Long-term cancer surveillance: results from the Forteo Patient Registry Surveillance Study

Abstract

The Forteo Patient Registry estimated the incidence of osteosarcoma in US patients treated with teriparatide and enrolled in the study between 2009 and 2019. No incident cases of osteosarcoma were identified among patients registered, and the crude incidence rate was 0 (95% confidence interval [CI], 0-10.2) cases per million person-years. Purpose The prospective, voluntary Forteo Patient Registry was established to estimate the incidence of osteosarcoma in patients who have received treatment with teriparatide (Forteo). Methods Information on US adults prescribed teriparatide and enrolled in the Forteo Patient Registry 2009-2019 was linked with data from participating state cancer registries annually (2010-2019) to identify incident osteosarcoma cases using a standardized linkage algorithm. Teriparatide exposure was ascertained from self-reported data that included teriparatide initiation and demographics necessary to complete linkage. Osteosarcoma cases diagnosed on or after January 1, 2009, were identified by participating state cancer registries. The crude incidence rate (IR) and standardized incidence ratio (SIR) of observed cases to the expected number of cases adjusted to the background rate (3 per million person-years) and corresponding 95% CIs for the occurrence of osteosarcoma were calculated whereby the cumulative amount of person-time observed was adjusted for mortality. Results Data for 75,247 enrolled patients (representing 361,763 cumulative person-years) were linked to each of 42 participating state cancer registries (covering 93% of the US population), which included information on 6180 cases of osteosarcoma. No matches with incident cases of osteosarcoma following registry enrollment were found. The crude IR was 0 (95% CI, 0-10.2) cases per million person-years and the SIR was 0 (95% CI, 0-3.0). Conclusions The ability to draw conclusions about the incidence of osteosarcoma among patients participating in the registry was limited due to the smaller than expected amount of patient follow-up time and the fact that no cases were identified.

Teriparatide and Osteosarcoma Risk: History, Science, Elimination of Boxed Warning, and Other Label Updates

“…In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times did not show an increase in risk of OS in humans (7,38,39,41,42) Warnings and precautions (osteosarcoma) In male and female rats, teriparatide caused an increase in the incidence of OS (a malignant bone tumor) that was dependent on dose and treatment duration. Teriparatide should not be prescribed for patients with increased baseline risk of OS.…”

“…Limitations of this study were that the study was not comparative and the number of patients enrolled was lower than the target number to evaluate the risk of developing osteosarcoma. (41) Although these earlier studies did not suggest an increased risk of osteosarcoma in patients treated with teriparatide, they were inadequate to sufficiently characterize osteosarcoma risk. Accordingly, two large, population-based, observational cohort studies were undertaken to identify a larger sample of patients treated with teriparatide using Medicare and a large commercial claims database.…”

“…(19,40,42) Overall, the real-world data collected since 2003 through 2019 showed that the incidence rate of osteosarcoma in patients treated with teriparatide (2.47 million patients) did not exceed the background incidence rate. (7,(40)(41)(42)(43) Additionally, observational studies of teriparatide use (without a focus on osteosarcoma) conducted in various geographies have also not reported any cases of osteosarcoma. (44)(45)(46)(47)(48) Thus, an increased risk of osteosarcoma has not been observed in observational studies in humans.…”

Effect of teriparatide on drug treatment of tuberculous spondylitis: An experimental study

“…11 The recombinant human PTH analog teriparatide was approved in 2002 by the US Food and Drug Administration (FDA) for the treatment of osteoporosis at high risk for fracture and increased bone mass in postmenopausal women. 12 This drug has been demonstrated to promote bone healing and prevent fragility fractures in both rats and humans. 13,14 In addition to its numerous clinical advantages, teriparatide has some less well-known contraindications, such as a history of radiation therapy, 15 the presence of primary malignant and metastatic bone tumors, 7,16 and Paget's disease.…”

Medication Related Osteonecrosis of the Jaw: 2021 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons

“…Meanwhile, a 15-year post-marketing surveillance study and Forteo Patient Registry Surveillance study demonstrated that the incidence of osteosarcoma associated with teriparatide use was no different than would be expected based on the background incidence rate of osteosarcoma. [ 132 , 133 ] Moreover, a recent study demonstrated the effectiveness of teriparatide for MRONJ in malignant bone disease patients [ 130 ] that might contribute to changing labels with further evidence.…”