Current treatments for CIDP

Allan H. Ropper, MD

Article abstract—This article reviews the efficacy and tolerability of currently available therapies, including intravenous
immunoglobulin (IVIg), corticosteroids, and plasma exchange (PE), for treatment of chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP). Data show that current therapies are effective in approximately two-thirds of patients.
However, they fail to provide a durable clinical response. Furthermore, current treatments have several limitations that
make them problematic for long-term therapy. IVIg dosing is required approximately every 2 to 8 weeks in most patients
to maintain improvement. It is expensive, time-consuming to administer, and availability can be a problem. Furthermore,
IVIg is a blood product that is associated with rare thromboembolic events. Corticosteroids have poor safety and tolerabil-
ity profiles, and PE is invasive, time-consuming, expensive, and can be performed only at specialized centers. An
alternative to single-agent therapy with current treatments is the use of combination therapy. Combination therapy may
increase the duration of response, provide increased efficacy or independent efficacy in unresponsive patients, and reduce
the need for standard therapies. Research is needed to find agents suitable for single and combination therapy in CIDP.
NEUROLOGY 2003;60(Suppl 3):S16–S22

The primary goals of current therapies for chronic
inflammatory demyelinating polyradiculoneuropathy
(CIDP) are control of symptoms (e.g., weakness, sen-
sory loss, imbalance, pain), improvement of func-
tional ability, and maintainance of long-term
remission.1 There are no clear guidelines concerning
the initial choice of therapy for CIDP, when to initi-
ate treatment, or the appropriate interval between
treatments (table 1). Similar to the treatment of MS,
it is probably more beneficial to attempt to prevent
CIDP progression than to attempt to recover func-
tion, because superimposed axon degeneration may
become irreversible. However, one issue associated
with early treatment is that patients with relatively
mild symptoms may suffer more from the adverse
events associated with current therapies. Therefore,
several factors must be considered in the choice of
therapy, including disease severity, long-term side
effects, age-related risks, venous access, concurrent
illnesses, and cost of treatment.2 This article reviews
the efficacy and safety of currently available treat-
ments for patients with CIDP, including intravenous
immunoglobulin (IVIg), corticosteroids, and plasma
exchange (PE).
Intravenous immunoglobulin (IVIg). Mecha-
nism of action. The mechanism by which IVIg exerts
its immunomodulatory effect in CIDP is not known.
Several theories include neutralization of pathoge-
netic autoantibodies by anti-idiotypes,3 attenuation
of complement-mediated tissue damage,4 and satura-
tion and functional blockade of Fc receptors on mac-
rophages.5,6 Other suggested mechanisms include
modulation of proinflammatory cytokines/T-cell me-
diators7 and a decrease in autoantibody production
through the binding of anti-idiotypes to antigen re-
ceptors on B cells.8 Because IVIg is prepared from
donations of several thousand healthy donors, a wide
spectrum of natural and induced antibodies results.
These antibodies presumably target a number of ex-
ternal antigens, autoantibodies, and anti-idiotypes.9
In addition, the fact that IVIg is prepared from vari-
ous donors could result in inconsistencies from batch
to batch with regard to the proportions of various
antibodies/cytokines.
Efficacy. Data from a number of randomized,
double-blind, placebo-controlled studies support the
use of IVIg in patients with CIDP.10-13 These results
are supported by the conclusion of a recent Cochrane
review.14 In one study,10 30 patients with CIDP re-
ceived IVIg 0.4 g/kg or placebo for 5 consecutive
days, followed by a washout period before crossing
over to the alternate treatment arm. Nineteen (63%)
patients treated with IVIg demonstrated short-term
benefit, prospectively defined as a ⱖ20-point im-
provement in neurologic disability score (NDS)15 or a
ⱖ1-point improvement in functional clinical grade.
The 11-point functional clinical grading scale ranged
from 0 (normal) to 10 (dead). Treatment was effec-
tive regardless of whether CIDP was of a chronic
progressive or chronic relapsing nature. Nine (56%)
of 16 patients with chronic progressive disease and
10 (71%) of 14 patients with chronic relapsing dis-
ease achieved the predefined criteria for improve-
ment. However, the median duration of improvement
among the 10 responders with relapsing disease was
only 6 weeks. These patients received additional
courses of ⱕ1 g/kg of IVIg as single infusions before
their anticipated relapses. The nine patients with
chronic progressive disease who showed gradual and
continuous improvement were treated with only a
single 5-day treatment course. The mean changes in

