INTRODUCTION — Chronic inflammatory demyelinating polyneuropathy (CIDP; also known as chronic inflammatory demyelinating polyradiculoneuropathy) is an entity that describes a group of related neuropathies, all having chronicity, demyelination, inflammation, and immune mediation in common.

In the classic form of CIDP, motor involvement is greater than sensory. The clinical course of CIDP is slowly progressive in a majority of patients, but a relapsing-remitting course is noted in at least one-third and is more common in the pediatric age group.

CIDP generally responds to immunosuppressive or immunomodulatory treatment with glucocorticoids, intravenous immune globulin, or plasma exchange.

The treatment and prognosis of CIDP will be reviewed here. Other aspects of CIDP are discussed separately. (See "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis".)

GOALS AND COURSE OF TREATMENT — Early administration of effective treatment is important in CIDP. The goal is to stop the immune attack against the myelin sheath of peripheral nerves so that secondary axonal degeneration is minimized [1]. This can improve symptoms and function and can prevent or minimize long-term disability.

The treatment approach depends on the severity and course of disease. While some patients with CIDP have such mild disease with minimal impact on function and quality of life that treatment is not required, most patients are significantly impaired and need treatment. Multiple medication trials may be required to optimize treatment response, particularly for patients with severe disease. Serial clinical examinations are used to monitor for relapses and guide changes in therapy.

Once symptoms stabilize, and for patients who present with milder symptoms, the treatment objective is for sustained improvement and to promote remission.

Consultation with a neuromuscular specialist, if available, is recommended for optimal management.

INITIAL THERAPY — For most treatment-naïve patients with CIDP who are more than mildly affected or for mildly affected patients who are rapidly worsening, we recommend initial immune-modulatory treatment using either intravenous immune globulin (IVIG), plasma exchange, or glucocorticoids [2-4]. In small studies, these treatments appear to be similarly effective [5-7]. The initial choice among these therapies is influenced by disease severity, concurrent illness, venous access, treatment side effects, availability, and cost [8].

Patients with the variant forms of CIDP associated with IgG4 antibodies, however, may be unresponsive to typical initial therapies such as IVIG. In these patients, we prefer rituximab or other immunosuppressive therapies. (See "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis", section on 'Atypical CIDP variants' and 'Patients with refractory disease' below.)

Intravenous immune globulin — IVIG is an effective therapy for CIDP. We start treatment with IVIG when a rapid response is a priority. IVIG is usually easier to administer than plasma exchange and may have a more rapid response for disability improvement than with glucocorticoids.

A number of small randomized controlled trials and systematic reviews have established that IVIG is effective for the short-term treatment of CIDP [3,7,9-14]. In one meta-analysis of five trials with a total of 269 patients, the rate of disability improvement within one month after treatment was significantly higher with IVIG than with placebo (44 versus 26 percent; risk ratio [RR] 2.4, 95% CI 1.72-3.36) [7]. To obtain improvement in one patient, the number needed to treat (NNT) was 3. Overall, IVIG improved disability for at least two to six weeks.

More long-term outcome data are limited. During a 24-week extension phase of the ICE study, 57 initial-phase IVIG responders were randomly reassigned to IVIG or placebo [9]. Patients who continued to receive IVIG had a significantly longer time to relapse than those reassigned to placebo during this phase, and the relapse rate was significantly lower for patients treated with IVIG (13 versus 45 percent, hazard ratio 0.19, 95% CI 0.05-0.70).

The meta-analysis [7] also identified small trials (20 to 46 patients each) that compared IVIG with plasma exchange [5], oral prednisolone [6], and intravenous (IV) methylprednisolone [14]. The benefit of IVIG appeared similar to that of plasma exchange, oral prednisolone, and IV methylprednisolone [7].

●Dosing regimens – The initial dose of IVIG is 2 g/kg infused over two to five days (eg, 0.4 g/kg per day for five days). Many patients with CIDP require a treatment trial of repeat IVIG dosing every two to six weeks depending on clinical course.

For most patients, we repeat infusion of IVIG (1 g/kg) every three weeks for two to three months after the initial treatment before determining efficacy. Observation with objective measures should determine if the treatment is effective. Benefit may not be apparent after the first course of IVIG treatment, but 94 percent of IVIG responders in the ICE trial did so within nine weeks [13].

At the completion of the treatment trial, objective signs of efficacy should be evident to continue treatment. However, while progression of disease indicates treatment failure, stability in a patient who previously was progressing may indicate a treatment response and warrant continued treatment for another two to three months before reassessment of treatment modality. (See 'Assessing response to therapy' below and 'Inadequate response to initial therapy' below.)

