Intervention Review

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Enzyme replacement therapy for Anderson-Fabry disease

  1. Regina P El Dib1,*,
  2. Paulo Nascimento2,
  3. Gregory M Pastores3

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 12 DEC 2012

DOI: 10.1002/14651858.CD006663.pub3

How to Cite

El Dib RP, Nascimento P, Pastores GM. Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD006663. DOI: 10.1002/14651858.CD006663.pub3.

Author Information

  1. 1

    Botucatu Medical School, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil

  2. 2

    UNESP - Univ Estadual Paulista, Botucatu, São Paulo, Brazil

  3. 3

    New York University School of Medicine, Neurogenetics Laboratory, New York, New York, USA

*Regina P El Dib, Botucatu Medical School, Universidade Estadual Paulista (UNESP), Distrito de Rubião Júnior, s/n, Botucatu, São Paulo, 18603-970, Brazil. eldib@fmb.unesp.br. re.lucci@terra.com.br.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
Banikazemi 2007

MethodsTrial design: double-blind RCT.

Multicenter

Setting: 41 referral centers (university or research hospitals) in nine countries in North America and Europe.

Period: February 2001 to January 2004.

Sample size: reported (80 participants to provide 80% power for detecting a treatment effect on the basis of log-ranking testing by using a 10% drop-out rate; a 14-month enrolment period and 18 months of follow-up; type I error of 0.05 (2-sided); and expected events rates over 2 years of 40% and 10% for participants in the placebo and agalsidase-beta groups, respectively, as predicted by an estimated 20% to 30% decline per year in estimated).


ParticipantsOf the 252 patients screened, 82 eligible patients (ITT population) were treated at 26 sites in 6 countries.

Mean age: agalsidase-beta group 46.9 years and, placebo group 44.3 years.

Sex: agalsidase-beta group 88% men and 12% women and, placebo group 87% man and 13 % women.

Inclusion criteria: participants were at least 16 years of age with clinical evidence of AFD.

Exclusion criteria: participants who were undergoing dialysis or were schedule for kidney transplantation; those with documented transient ischemic attacks, ischemic stroke, unstable angina, or myocardial infarction with 3 months of trial entry; and those with confounding conditions or other clinically significant comorbid conditions.


InterventionsIntravenous infusion of agalsidase beta (mg/kg of body weight) (n = 51) or placebo every two weeks (n = 31).

Follow up: 18 months.


OutcomesPrimary end point: the time to first clinical event (renal, cardiac, or cerebrovascular event or death).

A renal event was defined as a 33% increase in serum creatinine level from baseline (2 consecutive values) or end-stage kidney disease requiring long-term dialysis or transplantation.

A cardiac event was defined as myocardial infarction; new symptomatic arrhythmia requiring antiarrhythmic medication, pacemaker, direct current cardioversion, or defibrillator implantation; unstable angina defined by national practice guidelines and accompanied by electrocardiographic changes resulting in hospitalization; or worsening congestive heart failure requiring hospitalization.

A cerebrovascular event was defined as a stroke or transient ischemic attack documented by a physician. participants were allowed to transition to open-label agalsidase beta after an independent adjudication board confirmed that a primary end point event had occurred.

The following measures were also performed at baseline and at the final trial visit or time of trial withdrawal: serum creatinine level; proteinuria; ratio of urinary albumin to urinary cretinine; 12-lead electrocardiography; echocardiography; neurologic examination; head magnetic resonance imaging; Brief Pain Inventory; exercise tolerance; plasma globotriaosylceramide level; Fabry symptom assessment; physical examination; blood chemistries; urinalysis; IgG antibody titers to agalsidase beta; and optional skin biopsy. Safety monitoring included physician evaluation and documentation of adverse events.


NotesThe Genzyme Corporation and the National Center for Research Resources supported the trial.

For future updates of this review, we will contact authors to clarify methodological issues.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomization codes were computer-generated.