From Saint Elizabeth’s Medical Center/Tufts University School of Medicine, Boston, MA.
Publication of this supplement was supported by an unrestricted educational grant from Biogen, Inc. The sponsor has provided A.H.R. with honoraria for his
participation in this project.
Address correspondence and reprint requests to Dr. Allan H. Ropper, 736 Cambridge Street, Boston, MA 02135; e-mail: Allan㛭Ropper㛭MD@cchcs.org

S16 Copyright © 2003 by AAN Enterprises, Inc.

Table 1 Current treatment options for CIDP

Standard dosage/procedure Comments

IVIg 2 g/kg infused over 2 to 5 days
Frequency of administration every 2 to 8 weeks
Dose commonly tapered to 0.4–0.5 g/kg for maintenance
therapy
Prednisone 1–1.5 mg/kg daily
Titrate dose according to clinical response
Alternate-day therapy may be used after 2 to 3 months
in patients who respond favorably; taper dose by 5–10
mg every 2–4 weeks
Plasma exchange Severe disability: 5 exchanges (250 mL/kg each),
performed over 7–10 days, followed by same protocol,
as needed, to maintain improvement
Moderate disability: 2–3 exchanges per week for 2–3
weeks, followed by once- or twice-weekly exchanges
for 3 weeks
Many patients relapse within 1–4 weeks of
treatment
Expensive
Availability at times is limited
Response observed after several weeks of therapy
Maximal improvement may occur after 3–6 months
of therapy
Inexpensive/cost-effective for short-term treatment,
but long-term complications limit utility
Improvement occurs within several weeks
Patients may relapse within 2–8 weeks of treatment
Expensive, invasive, time-consuming, and requires
special equipment/well-trained personnel

CIDP ⫽ chronic inflammatory demyelinating polyradiculoneuropathy; IVIg ⫽ intravenous immunoglobulin.

all neurologic assessments significantly favored IVIg
over placebo (table 2), as did the summed motor con-
duction velocities and distal motor latencies of the
median, ulnar, tibial, and peroneal nerves (p ⬍ 0.05).
Differences between the two treatment groups in
summed distal and proximal motor amplitudes did
not reach statistical significance.
Two other small studies (N ⫽ 7 each) also showed
positive clinical benefits with IVIg relative to place-
bo.11,12 A recent study by Mendell et al.13 is of partic-
ular interest because it included 53 patients with
CIDP who had not been previously treated. Patients
received IVIg 1 g/kg (N ⫽ 30) or placebo (N ⫽ 23) on
2 consecutive days, followed by a third infusion 21
days later. Efficacy was judged by improvement in
average muscle score (assessed by manual muscle
testing using a modified Medical Research Council
scale18), functional disability (measured using the
Hughes Functional Disability Scale19), and forced vi-
tal capacity. Motor nerve conduction studies were
also performed. Approximately 76% of patients
treated with IVIg demonstrated improvement in
muscle strength. The benefit was observed as early
as 10 days after treatment, and muscle strength con-
tinued to increase over several weeks. In contrast,
patients who received placebo lost muscle strength

Table 2 Mean changes from baseline in neurologic assessments after treatment of CIDP patients with IVIg, prednisolone, or PE

Measure IVIg Placebo % Change p Value

Hahn et al.10
NDS 35.6 3.5 90 ⬍0.0001
Clinical grade 1.3 0.5 62 ⬍0.002
Grip strength, kg 9.8 0.7 93 ⬍0.001
Mendell et al.13
Average muscle score (modified MRC) 0.63 0.1 84 0.006

IVIg Prednisolone % Change p Value

Hughes et al.16
Disability grade 0.71 0.58 18 NS
Timed walk, m/s 0.01 0.01 0 0.75
Time to complete 9-HPT, s 1.64 2.40 32 0.70

IVIg PE % Change p Value

Dyck et al.17
NDS 36.1 38.3 6 NS
Summated muscle action potential, mV 3.3 3.7 11 NS

