title: Adherence to and gastrointestinal tolerability of monthly oral or quarterly intravenous ibandronate therapy in women with previous intolerance to oral bisphosphonates: a 12-month, open-label, prospective evaluation.
abstract: BACKGROUND
  Gastrointestinal (GI) symptoms and high dosing frequency have been cited as reasons for inadequate adherence to daily or weekly oral bisphosphonate therapy. Inadequate adherence may lead to poor therapeutic outcomes.
  
  
  OBJECTIVE
  The PRIOR study evaluated adherence to and GI tolerability of monthly therapy with oral and quarterly intravenous ibandronate in postmenopausal women with osteoporosis or osteopenia.
  
  
  METHODS
  This 12-month, multicenter, prospective, nonrandomized, open-label, noninferiority study included postmenopausal women with osteoporosis or osteopenia who had discontinued previous daily or weekly oral bisphosphonate therapy because of GI intolerance. Participants chose to receive either monthly oral ibandronate 150 mg or quarterly intravenous ibandronate 3 mg and were permitted to switch formulations once during the study. For oral treatment, adherence was assessed based on doses taken, as recorded on the case-report form; for intravenous treatment, adherence was assessed based on doses administered, as recorded by study site personnel. Participants who took >or=75% of protocol-specified doses were considered adherent. The rate of adherence to oral ibandronate was protocol defined as noninferior to that of intravenous ibandronate if the upper limit of the 2-sided 90% CI for the adjusted difference in adherence rates was >20%. At screening, participants assessed the tolerability of their previous bisphosphonate therapy using the GI Experience Survey; using the same instrument, they assessed the tolerability of ibandronate 1 month from baseline and at months 4, 7, and 10.
  
  
  RESULTS
  Of 543 participants in the intent-to-treat population, 147 (27.1%) chose to receive oral treatment and 396 (72.9%) chose to receive intravenous treatment. The mean age of participants was approximately 66 years in both groups, and >90% of participants were white. A significantly greater proportion of participants who selected intravenous versus oral treatment had a primary diagnosis of osteoporosis (72.2% vs 57.1%, respectively; P<0.001) and a history of fracture as an adult (35.6% vs 22.4%; P >or= 0.004); significantly fewer recipients of intravenous versus oral ibandronate were currently working (29.0% vs 39.5%; P >or= 0.021). Overall, 82.9% of participants had previously received alendronate and 44.9% had previously received risedronate. Eleven participants switched from oral to intravenous therapy and 16 switched from intravenous to oral therapy during the study. In the perprotocol population, 69.7% of participants in the oral group (101/145) and 82.9% of participants in the intravenous group (325/392) were adherent to their originally selected therapy. Adherence to oral therapy fell within the prespecified boundary for noninferiority to intravenous therapy (adjusted difference: 12.4%; 90% CI, 5.1-19.7). Mean GI tolerance scores were significantly improved from screening at all subsequent assessment times in both treatment groups (P < 0.001); >75% of participants had a >or=10% increase in GI tolerability scores from screening. Both dosing regimens were generally well tolerated.
  
  
  CONCLUSIONS
  Self-selected monthly oral or quarterly intravenous ibandronate therapy was associated with high adherence rates among these postmenopausal women with osteoporosis or osteopenia who had previously discontinued oral bisphosphonate treatment because of GI intolerance.
authors.affiliation: New Mexico Clinical Research & Osteoporosis Center, Albuquerque, New Mexico 87106, USA. lewiecki@aol.com
authors.forename: E Michael
authors.initials: EM
authors.lastname: Lewiecki
authors.forename: Ann M
authors.initials: AM
authors.lastname: Babbitt
authors.forename: Veronica K
authors.initials: VK
authors.lastname: Piziak
authors.forename: Zafer E
authors.initials: ZE
authors.lastname: Ozturk
authors.forename: Henry G
authors.initials: HG
authors.lastname: Bone
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001862:Bone Resorption; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006801:Humans; D000077557:Ibandronic Acid; D007275:Injections, Intravenous; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077557:Ibandronic Acid