Table 1.
Summary of outcomes with agalsidase beta 1.0 mg/kg EOW or agalsidase alfa 0.2 mg/kg EOW from clinical and observational studies of adult male patients with Fabry disease
| Outcome | Agalsidase alfa 0.2 mg/kg EOW | Agalsidase beta 1.0 mg/kg EOW | |
|---|---|---|---|
| 3.2. GL-3 and lyso-GL-3 accumulation | |||
| 3.2.1. | Plasma GL-3 | ↓ Significant (Clarke et al. 2007 [25]; Pastores et al. 2007 [35]; Schiffmann et al. 2006 [39]; Schiffmann et al. 2007 [52]; van Breemen et al. 2011 [102]) ↓ Significance unknown (Goker-Alpan et al. 2015 [26]; Goláň et al. 2015 [27]; Hughes et al. 2008 [29]; Schiffmann et al. 2001 [36]; Rombach et al. 2012 [101]) – No change (Goker-Alpan et al. 2015 [26 (switch study)]) |
↓ Significant (Eto et al. 2005 [70]; Goker-Alpan et al. 2016 [71 (switch study)]; Lubanda et al. 2009 [72]; Elliott et al. 2006 [76]; van Breemen et al. 2011 [102]) ↓ Non-significant (Bénichou et al. 2009 [75]; Mignani et al. 2004 [80]) ↓ Unknown significance (Eng et al. 2001 [69]; Rombach et al. 2012 [101]) |
| 3.2.2. | Plasma lyso-GL-3 | ↓ Significant (Goker-Alpan et al. 2015 [26 (switch study)]) ↓ Unknown significance (Rombach et al. 2012 [101]; van Breemen et al. 2011 [102]) ↑ Significant (Smid et al. 2011 [54 (switch study)]) |
↓ Significant (Goker-Alpan et al. 2016 [71 (switch study)]) ↓ Unknown significance (Rombach et al. 2012 [101]; van Breemen et al. 2011 [102]) |
| 3.2.3. | Urinary GL-3 | ↓ Significant (Goker-Alpan et al. 2015 [26 (12 months)]; Hughes et al. 2008 [29 (6 months)]; Schiffmann et al. 2001 [36]; Schiffmann et al. 2006 [38]; Schiffmann et al. 2007 [52]) ↓ Unknown significance (Pastores et al. 2007 [35 (1/12 pts)]; Whitfield et al. 2005 [55]; Rombach et al. 2012 [101]) ↑ Non-significant (Goker-Alpan et al. 2015 [26 (switch study)]) |
↓ Significant (Lubanda et al. 2009 [72]) ↓ Non-significant (Eto et al. 2005 [70]; Goker-Alpan et al. 2016 [71 (switch study)]) ↓ Unknown significance (Rombach et al. 2012 [101]) – No change (Mignani et al. 2004 [80]) |
| 3.2.4. | Urinary lyso-GL-3 | No data from clinical or observational studies with approved dose of agalsidase alfa | No data from clinical or observational studies with approved dose of agalsidase beta |
| 3.2.5. GL-3 accumulation: histology | |||
| 3.2.5.1. | Renal cells | ↓ Non-significant (Schiffmann et al. 2001 [36]) | ↓Significant (Lubanda et al. 2009 [72]; Najafian et al. 2016 [73 (proportion of podocytes without GL-3 inclusions)]) ↓ Non-significant (Eng et al. 2001 [69]; Najafian et al. 2016 [73 (volume of GL-3 inclusions/podocyte and podocyte GL-3 score)]) |
| 3.2.5.2. | Cardiac cells | ↓ Significance unknown (Hughes et al. 2008 [29]) | ↓ Significance unknown (Eng et al. 2001 [69]) |
| 3.2.5.3. | Other cell types | No data from clinical or observational studies with approved dose of agalsidase alfa |
↓ Significance unknown (Eng et al. 2001 [69]; Lubanda et al. 2009 [72]; Bénichou et al. 2009 [75]) |
| 3.3. Renal outcomes | |||