CIDP ⫽ chronic inflammatory demyelinating polyradiculoneuropathy; IVIg ⫽ intravenous immunoglobulin; PE ⫽ plasma exchange;
NDS ⫽ neurologic disability score; MRC ⫽ Medical Research Council; NS ⫽ not significant (actual p value not reported); 9-HPT ⫽
nine-hole peg test.
April 2003 NEUROLOGY 60(Suppl 3) S17
over the same period. Mean improvements in aver-
age muscle score were significantly greater in the
IVIg group compared with the placebo group (see
table 2). In the IVIg group, functional performance
improved by ⱖ1 grade in 11 (37%) patients and did
not worsen in any patient. In contrast, in the placebo
group, two (9%) patients improved, two (9%) wors-
ened, and the remaining patients were unchanged
(p ⫽ 0.019). Forced vital capacity was not affected.
There were significant differences between the two
treatment groups with regard to mean changes in ul-
nar distal latency, tibial distal compound muscle action
potential amplitude, and peroneal nerve conduction ve-
locity, each favoring the IVIg group (p ⬍ 0.05).
An open-label study of 52 patients with CIDP
found that the following factors were associated with
improvement after IVIg treatment: disease duration
of ⬍1 year, progression of weakness until treatment,
lack of a discrepancy in weakness between arms and
legs, areflexia of the arms, and slowed motor nerve
conduction in the motor median nerve.20 If all of
these factors were present, the probability of an ini-
tial improvement was estimated to be 93%. However,
in clinical practice only a small proportion of pa-
tients present with all these factors and, for the ma-
jority of patients, the outcome after treatment is less
certain.
Tolerability and dosing considerations. Adverse
effects reported with IVIg therapy are summarized
in table 3. In the largest randomized, double-blind,
placebo-controlled study, the most common adverse
effects reported were headache (67% IVIg versus
44% placebo), nausea (33% versus 9%), chills (30%
versus 4%), fever (33% versus 0%), and transient
hypertension (10% versus 9%).13 Patients with
known and substantial renal disease, and those with
a recent history of deep vein thrombosis, should re-
ceive IVIg only under careful guidance. Periodic
monitoring of renal function tests and urine output
is advisable in such patients. Anecdotal evidence in-
dicates that the number of cases of renal failure in-
duced by IVIg infusions has diminished over the past
several years. It has been speculated that the stabi-
lizing agent used in older IVIg preparations was the
cause of the renal toxicity. At Saint Elizabeth’s Med-
ical Center, considering the very large number of
patients treated, only a small number have had
large-vessel strokes or myocardial infarctions during
or soon after infusions of IVIg, despite having no
history of coronary or cerebrovascular disease. These
events obviously cannot be predicted. Therefore, pa-
tients with symptoms of severe coronary disease,
transient ischemic attacks, or evidence of recent MI
should be treated with IVIg very cautiously. Al-
though it is not known whether a distant past infarc-
tion or bypass surgery carries special risk, at our
center a patient with Guillain-Barré syndrome who
had undergone bypass surgery a week previously
died suddenly after several IVIg infusions. In such
patients it may be prudent to use slow infusions, to
pretreat with aspirin and heparin, and to carefully
S18 NEUROLOGY 60(Suppl 3) April 2003
Table 3 Adverse events associated with IVIg treatment
Systemic effects
Vasomotor symptoms (headache, nausea, fever, chills,
myalgias, shortness of breath, and local vein thrombosis)
Cardiovascular effects
Hypertension/tachycardia
Cardiac failure
Thromboembolic events, including myocardial infarction
Renal complications
Acute kidney failure
Acute renal tubular necrosis
Neurologic complications
Migraine
Aseptic meningitis
Reversible encephalopathy
Stroke
Hypersensitivity reactions
Anaphylaxis
Hemolytic anemia, neutropenia, lymphopenia
Immune-complex arthritis
Skin reaction
Pruritus
Petechiae
Changes in serum chemistry
Hyponatremia (artifactual)
Elevated ESR (rouleaux formation)
Decreased hemoglobin (dilutional)
Elevated liver enzymes
IVIg ⫽ intravenous immunoglobulin; ESR ⫽ erythrocyte sedi-
mentation rate.
Adapted from Hahn,9 with permission.
monitor them in an appropriate setting. Finally, pa-
tients with IgA deficiency, a history of known hyper-
sensitivity, or anaphylactic reaction after exposure to
human immunoglobulin should not be treated with
IVIg. However, it is my opinion that the congenital
absence of IgA, a risk for anaphylaxis, is so uncom-