For patients who respond well to therapy, the treatment can be tapered. (See 'Maintenance IVIG' below.)

●Adverse effects of IVIG include headache, nausea, fever, aseptic meningitis, rash, acute renal failure (mostly related to sucrose-containing products), and rarely hyperviscosity and thrombosis. The most common adverse effects from the ICE trial were transient headache, nausea, and fever [13]. In a meta-analysis, the risk of serious adverse effects for IVIG was similar to placebo (RR 0.82, 95% CI 0.36-1.87) [7].

Immunoglobulin A (IgA)-deficient patients should not be treated with IVIG since it can lead to anaphylaxis. IVIG should be used cautiously in patients with severe kidney disease because of its association with renal failure [8]. Only formulations without sucrose and with low osmolality should be considered.

Adverse effects of IVIG and strategies to minimize these are reviewed in greater detail separately. (See "Intravenous immune globulin: Adverse effects".)

Plasma exchange — Plasma exchange is an effective alternative to IVIG; however, it may be less convenient to administer. Plasma exchange is available only at specialized centers and has the added concerns of an invasive procedure that requires repeated venous access and (often) indwelling catheters.

Two small randomized clinical trials [15,16], as well as a number of observational studies [17-23], have found that plasma exchange is effective for the short-term treatment of CIDP. In a meta-analysis summarizing the clinical trials, approximately two-thirds of patients treated with plasma exchange showed meaningful short-term clinical improvement as measured by Neuropathy Impairment Score [24].

Like IVIG, a single treatment course with plasma exchange is unlikely to lead to remission. In one of the included trials [16], relapses of CIDP occurred in 8 of 12 patients (67 percent) who initially responded to plasma exchange, most occurring within a week or two after stopping plasma exchange.

●Dosing regimens – For patients with CIDP and severe disability, we suggest four to six exchanges over 8 to 10 days. The plasma exchange schedule after that depends on clinical response but can usually be decreased to one exchange every three to four weeks. However, if symptoms occur between treatments, the schedule would be modified to eliminate the interval changes.

The implementation of therapeutic plasma exchange, including techniques and regimens, is discussed in detail separately. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)

●Adverse effects – The main complications of plasma exchange are hypotension, sepsis, and problems with IV access. In addition, plasma exchange requires repeated venous access and (often) indwelling catheters that are susceptible to clotting and infection. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Complications".)

Glucocorticoids — For patients with more insidious CIDP, a rapid treatment response may be less critical than for more severely affected patients. For such patients, we suggest initial treatment with glucocorticoids as it appears more effective at achieving long-term remission [14,25]. In one retrospective study, the median time to relapse was shorter for those treated with IVIG compared with those who received high-dose pulse methylprednisolone (4.5 versus 14 months), although a similar proportion (77 to 86 percent) eventually relapsed in both groups [25].

No large controlled trials of glucocorticoids in CIDP have been performed. Substantial data from retrospective series suggest that oral glucocorticoids are beneficial for CIDP [26-30]. In a small trial, 28 patients completed a three-month regimen of oral prednisone, beginning with a dose of 120 mg every other day during the first week, followed by a slow taper off prednisone by the end of 12 weeks [31]. Patients who received prednisone demonstrated clinically meaningful improvement on disability and electrodiagnostic measures compared with patients assigned to placebo.

●Dosing schedule – For most patients, we prefer the use of pulse rather than daily glucocorticoids for initiation and initial titration of dosing [32]. Although not confirmed by clinical trials, pulse dosing may have both a greater chance for early efficacy, higher durability of response, and a better side effect profile.

We typically start with an initial dose of IV methylprednisolone (1000 mg/day) for three days, followed by 1000 mg one day a week for four weeks [33]. Oral pulsed steroids may be an efficacious alternative to an intravenous pulsed regimen. Options include dexamethasone 40 mg for four consecutive days once a month [32] or prednisone 600 mg once a week [34]. In patients who respond to therapy, we taper either the dose or frequency once improvement or clinical stabilization occurs. Earlier tapering and a switch to another agent is necessary if intolerable adverse effects develop.

