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Background and objectives <p>Spinal and bulbar muscular atrophy (<i>SBMA</i>) is a slowly progressive X-linked neuromuscular disorder for which disease-modifying therapies are under investigation. SBMA Functional Rating Scale (<i>SBMAFRS</i>), its subscale (mSBMAFRS), and Six-Minute Walk Test (<i>6MWT</i>) are commonly used trial endpoints, but thresholds for clinically meaningful change remain undefined. Minimal clinically important difference (<i>MCID</i>) estimates are needed to interpret longitudinal outcomes and inform trial design.</p> Methods <p>We retrospectively analysed ambulatory, genetically confirmed SBMA patients. Eighty consecutive visit pairs from 44 patients included concurrent Global Rating of Change (<i>GRC</i>) assessments, and 47 visit pairs from 30 patients included concurrent 6MWT data. At follow-up, patients rated overall change since the previous visit on a 3‑level GRC (unchanged, slightly worse, much worse). Anchor-based MCIDs for worsening were derived from differences in change scores between GRC categories and compared with distribution-based estimates (0.5 baseline standard deviation). Sensitivity analyses and Monte Carlo resampling assessed robustness.</p> Results <p>Anchor‑based MCID estimates for worsening were −1.13 and −1.46 points for the SBMAFRS total score, −0.53 and −1.09 points for the mSBMAFRS, and −34.5 and −32.4&#xa0;m for the 6MWT. The mSBMAFRS showed the most consistent gradient across GRC categories and remained significant in sensitivity analyses. Distribution‑based MCIDs (2.30, 1.42 points and 61.85&#xa0;m, respectively) were consistently larger than anchor‑based values. Age, disease duration, and CAG repeat length did not predict perceived worsening.</p> Discussion <p>These data provide the first patient‑anchored MCID estimates for SBMA outcome measures, support use of the mSBMAFRS, and offer thresholds for responder definitions and sample-size calculations in future SBMA trials.</p>

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Estimating the minimal clinically important difference of functional outcomes in spinal and bulbar muscular atrophy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月31日

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  • Matteo Zanovello,
  • Daniele Sabbatini,
  • Federica Paredi,
  • Alberto Romito,
  • Sara Andreetta,
  • Lorenzo Blasi,
  • Giulia Musso,
  • Angelo Poletti,
  • Rosario Vasta,
  • Manuela Basso,
  • Raffaele Dubbioso,
  • Maria Pennuto,
  • Giacomo Maria Minicuci,
  • Elena Pegoraro,
  • Luca Bello,
  • Gianni Sorarù

摘要

Background and objectives

Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive X-linked neuromuscular disorder for which disease-modifying therapies are under investigation. SBMA Functional Rating Scale (SBMAFRS), its subscale (mSBMAFRS), and Six-Minute Walk Test (6MWT) are commonly used trial endpoints, but thresholds for clinically meaningful change remain undefined. Minimal clinically important difference (MCID) estimates are needed to interpret longitudinal outcomes and inform trial design.

Methods

We retrospectively analysed ambulatory, genetically confirmed SBMA patients. Eighty consecutive visit pairs from 44 patients included concurrent Global Rating of Change (GRC) assessments, and 47 visit pairs from 30 patients included concurrent 6MWT data. At follow-up, patients rated overall change since the previous visit on a 3‑level GRC (unchanged, slightly worse, much worse). Anchor-based MCIDs for worsening were derived from differences in change scores between GRC categories and compared with distribution-based estimates (0.5 baseline standard deviation). Sensitivity analyses and Monte Carlo resampling assessed robustness.

Results

Anchor‑based MCID estimates for worsening were −1.13 and −1.46 points for the SBMAFRS total score, −0.53 and −1.09 points for the mSBMAFRS, and −34.5 and −32.4 m for the 6MWT. The mSBMAFRS showed the most consistent gradient across GRC categories and remained significant in sensitivity analyses. Distribution‑based MCIDs (2.30, 1.42 points and 61.85 m, respectively) were consistently larger than anchor‑based values. Age, disease duration, and CAG repeat length did not predict perceived worsening.

Discussion

These data provide the first patient‑anchored MCID estimates for SBMA outcome measures, support use of the mSBMAFRS, and offer thresholds for responder definitions and sample-size calculations in future SBMA trials.