Allocation concealment (selection bias)Low riskRandomization codes were maintained centrally at a secure location. The 2:1 randomization scheme was blocked (block size of 3, which was not revealed to investigators) at each site.

Blinding (performance bias and detection bias)
All outcomes
Low riskTrial materials were packaged identically, and sponsor staff, investigators, and patients were blinded to treatment allocation.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskWithdrawals and drop outs, were noted by Banikazemi to be less than 20%. ITT was used for the primary outcome only.

Selective reporting (reporting bias)Low risk

Other biasUnclear riskThe Genzyme Corporation and the National Center for Research Resources supported the trial.

Bierer 2006

MethodsTrial design: RCT.

Single-center or multicenter: not reported.

Setting: not reported.

Period: not reported.

Sample size: not reported.


Participants15 individuals with AFD, but only 6 participants were randomized (4 treatment; 2 placebo).

Sex: 5 male, and 1 female.

Mean age: male was 35 years and female was 42 years.


InterventionsPlacebo (saline) or enzyme replacement therapy (agalsidase beta 1 mg/kg every other week - Fabrazyme).

Follow up: 18 months.


OutcomesCardiopulmonar exercise test, forced expiratory volume and forced vital capacity. History and physical examination, a baseline electrocardiogram, transthoracic echocardiogram, and a pulmonary function test (spirometry) were also performed.


NotesFirst, the authors compared baseline cardiopulmonary exercise tests performed noninvasively, next, they assessed the impact of alfa galactosidase A on exercise tolerance by serial non-invasive cardiopulmonary exercise tests. The six participants randomized were part of a phase IV trial evaluating enzyme replacement therapy. 9 additional participants completed invasive cardiopulmonary exercise tests as baseline examinations. These participants did not have follow-up exercise tests and were not randomized to drug or placebo, neither evaluated in this systematic review.

The funding was provided by Genzyme Corporation.

For future updates of this review, we will contact authors to clarify methodological issues.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskStated as "randomized".

Allocation concealment (selection bias)Unclear riskUnclear

Blinding (performance bias and detection bias)
All outcomes
Unclear riskStated as "randomized in a double-blind fashion".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot discussed.

Selective reporting (reporting bias)Low risk

Other biasHigh riskThe funding was provided by Genzyme Corporation.

Eng 2001

MethodsTrial design: phase-3 double-blind RCT.

Single-center or multicenter: not reported.

Setting: not reported.

Period: not reported.

Sample size: not reported.


Participants58 participants with AFD (56 males) (29 each group).

Age average in the placebo group 28.4 years and in the treated group 32.0 years.

Inclusion criteria: patients should be over 16 years old, with alfa-galactosidases levels in the plasma lesser than 1.5 nmol/hour/mL or levels of leucocytes activity smaller than 4 nmol/hour/mg and, levels of creatine lesser than or equal to 2.2 mg/dL.

Exclusion criteria: participants who had carried through renal transplant or were carrying through dialysis.


InterventionsPatients received placebo or alfa-galactosidases 1 mg/kg intravenously every 2 weeks.

Follow up: 5 months.


OutcomesPrimay endpoint was percentage of patients in whom renal microvascular endothelial deposits og Gb3 were cleared. It was also evaluated the histologic clearance of microvascular endothelial deposits of Gb3 in the endomyocardium and skin, changes in the level of pain and the quality of life, urinary creatine, urinary proteic excretion, renal function and dermatological characteristics of glicolipides accumulation in the dermis. The individual scores for the kidney-, heart-, and skin-biopsy specimes and the composite scores for all three types of specimens were compared at baseline and after the week-20 infusion.


NotesAuthors of the trial belonged to Genzyme Corporation, Cambridge, Massachusetts, USA.

For future updates of this review, we will contact authors to clarify methodological issues.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskStated as "randomized".

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskStated as "double-blind". Information given on two outcomes: each renal biopsy was reviewed under light microscopy by three independent renal pathologists who were blinded to treatment status of the patient at the time of biopsy; immunofluorescence trials were scored blinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot discussed.