The use of daily (or alternate-day) oral glucocorticoids may be an appropriate alternative in some patients, such as those who are younger and have little risk for side effects. Some clinicians believe that adverse sleep and psychologic effects may be less problematic with daily treatment. In addition, daily dosing may be preferred in patients with diabetes, so that there is a more even daily effect on blood sugars. In such patients, we typically start prednisone at 1 to 1.5 mg/kg daily (usually around 50 to 80 mg daily; no more than 100 mg). Alternate-day glucocorticoid therapy may reduce the incidence of side effects, but some experts believe it is less effective than a daily dosing regimen [8].

In the PREDICT study, 40 patients with newly diagnosed, treatment-naive CIDP were randomly assigned to treatment with either high-dose pulsed oral dexamethasone (40 mg daily for four days followed by placebo for 24 days, repeated for six cycles) or daily prednisolone (starting with 60 mg daily for five weeks and tapering to alternate-day doses and then to zero over the following 27 weeks) [32]. The remission rate at 12 months was similar between the pulsed high-dose dexamethasone and standard prednisolone treatment groups (10 of 24 [42 percent] versus 6 of 16 [38 percent]; odds ratio 1.19, 95% CI 0.3-4.4).

●Route of administration – Whether to use oral or intravenous glucocorticoids is based on patient and physician preference. Oral steroids can be more convenient since intravenous access and nursing support are not necessary. Many patients prefer the convenience of oral therapy. Limited observational data suggest that IV therapy is associated with less weight gain and fewer cushingoid features but possibly more restlessness and sleep problems compared with oral therapy [33].

●Adverse effects and contraindications – Chronic glucocorticoid use is limited by common and clinically important side effects that include weight gain, cushingoid appearance, easy bruising and skin fragility, cataracts, aseptic necrosis of the femoral or humeral heads, hypertension, diabetes, and osteoporosis. Thus, glucocorticoid therapy is generally contraindicated in patients with peptic ulcer disease, brittle diabetes, refractory hypertension, severe osteoporosis, and systemic fungal infections [8].

Adverse effects of glucocorticoids are discussed in further detail separately. (See "Major side effects of systemic glucocorticoids".)

ASSESSING RESPONSE TO THERAPY

Frequency of assessments — Patients with CIDP should be reevaluated routinely (eg, at least every three months when treatments are initiated or changed, and at least twice a year when on maintenance therapy) to determine whether they are responding to therapy. In cases with rapid worsening despite treatment, evaluations at shorter intervals are necessary. For patients in remission, clinical surveillance can occur yearly.

Clinical methods — The success or failure of a treatment regimen should be judged using objective methods both before and during treatment to quantify clinical changes [35,36]. Although such objective measures have not been universally employed in clinical practice, there is accumulating evidence that relying on only the subjective impression of clinical improvement is associated with continuation of ineffective or inappropriate therapy and with the overdiagnosis and excessive treatment of CIDP [36]. By contrast, there may be improvements in energy and well-being with immunomodulatory treatments that do not necessarily point to an effect on the disease itself; it can at times be difficult to stop treatment in these patients because of their misperception of efficacy. (See "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis", section on 'Diagnostic pitfalls'.)

We suggest assessing clinical improvement and disease activity using the results of a disability scale and a quantitative grip measure. These can be completed in less than five minutes and can be done by the patient at home.

●Validated measures of impairment include the Inflammatory Rasch-built Overall Disability Scale (I-RODS) [37,38], the Overall Neuropathy Limitations Scale (ONLS) (table 1) [39], and the Inflammatory Neuropathy Cause and Treatment Disability Scale (INCAT) [6]. These measures have been shown to correlate with clinical disease activity [40-42].

●Portable devices assessing grip strength dynamometry can provide quantitative grip measures (eg, Jamar or Vigorimeter dynamometer) [9,40,43-45]. The Jamar and Vigorimeter grip devices are relatively inexpensive (<$500 USD).

Additional objective measures to assist in monitoring disease activity and treatment effect include the Timed Up and Go (TUG) test [46], the 10-meter walking test [11], and the Medical Research Council (MRC) sum score [47]. MRC sum score is the summation of MRC grades (0 to 5) given for the following muscle groups (upper arm abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and foot dorsiflexors) and can range from 0 to 60.

Ultimately, the value of any treatment should include whether the treatment has clinically made a meaningful change. A clinically meaningful change (CMC) threshold has been determined for clinical trials for some of these outcome measures:

●I-RODS >4 points in 48-point scale

●INCAT >1 point

●Grip strength >8 kilopascals or >1.2 pounds/inch²

●MRC sum score >3 points

The role of electrodiagnostic studies — Under most circumstances, we do not use repeat electrodiagnostic studies to guide treatment decisions.