mon that routine screening with immunoelectro-
phoresis is unnecessary.
The initial standard dosage of IVIg is typically
2 g/kg given over 2 to 5 days (see table 1), with the
frequency of subsequent treatment administration
individualized according to the duration of response.
Most patients require repeat dosing approximately
every 2 to 8 weeks to maintain improvement when
no other treatment is used concurrently.1,21,22 In
younger patients with normal renal and cardiovascu-
lar function, a total dose of 2 g/kg of IVIg infused
over 1 to 2 days (rapid infusion) may be as effective
as the same total dose infused over 5 days. However,
to avoid hypercoagulable problems, the infusion rate
should not exceed 200 mL/h.2,9,23 In case series, 89
adverse events were identified during and after 341
rapid infusions, but only a few were serious.23 Most
patients expressed a preference for rapid infusions
compared with the more time-consuming standard in-
fusions. In studies of IVIg for other immunologic condi-
tions, rapid achievement of high serum Ig appeared to
be associated with improved efficacy, but the clinical
utility of this observation is uncertain.24,25
Summary: IVIg. The efficacy and safety of IVIg
have been demonstrated in several randomized con-
trolled studies of CIDP. Approximately two-thirds of
patients respond to treatment as measured by the
NDS, functional clinical grade, and muscle strength.
The initial standard dosage (2 g/kg given over 2 to 5
days) of IVIg appears to be well established. How-
ever, trials directly comparing several dosing sched-
ules are needed to further investigate the optimal
utilization of IVIg. When IVIg is used as a single
agent, repeated dosing is required approximately ev-
ery 2 to 8 weeks in most patients to maintain im-
provement, an important consideration because each
infusion can cost up to $12,000 USD.1 IVIg is not
recommended in certain patient populations, such as
those with severe kidney disease, because of its asso-
ciation with renal dysfunction and acute renal fail-
ure. Furthermore, IVIg should be used with caution
in patients with cardiovascular disease.
Corticosteroids. Mechanism of action. Cortico-
steroids likely exert their benefits via several mech-
anisms. For example, they have been shown to
decrease the expression of several proinflammatory
cytokines, including interleukin-1 (IL-1), IL-2, IL-6,
and tumor necrosis factor (TNF), and to increase the
expression of anti-inflammatory cytokines (e.g., IL-4
and IL-10).26-28 Corticosteroids also inhibit T-cell pro-
liferation and T-cell-dependent immunity. The non-
specific anti-inflammatory and antiadhesion effects
of corticosteroids may prevent inflammatory cells
from entering peripheral tissues.26 In a recent study,
prednisone improved the defect in suppressor cell
function that is characteristic of CIDP.29
Efficacy. In a randomized, controlled trial con-
ducted by Dyck et al.,30 patients with CIDP who had
not received prior treatment with immunosuppres-
sive agents received either prednisone therapy (N ⫽
14) or no treatment (N ⫽ 14). In the active treatment
group, patients received prednisone 120 mg every
other day during the first week and were then slowly
tapered off this dose during the following 12 weeks.
Patients who received prednisone had a median im-
provement in NDS of 10.0, whereas controls had a
median worsening of 1.5 (p ⫽ 0.016). Other mea-
sures of neurologic function, including detection
threshold of touch-pressure of the hand,31 hand grip,
and conduction velocity of motor fibers in the median
nerve, also demonstrated significantly greater im-
provement in the prednisone group (p ⬍ 0.05).
Results from retrospective studies also support
the benefit of prednisone in patients with CIDP.18,32,33
In one of these studies, 49 (64%) of 76 patients
treated with corticosteroids showed improvement
ranging from increased functional ability to complete
remission, and 12 (16%) patients showed no bene-
fit.32 Quantitative data were not reported in this
study. The dosing regimen used in these patients
also was not reported and apparently varied. In an-
other study, patients received daily doses of pred-
nisone 100 mg for an initial 2- to 4-week period,
followed by single doses of prednisone 100 mg every
other day until clinical improvement, defined as an
increase in average muscle score, reached a pla-
teau.18 Azathioprine (2.5 mg/kg) was given concur-
rently if the patient’s response was poor or relapse
occurred, and PE was also given to nonresponders
and patients with severe disease. Initial improve-
ment was observed in 56 (95%) of 59 patients by 2
