, Rizzoli R, Di Munno O, Horlait S, Valent D, Watts NB (2004) Efficacy of risedronate on clinical vertebral fractures within 6 months. Curr Med Res Opin 4:433–439. doi:10.1185/030079903125003125

    Article  Google Scholar 

  23. Harrington JT, Ste-Marie LG, Brandi ML, Civitelli R, Fardellone P, Grauer A, Barton I, Boonen S (2004) Risedronate rapidly reduces the risk for nonvertebral fractures in women with postmenopausal osteoporosis. Calcif Tissue Int 74(2):129–135. doi:10.1007/s00223-003-0042-4

    Article  CAS  PubMed  Google Scholar 

  24. Silverman SL, Watts NB, Delmas PD et al (2007) Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. Osteoporos Int 18:25–34. doi:10.1007/s00198-006-0274-z

    Article  CAS  PubMed  Google Scholar 

  25. Cramer JA, Amonkar MM, Hebborn A, Altman R (2006) Compliance and persistence with bisphosphonate dosing regimens among women with postmenopausal osteoporosis. Curr Med Res Opin 21:1453–1460. doi:10.1185/030079905X61875

    Article  Google Scholar 

  26. Caro JJ, Ishak KJ, Huybrechts KF et al (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int 15:1003–1008. doi:10.1007/s00198-004-1652-z

    Article  PubMed  Google Scholar 

  27. Sebaldt RJ et al (2004) Impact of non-compliance and non-persistence with daily bisphosphonates on longer-term effectiveness outcomes in patients with osteoporosis treated in tertiary specialist care. Annual European Congress of Rheumatology “EULAR 2004”

  28. Siris ES, Harris ST, Rosen CJ et al (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from two US claims databases. Mayo Clin Proc 81(8):1013–1022

    Article  PubMed  Google Scholar 

  29. Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47

    PubMed  Google Scholar 

  30. Papaioannou A, Ioannidis G, Grima D, Adachi JD (2008) Quantification and description of gastrointestinal adverse events (GI AES) in patients switched from branded Fosamax® to generic alendronate. http://www.iscd.org/Visitors/pdfs/ISCD_abstracts.pdf. Abstract #152

  31. Actonel® einmal wöchentlich 35 mg Filmtabletten Fachinformation Januar 2003

  32. Fosamax® 10 mg Fachinformation Fachinformation Februar 2002

  33. Fosamax® einmal wöchentlich 70 mg Tabletten Fachinformation (Zusammenfassung der Merkmale des Arzneimittels, SPC) Mai 2002

  34. Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928. doi:10.1016/j.bone.2005.10.022

    Article  PubMed  Google Scholar 

  35. Weycker D, Macarios D, Edelsberg J, Oster G (2007) Compliance with osteoporosis drug therapy and risk fracture. Osteoporos Int 18:271–277. doi:10.1007/s00198-006-0230-y

    Article  CAS  PubMed  Google Scholar 

  36. McCombs JS, Thiebaud P, Laughlin-Miley C, Shi J (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 48:271–287. doi:10.1016/j.maturitas.2004.02.005

    Article  CAS  PubMed  Google Scholar 

  37. Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from two US claims databases. Mayo Clin Proc 81:1013–1022. doi:10.4065/81.8.1013

    Article  PubMed  Google Scholar 

  38. Penning-van Beest FJ, Erkens JA, Olson M, Herings RM (2008) Loss of treatment benefit due to low compliance with bisphosphonate therapy. Osteoporos Int 19:511–517. doi:10.1007/s00198-007-0466-1

    Article  CAS  PubMed  Google Scholar 

  39. Taggart H, Bolognese MA, Lindsay R, Ettinger MP, Mulder H, Josse RG, Roberts A, Zippel H, Adami S, Ernst TF, Stevens KP (2002) Upper gastrointestinal tract safety of risedronate: a pooled analysis of nine clinical trials. Mayo Clin Proc 77(3):262–270

    Article  CAS  PubMed  Google Scholar 

  40. Mellström DD, Sörensen OH, Goemaere S, Roux C, Johnson TD, Chines AA (2004) Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif Tissue Int 75(6):462–468

    Article  PubMed  Google Scholar 

  41. Adami S, Pavelka K, Cline GA, Hosterman MA, Barton IP, Cohen SB, Bensen WG (2005) Upper gastrointestinal tract safety of daily oral risedronate in patients taking NSAIDs: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 80(10):1278–1285

