Photo Credit: Antonio_Diaz
Researchers analyzed whether valbenazine’s impact on tardive dyskinesia symptoms varied between patients with schizophrenia versus bipolar disorder.
Long-term valbenazine therapy for tardive dyskinesia (TD) benefited patients no matter what underlying psychiatric condition they had, according to recent findings.
Mieko Nagano, BPharm, and colleagues conducted a post-hoc analysis of data from the J-KINECT study, a multicenter, phase 2/3, randomized trial that tested valbenazine in patients with moderate-to-severe TD in Japan. The researchers evaluated differences in the drug’s efficacy and safety depending on whether patients had schizophrenia/schizoaffective disorder or bipolar disorder/depressive disorder.
Patients participated in a 6-week placebo-controlled period followed by a 42-week extension wherein they received placebo, 40 mg valbenazine, or 80 mg valbenazine once daily. The researchers examined changes in Abnormal Involuntary Movement Scale (AIMS) scores, Clinical Global Impression of TD (CGI-TD) scores among patients with different conditions, and the frequency of treatment-emergent adverse events (TEAEs).
Of the 256 participants in the placebo-controlled period, 211 received treatment in the extension period.
For the group with schizophrenia/schizoaffective disorder, AIMS scores improved by an average of −1.8 (−3.2 to −0.5) and −3.3 (−4.7 to −1.9) in the 40- and 80-mg groups, respectively, at week 6 (95% CI). The mean change was −2.4 (−3.9 to −0.9) and −3.5 (−5.1 to −1.9) for those with bipolar disorder/depressive disorder (95% CI). The researchers found no associations between treatment group and type of underlying condition (P=0.876).
“The AIMS total score during the valbenazine extension period remained lower than that at baseline (continued improvement in score) until week 48, confirming that long-term treatment also sustained the effect, regardless of the underlying disease,” the researchers noted.
They also found continued improvements at week 52, which were comparable between both valbenazine groups. The study team concluded valbenazine’s efficacy continued after treatment completion regardless of a patient’s psychiatric condition. Nagano and colleagues also found similar improvements in CGI-TD scores.
TEAEs were more common in the valbenazine groups compared with the placebo group, but their incidence did not vary significantly by patients’ underlying conditions.
“During the long-term treatment period, the incidences of TEAEs in the valbenazine 40- and 80-mg groups were 91.5% (75 of 82) and 94.9% (75 of 79), respectively, for patients with schizophrenia/schizoaffective disorder, and 86.4% (38 of 44) and 93.2% (41 of 44), respectively, for patients with bipolar disorder/depressive disorder,” the researchers reported. “There were no notable differences in the incidence of serious or fatal TEAEs by underlying disease.”
Somnolence was the most common TEAE, occurring in 19.3% (21 of 109) of patients with schizophrenia/schizoaffective disorder and 16.7% (10 of 60) of those with bipolar disorder/depressive disorder. The rate of suicidal ideation and attempt was less than 5% throughout the study, with no increased incidence in the valbenazine or placebo groups during the placebo-controlled period.
“Overall, the incidence of TEAEs and individual TEAE profiles did not tend to differ greatly depending on the underlying disease. The differences in the incidence of schizophrenia (worsening) and depression (worsening) for patients with schizophrenia/schizoaffective disorder and bipolar disorder/depressive disorder, respectively, were attributed to progression of the underlying disease,” Nagano and colleagues wrote.
The researchers reported that their findings were similar to those of the KINECT 2 and KINECT 3 studies conducted in North America.
“This suggests that racial differences… do not seem to influence the efficacy or safety of valbenazine,” Nagano and colleagues said. “Moreover, a recent pharmacokinetic study reported similar plasma concentrations of valbenazine after administration in Korean and North American populations; thus, it is likely that exposure responses after administration of valbenazine are also similar between Asians and North Americans.”
The study had several limitations, including a relatively short placebo-controlled period and no long-term placebo-controlled data for comparison. The post-hoc analysis included limited cases because the J-KINECT study was not originally designed to evaluate differences by underlying conditions. In addition, all patients had stable symptoms and treatment regimens, so it is unclear whether the findings apply to patients with unstable psychiatric symptoms.
Nevertheless, Nagano and colleagues said their results “suggest that the efficacy and safety of valbenazine for treatment of TD are not influenced by the nature of the patient’s underlying psychiatric disorder. Our study supports the use of valbenazine for TD in patients with bipolar disorder/depressive disorder or schizophrenia/schizoaffective disorder.”
