Sublingual apomorphine for Parkinsonian tremor: a post-hoc analysis of pivotal trial data

Tremor is a common and disabling feature of Parkinson's disease (PD) and often responds suboptimally to oral dopaminergic therapy. This post‑hoc analysis evaluated tremor outcomes associated with apomorphine sublingual film (SL‑APO) in patients with a tremor‑dominant PD phenotype, using data from a 12‑week randomised, double‑blind, placebo‑controlled trial (NCT02469090) and a 12‑month open‑label study (NCT02542696) conducted in levodopa‑responsive patients with OFF episodes. Tremor‑dominant phenotype was defined according to Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS‑UPDRS) criteria, and tremor severity was assessed using a derived tremor index. In the randomised trial, 31 of 108 patients (28.7%) met tremor‑dominant criteria. At Week 12 (n = 10 per group), greater reductions in tremor index scores were observed 30 min post‑dose with SL‑APO versus placebo (mean change - 5.3 vs. - 1.1), with an exploratory between‑group difference of - 4.4 (p < 0.001) and an effect size (Cohen's d) of - 1.83. Clinically important improvement occurred more frequently with SL‑APO (80%) than placebo (30%), corresponding to an estimated number needed to treat of 1.3. Median time to ON with SL‑APO was 13.0 min. In the open‑label study, tremor reductions of 31-37% were maintained over 12 months, with responder rates remaining above 70%. These exploratory findings in a small subgroup are consistent with a potential for early and maintained tremor improvement with SL‑APO in patients with tremor‑dominant PD; however, the results are hypothesis‑generating and require prospective confirmation.