| 3.3.1. | eGFR | ↑ Significant (Hughes et al. 2008 [29]) Significantly slower decline (vs placebo, creatinine clearance (Schiffmann et al. 2001 [36]) ↓ Significant (Schiffmann et al. 2006 [39]; Feriozzi et al. 2009 [43]; Feriozzi et al. 2012 [44]; Hughes et al. 2011 [48]; Schiffmann et al. 2007 [52]) ↓ Non-significant (Schiffmann et al. 2006 [38]; Smid et al. 2011 [54 (switch study)]) ↓ Unknown significance (Beck et al. 2015 [41]) – No change (Kampmann et al. 2015 [49]) |
↓ Non-significant (Eto et al. 2005 [70]) ↓ Significance unknown, reduced decline (Warnock et al. 2012 [82]) ↓ Significance unknown (Kim et al. 2016 [79]) – No change (Lubanda et al. 2009 [72]) |
| 3.3.2. | Albuminuria/ Proteinuria |
↑ Significant, CKD1 pts (Feriozzi et al. 2012 [44]; Kampmann et al. 2015 [49 (pts with baseline proteinuria)]) ↑ Unknown significance (Schiffmann et al. 2006 [39]) ↓ Non-significant (Bongiorno et al. 2003 [42]) – No change, stabilization (Schiffmann et al. 2001 [36]; Feriozzi et al. 2009 [43]; Feriozzi et al. 2012 [44 (CKD2/3)]; Hughes et al. 2011 [48]; Kampmann et al. 2015 [49 (pts without baseline proteinuria)]; Schiffmann et al. 2007 [52]) |
– No change (Lubanda et al. 2009 [72]; Kim et al. 2016 [79]) ↓ Non-significant (Najafian et al. 2016 [73]) |
| 3.4. Cardiac outcomes | |||
| 3.4.1. | LVM/LVMi | ↓ Significant improvement (Hughes et al. 2008 [29]; Hughes et al. 2011 [48 (pts with baseline LVH]); Kampmann et al. 2015 [49 (pts with baseline LVH)]) ↓ Improvement of unknown significance (Tsuboi et al. 2012 [189]) ↑ Significant (Beck et al. 2015 [41 (slowed progression)]) ↑ Non-significant (Goláň et al. 2015 [27]) – No change (Kampmann et al. 2015 [49 (pts without baseline LVH)]) |
↓ Significant improvement (Germain et al. 2013 [7]; Motwani et al. 2012 [81]) — No change (Elliott et al. 2006 [76]; Kim et al. 2016 [79]; Mignani et al. 2004 [80]) |
| 3.4.2. | LVWT | ↓ Significant (Kampmann et al. 2015 [49]) ↓ Improvement of unknown significance (Tsuboi et al. 2012 [189]) |
↓ Significant (Motwani et al. 2012 [81]) ↓ Non-significant (Mignani et al. 2004 [80 (2/3 patients)]) ↑ Non-significant (Mignani et al. 2004 [80 (1/3 patients)]) — No change (Elliott et al. 2006 [76]) |
| 3.4.3. | LVEF | – No change (Hughes et al. 2008 [29]; Kampmann et al. 2015 [49]) | ↑ Significant (Motwani et al. 2012 [81]) ↑ Non-significant improvement (Mignani et al. 2004 [80 (1/3 patients)]) |
| 3.4.4. | ECG measures | ↓ Significant improvement in QRS duration (Schiffmann et al. 2001 [36]) ↓ Non-significant improvement in QRS duration (Hughes et al. 2008 [29]) – Conduction abnormality (Kampmann et al. 2015 [49 (1/21 pts)]) |
↑ Significant improvement in PQ interval, P-wave duration (Motwani et al. 2012 [81]) ↑ Significant improvement (Eng et al. 2001 [69]) ↓ Significant improvement of QTc interval (Motwani et al. 2012 [81]) – No change (Mignani et al. 2004 [80]) |
| 3.4.5. | Exercise testing | No data from clinical or observational studies with approved dose of agalsidase alfa | No data from clinical or observational studies with approved dose of agalsidase beta |
| 3.5. Nervous system outcomes | |||
| 3.5.1. | Sweat function | ↑ Significant improvement, short-term (Schiffmann et al. 2003 [37]) ↑ Non-significant improvement (Bongiorno et al. 2003 [42]) ↑ Significance unknown (Hughes et al. 2011 [48]) — No change (Gupta et al. 2008 [45]; Schiffmann et al. 2007 [52]) |