months. However, the clinical changes were modest
at best, and only 40% of patients remained in partial
or complete remission without need for additional
medication. The maximal effect of prednisone treat-
ment was typically observed within 1 to 6 months after
initiation of treatment.18,33 Based on my own experi-
ence, some beneficial effect can be anticipated in most
patients within 2 months of beginning treatment.
A recent European study compared prednisolone
and IVIg therapy during a 6-week, randomized,
double-blind, crossover trial.16 During the first phase
of the study, patients with CIDP received either oral
prednisolone 60 mg once daily for 2 weeks (tapered
down to 10 mg over the course of the following
month) or IVIg 2 g/kg administered over 1 to 2 days.
After a 4-week washout period, patients were to be
crossed over; subsequent treatment was delayed in
select patients until treatment became necessary. Ef-
ficacy was assessed using a novel 12-point disability
scale, the Inflammatory Neuropathy Cause and
Treatment (INCAT) Disability Scale, which assesses
arm disability on a 6-point scale (0 ⫽ no upper limb
problems, 5 ⫽ inability to use either arm for any
purposeful movement), leg disability on a 6-point
scale (0 ⫽ walking not affected, 5 ⫽ restricted to
wheelchair, unable to stand and walk a few steps
with help), and overall disability (sum of arm and leg
disability). Other clinical end points included a timed
10-meter walk, a nine-hole peg test (9-HPT),34 maxi-
mal grip strength, and a modified Rankin scale.35
Assessments were performed on the 24 patients who
completed both treatment periods. Comparable mean
improvements in the disability scale were observed
in both treatment groups (see table 2). In addition,
no significant differences were identified between
the two treatment groups with regard to the other
predetermined efficacy variables, such as the timed
walk and the 9-HPT (see table 2), grip strength, and
the modified Rankin scale. The authors noted that
the study was not powered to detect equivalence be-
tween prednisolone and IVIg. The only conclusion
that could be drawn was that overall improvement
after 2 weeks of treatment was one-third of a point
on the disability scale for prednisolone and two-
thirds of a point for IVIg.
April 2003 NEUROLOGY 60(Suppl 3) S19
 Several factors were found to be predictive of the
clinical response to prednisone (1 to 1.5 mg/kg per
day), including shorter disease duration, milder neu-
rologic deficit, a smaller decrease in motor nerve con-
duction velocity, age ⬍40 years, and female gender.33
In contrast, global distribution of weakness, muscle
atrophy, and a Babinski sign correlated with a poor
response to prednisone.
Tolerability and dosing considerations. The risks
associated with corticosteroid therapy are well
known, and although side effects are variably
present, patients may be intolerant of them. Many
complications may arise as a result of long-term
treatment, including weight gain, insomnia, hyper-
trichosis, altered Cushingoid appearance, hypergly-
cemia, hyperlipidemia, psychosis, gastric ulcer,
osteoporosis, aseptic necrosis of the femoral head,
and infection.36 Based on my experience, one of the
oddest of such complications occurred in a patient
who developed a lung mass that was initially be-
lieved to be neoplastic but was later identified as a
cryptococcoma.
In the 6-week comparative study described previ-
ously, the short-term safety profiles of prednisolone
and IVIg were similar.16 The most common adverse
effects reported were headache (26% of prednisolone
courses and 33% of IVIg courses) and indigestion
(20% and 20%). One case of psychosis, which led to
discontinuation, was the only serious adverse event
attributed to prednisolone treatment.
Dosing information is presented in table 1. Given
the tolerability issues with prednisone, Dyck et al.30
recommend reducing the dosage of prednisone to the
lowest effective level and administering it only to
patients with at least moderately severe disease.
However, there are no established criteria for dose
tapering. It is my opinion that alternate-day therapy
is not usually effective, although this needs to be
confirmed. Prednisone is contraindicated in patients
with active peptic ulcer disease, brittle diabetes, hy-
pertension, severe osteoporosis, and systemic fungal
infections.
Summary: corticosteroids. The efficacy of cortico-
steroids in treatment of patients with CIDP is simi-
lar to that of IVIg. However, relapses are common
and many patients cannot tolerate long-term therapy
with these agents. Although treatment with cortico-
