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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 ceptors on B cells.8 Because IVIg is prepared from
inflammatory demyelinating polyradiculoneuropathy donations of several thousand healthy donors, a wide
(CIDP) are control of symptoms (e.g., weakness, sen- spectrum of natural and induced antibodies results.
sory loss, imbalance, pain), improvement of func- These antibodies presumably target a number of ex-
tional ability, and maintainance of long-term ternal antigens, autoantibodies, and anti-idiotypes.9
remission.1 There are no clear guidelines concerning In addition, the fact that IVIg is prepared from vari-
the initial choice of therapy for CIDP, when to initi- ous donors could result in inconsistencies from batch
ate treatment, or the appropriate interval between to batch with regard to the proportions of various
treatments (table 1). Similar to the treatment of MS, antibodies/cytokines.
it is probably more beneficial to attempt to prevent Efficacy. Data from a number of randomized,
CIDP progression than to attempt to recover func- double-blind, placebo-controlled studies support the
tion, because superimposed axon degeneration may use of IVIg in patients with CIDP.10-13 These results
become irreversible. However, one issue associated are supported by the conclusion of a recent Cochrane
with early treatment is that patients with relatively review.14 In one study,10 30 patients with CIDP re-
mild symptoms may suffer more from the adverse ceived IVIg 0.4 g/kg or placebo for 5 consecutive
events associated with current therapies. Therefore, days, followed by a washout period before crossing
several factors must be considered in the choice of over to the alternate treatment arm. Nineteen (63%)
therapy, including disease severity, long-term side patients treated with IVIg demonstrated short-term
effects, age-related risks, venous access, concurrent benefit, prospectively defined as a ⱖ20-point im-
illnesses, and cost of treatment.2 This article reviews provement in neurologic disability score (NDS)15 or a
the efficacy and safety of currently available treat- ⱖ1-point improvement in functional clinical grade.
ments for patients with CIDP, including intravenous The 11-point functional clinical grading scale ranged
immunoglobulin (IVIg), corticosteroids, and plasma from 0 (normal) to 10 (dead). Treatment was effec-
exchange (PE). tive regardless of whether CIDP was of a chronic
progressive or chronic relapsing nature. Nine (56%)
Intravenous immunoglobulin (IVIg). Mecha- of 16 patients with chronic progressive disease and
nism of action. The mechanism by which IVIg exerts 10 (71%) of 14 patients with chronic relapsing dis-
its immunomodulatory effect in CIDP is not known. ease achieved the predefined criteria for improve-
Several theories include neutralization of pathoge- ment. However, the median duration of improvement
netic autoantibodies by anti-idiotypes,3 attenuation among the 10 responders with relapsing disease was
of complement-mediated tissue damage,4 and satura- only 6 weeks. These patients received additional
tion and functional blockade of Fc receptors on mac- courses of ⱕ1 g/kg of IVIg as single infusions before
rophages.5,6 Other suggested mechanisms include their anticipated relapses. The nine patients with
modulation of proinflammatory cytokines/T-cell me- chronic progressive disease who showed gradual and
diators7 and a decrease in autoantibody production continuous improvement were treated with only a
through the binding of anti-idiotypes to antigen re- 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 Many patients relapse within 1–4 weeks of
Frequency of administration every 2 to 8 weeks treatment
Dose commonly tapered to 0.4–0.5 g/kg for maintenance Expensive
therapy Availability at times is limited
Prednisone 1–1.5 mg/kg daily Response observed after several weeks of therapy
Titrate dose according to clinical response Maximal improvement may occur after 3–6 months
Alternate-day therapy may be used after 2 to 3 months of therapy
in patients who respond favorably; taper dose by 5–10 Inexpensive/cost-effective for short-term treatment,
mg every 2–4 weeks but long-term complications limit utility
Plasma exchange Severe disability: 5 exchanges (250 mL/kg each), Improvement occurs within several weeks
