Scholarlink

Introduction <p>Lack of head-to-head comparative safety and efficacy data for abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) represented an important gap for informed spasticity management. This study compared the safety and efficacy of aboBoNT-A and onaBoNT-A for upper limb spasticity (ULS).</p> Methods <p>DIRECTION (NCT04936542), a phase IV, randomized, double-blind, crossover study, involved 72 sites. Patients stratified by botulinum toxin A status (naïve/non-naïve) were randomized (1:1) to aboBoNT-A 900U followed by onaBoNT-A 360U (one cycle each), or vice versa. Muscles (wrist/finger flexors, biceps brachii) were injected with a fixed volume, using instrument-guided injection techniques. Participants fulfilling retreatment criteria received a second cycle at Week 12; otherwise, they were reassessed every 4&#xa0;weeks (to Week 24) until requiring retreatment. Primary analyses tested non-inferiority based on treatment-emergent adverse events (TEAEs) from injection to Week 12 using a 5% non-inferiority margin [non-inferiority demonstrated if upper bound of the 80% confidence interval (CI) of the adjusted difference in TEAE rates was &lt; 5%]. Secondary analyses compared duration of response based on time to symptom re-emergence.</p> Results <p>Overall, 464 patients [mean (standard deviation) age 56.8 (13.1) years, 34.1% female] were randomized (aboBoNT-A → onaBoNT-A [<i>n</i> = 231]; onaBoNT-A → aboBoNT-A [<i>n</i> = 233)]. Baseline characteristics were similar in both sequence arms. Adjusted rate of TEAEs for aboBoNT-A (20.3%) was non-inferior to onaBoNT-A (23.0%); adjusted difference (aboBoNT-A&#xa0;–&#xa0;onaBoNT-A) was − 2.7% (80%CI − 6.2%, 0.9%). Adjusted mean duration of response was 99.3&#xa0;days for aboBoNT-A and 96.3&#xa0;days for onaBoNT-A; adjusted difference of 3.0 (80%CI 0.2, 5.9) days favoring aboBoNT-A (<i>p</i> = 0.17; statistically significant under the pre-specified <i>α</i> = 0.20 framework). Longer duration of response with aboBoNT-A versus onaBoNT-A was seen across most subgroups over a fixed-interval follow-up.</p> Conclusion <p>In this first head-to-head study of aboBoNT-A and onaBoNT-A in ULS, the aboBoNT-A TEAE rate was non-inferior to onaBoNT-A. At 90% of the maximum unit dose for adult ULS in the approved label for each formulation, duration of response was 3&#xa0;days longer with aboBoNT-A than onaBoNT-A. These findings may support informed therapeutic decision-making.</p> Trial Registration <p><i>ClinicalTrials.gov:</i> NCT04936542; <i>EudraCT:</i> 2023-509196-16-00.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A Phase IV, Randomized, Double-Blind, Crossover Study to Compare the Clinical Safety and Efficacy of AbobotulinumtoxinA and OnabotulinumtoxinA in Adult Upper Limb Spasticity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月20日

