Establishing how much improvement in lung function and distance walked is clinically important for adult patients...

Pompe disease is a rare, inheritable, progressive metabolic myopathy. This study aimed to estimate the minimal clinically important difference (MCID) for an improvement in forced vital capacity in the upright seated position (FVC_up) and the 6-min walk test (6MWT) after a year of treatment with enzyme replacement therapy.

Data were obtained from two prospective follow-up studies. Between-group and within-group MCIDs were estimated using anchor-based methods. Additionally, a distribution-based method was used to generate supportive evidence. As anchors, self-reported change in health and in physical functioning, shortness of breath and a categorization of the Short-Form 36 Physical Component Summary score were used. Anchor appropriateness was assessed using Spearman correlations (absolute values ≥0.29) and a sufficient number of observations in each category.

In all, 102 patients had at least one FVC_up or 6MWT measurement during enzyme replacement therapy. Based on the anchors assessed as appropriate, the between-group MCID for an improvement in FVC_up ranged from 2.47% to 4.83% points. For the 6MWT, it ranged from 0.35% to 7.47% points which is equivalent to a distance of 2.18-46.61 m and 1.97-42.13 m for, respectively, a man and a woman of age 50, height 1.75 m and weight 80 kg. The results of the distribution-based method were within these ranges when applied to change in the outcome values.

The MCIDs for FVC_up and 6MWT derived in this study can be used to interpret differences between and within groups of patients with Pompe disease in clinical trials and cohort studies.