Objectives: To assess differences in efficacy of a 28.2-μg teriparatide formulation for twice-weekly use (2/W-TPTD) by patient characteristics. Methods: A post hoc analysis was performed using data from a multicenter, randomized, double-blind, double-dummy, non-inferiority trial (TWICE study) conducted in Japan comparing the efficacies of once-weekly and twice-weekly injections of teriparatide (TPTD). Specifically, a stratified analysis of percentage changes from baseline was performed using the final data on lumbar spine bone mineral density (BMD) after a 48-week treatment period (n = 251, 2/W-TPTD; n = 239, a 56.5-μg teriparatide formulation for once-weekly use [1/W-TPTD]). Results: Across all subgroups defined by patient characteristics that included 9 or more subjects, the lumbar spine BMD increased significantly in both groups. In the 2/W-TPTD group, the percentage change was significantly higher in subjects with no non-vertebral fractures without large external force occurring at or after age 50 years versus those with such fractures. The lower the stratification in baseline lumbar spine BMD, total hip BMD, or femoral neck BMD, the greater was the percentage change. Conclusions Whereas all subgroups can expect a significant improvement in lumbar spine BMD, there were some patient characteristics that affected the percentage increase in BMD.

Objectives: To assess differences in efficacy of a 28.2-μg teriparatide formulation for twice-weekly use (2/W-TPTD) by patient characteristics. Methods: A post hoc analysis was performed using data from a multicenter, randomized, double-blind, double-dummy, non-inferiority trial (TWICE study) conducted in Japan comparing the efficacies of once-weekly and twice-weekly injections of teriparatide (TPTD). Specifically, a stratified analysis of percentage changes from baseline was performed using the final data on lumbar spine bone mineral density (BMD) after a 48-week treatment period (n = 251, 2/W-TPTD; n = 239, a 56.5-μg teriparatide formulation for once-weekly use [1/W-TPTD]). Results: Across all subgroups defined by patient characteristics that included 9 or more subjects, the lumbar spine BMD increased significantly in both groups. In the 2/W-TPTD group, the percentage change was significantly higher in subjects with no non-vertebral fractures without large external force occurring at or after age 50 years versus those with such fractures. The lower the stratification in baseline lumbar spine BMD, total hip BMD, or femoral neck BMD, the greater was the percentage change. Conclusions Whereas all subgroups can expect a significant improvement in lumbar spine BMD, there were some patient characteristics that affected the percentage increase in BMD.

OBJECTIVES: To reassess the safety and efficacy of once-weekly teriparatide 56.5 mg in osteoporosis patients with a high fracture risk. METHODS: This postmarketing observational study was conducted at 72 weeks according to the package insert. Of the 3573 Japanese osteoporosis patients in the safety analysis set, 91.80% were women, the mean age was 78.1 years, and 69.89% had a history of prevalent fragility fractures, indicating that a high proportion of patients at high risk of fracture were enrolled. RESULTS: Persistence with weekly teriparatide treatment was 59.36%, and 38.95% at 24 and 72 weeks, respectively. Adverse drug reactions (ADRs) were reported in 898 patients (25.13%), and serious ADRs were reported in 26 patients (0.73%). The most frequent ADRs were nausea, vomiting, and headache. The cumulative incidence of new vertebral fractures 72 weeks after the start of treatment was 3.31%. Increases in the bone mineral density were observed in the lumbar spine, femoral neck, and proximal femur. The serum levels of the bone formation markers, procollagen type I N-terminal propeptide and bone-type alkaline phosphatase, increased slightly at 24 weeks and then decreased to baseline levels. At 24 and 72 weeks, the bone resorption markers, serum cross-linked N-terminal telopeptide of type I collagen and urinary cross-linked N-terminal telopeptide of type I collagen, were the same as or slightly lower than at baseline. Visual analogue scale scores for low back pain also decreased. CONCLUSIONS: The present results showed that once-weekly teriparatide may also be useful for osteoporosis patients with a high risk of fracture.
Alkaline Phosphatase ; Asian Continental Ancestry Group ; Biomarkers ; Bone Density ; Bone Resorption ; Collagen Type I ; Drug-Related Side Effects and Adverse Reactions ; Female ; Femur ; Femur Neck ; Headache ; Humans ; Incidence ; Low Back Pain ; Nausea ; Observational Study ; Osteogenesis ; Osteoporosis ; Product Labeling ; Spine ; Teriparatide ; Vomiting

Objectives: On July 20, 2012, the European Medicines Agency (EMA) provided a recommendation that limits the long-term use of calcitonin. Based on this recommendation, we investigate the presence or absence of a cancer diagnosis in subjects who participated in the ongoing clinical trial of elcatonin. Methods: When the EMA gave this recommendation, we were conducting “a 3-year placebo-controlled clinical study for elcatonin” (hereinafter, referred to as “the original study”). In accordance with the recommendation of EMA, we performed an intermediate analysis on the subjects of the original study to assess whether the study could be safely continued. We also added a 2-year follow-up study to investigate the risk of carcinogenesis for 5 years from the start of administration. We compared the risk of carcinogenesis estimated by person-year method in elcatonin group with that in placebo group. Results: In the original study, there were 433 subjects in the elcatonin group and 437 in the placebo group, of whom 322 and 323, respectively, agreed to participate in the additional follow-up study. The average cancer incidence rate per 100 person-years 5 years from the start of administration was 1.02 in the elcatonin group and 1.08 in the placebo group, respectively, and there was no clear difference. Conclusions Since the number of cases in this study was small, we cannot completely deny the cancer risk due to long-term administration of this drug. However, the results do not suggest that once-weekly administration of 20 units of elcatonin increases the carcinogenic risk.

Objectives: On July 20, 2012, the European Medicines Agency (EMA) provided a recommendation that limits the long-term use of calcitonin. Based on this recommendation, we investigate the presence or absence of a cancer diagnosis in subjects who participated in the ongoing clinical trial of elcatonin. Methods: When the EMA gave this recommendation, we were conducting “a 3-year placebo-controlled clinical study for elcatonin” (hereinafter, referred to as “the original study”). In accordance with the recommendation of EMA, we performed an intermediate analysis on the subjects of the original study to assess whether the study could be safely continued. We also added a 2-year follow-up study to investigate the risk of carcinogenesis for 5 years from the start of administration. We compared the risk of carcinogenesis estimated by person-year method in elcatonin group with that in placebo group. Results: In the original study, there were 433 subjects in the elcatonin group and 437 in the placebo group, of whom 322 and 323, respectively, agreed to participate in the additional follow-up study. The average cancer incidence rate per 100 person-years 5 years from the start of administration was 1.02 in the elcatonin group and 1.08 in the placebo group, respectively, and there was no clear difference. Conclusions Since the number of cases in this study was small, we cannot completely deny the cancer risk due to long-term administration of this drug. However, the results do not suggest that once-weekly administration of 20 units of elcatonin increases the carcinogenic risk.