Result card

  • SAF3: What are the incidence, severity and duration of adverse events when compared with placebo or with drugs approved (acetylcholinesterase inhibitors, memantine) for the treatment of Alzheimer’s disease?
Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment
C0008
English
Guidance Resources

What are the incidence, severity and duration of adverse events when compared with placebo or with drugs approved (acetylcholinesterase inhibitors, memantine) for the treatment of Alzheimer’s disease?

Authors: Luca Vignatelli, Luciana Ballini, Susanna Maltoni, Jelena Barbaric, Mirjana Huic, Pernilla Östlund

Internal reviewers: Gerardo Atienza, Lavinia Panait

The same methodology was used as described in section for the whole domain.

MCI

No trials on patients with MCI were retrieved.

AD

Placebo-controlled trials

Data from three RCTs (1 multiple dose study {Arai 2014}, 1 phase 2, dose-finding study {Dodel 2013}, and 1 phase 3 study {NCT00818662}) were available for analysis (see Table 8).

 

Table 8. Characteristic and adverse events data on one RCT (IVIG versus placebo) {Dodel 2013}.

Authors, Year, Reference number

Arai 2014

Dodel 2013

NCT00818662, data posted on clinicaltrial.gov in October 23rd 2014

Register number

Not reported

NCT00812565

NCT00818662

Design of the study

RCT placebo-controlled, multiple dose

RCT phase 2, placebo-controlled, dose-finding

RCT phase 3, placebo controlled

Disease severity

Mild-to-moderate

Mild-to-moderate

Mild-to-moderate

Intervention (N pts)

IVIG (two doses, N = 12)

IVIG (different doses, N = 42)

IVIG (two doses, N = 262)

Control (N pts)

Placebo (0.25% human albumin) (N =4)

Placebo (N =14)

Placebo (N = 121)

Duration (weeks)

26

24

70

Adverse events data

 

 

 

Any AE, n (%)

10 (83.3) vs 4 (100), p not reported

25 (60.0)  vs 9 (64.0), p=0.75

Not reported

Treatment related AEs, n (%)

1 (8.3) vs 0, p not reported

Non reported

Not reported

AEs leading to discontinuation, n (%)

1 (8.3) vs 0, p not reported

3 (7.1) vs 0*, p not reported

19 (7.3) : 7 (5.8), p not reported

Serious AEs, n (%)

1 (8.3) vs 3 (75.0), p not reported

4 (10.0) vs 4 (29.0), p=0.07

53 (20.2) vs 26 (21.5), p not reported

*AEs leading to discontinuation in three patients assigned to intravenous immunoglobulin (according the register and publication, N=3 in intervention group; 2 on 0.4 g/kg Octagam 10% every 2 weeks; 1 0.8 g/kg Octagam 10% every 4 weeks);

 

Comparative statistical analysis was reported only by Dodel at al. {Dodel 2013}. The proportions of individuals with one or more adverse event in the placebo group (n=9; 64%) and treatment group (n=25; 60%) were not significantly different (p=0·75). Similarly, the groups did not differ significantly in the proportion of serious adverse events: 4 (29%) patients in placebo group, 4 (10%) patients in IVIg group; p=0·078.

 

Active comparator trials

None were identified.

Critical
Completely
Vignatelli L et al. Result Card SAF3 In: Vignatelli L et al. Safety In: Jefferson T, Cerbo M, Vicari N [eds.]. Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 7 February 2023]. Available from: http://corehta.info/ViewCover.aspx?id=267

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