Selective reporting (reporting bias)Low risk

Other biasUnclear riskAuthors of the trial belonged to Genzyme Corporation, Cambridge, Massachusetts, USA.

Hughes 2008

MethodsTrial design: double-blind RCT.

Single-center or multicenter: not reported.

Setting: not reported.

Period: not reported.

Sample size: not reported.


Participants15 male with AFD.

Age: average of 37 years.


InterventionsThe participants received placebo (N=8) or enzyme replacement therapy with alfa agalsidase 0.2 mg/kg every 40 minutes, twice a week and, an additional of more 36 months.

Follow up: 6 months.


OutcomesThe primary efficacy endpoint was myocardial Gb3 content; the secondary efficacy endpoint was reduction of the left ventricular mass by MRI assessment. In addition, QRS duration and levels of Gb3 in cardiac tissue, urine sediment and plasma, echocardiography, electrocardiography, pure-tone audiometry, impedance audiometry and otoacoustic emission testing were also performed. Adverse events were computed.


NotesNo conflict of interest reported by the trial investigators.

For future updates of this review, we will contact authors to clarify methodological issues.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
Low riskStated as double-blind. All data were independently analysed by Royal Free Hospital investigators. The data remained blinded until the database was unlocked and the statistical analyses performed.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot described.

Selective reporting (reporting bias)Low risk

Other biasLow riskNo conflict of interest reported by the trial investigators.

Schiffmann 2001

MethodsTrial design: double-blinded placebo RCT.

Single-center or multicenter: not reported.

Setting: the Clinical Research Center of the National Institutes of Health.

Period: 6 months.

Sample size: not reported.


Participants26 males with AFD.

Age ranged between 16 and 56 years.


InterventionsPlacebo or alfa-galactosidase A, twice a week managed intravenously.


OutcomesTransversal Doppler, left ventricular volume, heart rate, stroke volume, cerebral blood flow.

The following Doppler parameters were obtained: peak flow velocity, mean flow velocity, end-diastolic velocity, pulsatility index, and resistance index.

Neuropathic pain measured by the Brief Pain Inventory, renal function and struction, cardiac function, storage material, quantitative sensory testing, skin biopsy, and Gb3 analyses.


NotesNo conflict of interest reported by the trial investigators.

For future updates of this review, we will contact authors to clarify methodological issues.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskA randomization schedule was prepared prior to the start of the trial. Randomization was
blocked to minimize imbalances between trial groups.

Allocation concealment (selection bias)Unclear riskRandomization schedule was prepared prior to the start of the trial and was provided to an unblinded pharmacist in the research pharmacy at the National Institutes of Health. No other medical or sponsor personnel had access to the randomization code until the trial was completed.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskThere was no detail whether clinicians/patients/outcome assessors were blinded to the treatment groups.

Incomplete outcome data (attrition bias)
All outcomes
Low risk1 participant, randomized to the placebo trial arm, withdrew from the trial for personal reasons and 3 further participants (1 from the ERT group and 2 from the placebo group) declined the follow-up acetazolamide challenge arm of the trial at completion of the trial. A further patient had suffered a lacunar infarct 10 years prior to commencement of the present trial.

Selective reporting (reporting bias)Low risk

Other biasLow riskNo conflict of interest reported by the trial investigators.

Vedder 2007

MethodsTrial design: open-label RCT.

Multicenter.

Setting: two centers in Norway (the Academic Medical Center and the Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital).

Period: May 2002 and December 2004.

Sample size: reported (90% and an alpha of 5% (one-sided), it was predicted that at least 18 patients (9 in each group) with an increased LVmass were required, i.e. a 10% larger reduction in LVmass by agalsidase alfa treatment than agalsidase beta treatment).


Participants36 randomized patients (18 males and 18 females).

Age range: 19 and 76 years.


InterventionsAgalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly for at least 12 months.


