Elsevier

Bone

Volume 116, November 2018, Pages 58-66
Bone

Full Length Article
Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporosis and comorbidities or risk factors for fractures: Integrated analysis of 4 prospective observational studies

https://doi.org/10.1016/j.bone.2018.07.013Get rights and content

Highlights

  • Limited information is available regarding the fracture efficacy of teriparatide in clinically important subgroups.

  • We merged the primary data from 8828 patients treated with teriparatide in four prospective observational studies.

  • Clinical vertebral, non-vertebral, clinical, and hip fracture rates decreased versus the first six months of treatment.

  • The fracture results with teriparatide were generally consistent across clinically relevant subgroups of patients.

  • The results should be interpreted in the context of the non-controlled design of the source studies.

Abstract

Introduction

Teriparatide significantly reduces fracture rates in clinical trials; however, those study populations were relatively restricted and included too few patients to analyze fracture outcomes within clinically important patient subgroups. We assessed fracture outcomes in subgroups of osteoporosis patients from 4 real-world teriparatide observational studies.

Methods

Patients received teriparatide 20 μg/day for up to 24 months. Fracture rates were compared between 0 to 6 months versus >6 months using a piecewise exponential model for first fracture. Analyses included incident clinical vertebral fractures (CVF) and nonvertebral fractures (NVF), and clinical fractures (CVF and NVF) by subgroups of gender, age <75 or ≥75 years, diabetes, prior bisphosphonates use, rheumatoid arthritis (RA), glucocorticoid use, prior hip, and prior vertebral fracture.

Results

The population included 8828 patients (8117 women, 92%) with mean (SD) age 71 (10.6) years and teriparatide treatment duration 17.4 (8.6) months. Overall, CVF, NVF, clinical fracture, and hip fracture rates decreased by 62%, 43%, 50%, and 56%, respectively (all p < .005) for >6 months versus 0 to 6 months. Subgroup analyses all showed significantly decreased rates after >6 months except for NVF reduction in males (n = 710, fracture rate low during months 0 to 6) and in patients using glucocorticoids, and CVF in patients with prior hip fracture. The effects of teriparatide on CVF, NVF, and clinical fractures over time were statistically consistent in all subgroups except age for CVF (p = .074, patients <75 years of age responded better), and diabetes for clinical fractures (p = .046, patients with diabetes responded better), although all of these subgroups experienced significant reductions over time. Glucocorticoids, prior bisphosphonate, and prior vertebral fracture were associated with increased CVF, NVF, and clinical fracture rates; RA, prior hip fracture and female gender were associated with higher NVF and clinical fracture rates; increased age was associated with higher CVF and clinical fracture rates.

Conclusions

Data from 4 real-world observational studies showed statistically significant reductions during teriparatide treatment in rates of CVF, NVF, and clinical fractures in clinically relevant patient subgroups. These results should be interpreted in the context of the non-controlled design of the source studies.

Introduction

Teriparatide [recombinant human parathyroid hormone (1–34)] stimulates bone formation and is approved worldwide for the treatment of men and postmenopausal women with osteoporosis at high risk for fracture and in some geographies for the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture.

Teriparatide reduced osteoporotic fracture risk in clinical trials compared with placebo [1] or oral bisphosphonates [[2], [3], [4]], and in observational studies [[5], [6], [7], [8]]. While randomized, controlled trials remain the gold standard in establishing the efficacy of therapies in defined populations, they also exclude many patients, including prior or concomitant therapies, and include visit structures, interactions, information collection, and other factors that may differ substantially from common clinical practice [9]. Thus, observational studies may be useful to assess the effectiveness of drugs in the setting of community care of patients having particular comorbid conditions, risk factors, or prior therapies.

The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) [7], European Forsteo Observational Study (EFOS) [5], Extended Forsteo Observational Study (ExFOS) [6], and Japan Fracture Observational Study (JFOS) [8] were prospective, observational studies conducted at a large numbers of sites in the United States, Europe, and Japan, respectively. Each assessed fracture rates during up to either 18 to 24 months of teriparatide therapy in patients selected according to normal clinical practice and the local approved label. In a separate report, we have presented detailed analysis of fracture rates for clinical vertebral fracture (CVF), nonvertebral fracture (NVF), clinical fracture, hip fracture, and wrist fracture in the combined study population (submitted). In the present report, we used the combined database to examine rates of CVF, NVF, and clinical fractures during teriparatide treatment in clinically relevant subgroups.

Section snippets

Study designs and populations

DANCE, EFOS, ExFOS, and JFOS were multicenter, prospective, observational studies to examine the long-term effectiveness, safety, and tolerability of teriparatide in a community-based population of men and women (or women only, in EFOS). These studies were conducted in the USA, Japan and 12 European countries (Supplemental Table 1), and the results have been reported previously for each study [[5], [6], [7], [8]]. Patients were enrolled based on the local product labeling and investigators'

Patient characteristics

These analyses included data from 8828 patients, including 3720 from DANCE, 1581 from EFOS, 1531 from ExFOS, and 1996 from JFOS. Patient demographics and risk factors in these studies have been reported previously [[5], [6], [7],12]. In this pooled population from the 4 studies, 92% of patients were female (only women participated in EFOS) and mean age was 71 years (Table 1). Mean (standard deviation) teriparatide treatment duration was 17.4 (8.6) months.

Fracture rates

A summary of rates for CVF, NVF,

Discussion

In this report, we assessed pooled data for 8828 patients from 4 prospective observational studies conducted in Europe, the United States, and Japan [[5], [6], [7], [8]], comparing rates of fracture between the first 6 months of teriparatide treatment to the rate of fracture for the remaining treatment period of up to 24 months. The analyses also provided information on the clinical risk factors that could influence the effects of teriparatide in reducing fractures during real-world treatment.

Disclosures

B.L.L. has received fees for serving on advisory boards, speaking at symposia, and has received research grants from Eli Lilly and Co. Amgen, UCB, Merck, Novo Nordisk; S.·Silverman is on the Speaker's Bureau and is a consultant for and has received research support from Eli Lilly and Company; K.S. has received consultant fees and has research grants from Eli Lilly and Company; N.N. has received consultant and speaker fees from Eli Lilly and Company; S.F. and S.·Soen have nothing to declare;

Funding

This work was funded by Eli Lilly and Company or one of its affiliates.

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