steroids is inexpensive, the serious complications
that may result during prolonged therapy (e.g., asep-
tic necrosis of the hip, sepsis) may add substantially
to the total cost of therapy.
Plasma exchange (PE). Mechanism of action.
Based on indirect evidence, humoral effector mecha-
nisms have been thought to underlie or at least par-
ticipate in the pathogenesis of CIDP.37 Heininger et
al.37 designed a trial to test the potential pathogenic
role of IgG fractions isolated from CIDP patients who
had improved after PE therapy. Subsequent passive
transfer of these crude or purified IgG fractions into
marmoset monkeys demonstrated a clear and par-
S20 NEUROLOGY 60(Suppl 3) April 2003
tially reversible reduction in motor nerve conduction
velocity compared with pretreatment values. The au-
thors hypothesized that removal of these pathogenic
humoral factors may be responsible for the recovery
of nerve conduction velocity in CIDP patients after
therapeutic PE, thereby providing a rationale for the
use of PE in CIDP.
Efficacy. Results of early studies of PE in patients
with CIDP were based on nonblinded assessments.38-40
The first randomized, double-blind, sham-controlled
study of PE in patients with CIDP provided more
substantial support for the use of PE.41 In that study,
5 (33%) of 15 patients who received PE experienced
greater improvements from baseline NDS scores at 3
weeks compared with the 14 patients who received
sham exchange. Furthermore, during a subsequent
open-label period, these results were reproduced
when patients who had previously received sham ex-
change demonstrated similar improvement in NDS af-
ter receiving PE. However, this trial was relatively
brief (3 weeks), and patients differed considerably with
regard to duration of disease and prior treatment.41
Furthermore, the results may have been influenced
by the concurrent use of immunosuppressive drugs.
A randomized, double-blind, sham-controlled,
crossover study by Hahn et al.42 evaluated PE and
corticosteroid therapy in 18 patients with untreated
CIDP. The study consisted of three phases. In phase
I, patients received 10 PEs or sham exchanges over
the course of 4 weeks. During phase II, after a
5-week washout period, patients were crossed over,
and in phase III the symptomatic patients received
daily doses of prednisone 60 mg for 1 month (each
subsequent month the dose was tapered by 10 mg).
Patients also received PE twice weekly during phase
III. Fifteen patients completed the trial, and 12
(80%) improved substantially with PE, as assessed
by NDS and grip strength measurements. The more
vigorous PE regimen (10 versus six treatments), or
possibly the selection of patients with more readily
reversible demyelination, may have been associated
with the dramatically better results compared with
those previously reported by Dyck et al.41 It was con-
cluded that patients with either relapsing or chronic
progressive disease could benefit from PE treatment
if the clinical, electrophysiologic, and histologic fea-
tures of CIDP were supportive of primary demyelina-
tion and chronic secondary axon loss was not yet
present. However, prednisone therapy was needed to
maintain long-term remission of disease because 8
(67%) of the 12 patients who improved relapsed
within 7 to 14 days after the final PE treatment.
There is little information about direct compari-
sons between treatments. In a randomized, observer-
blinded study conducted by Dyck et al.,17 patients
with CIDP received either PE or IVIg for 6 weeks.
PE was administered twice weekly for the first 3
weeks and then once weekly for the second 3 weeks.
IVIg was administered once weekly at a dose of 0.4
g/kg for the first 3 weeks and 0.2 g/kg for the second
3 weeks. After a washout phase, patients were
switched over to the alternate therapy. Among the
17 patients who received PE and 15 who received
IVIg in either treatment period, significant improve-
ments from baseline (p ⬍ 0.01) in NDS and sum-
mated compound muscle action potentials of the
ulnar, median, and peroneal nerves were observed
(see table 2). Although no significant differences in
efficacy were demonstrated between PE and IVIg as
initial treatment in patients with CIDP, IVIg may be
considered preferable because treatment is simpler,
expensive equipment is not required (although the
total costs are comparable), and it is less invasive.
Tolerability and dosing considerations. Although
PE is relatively free of adverse effects and long-term
complications, some disadvantages are associated
with its use. Acute occurrences of lightheadedness
and tiredness are reported in approximately one-
