Persistence at 24 months with denosumab among postmenopausal women with osteoporosis: results of a prospective cohort study.

Persistence with prescribed medications for chronic diseases is important; however, persistence with osteoporosis treatments is historically poor. In this prospective cohort study of postmenopausal women treated for osteoporosis in real-world clinical practice settings in the USA and Canada, 24-month persistence with denosumab was 58%. PURPOSE: Patients who persist with their prescribed osteoporosis treatment have increased bone mineral density (BMD) and reduced risk of fracture. Twelve-month persistence with denosumab in routine clinical practice is as high as 95%, but there are limited data on longer-term persistence with denosumab in this setting. METHODS: This single-arm, prospective, cohort study evaluated 24-month persistence with denosumab administered every 6 months in postmenopausal women receiving treatment for osteoporosis in real-world clinical practice in the USA and Canada. Endpoints and analyses included the percentage of patients who persist with denosumab at 24 months (greater than or equal to four injections with a gap between injections of no more than 6 months plus 8 weeks), the total number of injections received by each patient, changes in BMD in persistent patients, and the incidence of serious adverse events (SAEs) and fractures. RESULTS: Among 935 enrolled patients, 24-month persistence was 58% (50% in US patients and 75% in Canadian patients). A majority of patients received at least four injections over the observation period (62% of US patients and 81% of Canadian patients). Among patients who were persistent at 24 months and who had a baseline, 12-month, and 24-month DXA scan, mean BMD increased from baseline to 24 months by 7.8% at the lumbar spine and 2.1% at the femoral neck. SAEs and fractures were reported for 122 (13.0%) patients and 54 (5.8%) patients, respectively. CONCLUSIONS: Persistence with denosumab for 24 months yields improvement in BMD among postmenopausal women with osteoporosis treated in routine clinical practice in the USA and Canada.

Open-label study of etanercept treatment in patients with moderate-to-severe plaque psoriasis who lost a satisfactory response to adalimumab.

BACKGROUND: Some patients with plaque psoriasis experience secondary failure of tumour necrosis factor inhibitor therapy. OBJECTIVES: To evaluate efficacy, safety and patient-reported outcomes (PROs) with etanercept in patients with secondary adalimumab failure. METHODS: This phase IV open-label single-arm estimation study (NCT01543204) enrolled patients on adalimumab who had achieved static Physician's Global Assessment (sPGA) score 0/1 (clear/almost clear). Patients subsequently lost response, defined as sPGA ≥ 3 or loss of 50% improvement in Psoriasis Area and Severity Index (PASI 50). At baseline, patients had involved body surface area ≥ 10%, sPGA ≥ 3 and PASI ≥ 10. Antiadalimumab antibodies (ADAs) were measured at screening. Patients received etanercept 50 mg twice weekly for 12 weeks, followed by 50 mg weekly. The primary end point was sPGA 0/1 at week 12 (intention-to-treat analysis; no hypothesis tested). Additional outcomes included rates of sPGA 0/1, PASI responses, safety, PROs of itch, pain and flaking, Dermatology Life Quality Index, treatment satisfaction and Work Productivity and Activity Impairment questionnaire. RESULTS: Sixty-four patients enrolled; 67% had ADAs. sPGA 0/1 rates at week 12 were 39·7% [95% confidence interval (CI) 27·6-52·8; primary end point] and 45% (95% CI 29·3-61·5) for patients positive for ADAs and 35% (95% CI 15·4-59·2) for patients negative for ADAs. PASI 75 response rates at week 12 were 47·5% (95% CI 31·5-63·9) for patients who were positive for ADAs and 50% (95% CI 27·2-72·8) for patients negative for ADAs. No new safety signals were observed. PROs of itch, pain and flaking consistently improved at week 12 and were maintained through week 24. CONCLUSIONS: Patients with psoriasis who experienced secondary failure of adalimumab achieved satisfactory response to etanercept regardless of ADA status.

Self-reported calcium use in a cohort of postmenopausal women receiving osteoporosis therapy: results from POSSIBLE US™.

UNLABELLED: Calcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0% in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7%) and women supplementing pharmacologic therapy with calcium (22.5%). INTRODUCTION: Calcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort. METHODS: Subject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US(TM)) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use. RESULTS: At entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0% during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7% (95 % confidence interval [CI], 20.7 - 27.0) among calcium-only subjects and 22.5% (95% CI, 20.7-24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8%). Overall 54.2% of calcium-only subjects who discontinued calcium and 42.3% of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry. CONCLUSIONS: Calcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.

Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study.

UNLABELLED: To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82%, with 66 patients (7%) reporting serious adverse events and 19 patients (2%) reporting fractures. INTRODUCTION: Increased persistence with osteoporosis therapy is associated with reduced fracture risk. Denosumab reduced fracture risk in clinical trials; persistence in community settings is undetermined. This study evaluates persistence with denosumab in community practice in the United States (US) and Canada. METHODS: In a 24-month multicenter, prospective, single-arm, observational study, women being treated for osteoporosis were enrolled ≤4 weeks after the first subcutaneous injection of denosumab. For this 12-month prespecified interim analysis, endpoints include persistence (one injection at study entry and another within 6 months + 8 weeks), attributes associated with persistence (univariate analysis), and serious adverse events (SAEs). RESULTS: Among 935 patients (mean age 71 years), mean baseline T-scores were -2.18 (femoral neck) and -2.00 (lumbar spine); 50% of patients had experienced osteoporotic fracture(s). At 12 months, 82 % of patients were persistent with denosumab. Baseline factors significantly (p < 0.05) associated with higher persistence included use of osteoporosis medications >5 years previously, lumbar spine T-score > -2.5, and treatment by female physicians (US). Lower persistence was associated (p < 0.05) with psychiatric diagnoses including depression, southern US residence, being divorced, separated, or widowed (US), and prior hip fracture (Canada). SAEs were reported in 66 patients (7%); no SAEs of osteonecrosis of the jaw, atypical femoral fracture, fracture healing complications, hypocalcemia, eczema, or hypersensitivity were reported. Nineteen patients (2%) reported osteoporotic fractures. CONCLUSIONS: The 12-month persistence observed in this single-arm open-label study of US and Canadian community practice extends the evidence regarding denosumab's potential role in reducing fracture risk in postmenopausal women with osteoporosis.