↑ Subjective improvement (Eng et al. 2001 [69]; Hilz et al. 2004 [77]) |
| 3.5.2. | PNS nerve sensitivity | ↓ Significant improvement IENFD (Schiffmann et al. 2006 [38]) ↓ Significant improvement cold/warm threshold (Schiffmann et al. 2003 [37]) — No change in cold/warm sensation (Schiffmann et al. 2006 [38]) — No change in neurological examination score (Jardim et al. 2004 [30]; Jardim et al. 2006 [31]) |
↓ Significant improvement (Hilz et al. 2004 [77]) |
| 3.5.3. | Vestibular/auditory and other CNS outcomes | ↑ Significant improvement hearing loss (Hajioff et al. 2003 [28]) ↑ Non-significant improvement peripheral vestibular function (Palla et al. 2003 [34]) — Stabilization of hearing (Sergi et al. 2010 [53]) — No change, neurological examination (Jardim et al. 2004 [30]) ↓ Significant improvement in cerebral blood flow (Moore et al. 2001 [32]) ↓ Improvement of unknown significance in cerebral blood flow (Moore et al. 2002 [33]) |
— No change, neurological examination (Hilz et al. 2004 [77]) |
| 3.5.4. | White matter hyperintensities | No data from clinical or observational studies with approved dose of agalsidase alfa | No data from clinical or observational studies with approved dose of agalsidase beta |
| 3.6. | Pain outcomes | ↓ Significant improvement (Schiffmann et al. 2001 [36]; Schiffmann et al. 2003 [37]; Hoffmann et al. 2007 [47]) ↓ Non-significant improvement in acroparesthesias (Jardim et al. 2006 [31]; Bongiorno et al. 2003 [42]) ↓ Unknown significance, improvement (Bongiorno et al. 2003 [42]) — No change (Hughes et al. 2011 [48]; Sergi et al. 2010 [53]; Whitfield et al. 2005 [55]) |
↓ Significant improvement (Eng et al. 2001 [69]; Hilz et al. 2004 [77]) ↓ Non-significant improvement (Eto et al. 2005 [70]; Mignani et al. 2004 [80]) |
| 3.7. | GI outcomes | ↓ Unknown significance, improvement (Jardim et al. 2006 [31]; Hoffmann et al. 2007 [46]; Hughes et al. 2011 [48]) ↑ Unknown significance, diarrhea (Hughes et al. 2011 [48]; |
No data from clinical or observational studies with approved dose of agalsidase beta |
| 3.8. | QoL | ↑ Non-significant improvement (Hughes et al. 2011 [48]) — No change, energy levels (Ghali et al. 2012 [100]) — No change, SF-36 (Smid et al. 2011 [54]) |
↑ Significant improvement (Eto et al. 2005 [70]) ↑ Unknown significance (Eng et al. 2001 [69]; Watt et al. 2010 [83]) |
Results are summarized as increase (↑), decrease (↓) or no change from baseline to follow-up after ERT initiation. Significance refers to statistical significance. Results are not adjusted for differences in study designs, patient characteristics, or disease stage. Case reports, mixed-ERT publications, and publications with other dose regimens are not included.
CNS, central nervous system; ECG, electrocardiography; eGFR, estimated glomerular filtration rate; EOW, every other week; GI, gastrointestinal; GL-3, globotriaosylceramide; IENFD, intra-epidermal nerve fibre density; LVEF, left ventricular ejection fraction; LVM, left ventricular mass; LVMi, left ventricular mass index; LVWT, left ventricular wall thickness; lyso-GL-3, globotriaosylsphingosine; PNS, peripheral nervous system; pts, patients; QoL, quality of life; SF-36, 36-Item Short Form Health Survey.