查看全文
  • Alberto Esquenazi,
  • Theodore H. Wein,
  • Monica Verduzco-Gutierrez,
  • Ziyad Ayyoub,
  • Simon Page,
  • Sarah Harding,
  • Pascal Maisonobe,
  • Mathieu Beneteau,
  • Atul Patel,
  • Keith Sequeira,
  • Theodore Wein,
  • Masoud Sangani,
  • Pierre Blanc,
  • Hélène Cassoudesalle,
  • Emmanuel Amauger,
  • Philippe Gallien,
  • Dominic Pérennou,
  • Jacques Luauté,
  • Ido Ghassan,
  • David Gasq,
  • Anne-Laure Ferrapie,
  • Isner- Marie-Eve Horobeti,
  • Raphaël Gross,
  • Simon Butet,
  • Tanguy Le Corre,
  • Florence Angioni,
  • Thibaud Honore,
  • Steven Edgley,
  • Joan Stilling,
  • David Bowers,
  • Kore Liow,
  • David Charles,
  • Vivian Roy,
  • Richard Zorowitz,
  • Heidi Fusco,
  • Karin Goodfriend,
  • Peter Hedera,
  • Khashayar Dashtipour,
  • Ahmet Arac,
  • James Stevens,
  • Joseph Burris,
  • Periminder Bhatia,
  • Daniel Truong,
  • Francois Bethoux,
  • Fatma Gul,
  • Peter McAllister,
  • Edward Dabrowski,
  • Scott Sherman,
  • Anne Hatch,
  • Tuan Vu,
  • Michael Wainberg,
  • Richard Weiss,
  • Xiaohua Zhou,
  • Johnathan Ho,
  • Mayer Joshua Hasbani,
  • S Byron Milton III,
  • Yuxi Chen,
  • Wissam Deeb,
  • Robert Balsiger,
  • Brian Copeland,
  • Jonathan Vandenberg,
  • Asare Christian,
  • Natasha Romanoski,
  • Michael Munin,
  • Nirav Patel,
  • Mark Linsenmeyer,
  • Cindy Beth Ivanhoe,
  • Virgilio Evidente,
  • Angeli Mayadev,
  • Bharathy Sundaram,
  • Patricio Espinosa,
  • Warren Spinner,
  • Marissa McCarthy,
  • Michael Saulino,
  • Edwardo Ramos,
  • Dabrowski Edward,
  • Harmony Sierens

摘要

Introduction

Lack of head-to-head comparative safety and efficacy data for abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) represented an important gap for informed spasticity management. This study compared the safety and efficacy of aboBoNT-A and onaBoNT-A for upper limb spasticity (ULS).

Methods

DIRECTION (NCT04936542), a phase IV, randomized, double-blind, crossover study, involved 72 sites. Patients stratified by botulinum toxin A status (naïve/non-naïve) were randomized (1:1) to aboBoNT-A 900U followed by onaBoNT-A 360U (one cycle each), or vice versa. Muscles (wrist/finger flexors, biceps brachii) were injected with a fixed volume, using instrument-guided injection techniques. Participants fulfilling retreatment criteria received a second cycle at Week 12; otherwise, they were reassessed every 4 weeks (to Week 24) until requiring retreatment. Primary analyses tested non-inferiority based on treatment-emergent adverse events (TEAEs) from injection to Week 12 using a 5% non-inferiority margin [non-inferiority demonstrated if upper bound of the 80% confidence interval (CI) of the adjusted difference in TEAE rates was < 5%]. Secondary analyses compared duration of response based on time to symptom re-emergence.

Results

Overall, 464 patients [mean (standard deviation) age 56.8 (13.1) years, 34.1% female] were randomized (aboBoNT-A → onaBoNT-A [n = 231]; onaBoNT-A → aboBoNT-A [n = 233)]. Baseline characteristics were similar in both sequence arms. Adjusted rate of TEAEs for aboBoNT-A (20.3%) was non-inferior to onaBoNT-A (23.0%); adjusted difference (aboBoNT-A – onaBoNT-A) was − 2.7% (80%CI − 6.2%, 0.9%). Adjusted mean duration of response was 99.3 days for aboBoNT-A and 96.3 days for onaBoNT-A; adjusted difference of 3.0 (80%CI 0.2, 5.9) days favoring aboBoNT-A (p = 0.17; statistically significant under the pre-specified α = 0.20 framework). Longer duration of response with aboBoNT-A versus onaBoNT-A was seen across most subgroups over a fixed-interval follow-up.

Conclusion

In this first head-to-head study of aboBoNT-A and onaBoNT-A in ULS, the aboBoNT-A TEAE rate was non-inferior to onaBoNT-A. At 90% of the maximum unit dose for adult ULS in the approved label for each formulation, duration of response was 3 days longer with aboBoNT-A than onaBoNT-A. These findings may support informed therapeutic decision-making.

Trial Registration

ClinicalTrials.gov: NCT04936542; EudraCT: 2023-509196-16-00.

Graphical Abstract