Bril_edit_Layout 1 28/10/2009 11:31 Page 74
Chronic Inflammatory Demyelinating Polyneuropathy
Figure 1: Improvements in Quality of Life Figure 3: Frequency of Adverse Events
A
7
8
p=0.020
IGIV-C (1,096 infusions)
6
7
Placebo (575 infusions) 5.2
5.7
6
5
5
4
p=0.241
4 3
2.6
3.3
2.5
3
Improvement 2
1.8
2
Events per 100 infusions 1.2
0.8 1 0.9 0.9 0.9 1
1.3
1
0.7
0.9 0.5
0.6
0.3
0.5 0.5
1
0.2 0.2 0.2
0
0 0
LSM change from baseline in SF-36 score 0
Physical component Mental component algia Rash
Chills
IGIV-C (n=59) Placebo (n=58)
Nausea Pyrexia
Influenza Dizziness
Arthr Back pain
Asthenia
Headache
B Hypertension
p=0.001
Adverse event
3
2.7
Number of adverse events per 100 infusions reported in ≥5% of patients in any treatment
group. Events per 100 infusions were calculated by taking the total number of adverse
2
events in the group divided by the total number of infusions in the group (1,096 for the
immunoglobulin intravenous, 10% caprylate/chromatography purified [IGIV-C] group and 575
for the placebo group) x 100. Data from Hughes et al., 2008.
20
1
electrophysiological parameters did not predict response to IGIV-C
Improvement
-0.8
treatment, suggesting that patients should not be excluded from
0
receiving treatment based on the severity of abnormal nerve
conduction findings.
27
The data were analysed for the subset of
-1
patients who had responded to IGIV-C during initial treatment (primary
LSM change from baseline in RHS score IGIV-C (n=59) Placebo (n=58)
end-point) or rescue therapy and were re-randomised to the 24-week,
A: Larger improvements during the first period in Short Form-36
®
(SF-36) component
summary scores were observed with intravenous immunoglobulin, 10% caprylate/
double-blind extension phase: 31 patients were randomly re-assigned
chromatography purified (IGIV-C) versus placebo, with a greater difference observed in the to continue IGIV-C therapy 1g/kg every three weeks and 26 patients
physical component summary score (p=0.020). B: A significantly larger improvement from
baseline in the Rotterdam Handicap Scale (RHS) scores was observed in patients treated with
were randomly assigned to be switched to placebo.
20
Continued
IGIV-C compared with patients treated with placebo (p=0.001). LSM = least squares mean. treatment with IGIV-C every three weeks generally maintained or
Reprinted with permission from Merkies et al., 2009.
25
slightly improved several efficacy outcome measures from extension
Figure 2: Trend in Quality of Life Improvements versus
baseline values, whereas patients switched to placebo (withdrawal of
US Normative Values
IGIV-C) appeared to show a decline, with loss of the improvements
initially gained with IGIV-C therapy (see Table 1). Patients who
100
continued to receive IGIV-C had a significantly longer time to relapse
US healthy population
than patients who received placebo (p=0.011), with a probability of
80 relapse of 13% with IGIV-C compared with 45% with placebo (hazard
IGIV-C for 48 weeks
ratio 0.19, 95% CI 0.05–0.70). In addition to long-term benefits in
60
functional disability, when quality of life was assessed over the
IGIV-C for 24 weeks duration of the entire study (48 weeks), patients treated with IGIV-C
Mean score
40
maintenance therapy every three weeks experienced a gradual shift
IGIV-baseline
over time (up to 48 weeks) in all SF-36 domain scores towards US
normative values (see Figure 2).
25
These results are consistent with a
20
small open-label study (n=13) that evaluated IVIg as CIDP
maintenance therapy over one year, in which general improvements
0
Physical Role Role Social Body Mental Vitality General
from baseline in SF-36 scores also shifted towards normative values.
28
functioning physical emotional functioning pain health health
Short Form-36
®
(SF-36) domain changes over time in patients treated with intravenous
Overall, IGIV-C 1g/kg every three weeks for up to 48 weeks was safe and
immunoglobulin, 10% caprylate/chromatography purified (IGIV-C) were compared with a
sample of a healthy US population. A gradual improvement from baseline (blue) (n=58) with well-tolerated in patients with CIDP, particularly given the short infusion
IGIV-C maintenance therapy every three weeks was observed after 24 weeks (green) (n=57)
duration for both loading and maintenance doses.
20
The majority of IGIV-
and 48 weeks (red) (n=27) in all mean SF-36 domain scores, with a trend towards US
normative scores (grey) observed. Data from 2,474 healthy volunteers were used to calculate C infusions were administered over two days for the 2g/kg loading
mean normal values.
36
Reprinted with permission from Merkies et al., 2009.
25
doses (IGIV-C 79% of 227 infusions, placebo 73% of 182 infusions) and
one day for the 1g/kg maintenance doses (IGIV-C 80% of 869 infusions,
amplitudes and conduction block (see Table 1).
24
In addition to placebo 83% of 393 infusions). The safety data were pooled from each
improvements in disability and electrophysiological parameters, period (first period, cross-over period, extension phase) for the 113
significant improvements in quality-of-life measures were patients exposed to IGIV-C and 95 patients exposed to placebo.
demonstrated with IGIV-C versus placebo, notably in the physical Exposure to IGIV-C was approximately twice that of placebo (1,096
component summary score of the Short Form-36
®
(SF-36) and the versus 575 infusions, respectively). To correct for the difference in drug
Rotterdam Handicap Scale score (see Figure 1).
25
Interestingly, a post exposure between the two treatment groups, the authors reported the
hoc correlation analysis revealed that the baseline severity of the number of adverse events per infusion. The frequency of adverse
74 EUROPEAN NEUROLOGICAL REVIEW