performed over 7–10 days, followed by same protocol, Patients may relapse within 2–8 weeks of treatment
as needed, to maintain improvement Expensive, invasive, time-consuming, and requires
Moderate disability: 2–3 exchanges per week for 2–3 special equipment/well-trained personnel
weeks, followed by once- or twice-weekly exchanges
for 3 weeks

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

all neurologic assessments significantly favored IVIg 2 consecutive days, followed by a third infusion 21
over placebo (table 2), as did the summed motor con- days later. Efficacy was judged by improvement in
duction velocities and distal motor latencies of the average muscle score (assessed by manual muscle
median, ulnar, tibial, and peroneal nerves (p ⬍ 0.05). testing using a modified Medical Research Council
Differences between the two treatment groups in scale18), functional disability (measured using the
summed distal and proximal motor amplitudes did Hughes Functional Disability Scale19), and forced vi-
not reach statistical significance. tal capacity. Motor nerve conduction studies were
Two other small studies (N ⫽ 7 each) also showed also performed. Approximately 76% of patients
positive clinical benefits with IVIg relative to place- treated with IVIg demonstrated improvement in
bo.11,12 A recent study by Mendell et al.13 is of partic- muscle strength. The benefit was observed as early
ular interest because it included 53 patients with as 10 days after treatment, and muscle strength con-
CIDP who had not been previously treated. Patients tinued to increase over several weeks. In contrast,
received IVIg 1 g/kg (N ⫽ 30) or placebo (N ⫽ 23) on 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- Table 3 Adverse events associated with IVIg treatment
age muscle score were significantly greater in the Systemic effects
IVIg group compared with the placebo group (see
Vasomotor symptoms (headache, nausea, fever, chills,
table 2). In the IVIg group, functional performance
myalgias, shortness of breath, and local vein thrombosis)
improved by ⱖ1 grade in 11 (37%) patients and did
not worsen in any patient. In contrast, in the placebo Cardiovascular effects
group, two (9%) patients improved, two (9%) wors- Hypertension/tachycardia
ened, and the remaining patients were unchanged Cardiac failure
(p ⫽ 0.019). Forced vital capacity was not affected. Thromboembolic events, including myocardial infarction
There were significant differences between the two
Renal complications
treatment groups with regard to mean changes in ul-
nar distal latency, tibial distal compound muscle action Acute kidney failure
potential amplitude, and peroneal nerve conduction ve- Acute renal tubular necrosis
locity, each favoring the IVIg group (p ⬍ 0.05). Neurologic complications
An open-label study of 52 patients with CIDP Migraine
found that the following factors were associated with
Aseptic meningitis
improvement after IVIg treatment: disease duration
of ⬍1 year, progression of weakness until treatment, Reversible encephalopathy
lack of a discrepancy in weakness between arms and Stroke
legs, areflexia of the arms, and slowed motor nerve Hypersensitivity reactions
conduction in the motor median nerve.20 If all of
Anaphylaxis
these factors were present, the probability of an ini-
tial improvement was estimated to be 93%. However, Hemolytic anemia, neutropenia, lymphopenia
in clinical practice only a small proportion of pa- Immune-complex arthritis
tients present with all these factors and, for the ma- Skin reaction
jority of patients, the outcome after treatment is less Pruritus
certain.
Petechiae
Tolerability and dosing considerations. Adverse
effects reported with IVIg therapy are summarized Changes in serum chemistry
in table 3. In the largest randomized, double-blind, Hyponatremia (artifactual)
placebo-controlled study, the most common adverse Elevated ESR (rouleaux formation)
effects reported were headache (67% IVIg versus
Decreased hemoglobin (dilutional)
44% placebo), nausea (33% versus 9%), chills (30%
versus 4%), fever (33% versus 0%), and transient Elevated liver enzymes
hypertension (10% versus 9%).13 Patients with IVIg ⫽ intravenous immunoglobulin; ESR ⫽ erythrocyte sedi-
known and substantial renal disease, and those with mentation rate.
a recent history of deep vein thrombosis, should re-
Adapted from Hahn,9 with permission.
ceive IVIg only under careful guidance. Periodic
monitoring of renal function tests and urine output
is advisable in such patients. Anecdotal evidence in- monitor them in an appropriate setting. Finally, pa-
dicates that the number of cases of renal failure in- tients with IgA deficiency, a history of known hyper-
duced by IVIg infusions has diminished over the past sensitivity, or anaphylactic reaction after exposure to
several years. It has been speculated that the stabi- human immunoglobulin should not be treated with
lizing agent used in older IVIg preparations was the IVIg. However, it is my opinion that the congenital
cause of the renal toxicity. At Saint Elizabeth’s Med- absence of IgA, a risk for anaphylaxis, is so uncom-
ical Center, considering the very large number of mon that routine screening with immunoelectro-
patients treated, only a small number have had phoresis is unnecessary.
large-vessel strokes or myocardial infarctions during The initial standard dosage of IVIg is typically
or soon after infusions of IVIg, despite having no 2 g/kg given over 2 to 5 days (see table 1), with the
history of coronary or cerebrovascular disease. These frequency of subsequent treatment administration
events obviously cannot be predicted. Therefore, pa- individualized according to the duration of response.
tients with symptoms of severe coronary disease, Most patients require repeat dosing approximately
transient ischemic attacks, or evidence of recent MI every 2 to 8 weeks to maintain improvement when
should be treated with IVIg very cautiously. Al- no other treatment is used concurrently.1,21,22 In
though it is not known whether a distant past infarc- younger patients with normal renal and cardiovascu-
tion or bypass surgery carries special risk, at our lar function, a total dose of 2 g/kg of IVIg infused
center a patient with Guillain-Barré syndrome who over 1 to 2 days (rapid infusion) may be as effective
had undergone bypass surgery a week previously as the same total dose infused over 5 days. However,
died suddenly after several IVIg infusions. In such to avoid hypercoagulable problems, the infusion rate
patients it may be prudent to use slow infusions, to should not exceed 200 mL/h.2,9,23 In case series, 89
pretreat with aspirin and heparin, and to carefully adverse events were identified during and after 341
S18 NEUROLOGY 60(Suppl 3) April 2003
rapid infusions, but only a few were serious.23 Most treated with corticosteroids showed improvement
patients expressed a preference for rapid infusions ranging from increased functional ability to complete
compared with the more time-consuming standard in- remission, and 12 (16%) patients showed no bene-
fusions. In studies of IVIg for other immunologic condi- fit.32 Quantitative data were not reported in this
tions, rapid achievement of high serum Ig appeared to study. The dosing regimen used in these patients
be associated with improved efficacy, but the clinical also was not reported and apparently varied. In an-
utility of this observation is uncertain.24,25 other study, patients received daily doses of pred-
Summary: IVIg. The efficacy and safety of IVIg nisone 100 mg for an initial 2- to 4-week period,
have been demonstrated in several randomized con- followed by single doses of prednisone 100 mg every
trolled studies of CIDP. Approximately two-thirds of other day until clinical improvement, defined as an
patients respond to treatment as measured by the increase in average muscle score, reached a pla-
NDS, functional clinical grade, and muscle strength. teau.18 Azathioprine (2.5 mg/kg) was given concur-
The initial standard dosage (2 g/kg given over 2 to 5 rently if the patient’s response was poor or relapse
days) of IVIg appears to be well established. How- occurred, and PE was also given to nonresponders
ever, trials directly comparing several dosing sched- and patients with severe disease. Initial improve-
ules are needed to further investigate the optimal ment was observed in 56 (95%) of 59 patients by 2
utilization of IVIg. When IVIg is used as a single months. However, the clinical changes were modest
agent, repeated dosing is required approximately ev- at best, and only 40% of patients remained in partial
ery 2 to 8 weeks in most patients to maintain im- or complete remission without need for additional
provement, an important consideration because each medication. The maximal effect of prednisone treat-
infusion can cost up to $12,000 USD.1 IVIg is not ment was typically observed within 1 to 6 months after
recommended in certain patient populations, such as initiation of treatment.18,33 Based on my own experi-
those with severe kidney disease, because of its asso- ence, some beneficial effect can be anticipated in most
ciation with renal dysfunction and acute renal fail- patients within 2 months of beginning treatment.
ure. Furthermore, IVIg should be used with caution A recent European study compared prednisolone
in patients with cardiovascular disease. 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
Corticosteroids. Mechanism of action. Cortico- prednisolone 60 mg once daily for 2 weeks (tapered
steroids likely exert their benefits via several mech- down to 10 mg over the course of the following
anisms. For example, they have been shown to month) or IVIg 2 g/kg administered over 1 to 2 days.
decrease the expression of several proinflammatory After a 4-week washout period, patients were to be
cytokines, including interleukin-1 (IL-1), IL-2, IL-6, crossed over; subsequent treatment was delayed in
and tumor necrosis factor (TNF), and to increase the select patients until treatment became necessary. Ef-
expression of anti-inflammatory cytokines (e.g., IL-4 ficacy was assessed using a novel 12-point disability
and IL-10).26-28 Corticosteroids also inhibit T-cell pro- scale, the Inflammatory Neuropathy Cause and
liferation and T-cell-dependent immunity. The non- Treatment (INCAT) Disability Scale, which assesses
specific anti-inflammatory and antiadhesion effects arm disability on a 6-point scale (0 ⫽ no upper limb
of corticosteroids may prevent inflammatory cells problems, 5 ⫽ inability to use either arm for any
from entering peripheral tissues.26 In a recent study, purposeful movement), leg disability on a 6-point
prednisone improved the defect in suppressor cell scale (0 ⫽ walking not affected, 5 ⫽ restricted to
function that is characteristic of CIDP.29 wheelchair, unable to stand and walk a few steps
Efficacy. In a randomized, controlled trial con- with help), and overall disability (sum of arm and leg
ducted by Dyck et al.,30 patients with CIDP who had disability). Other clinical end points included a timed
not received prior treatment with immunosuppres- 10-meter walk, a nine-hole peg test (9-HPT),34 maxi-
sive agents received either prednisone therapy (N ⫽ mal grip strength, and a modified Rankin scale.35
14) or no treatment (N ⫽ 14). In the active treatment Assessments were performed on the 24 patients who
group, patients received prednisone 120 mg every completed both treatment periods. Comparable mean
other day during the first week and were then slowly improvements in the disability scale were observed
tapered off this dose during the following 12 weeks. in both treatment groups (see table 2). In addition,
Patients who received prednisone had a median im- no significant differences were identified between
provement in NDS of 10.0, whereas controls had a the two treatment groups with regard to the other
median worsening of 1.5 (p ⫽ 0.016). Other mea- predetermined efficacy variables, such as the timed
sures of neurologic function, including detection walk and the 9-HPT (see table 2), grip strength, and
threshold of touch-pressure of the hand,31 hand grip, the modified Rankin scale. The authors noted that
and conduction velocity of motor fibers in the median the study was not powered to detect equivalence be-
nerve, also demonstrated significantly greater im- tween prednisolone and IVIg. The only conclusion
provement in the prednisone group (p ⬍ 0.05). that could be drawn was that overall improvement
Results from retrospective studies also support after 2 weeks of treatment was one-third of a point
the benefit of prednisone in patients with CIDP.18,32,33 on the disability scale for prednisolone and two-
In one of these studies, 49 (64%) of 76 patients thirds of a point for IVIg.
April 2003 NEUROLOGY 60(Suppl 3) S19
Several factors were found to be predictive of the tially reversible reduction in motor nerve conduction
clinical response to prednisone (1 to 1.5 mg/kg per velocity compared with pretreatment values. The au-
day), including shorter disease duration, milder neu- thors hypothesized that removal of these pathogenic
rologic deficit, a smaller decrease in motor nerve con- humoral factors may be responsible for the recovery
duction velocity, age ⬍40 years, and female gender.33 of nerve conduction velocity in CIDP patients after
In contrast, global distribution of weakness, muscle therapeutic PE, thereby providing a rationale for the
atrophy, and a Babinski sign correlated with a poor use of PE in CIDP.
response to prednisone. Efficacy. Results of early studies of PE in patients
Tolerability and dosing considerations. The risks with CIDP were based on nonblinded assessments.38-40
associated with corticosteroid therapy are well The first randomized, double-blind, sham-controlled
known, and although side effects are variably study of PE in patients with CIDP provided more
present, patients may be intolerant of them. Many substantial support for the use of PE.41 In that study,
complications may arise as a result of long-term 5 (33%) of 15 patients who received PE experienced
treatment, including weight gain, insomnia, hyper- greater improvements from baseline NDS scores at 3
trichosis, altered Cushingoid appearance, hypergly- weeks compared with the 14 patients who received
cemia, hyperlipidemia, psychosis, gastric ulcer, sham exchange. Furthermore, during a subsequent
osteoporosis, aseptic necrosis of the femoral head, open-label period, these results were reproduced
and infection.36 Based on my experience, one of the when patients who had previously received sham ex-
oddest of such complications occurred in a patient change demonstrated similar improvement in NDS af-
who developed a lung mass that was initially be- ter receiving PE. However, this trial was relatively
lieved to be neoplastic but was later identified as a brief (3 weeks), and patients differed considerably with
cryptococcoma. regard to duration of disease and prior treatment.41
In the 6-week comparative study described previ- Furthermore, the results may have been influenced
ously, the short-term safety profiles of prednisolone by the concurrent use of immunosuppressive drugs.
and IVIg were similar.16 The most common adverse A randomized, double-blind, sham-controlled,
effects reported were headache (26% of prednisolone crossover study by Hahn et al.42 evaluated PE and
courses and 33% of IVIg courses) and indigestion corticosteroid therapy in 18 patients with untreated
(20% and 20%). One case of psychosis, which led to CIDP. The study consisted of three phases. In phase
discontinuation, was the only serious adverse event I, patients received 10 PEs or sham exchanges over
attributed to prednisolone treatment. the course of 4 weeks. During phase II, after a
Dosing information is presented in table 1. Given 5-week washout period, patients were crossed over,
the tolerability issues with prednisone, Dyck et al.30 and in phase III the symptomatic patients received
recommend reducing the dosage of prednisone to the daily doses of prednisone 60 mg for 1 month (each
lowest effective level and administering it only to subsequent month the dose was tapered by 10 mg).
patients with at least moderately severe disease. Patients also received PE twice weekly during phase
However, there are no established criteria for dose III. Fifteen patients completed the trial, and 12
tapering. It is my opinion that alternate-day therapy (80%) improved substantially with PE, as assessed
is not usually effective, although this needs to be by NDS and grip strength measurements. The more
confirmed. Prednisone is contraindicated in patients vigorous PE regimen (10 versus six treatments), or
with active peptic ulcer disease, brittle diabetes, hy- possibly the selection of patients with more readily
pertension, severe osteoporosis, and systemic fungal reversible demyelination, may have been associated
infections. with the dramatically better results compared with
Summary: corticosteroids. The efficacy of cortico- those previously reported by Dyck et al.41 It was con-
steroids in treatment of patients with CIDP is simi- cluded that patients with either relapsing or chronic
lar to that of IVIg. However, relapses are common progressive disease could benefit from PE treatment
and many patients cannot tolerate long-term therapy if the clinical, electrophysiologic, and histologic fea-
with these agents. Although treatment with cortico- tures of CIDP were supportive of primary demyelina-
steroids is inexpensive, the serious complications tion and chronic secondary axon loss was not yet
that may result during prolonged therapy (e.g., asep- present. However, prednisone therapy was needed to
tic necrosis of the hip, sepsis) may add substantially maintain long-term remission of disease because 8
to the total cost of therapy. (67%) of the 12 patients who improved relapsed
within 7 to 14 days after the final PE treatment.
Plasma exchange (PE). Mechanism of action. There is little information about direct compari-
Based on indirect evidence, humoral effector mecha- sons between treatments. In a randomized, observer-
nisms have been thought to underlie or at least par- blinded study conducted by Dyck et al.,17 patients
ticipate in the pathogenesis of CIDP.37 Heininger et with CIDP received either PE or IVIg for 6 weeks.
al.37 designed a trial to test the potential pathogenic PE was administered twice weekly for the first 3
role of IgG fractions isolated from CIDP patients who weeks and then once weekly for the second 3 weeks.
had improved after PE therapy. Subsequent passive IVIg was administered once weekly at a dose of 0.4
transfer of these crude or purified IgG fractions into g/kg for the first 3 weeks and 0.2 g/kg for the second
marmoset monkeys demonstrated a clear and par- 3 weeks. After a washout phase, patients were
S20 NEUROLOGY 60(Suppl 3) April 2003
switched over to the alternate therapy. Among the couraging with the addition of this drug. No firm
17 patients who received PE and 15 who received conclusions can be drawn about the efficacy of any of
IVIg in either treatment period, significant improve- these drugs, and there is little to support their use as
ments from baseline (p ⬍ 0.01) in NDS and sum- independent treatments.
