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Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Table 1: Efficacy of Intravenous Immunoglobulin, 10% Caprylate/Chromatography Purified versus Placebo in
Patients with Chronic Inflammatory Demyelinating Polyneuropathy
First Period Extension Phase
Change from Baseline, Change from Baseline
a
Mean ± SD Mean ± SD
Parameter IGIV-C Placebo LSM Difference p-value IGIV-C Placebo LSM Difference p-value
(n=59) (n=58) (95% CI) (n=31) (n=26) (95% CI)
Adjusted INCAT -1.1±1.8 -0.3±1.3 -0.7 0.010 0.1±0.7 0.4±1.7 -0.5 0.181
disability score
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(-1.3 to -0.2) (-1.2 to 0.2)
Grip strength, kPa
20
Dominant hand 13.2±19.3 1.5±15.6 10.9 0.0008 -0.8±11.3 -3.9±20.9 4.3 0.353
(4.6–17.2) (-5 to 13.6)
Non-dominant 13.3±17.4 4.3±14.9 8.6 0.005 -0.3±11 -5.6±22.7 5.8 0.247
hand (2.6–14.6) (-4.1 to 15.7)
MRC sum 3.3±5.6 0.2±4.5 3.1 0.001 0.8±4.1 -1±4.4 2 0.081
score
20
(1.3–4.9) (-0.3 to 4.3)
ISS score
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-1.2±3.4 0.2±3.9 -1.5 0.021 -0.5±4 0.2±2.6 -0.4 0.667
(-2.7 to -0.2) (-2.3 to 1.5)
Most severely 1.08±2.15
c
0.46±2.03
c
0.66 0.089
affected motor (-0.10, 1.41)
nerve, excluding
Erb’s* point
24,b
Averaged CMAP 0.75
c
0.13
c
0.62 0.035
amplitude of all (0.05, 1.2)
motor nerves, mV
24,b
Conduction -4.91±16.51 1.44±12.79 -5.54 0.027
block for all (-10.43, -0.64)
extremity motor
nerves, %
24,b,d
SD = standard deviation; CI = confidence interval; CMAP = compound muscle action potential; IGIV-C = intravenous immunoglobulin , 10% caprylate/chromatography purified; INCAT =
inflammatory neuropathy cause and treatment; ISS = INCAT sensory sum; LSM = least squares mean; MRC = Medical Research Council.
a. Baseline refers to the last measurement before starting treatment during the extension phase; b. Data reported for first period only; c. Data are least squares mean; d. Conduction block
was calculated as the reduction in amplitude from the most distal measurement site to the most proximal measurement site divided by the amplitude in the most distal measurement site
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and multiplied by 100. *Erb’s point was excluded from consideration of most proximal site in conduction block calculation. Adapted with permission from Hughes et al., 2008.
study in CIDP published to date, assessed the efficacy and safety of considered non-responders. Response was defined as ≥1-point
IVIg scheduled maintenance therapy for up to 48 weeks.
20,24,25
improvement from baseline in the adjusted INCAT disability score to
week 24. Patients who responded to initial treatment (primary end-
The ICE Study point) or responded to rescue therapy (cross-over period) and
The ICE study was a randomised, double-blind, placebo-controlled completed 24 weeks of treatment were re-randomised to receive
trial that employed a unique study design.
20
The design included an IGIV-C 1g/kg every three weeks or placebo in a double-blind 24-
initial 24-week period, a response-conditional cross-over period to week extension phase. A goal of the extension phase was to
provide rescue therapy if needed (24 weeks) and an additional 24- determine whether initial clinical benefits of routinely scheduled
week re-randomised, blinded extension phase for patients who IGIV-C therapy were maintained. During the extension phase,
responded to study medication during the initial treatment period or patients who relapsed (defined as ≥1-point worsening in extension-
the cross-over (rescue) period. A total of 117 adults with previously phase baseline-adjusted INCAT score) were discontinued from the
or newly diagnosed CIDP, progressive or relapsing motor and study. A significantly greater percentage of patients treated with
sensory dysfunction of at least one limb resulting from neuropathy IGIV-C responded versus placebo (54 versus 21%, respectively;
over the two months before study entry and significant disability as p=0.0002).
20
Of the 32 individuals who responded to IGIV-C, 41%
defined by an inflammatory neuropathy cause and treatment improved after the first IGIV-C treatment course and 94% improved
(INCAT) disability score of 2–9 were treated with IVIg (human), 10% after the second IGIV-C treatment course.
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However, some patients
caprylate/chromatography purified (IGIV-C, Gamunex
®
, Talecris who responded continued to show improvement in disability (INCAT
Biotherapeutics, Inc., Research Triangle Park, NC) or placebo. score) after the second treatment course. In fact, the mean time to
Patients received a baseline loading dose of 2g/kg over two to four maximal improvement in IGIV-C responders was 10.2 weeks (range
days and then a maintenance infusion of 1g/kg over one to two days 2.3–24 weeks), suggesting that treatment courses every three
every three weeks for up to 24 weeks (first period). Patients whose weeks beyond six weeks (i.e. two courses) could be beneficial and
adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) allow for maximal improvement in disability.
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score did not improve from baseline by ≥1 point by week six or
deteriorated at any visit crossed over to the alternative (rescue) Treatment with IGIV-C significantly improved other measurements of
therapy and were treated for up to 24 weeks (cross-over period). The clinical disability versus placebo, including hand-grip strength,
primary efficacy end-point was the percentage of patients who Medical Research Council sum score and INCAT sensory sum score
responded to initial treatment (first period) without crossing over to (see Table 1).
20
Improvements in electrophysiological parameters were
rescue therapy. Patients who crossed over to rescue therapy were also observed, including significant improvements in averaged motor
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