Testing may be useful in some patients who do not improve clinically in order to assess whether a specific deficit is from prior axon loss or ongoing demyelination. Some clinical deficits due to severe axonal loss may be fixed and unresponsive to immunotherapy. In such patients, the treatment goal may be stabilization of disease rather than rapid improvement, although slow improvement over time related to axonal regeneration is possible. It is important for the clinician and patient to be as clear as possible on what is likely to respond and the anticipated timing of the response.

Some institutions have used summed scores of the compound muscle action potential (CMAP) amplitudes for the motor nerves in the arm and leg to monitor disease activity [48]. We have not found that to be useful in practice.

MANAGING ONGOING THERAPY — The goal for patients with CIDP whose clinical symptoms have stabilized is to promote sustained remission of disease activity.

●Some patients will not respond adequately to initial therapy and may benefit from a different therapy or escalation of treatment.

●Patients who respond to initial therapy may transition to maintenance therapies.

●A small portion of patients (<20 percent) who respond to the initial therapy (treatment until improvement is complete, with slow taper after that) may need no further treatment. However, most patients will relapse either during the taper or after taper is complete.

Inadequate response to initial therapy — If symptoms do not improve or continue to progress after an initial two-to-three-month treatment trial, the patient should be reevaluated to verify the diagnosis of CIDP. (See "Chronic inflammatory demyelinating polyneuropathy: Etiology, clinical features, and diagnosis".)

For patients with CIDP who are nonresponders, a different therapy should be substituted. For those who respond suboptimally to initial therapy, an escalated dose or different therapy should be substituted. As an example, failure to respond to intravenous immune globulin (IVIG) might trigger intervention with plasma exchange and/or immunosuppression with glucocorticoids.

In one series of 67 patients with CIDP, 26 did not respond to initial therapy [23]. Of these, benefit from an alternative treatment was observed in nine (35 percent). For 11 patients who required a third alternative treatment, benefit was observed in three (27 percent).

Managing and preventing relapse — For patients who relapse (during taper or after stopping therapy) after responding to initial therapy, we suggest escalating or repeating the initially successful treatment modality. The timing and dose of ongoing intermittent treatments should be titrated to avoid relapses; this becomes maintenance therapy. Patients treated with IVIG or plasma exchange may require repeated treatment at intervals that typically range from two to six weeks. (See 'Intravenous immune globulin' above and 'Plasma exchange' above.)

If intermittent therapies are insufficient to avoid relapse and/or cannot be tapered, treatment with glucocorticoids may improve the rate of sustained remission. (See 'Maintenance glucocorticoids' below.)

Specific treatment options

Maintenance IVIG — For patients who respond well to initial treatment and remain clinically stable, the maintenance dose of intravenous immune globulin (IVIG) can be tapered to 1 g/kg, or as low as 0.4 g/kg per dose, given over one to two days. The taper of IVIG dose and/or frequency should be adjusted so that the patient does not deteriorate between doses. We favor tapering the IVIG dose and/or frequency rather than stopping it abruptly. In the PATH study, some of the patients who stopped IVIG did not return back to baseline even after reinstituting treatment [49].

While IVIG therapy can usually control CIDP, most patients require repeated expensive treatments every two to six weeks often for many years; IVIG monotherapy does not usually lead to remission. In a 20-year review of 95 patients treated with IVIG for CIDP, more than 75 percent of the patients improved initially [50]. However, of those who improved, over 85 percent required repeated treatment; fewer than 15 percent were able to discontinue treatment at a mean of 3.5 years and median of 2.1 years. Severity at onset and residual deficit were negative predictors of discontinuation. Maintenance IVIG may be continued in patients who continue to respond and are stable with treatment. When tapering of IVIG leads to worsening of the neuropathy, a long-term immunosuppressant can be used as an alternative.

Subcutaneous immune globulin — As an alternative to maintenance IVIG, subcutaneous immune globulin (SCIG) therapy may be used as maintenance therapy for patients with CIDP who respond to IVIG treatment [51,52]. SCIG may be preferred by patients with poor venous access or who live distant from an infusion center. Observational data suggest that SCIG may be better tolerated than IVIG with a reduction in adverse effects including headache and nausea [53,54]. In addition, thrombotic complications seen with IVIG have rarely been seen with SCIG. Although IVIG and SCIG have not been directly compared in clinical trials, they are considered to be similarly effective. SCIG is not approved for use as initial therapy in CIDP.