    Article  CAS  PubMed  Google Scholar 

  42. Watts NB, Worley K, Solis A, Doyle J, Sheer R (2004) Comparison of risedronate to alendronate and calcitonin for early reduction of nonvertebral fracture risk: results from a managed care administrative claims database. J Manag Care Pharm 10(2):142–151

    PubMed  Google Scholar 

  43. Lanza FL, Hunt RH, Thomson AB, Provenza JM, Blank MA (2000) Endoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women. Gastroenterology 119:631–638. doi:10.1053/gast.2000.16517

    Article  CAS  PubMed  Google Scholar 

  44. Thomson AB, Marshall JK, Hunt RH, Provenza JM, Lanza FL, Royer MG, Li Z, Blank MA, Risedronate Endoscopy Study Group (2002) 14 day endoscopy study comparing risedronate and alendronate in postmenopausal women stratified by Helicobacter pylori status. J Rheumatol 29(9):1965–1974

    CAS  PubMed  Google Scholar 

  45. Adachi JD, Adami S, Miller PD, Olszynski WP, Kendler DL, Silverman SL, Licata AA, Li Z, Gomez-Panzani E (2001) Tolerability of risedronate in postmenopausal women intolerant of alendronate. Aging (Milano) 13(5):347–354

    CAS  Google Scholar 

  46. deGroen PC, Lubbe DF, Hirsch LJ et al (1996) Esophagitis associated with the use of alendronate. N Engl J Med 335:1016–1021. doi:10.1056/NEJM199610033351403

    Article  CAS  Google Scholar 

  47. Dansereau RJ, Crail DJ, Perkins AC (2008) In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications. Curr Med Res Opin 24:1137–1145. doi:10.1185/030079908X280725

    Article  CAS  PubMed  Google Scholar 

  48. Perkins AC, Blackshaw PE, Hay PD, Lawes SC, Atherton CT, Dansereau RJ, Wagner LK, Schnell DJ (2008) Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center, single blind, si-period crossover study in healthy female subjects. Clin Ther 30:834–844. doi:10.1016/j.clinthera.2008.04.018

    Article  CAS  PubMed  Google Scholar 

  49. Epstein S, Geusens P, Fisher JE et al (2005) Disintegration and esophageal irritation profiles of alendronate formulations: implications for clinical safety and efficacy. J Appl Res 5:253–264

    CAS  Google Scholar 

  50. Epstein S, Cryer B, Gagi S et al (2003) Disintegration/dissolution profiles of copies of fosamax (alendronate). Curr Med Res Opin 19:781–789. doi:10.1185/030079903125002577

    Article  CAS  PubMed  Google Scholar 

  51. Lin JH (1996) Bisphosphonates: a review of their pharmacokinetic properties. Bone 18:75–85. doi:10.1016/8756-3282(95)00445-9

    Article  CAS  PubMed  Google Scholar 

  52. Fleisch H (2000) Bisphosphonates in bone disease: from the laboratory to the patient. Academic Press, New York. ISBN: 0-12-260370-2. 2.4 Pharmacokinetics, pp 56–62

  53. Grimes DA, Schulz KF (2002) Bias and causal associations in observational research. Lancet 359:248–252. doi:10.1016/S0140-6736(02)07451-2

    Article  PubMed  Google Scholar 

  54. Black N (1996) Why we need observational studies to evaluate the effectiveness of health care. BMJ 312:1215–1218

    CAS  PubMed  Google Scholar 

  55. Dowd R, Recker RR, Heaney RP (2000) Study subjects and ordinary patients. Osteoporos Int 11:533–536. doi:10.1007/s001980070097

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This are results of an investigator initiated trial. Johann D. Ringe, MD, PhD was the principal investigator and he received no payments related to the collection and evaluation of patient’s data and preparation of the manuscript from any pharmaceutical company. Johann D. Ringe, MD, PhD received consultancy fees and other payments from MSD Sharp & Dohme, Procter & Gamble Pharmaceuticals—Germany GmbH, Lilly Deutschland, Sanofi-Aventis Deutschland GmbH. Gerd Möller, MD, PhD, Health Economist (ebs) was an employee of Procter & Gamble Pharmaceuticals—Germany GmbH, D-65824 Schwalbach am Taunus, Germany from May 15th 2001 until September 5th 2008. Gerd Möller, MD, PhD, Health Economist (ebs) received no consultancy fees and other payments from any pharmaceutical company.

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Ringe, J.D., Möller, G. Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis. Rheumatol Int 30, 213–221 (2009). https://doi.org/10.1007/s00296-009-0940-5

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  • DOI: https://doi.org/10.1007/s00296-009-0940-5

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