Long-term persistence and switching patterns among women using osteoporosis therapies: 24- and 36-month results from POSSIBLE US™.

UNLABELLED: Persistence with postmenopausal osteoporosis (PMO) medications is not well characterized beyond 12 months. Of 3,011 postmenopausal women treated in primary care, 36.8 % continued baseline PMO medication during 36 months of follow-up. Many factors were associated with nonpersistence, including newly initiating or switching therapy, and reporting moderate to severe side effects. INTRODUCTION: Persistence with postmenopausal osteoporosis (PMO) medications is not well characterized beyond 12 months. We describe 24- and 36-month persistence using patient-reported data from women with different PMO treatment histories in the US primary care setting. METHODS: Data from 3,011 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US™, 10/2005-12/2008) and Kaplan-Meier methods were used to estimate the probability of persisting (i.e., not discontinuing or switching PMO agents) with baseline PMO medication and hazard ratios for predictors of nonpersistence 24 and 36 months after study entry. RESULTS: The probability of persisting with the baseline medication was 46.2 % (95 % confidence interval [CI] 44.2-48.1 %) during 24 months of follow-up and 36.8 % (95 % CI 34.7-38.9 %) during 36 months of follow-up. In adjusted analyses, newly initiating therapy or switching to a new agent, reporting moderate to severe side effects, having lower disease-specific quality of life scores, smoking, and residing in the South or West USA (all measured at study entry) were independent predictors of nonpersistence in both time periods. The majority of participants who discontinued therapy and had the opportunity to reinitiate (i.e., discontinued ≥4 months before the end of follow-up) restarted therapy (24 months 69 %; 36 months 75 %). CONCLUSIONS: In this primary care cohort, a minority of women continued their baseline PMO therapy during a 24- to 36-month follow-up. Supporting patients during the initiation of a new therapy or if side effects occur may improve persistence and increase the therapeutic benefit of PMO medications.

Association between osteoporosis treatment change and adherence, incident fracture, and total healthcare costs in a Medicare Advantage Prescription Drug plan.

UNLABELLED: We examined the association between osteoporosis treatment change and adherence, incident fractures, and healthcare costs among Medicare Advantage Prescription Drug (MAPD) plan members. Treatment change was associated with a small but significant increase in adherence, but was not associated with incident fracture or total healthcare costs. Overall adherence remained low. INTRODUCTION: We examined the association between osteoporosis treatment change and adherence, incident fractures, and healthcare costs among MAPD plan members in a large US health plan. METHODS: We conducted a retrospective cohort study of MAPD plan members aged≥50 years newly initiated on an osteoporosis medication between 1 January 2006 and 31 December 2008. Members were identified as having or not having an osteoporosis treatment change within 12 months after initiating osteoporosis medication. Logistic regression analyses and difference-in-difference (DID) generalized linear models were used to investigate the association between osteoporosis treatment change and (1) adherence to treatment, (2) incident fracture, and (3) healthcare costs at 12 and 24 months follow-up. RESULTS: Of the 33,823 members newly initiated on osteoporosis treatment, 3,573 (10.6%) changed osteoporosis treatment within 12 months. After controlling for covariates, osteoporosis treatment change was associated with significantly higher odds of being adherent (medication possession ratio [MPR]≥0.8) at 12 months (odds ratio [OR]=1.18) and 24 months (OR=1.13) follow-up. However, overall adherence remained low (MPR=0.59 and 0.51 for the change cohort and MPR=0.51 and 0.44 for the no-change cohort at 12 and 24 months, respectively). Osteoporosis treatment change was not significantly associated with incident fracture (OR=1.00 at 12 months and OR=0.98 at 24 months) or total direct healthcare costs (p>0.4) in the DID analysis, but was associated with higher pharmacy costs (p<0.004). CONCLUSIONS: Osteoporosis treatment change was associated with a small but significant increase in adherence, but was not associated with incident fracture or total healthcare costs in the MAPD plan population. Overall adherence to therapy remained low.

Assessing health-related quality-of-life and health state preference in persons with obesity: a validation study.

The objective of this study was to assess the reliability, validity and responsiveness of a new health-related quality-of-life (HRQOL) measure containing global and obesity-specific domains and an obesity-specific health state preference (HSP) assessment. A total of 417 obese and 'normal' weight individuals completed these assessments. Internal consistency and test-retest reliability were demonstrated, with Cronbach's alpha, intraclass correlation coefficient and kappa values well above the acceptable level for most scales. Construct validity hypotheses were confirmed by examining scale correlations. The normal weight individuals reported statistically significantly better functioning and well-being on the majority of the HRQOL scales and HSP than obese individuals. Guyatt's statistic of responsiveness was moderate to high for all the scales and items in the weight-loss and weight-gain groups; however, many of the scales and items in the weight-stable group also displayed responsiveness. The results of this study support the reliability and validity of these assessments. However, further testing is needed to evaluate the responsiveness of both assessments in a weight-stable group.