Article Summary
Clinical Summary: Improvements Over Time with Valbenazine in Elderly Adults (≥65 Years) with Tardive Dyskinesia: Post Hoc Analyses of 2 Long-Term Studies
Older adults exposed to antipsychotics and other dopamine receptor blocking agents are at especially high risk for tardive dyskinesia, yet treatment data in patients aged 65 years and older have been limited. These analyses address a common clinical dilemma: whether long-term valbenazine provides meaningful TD improvement in elderly patients without destabilizing psychiatric status or adding new safety concerns.
Design
post hoc analyses of 2 phase 3 trials, KINECT 3 extension and KINECT 4
N
304 participants, 55 (18.1%) of whom were 65 years and older
Population
participants aged 65 years and older
Duration
up to 48 weeks
Key Findings
- In participants ≥65 years of age who received either dose of valbenazine (40 mg or 80 mg), mean AIMS total score changes from baseline were −4.5 ± 0.7 at Week 8 (n = 50), −8.6 ± 0.9 at Week 24 (n = 26), and −8.8 ± 0.9 at Week 48 (n = 28), exceeding the estimated minimal clinically important difference of −2 points at all analysis timepoints.
- Among elderly participants, the proportion meeting the clinically meaningful ≥30% AIMS response threshold increased from 58.0% at Week 8 to 88.5% at Week 24 and 89.3% at Week 48; using the protocol-defined ≥50% threshold, response increased from 40.0% at Week 8 to 65.4% at Week 24 and 82.1% at Week 48.
- At Week 48, clinician-rated global improvement was achieved by 92.9% of elderly participants on CGI-TD, compared with 76.5% of younger participants, and this difference was significant (P = .050); patient-rated PGIC response in elderly participants was 85.7% and was not statistically significant relative to the younger subgroup.
- By end of treatment at Week 48, mean AIMS total score improvement in elderly participants was −6.4 (n = 8) with 40 mg and −9.8 (n = 20) with 80 mg; corresponding values in younger participants were −5.5 (n = 46) and −8.3 (n = 105).
- Safety was broadly similar across age groups for TEAEs and serious TEAEs, but discontinuation due to a TEAE was more frequent in elderly participants than younger participants (25.5% vs 13.3%, P =.023); urinary tract infection occurred in 10.9% and 8.4%, and somnolence occurred in 10.9% and 7.2%, respectively.
Clinical Bottom Line
For adults aged ≥65 years with tardive dyskinesia, once-daily valbenazine produced substantial and sustained improvement through 48 weeks while psychiatric status remained stable. The main practice caveat is a higher rate of discontinuation due to TEAEs in the elderly subgroup, making ongoing tolerability monitoring important.
Practice Implications
- Expect clinically meaningful TD improvement by Week 8 in many elderly patients, and reassess over longer treatment because response rates continued to rise through Week 24 and were sustained through Week 48.
- If treatment is continued long term, monitor both objective TD change and global improvement, as 89.3% of elderly participants reached ≥30% AIMS response and 92.9% were rated much improved or very much improved on CGI-TD at Week 48.
- Discuss tolerability early and monitor persistence, because TEAE-related discontinuation was higher in elderly participants (25.5% vs 13.3%, P =.023), with somnolence among the adverse events leading to discontinuation.
- Psychiatric worsening, akathisia, and drug-induced parkinsonism were not seen as emerging signals in these analyses, so valbenazine can be monitored alongside routine psychiatric and movement assessments during long-term use in stable patients.
