• Hummel, Noemi
• Raza, Syed
• Das, Sheela Sitaraman
• Castelli, Jeffrey P.
• Kopiec, Agnieszka
• Jiang, Heng
• Keyzor, Ian
• Hahn, Andreas
• Kishnani, Priya S.
• Shohet, Simon

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The construct validity and interpretation of the Patient-Reported Outcome Measurement Information System (PROMIS<jats:sup>®</jats:sup>) Physical Function short form 20a (PF20a) questionnaire were evaluated for patients with late-onset Pompe disease (LOPD), a rare, autosomal recessive, progressive neuromuscular disorder treatable by enzyme replacement therapy (ERT).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In the phase 3 PROPEL study, adults with LOPD underwent testing of physical functioning and had PRO measurements at baseline and at weeks 12, 26, 38, and 52 while receiving experimental or standard-of-care ERT. All patients were pooled for analyses, without comparisons between treatment groups. Associations and correlations between PROMIS PF20a scores and the 6-minute walk distance (6MWD), % predicted forced vital capacity (FVC), manual muscle test (MMT) of the lower extremities, Gait, Stairs, Gowers’ maneuver, Chair (GSGC) score, and Rasch-built Pompe-specific Activity (R-PAct) scale were evaluated by calculating regression coefficients in linear regression models and Pearson correlation coefficients (R); patients’ age, sex, race, ERT prior to study, body mass index, and study treatment were included as covariables. The minimal clinically important difference (MCID) of PROMIS PF20a was determined using distribution- and anchor-based methods.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>123 patients received at least 1 dose of ERT. In multivariable analyses, PROMIS PF20a scores had strong correlations with R-PAct scores (<jats:italic>R</jats:italic> = 0.83 at baseline and <jats:italic>R</jats:italic> = 0.67 when evaluating changes between baseline and 52 weeks) and moderate correlations with the 6MWD (<jats:italic>R</jats:italic> = 0.57 at baseline and <jats:italic>R</jats:italic> = 0.48 when evaluating changes between baseline and 52 weeks). Moderate correlations were also observed between PROMIS PF20a and MMT (<jats:italic>R</jats:italic> = 0.54), GSGC (<jats:italic>R</jats:italic>=-0.51), and FVC (<jats:italic>R</jats:italic> = 0.48) at baseline. In multivariable linear regression models, associations were significant between PROMIS PF20a and 6MWD (<jats:italic>P</jats:italic> = 0.0006), MMT (<jats:italic>P</jats:italic> = 0.0034), GSGC (<jats:italic>P</jats:italic> = 0.0278), and R-PAct (<jats:italic>P</jats:italic> &lt; 0.0001) at baseline, between PROMIS PF20a and 6MWD (<jats:italic>P</jats:italic> &lt; 0.0001), FVC (<jats:italic>P</jats:italic> = 0.0490), and R-PAct (<jats:italic>P</jats:italic> &lt; 0.0001) when combining all measurements, and between PF20a and 6MWD (<jats:italic>P</jats:italic> = 0.0016) and R-PAct (<jats:italic>P</jats:italic> = 0.0001) when evaluating changes in scores between baseline and 52 weeks. The anchor-based and distribution-based MCID for a clinically important improvement for PROMIS PF20a were 2.4 and 4.2, respectively.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>PROMIS PF20a has validity as an instrument both to measure and to longitudinally follow physical function in patients with LOPD.</jats:p></jats:sec><jats:sec><jats:title>Trial registration</jats:title><jats:p>ClinicalTrials.gov, NCT03729362. Registered 2 November 2018, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov/search?term=NCT03729362">https://www.clinicaltrials.gov/search?term=NCT03729362</jats:ext-link>.</jats:p></jats:sec>

Topics

• phase
• size-exclusion chromatography