OutcomesPrimary endpoint:

  • Reduction of left ventricular mass on echocardiography


Secondary endpoints:

  • Improvement of renal function as measured by GFR.
  • Reduction of glycolipid accumulation in skin tissue (LM and biochemistry).
  • Reduction in pain as measured by the BPI.
  • Reduction in glycosphingolipid in plasma and 24-hour urine.


Tertiary endpoint:

  • Quality of life scores (SF-36).
  • Treatment failure defined as:


    • progression of renal disease (33% increase in serum creatinin, need for dialysis or transplantation);
    • progression of cardiac disease (new infarction, need for cardioversion, or anti-arrythmic drugs, heart-failure necessitating hospitalization);
    • occurrence of a new CVA as diagnosed by a neurologist or new lacunar infarctions on magnetic resonance imaging (MRI) as assessed by an experienced neuroradiologist.


NotesInternational Standard Randomized Clinical Trial: ISRCTN45178534


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPermuted block randomisation, with a block size of 4 patients. Manual randomization, envelopes generated by people not involved in obtaining informed consent.

Allocation concealment (selection bias)Low riskEnvelopes checked by 2 people not involved in obtaining informed consent.

Blinding (performance bias and detection bias)
All outcomes
High riskThe authors reported that the envelopes were opened by the investigator in the presence of the patient.

Incomplete outcome data (attrition bias)
All outcomes
High riskIn the LVMass analysis there were withdrawal rates of 50% and 62.5% in the agalsidase alfa and beta groups, respectively.

Selective reporting (reporting bias)High riskQuality of life is included as an outcome in the protocol, but not stated in the paper. However, we contacted the author to know if they have assessed this outcome. The author replied and said that they evaluated the QoL using SF36 questionnaires, but for the analysis presented in the paper, they did not use these data. They are willing to send us the data and we will include these in a future update.

Other biasLow riskNo conflict of interest was reported by the trial investigators.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Alamartine 2005Case series.

Banikasemi 2005Case series.

Beck 2004Cohort study.

Beer 2006Case series.

Breunig 2006Case series.

Cartwright 2004Case series.

Elliott 2006Cohort study.

Eto 2005Case series (all participants received 1 mg/kg of agalsidase beta, no comparator treatment). The authors reported the results of an open-label phase-2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta treatment of Fabry patients.

Fernhoff 2011Case series.

Germain 2007Case series (58 patients who had classic Fabry disease and completed a 20-week, double-blind, randomized, placebo-controlled, phase-3 study of agalsidase were transitioned to an open-label extension trial to receive bi-weekly 1 mg/kg agalsidase for up to an additional 54 months, no placebo).

Guffon 2002Case series.

Guffon 2004Case-control study.

Hajioff 2006Case series.

Hilz 2004Cohort study.

Jardim 2006Case series.

Jardim 2006bCase series.

Kalliokoshi 2006Case series.

Kampmann 2002Controlled trial with a cross-over to open label.

Kobayashi 2005Case series.

Kosch 2004Case series.

Linthorst 2004Case series.

Linthorst 2006Case series.

Mignani 2004Case series.

Mills 2004Case series.

Pisani 2005Case series.

Ramaswami 2007Case series.

Ries 2006Case series.

Schiffmann 2003Case series.

Schiffmann 2006Case series (participants who had completed a 6-month randomized placebo-controlled trial enrolled in an open-label extension study. All the participants received agalsidase alfa o.2 mg/kg).

Spinelli 2004Case series.

Utsumi 2005Case series.

Weidemann 2003Case series.

West 2011Cohort study.

