Study of twice-weekly injections of Teriparatide by comparing efficacy with once-weekly injections in osteoporosis patients: the TWICE study

Abstract

SummaryA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen of teriparatide, while also improving safety.IntroductionWhile a 56.5-μg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-μg teriparatide can provide comparable efficacy to the 56.5-μg once-weekly regimen while improving safety.MethodsA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-μg twice-weekly group (n = 277) or the 56.5-μg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2–L4) bone mineral density (BMD) at final follow-up.ResultsThe percentage changes in lumbar spine (L2–L4) BMD at final follow-up in the 28.2-μg twice-weekly and 56.5-μg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400–2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (− 1.6%), non-inferiority of the 28.2-μg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-μg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-μg twice-weekly group.ConclusionsA 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen while improving safety.Clinical trial registrationJapicCTI-163477.Electronic supplementary materialThe online version of this article (10.1007/s00198-019-05111-6) contains supplementary material, which is available to authorized users.

Efficacy of once-weekly and twice-weekly injections of teriparatide by patient characteristics: A post hoc analysis of the TWICE study

“…The present report omits the finding from a detailed safety analysis that 2/W-TPTD was associated with lower incidences of adverse drug reactions than 1/W-TPTD, which has been reported previously [ 4 , 7 ].…”

“…The disposition of subjects and the characteristics of the subject population, which have been reported in a previous publication, are summarized below [ 4 ].…”

“…A previous report showed that 2/W-TPTD provides comparable efficacy to 1/W-TPTD [ 4 ]. In the present study, a post hoc analysis of study data was performed to assess the effects of background factors on percentage change in lumbar spine BMD.…”

“…The participants in this post hoc study were 553 patients who took part in a 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority study (JapicCTI-163477) conducted in Japan [ 4 ] and were randomized to 1 of 2 groups: a twice-weekly group that received TPTD 28.2 μg twice weekly and placebo once weekly, or a once-weekly group that received TPTD 56.5 μg once weekly and placebo twice weekly in a 1:1 ratio by dynamic allocation based on the minimization method. In principle, the TPTD 28.2 μg twice-weekly and placebo injections were self-administered using an autoinjector every 3 or 4 days, with 2 or 3 days between injections, whereas the TPTD 56.5 μg once-weekly and placebo injections were administered during outpatient visits.…”

“…Thus, 2/W-TPTD was developed to overcome these issues. We previously reported that, in a comparative study against 1/W-TPTD, 2/W-TPTD was associated with lower incidences of adverse drug reactions and resulted in significantly higher percentage changes in lumbar spine BMD at weeks 24 and 48 and at the final time point [ 4 ]. The percentage change in lumbar spine BMD at the final time point was 7.3% and 5.9%, respectively, with 2/W-TPTD and 1/W-TPTD.…”