Background: The construct validity and interpretation of the Patient-Reported Outcome Measurement Information System (PROMIS®) 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).
Methods: 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.
Results: 123 patients received at least 1 dose of ERT. In multivariable analyses, PROMIS PF20a scores had strong correlations with R-PAct scores (R = 0.83 at baseline and R = 0.67 when evaluating changes between baseline and 52 weeks) and moderate correlations with the 6MWD (R = 0.57 at baseline and R = 0.48 when evaluating changes between baseline and 52 weeks). Moderate correlations were also observed between PROMIS PF20a and MMT (R = 0.54), GSGC (R=-0.51), and FVC (R = 0.48) at baseline. In multivariable linear regression models, associations were significant between PROMIS PF20a and 6MWD (P = 0.0006), MMT (P = 0.0034), GSGC (P = 0.0278), and R-PAct (P < 0.0001) at baseline, between PROMIS PF20a and 6MWD (P < 0.0001), FVC (P = 0.0490), and R-PAct (P < 0.0001) when combining all measurements, and between PF20a and 6MWD (P = 0.0016) and R-PAct (P = 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.
Conclusions: PROMIS PF20a has validity as an instrument both to measure and to longitudinally follow physical function in patients with LOPD.
Trial registration: ClinicalTrials.gov, NCT03729362. Registered 2 November 2018, https://www.
Clinicaltrials: gov/search?term=NCT03729362 .
Late-onset Pompe disease (LOPD) is a rare, hereditary disease. Patients with LOPD have decreased production of an enzyme, which leads to symptoms that gradually get worse, including muscle weakness and trouble breathing. Enzyme replacement therapy may slow down the disease progression. In recent years, enzyme replacement therapies have been improved. To measure the benefit of such new therapies, patients with LOPD are asked to fill in surveys about their symptoms before and during treatment, but there is no standard survey to use. In this study, we used a survey called the Patient-Reported Outcome Measurement Information System (PROMIS®) Physical Function short form 20a (PF20a) questionnaire. This questionnaire is used for various diseases and tests someone’s ability to perform daily physical activities such as getting dressed. We compared the results of this survey to other tests which evaluate a variety of functions, such as how far a patient can walk in 6 minutes, leg muscle strength, and a patient’s lung capacity. In general, we found that the score provided by the PROMIS PF20a questionnaire had moderate to strong agreement with other test scores. Furthermore, we looked at the minimum difference in PROMIS PF20a scores that a patient found a relevant difference (i.e., a relevant improvement or worsening of the disease). Patients found a difference between 2.4 and 4.2 points in the score relevant. The results from this study show that PROMIS PF20a may be used to measure symptoms and follow symptoms over time in patients with LOPD.
Keywords: Late-onset Pompe disease; PROPEL; Patient-Reported Outcome Measurement Information System (PROMIS); Patient-reported outcomes; Physical function; Quality of life; Validation.
© 2024. The Author(s).