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. 2012 Sep 26:7:73.
doi: 10.1186/1750-1172-7-73.

Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study

Juna M de Vries  1 , Nadine A M E van der Beek, Wim C J Hop, Francois P J Karstens, John H Wokke, Marianne de Visser, Baziel G M van Engelen, Jan B M Kuks, Anneke J van der Kooi, Nicolette C Notermans, Catharina G Faber, Jan J G M Verschuuren, Michelle E Kruijshaar, Arnold J J Reuser, Pieter A van Doorn, Ans T van der Ploeg
Affiliations

Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study

Juna M de Vries et al. Orphanet J Rare Dis. .

Abstract

Background: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors.

Methods: Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3-6 months and analyzed using repeated-measures ANOVA.

Results: Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (-1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness.Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC.

Conclusions: We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.

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Figures

Figure 1
Figure 1
The clinical course of disease before and after the start of enzyme replacement therapy (ERT) in the 49 patients with ERT and pre-ERT follow-up data for A) MRC sumscore; B) hand-held dynamometry (HHD) sumscore; C) forced vital capacity (FVC) in upright position; and D) FVC in supine position. The figure shows all the individual observations for the different outcome measures (shown as dots) and the solid lines represent the estimated mean trend in these observations as calculated by the ‘broken stick’ repeated-measures ANOVA. The dotted lines represent the extrapolated natural course slopes.
Figure 2
Figure 2
Individual response groups for skeletal muscle strength and pulmonary function. The number and percentage of good responders, moderate responders and non-responders are shown for MRC sumscore, and forced vital capacity (FVC) in upright and supine positions.
See this image and copyright information in PMC

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