Incidence of Osteosarcoma in Patients with History of Teriparatide Treatment
Introduction
The US prescribing information for teriparatide includes a warning about a potential risk of osteosarcoma and precautions against use of the product for patients with risk factors for osteosarcoma (e.g., Paget’s disease of the bone, unexplained increase in alkaline phosphatase, open epiphyses, prior radiation therapy). Osteosarcoma is a primary malignant bone tumour characterized by the production of osseous matrix by neoplastic cells.
Aim
To identify newly diagnosed cases of osteosarcoma among men and women aged ≥40 years and to determine incident osteosarcoma cases, if any, with a history of teriparatide treatment
Patient Profile
- Patient aged ≥40 years at the time of diagnosis
- Diagnosis reported from a participating cancer registry
- Diagnosis of osteosarcoma based on at least one of 12 ICD-O-3 oncology codes for osteosarcoma or one of five other ICD-O-3 oncology codes for which the primary tumour site was bone
Methods
- Case series
- This US case-series study started 90 days after the first marketed use of teriparatide and had a duration of 15 years
- Patients diagnosed with osteosarcoma from 2003 through 2016
- N=1173 patients with osteosarcoma were interviewed
- Exposure information was verified through medical record abstraction for a sample of patients
- A standardized incidence ratio was estimated to compare the observed and expected numbers of osteosarcoma patients with a prior history of teriparatide treatment
Results
- 24% of patients diagnosed with osteosarcoma between 2003 and 2016 completed interviews
- Three patients had valid teriparatide exposure before diagnosis of osteosarcoma (primary case group diagnosed with one of the 12 ICD-O-3 codes)
- The histological type for all three cases was the most common overall (Osteosarcoma, NOS) and location of the tumour varied for each exposed case
- Based on background incidence rate, the expected number of osteosarcoma cases among patients treated with teriparatide was 4.17
- The standardized incidence ratio was 0.72
- The prevalence of suspected risk factors for development of osteosarcoma was
- History of X-ray or radiation treatment for prior conditions reported in 19% patients
- Paget’s disease of the bone in 4% of patients
|
Analysis |
Number of cases |
| |
|
Observed |
Expecteda |
SIR | |
|
Based on the reference values b |
3 |
4.17 |
0.72 |
|
Include 5 other ICD-O-3 codes (8800, 8801, 8810, 8830, 9243) |
|
|
|
|
1 additional case (chondrosarcoma) gets included |
4 |
4.17 |
0.96 |
|
Include an induction period with 5 other ICD-O-3 codes (8800, 8801, 8810, 8830, 9243) |
|
|
|
|
1 year (1 case gets excluded and person-years decreases to 4,651,698) |
3 |
3.57 |
0.84 |
|
2 years (2 cases get excluded and person-years decreases to 3,934,149) |
2 |
3.02 |
0.66 |
|
3 years (3 cases get excluded and person-years decreases to 3,282,047) |
1 |
2.52 |
0.40 |
|
Assume a background rate of 2.5 per million per year |
3 |
3.26 |
0.92 |
|
Include 5 other ICD-O-3 codes (8800, 8801, 8810, 8830, 9243) |
4 |
3.26 |
1.23 |
|
Decrease person-years by 25% (4,074,573) |
3 |
3.13 |
0.96 |
|
Include 5 other ICD-O-3 codes (8800, 8801, 8810, 8830, 9243) |
4 |
3.13 |
1.28 |
|
Assume a lower estimated study coverage of 20% |
3 |
3.48 |
0.86 |
|
Include 5 other ICD-O-3 codes (8800, 8801, 8810, 8830, 9243) |
4 |
3.48 |
1.15 |
|
In combination (decrease person-years by 25%, 20% study coverage) |
3 |
2.61 |
1.15 |
|
Include 5 other ICD-O-3 codes (8800, 8801, 8810, 8830, 9243) |
4 |
2.61 |
1.53 |
|
Assume a background rate of 2.5 per million per year |
4 |
2.04 |
1.96 |
CI = confidence interval; ICD-O-3 = International Classification of Diseases for Oncology, 3rd Edition; SEER = Surveillance, Epidemiology, and End Results;
SIR = standardized incidence ratio.
a Expected = person-years at risk × background rate × study coverage.
b Reference values: 5,432,764 is the estimated age- and mortality-adjusted person-years at risk following exposure to teriparatide; 3.2 cases per million per year was derived from the incidence rate from the National Cancer Institute SEER program, age- and sex-adjusted to the teriparatide-treated population; 24% is the study coverage, which is the number of patients with osteosarcoma interviewed to determine if the patient had taken teriparatide, divided by the estimated total number of patients aged 40 years and older who diagnosed with osteosarcoma in the United States for diagnosis years 2003–2016.
Conclusion
This study found that the incidence of osteosarcoma associated with teriparatide use during the 15-year surveillance period was no different than would be expected based on the background incidence rate of osteosarcoma.
Reference
J. Bone Miner. Res.2021: 244–251