 
Comparison 1. Agalsidase alfa versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Plasma Gb32Mean Difference (IV, Random, 95% CI)Subtotals only

    1.1 At up to 6 months
239Mean Difference (IV, Random, 95% CI)-2.07 [-6.64, 2.50]

 2 Urine sediment Gb31Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 At up to 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Kidney Gb31Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 At up to 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Myocardial globotriaosylceramide levels1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 Over 3 months and up to 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 The Brief Pain Inventory Severity1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 Over one month and up to three months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Over three months and up to five months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.3 Over five months and up to six months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 The Brief Pain Inventory pain-related quality of life1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 Over one month and up to three months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Over three months and up to five months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.3 Over five months and up to six months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Creatinine clearance1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 At up to 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Insulin clearance1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 At up to 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Glomeruli with mesangial widening1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    9.1 At up to 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Glomeruli with segmental sclerosis1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    10.1 At up to 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 11 Obsolescent glomeruli1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    11.1 At up to 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 12 Echocardiographic data on left ventricular structure and function over three months and up to six months1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    12.1 Mean left ventricular wall thickness (mm)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    12.2 Left ventricular internal diameter (mm) (diastolic)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    12.3 Left ventricular internal diameter (mm) (systolic)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    12.4 Left ventricular ejection fraction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Agalsidase beta versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Microvascular endothelial deposits of globotriaosylceramide1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Kidney - over three months and up to six months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Heart - over three months and up to six months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Composite - over three months and up to six months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Death (intention-to-treat population)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Renal events (intention-to-treat population)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Cardiopulmonary exercise test1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 Average heart rate reserve
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Average maximum oxygen uptake measured at peak exercise (L/minutes)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.3 Maximum oxygen uptake measured at peak exercise (ml/kg/mins)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.4 Oxygen pulse average at peak exercise
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Cardiopulmonary exercise test1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 Decrease in diastolic blood pressure
16Risk Ratio (M-H, Fixed, 95% CI)1.5 [0.34, 6.70]

 6 Cardiac events182Risk Ratio (M-H, Fixed, 95% CI)0.46 [0.11, 1.90]

 7 Cerebrovascular events (intention-to-treat population)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 8 Participants achieving zero scores in skin over three months and up to six months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    8.1 Superficial endothelial cells
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.2 Deep endothelial cells
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.3 Smooth muscle cells
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    8.4 Perineurium
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Participants achieving zero score or reduction in skin over three months and up to six months1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    9.1 Superficial endothelial cells
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 Deep endothelial cells
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.3 Smooth muscle cells
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.4 Perineurium
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Adverse event: Rigors2140Risk Ratio (M-H, Fixed, 95% CI)16.12 [3.35, 77.58]

    10.1 Over three and up to six months
158Risk Ratio (M-H, Fixed, 95% CI)29.0 [1.81, 464.38]

    10.2 At 24 months
182Risk Ratio (M-H, Fixed, 95% CI)10.94 [1.54, 77.95]

 11 Adverse event: Fever2140Risk Ratio (M-H, Fixed, 95% CI)7.84 [1.88, 32.68]

    11.1 Over three and up to six months
158Risk Ratio (M-H, Fixed, 95% CI)7.0 [0.92, 53.36]

    11.2 At 24 months
182Risk Ratio (M-H, Fixed, 95% CI)8.51 [1.18, 61.58]

 12 Adverse event: Temperature changed sensation1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    12.1 At 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 13 Adverse event: Chills1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    13.1 Over three and up to six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 14 Adverse event: Hypertension2140Risk Ratio (M-H, Fixed, 95% CI)2.94 [0.80, 10.86]

    14.1 Over three and up to six months
158Risk Ratio (M-H, Fixed, 95% CI)7.0 [0.38, 129.74]

    14.2 At 24 months
182Risk Ratio (M-H, Fixed, 95% CI)2.13 [0.47, 9.60]

 15 Adverse event: Vomiting1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    15.1 At 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 16 Adverse event: Chest pain1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    16.1 At 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 17 Adverse event: Fatigue1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    17.1 At 24 months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 18 Adverse event: Headache1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    18.1 Over three and up to six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 19 Adverse event: Pain related to Fabry Disease1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    19.1 Over three and up to six months
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Agalsidase alfa versus agalsidase beta

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Death1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 2 Cardiac events1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 3 Any adverse event1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 4 Any serious adverse events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected