OnabotulinumtoxinA for Painful Foot Dystonia in Parkinson Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract

Pain associated with foot dystonia is a common and disabling symptom of Parkinson disease (PD), often occurring during OFF periods, yet frequently refractory to medication optimization. Evidence supporting treatments for dystonia-related pain in PD remains limited. This study evaluated the efficacy and safety of onabotulinumtoxinA (BTXA) for pain associated with foot dystonia in patients with PD. This single-center, randomized, double-blind, placebo-controlled trial assessed outcomes at 6 and 12 weeks, followed by a 12-week open-label extension. Adults with unilateral PD and painful foot dystonia refractory to medication optimization were randomized 1:1 to receive BTXA (100 units) or placebo using a guided injection protocol targeting the tibialis posterior, extensor hallucis longus, and flexor digitorum brevis. The primary outcome was change from baseline in dystonia-related pain assessed using Item 5 of the King's Parkinson's Disease Pain Scale (KPPS). Secondary outcomes included responder rates (&#x2265;30% pain reduction), KPPS Domain 3 total score, KPPS Item 5 pain severity and frequency subitems, Visual Analogue Scale (VAS) pain, Clinical Global Impression, motor outcomes (Movement Disorder Society-Unified Parkinson's Disease Rating Scale III and IV), quality of life, and safety. Thirty-three participants were randomized (BTXA, n = 16; placebo, n = 17). BTXA resulted in significantly greater reduction in dystonia-related pain assessed by KPPS Item 5 total score compared with placebo at 6 weeks (mean difference -3.60), with effects sustained at 12 weeks (<i>p</i> &lt; 0.001). The between-group effect size for the primary outcome was large (Hedges' g -1.33; 95% CI -2.13 to -0.53). Improvements were observed in KPPS Item 5 pain severity and frequency and in KPPS Domain 3 total scores at 6 and 12 weeks. VAS pain was reduced at 6 weeks, with no significant between-group difference at 12 weeks. Responder rates (&#x2265;30% pain reduction) were higher with BTXA at both 6 and 12 weeks (75.0% vs &#x2264; 11.8 and 5.6%, respectively; <i>p</i> &lt; 0.001). No differences were observed in motor outcomes, quality of life, or adverse events, which were mild. BTXA reduced pain associated with foot dystonia in PD without adversely affecting motor outcomes and was well tolerated, supporting its use as a targeted treatment for this disabling symptom. NCT04277247.