mated compound muscle action potentials of the
ulnar, median, and peroneal nerves were observed Conclusions. Data show that the extent and dura-
(see table 2). Although no significant differences in tion of clinical responses observed during treatment
efficacy were demonstrated between PE and IVIg as with current therapies vary greatly. Although the
initial treatment in patients with CIDP, IVIg may be majority of patients improve to some extent on cur-
considered preferable because treatment is simpler, rent therapies, the response to treatment is short-
expensive equipment is not required (although the lived, with most patients requiring ongoing
total costs are comparable), and it is less invasive. intermittent therapy. Prolonged remission or cure is
Tolerability and dosing considerations. Although the exception, not the rule. In addition to lack of
PE is relatively free of adverse effects and long-term durability of response, current therapies have the
complications, some disadvantages are associated following limitations: IVIg is expensive, time-
with its use. Acute occurrences of lightheadedness consuming, and its supply is at times limited2; corti-
and tiredness are reported in approximately one- costeroids have poor safety and tolerability profiles;
third of patients.36 Anemia also has been reported but and PE is invasive, time-consuming, expensive, and
is safely treated with supplemental iron. Paresthesias can be performed only at specialized centers. The
during the procedure are often helped by the addition problems associated with current therapies make
of calcium to the return line; the anticoagulant citrate them difficult to manage for a chronic disease such
dextrose used in the machine binds calcium. as CIDP.
Some general guidelines for treatment with PE Based on my experience, persistence with an ini-
are presented in table 1. PE can be performed only at tially failed modality (IVIg or PE) is not likely to be
special centers, and the procedure is invasive and beneficial despite anecdotal reports to the contrary.
time-consuming. Repeated venous access may be Furthermore, sequential treatment with standard
particularly problematic, and implanted subclavian therapies does not increase response rates. In one
and jugular vein catheters of various types are sub- series, 9 (35%) of 26 patients who failed an initial
ject to clotting and infection. The cost of PE is high, approach benefited from an alternative treatment,
ranging from $5,000 to $10,000 USD per series of and 2 (8%) additional patients who failed two types
exchanges.1 Although some patients may receive of treatment did well after resorting to a third type.21
only one PE series every 6 months, other patients No particular order of treatments appeared prefera-
may require monthly treatment. Contraindications ble to another.
include coagulopathy, thrombocytopenia, and hemo- The use of concurrent treatment modalities may
dynamic instability. increase the durability of response in patients with
Summary: PE. PE is a well-established treat- CIDP because the mechanisms of action among
ment for CIDP, with efficacy similar to that of IVIg treatments do not typically overlap. However, it is
and good overall tolerability. As with IVIg and corti- not clear whether treating CIDP with combinations
costeroids, relapses occur in a majority of patients. of current standard therapies provides more benefit
PE has several limitations: it is invasive, time- than single-agent standard therapy. One recent re-
consuming, expensive, can be performed only at a view of combination therapy indicated that four
limited number of centers, and requires special (67%) of six patients with severe cases of CIDP im-
equipment and well-trained personnel. proved after combined treatment with PE and cyclo-
phosphamide, and one of these patients had no
Other treatments. Interestingly, several patients further progression of symptoms.1,21 PE and IVIg are
have achieved complete spontaneous recovery of usually not used concurrently, and corticosteroids
CIDP after an episode of severe sepsis,43 suggesting are problematic as long-term agents, thereby pre-
that certain immune responses involved in CIDP senting a challenge for combination therapy. There
may be suppressed in a durable manner. Immuno- is a need for new treatments that can be used alone
suppressive drugs, including azathioprine, cyclo- or in combination to increase efficacy, increase the
sporin A, fludarabine, and cyclophosphamide, are duration of response, and reduce reliance on current
reported to be effective alone or in combination with therapies.
other therapies in small, uncontrolled trials and case
reports of patients with CIDP.44-49 However, one References
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