Pain-Specific Benefits of Higher-Dose Neubotulinum Toxin Type A in Cervical Dystonia: A Multicenter Randomized...

Pain is a major contributor to disability in cervical dystonia (CD) and may persist despite improvement in abnormal head posture after botulinum toxin treatment. Whether increasing the dose of Neubotulinum toxin type A (Neu-BoNT-A) provides additional analgesic benefit without compromising safety remains uncertain. In this prospective, multicenter, randomized, double-blind, two-period crossover trial, 50 adults with CD were randomized 1:1 to Neu-BoNT-A 100 U followed by 50 U or 50 U followed by 100 U, with each treatment period lasting 12 weeks. The principal between-dose TWSTRS analysis used a crossover mixed-effects model including treatment, period, and randomized sequence, with participant as a random effect. TWSTRS total, severity, and disability did not differ significantly between regimens. Neu-BoNT-A 100 U produced greater improvement in TWSTRS pain (adjusted 100 U minus 50 U difference, -1.83 points; 95% CI, -2.93 to -0.73; p = 0.0011). The pain finding remained significant in a robust GEE sensitivity analysis (difference, -1.83 points; 95% CI, -3.04 to -0.62; p = 0.003). CDIP-58 psychosocial functioning also improved more with 100 U (nominal p = 0.001). In a Holm sensitivity analysis across all 24 efficacy comparisons, TWSTRS pain and CDIP-58 psychosocial functioning remained significant (adjusted p ≈ 0.025 and 0.024, respectively); no other comparison remained significant. No serious adverse events occurred. Neu-BoNT-A 100 U did not improve overall CD severity compared with 50 U but was associated with greater pain relief and improved psychosocial functioning without compromising tolerability. These secondary findings remained significant after multiplicity adjustment but should be interpreted in the context of the nonsignificant overall TWSTRS result and require confirmation.