third of patients.36 Anemia also has been reported but
is safely treated with supplemental iron. Paresthesias
during the procedure are often helped by the addition
of calcium to the return line; the anticoagulant citrate
dextrose used in the machine binds calcium.
Some general guidelines for treatment with PE
are presented in table 1. PE can be performed only at
special centers, and the procedure is invasive and
time-consuming. Repeated venous access may be
particularly problematic, and implanted subclavian
and jugular vein catheters of various types are sub-
ject to clotting and infection. The cost of PE is high,
ranging from $5,000 to $10,000 USD per series of
exchanges.1 Although some patients may receive
only one PE series every 6 months, other patients
may require monthly treatment. Contraindications
include coagulopathy, thrombocytopenia, and hemo-
dynamic instability.
Summary: PE. PE is a well-established treat-
ment for CIDP, with efficacy similar to that of IVIg
and good overall tolerability. As with IVIg and corti-
costeroids, relapses occur in a majority of patients.
PE has several limitations: it is invasive, time-
consuming, expensive, can be performed only at a
limited number of centers, and requires special
equipment and well-trained personnel.
Other treatments. Interestingly, several patients
have achieved complete spontaneous recovery of
CIDP after an episode of severe sepsis,43 suggesting
that certain immune responses involved in CIDP
may be suppressed in a durable manner. Immuno-
suppressive drugs, including azathioprine, cyclo-
sporin A, fludarabine, and cyclophosphamide, are
reported to be effective alone or in combination with
other therapies in small, uncontrolled trials and case
reports of patients with CIDP.44-49 However, one
small randomized trial found that azathioprine was
not beneficial when added to corticosteroids.50 Never-
theless, further study of these agents may be war-
ranted. Mycophenolate and other similar agents
have been used in a few cases in which no other
available treatments were appropriate. However,
based on my experience, results have not been en-
couraging with the addition of this drug. No firm
conclusions can be drawn about the efficacy of any of
these drugs, and there is little to support their use as
independent treatments.
Conclusions. Data show that the extent and dura-
tion of clinical responses observed during treatment
with current therapies vary greatly. Although the
majority of patients improve to some extent on cur-
rent therapies, the response to treatment is short-
lived, with most patients requiring ongoing
intermittent therapy. Prolonged remission or cure is
the exception, not the rule. In addition to lack of
durability of response, current therapies have the
following limitations: IVIg is expensive, time-
consuming, and its supply is at times limited2; corti-
costeroids have poor safety and tolerability profiles;
and PE is invasive, time-consuming, expensive, and
can be performed only at specialized centers. The
problems associated with current therapies make
them difficult to manage for a chronic disease such
as CIDP.
Based on my experience, persistence with an ini-
tially failed modality (IVIg or PE) is not likely to be
beneficial despite anecdotal reports to the contrary.
Furthermore, sequential treatment with standard
therapies does not increase response rates. In one
series, 9 (35%) of 26 patients who failed an initial
approach benefited from an alternative treatment,
and 2 (8%) additional patients who failed two types
of treatment did well after resorting to a third type.21
No particular order of treatments appeared prefera-
ble to another.
The use of concurrent treatment modalities may
increase the durability of response in patients with
CIDP because the mechanisms of action among
treatments do not typically overlap. However, it is
not clear whether treating CIDP with combinations
of current standard therapies provides more benefit
than single-agent standard therapy. One recent re-
view of combination therapy indicated that four
(67%) of six patients with severe cases of CIDP im-
proved after combined treatment with PE and cyclo-
phosphamide, and one of these patients had no
further progression of symptoms.1,21 PE and IVIg are
usually not used concurrently, and corticosteroids
are problematic as long-term agents, thereby pre-
senting a challenge for combination therapy. There
is a need for new treatments that can be used alone
or in combination to increase efficacy, increase the
duration of response, and reduce reliance on current
therapies.
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