The PATH trial enrolled 172 adults with CIDP who responded to and were dependent upon IVIG [51]. Subjects were randomly assigned in a 1:1:1 ratio to weekly maintenance treatment with low-dose SCIG (20% solution at 0.2 g/kg), high-dose SCIG (20% solution at 0.4 g/kg), or placebo. At 24 weeks, both doses of SCIG were superior to placebo for reducing the composite risk of a CIDP relapse or withdrawal from the trial for reason other than relapse. Compared with placebo, the absolute risk reduction with low-dose SCIG was 25 percent (95% CI 6-41) and with high-dose SCIG was 30 percent (95% CI 12-46). Adverse events were generally unrelated to SCIG treatment with the exception of one patient who developed an allergic skin reaction.

The administration and dosing of SCIG are reviewed in detail separately. (See "Subcutaneous and intramuscular immune globulin therapy", section on 'Administration and dosing of SCIG'.)

Maintenance glucocorticoids — For most patients who experience ongoing relapses with IVIG or other maintenance therapy, we suggest starting glucocorticoids. Clinical experience and some studies suggest that glucocorticoid therapy is more likely to produce a clinical remission than either IVIG or plasma exchange. (See 'Glucocorticoids' above.)

Selection among multiple dosing regimens using either oral or intravenous glucocorticoids depends on severity of symptoms, response to treatment and weaning, and patient preference.

●Treatment regimens, duration, and tapering – A glucocorticoid course of up to eight weeks may be required to decide whether there is a treatment response [2]. The maximum benefit of glucocorticoid therapy in these studies was seen after one to six months of treatment [8]. However, relapses were common, particularly when tapering the dose [28]. How fast to taper and when to taper also depend on a variety of factors.

•Oral – We typically start prednisone at 1 to 1.5 mg/kg daily (usually around 50 to 80 mg daily; no more than 100 mg). The dose is then titrated according to clinical response. Patients who have a good response can begin dose tapering after one to three months.

Glucocorticoid tapering can be done in many ways as a daily or every-other-day regimen. The dose can be tapered by 5 to 10 mg every two to four weeks in clinically stable patients. As an example, with the every-other-day tapering regimen starting from prednisone 80 mg daily:

-Begin with 80 mg alternating with 60 mg for one month, then

-80 mg alternating with 40 mg for one month, then

-80 mg alternating with 0 mg, then

-Taper the every-other-day daily dose by 10 mg each month until 30 mg every other day (or 15 mg daily)

We suggest slowing down the rate of the taper to 5 mg monthly once a dose of 30 mg every other day is reached. It is usually necessary to go back up to a higher dose by at least 10 to 20 mg if symptoms recur during the taper.

Alternatively, pulsed oral steroids at the initial therapeutic dose may be used and tapered every three to four weeks. (See 'Glucocorticoids' above.)

•Intravenous – Limited evidence suggests that weekly pulse methylprednisolone (500 mg once a week) is also an effective option for long-term treatment of CIDP [25,34]. Tapering is accomplished by slowly decreasing the frequency of dosing to once every 2 to 12 weeks. As with oral glucocorticoid therapy, there is no standard regimen for pulse intravenous glucocorticoids.

Alternative therapies — Alternative immunosuppressive agents are employed when glucocorticoids are contraindicated or are considered too risky or as steroid-sparing agents. However, the effectiveness of these drugs for CIDP is based on anecdotal reports and small series rather than placebo-controlled trials [55]. They may be useful in patients who do not respond to initial therapy as well as for patients who are refractory to alternative maintenance regimens. (See 'Patients with refractory disease' below.)

The list of immune-modulator drugs that have been used to treat CIDP includes the following:

●Azathioprine [29,30,56-58]

●Cyclophosphamide [30,59-63]

●Cyclosporine [64-67]

●Etanercept [68]

●Interferon alpha-2a [69,70]

●Interferon beta-1a [71,72]

●Mycophenolate mofetil [73-75]

●Methotrexate [76-78]

●Rituximab [79-84]

●Tacrolimus [85]

●Autologous hematopoietic stem cell transplantation [86,87]

Azathioprine and cyclophosphamide have probably been the most commonly used drugs for CIDP from this list. Azathioprine is generally used as a steroid-sparing medication or reserved for patients with mild disease; a therapeutic response may take over six months. An alternative is mycophenolate mofetil, and clinical improvement with this agent may also take a long time.

While many of these agents remain promising, evidence from larger clinical trials is needed to determine whether they are effective for CIDP. Of note, a small randomized placebo-controlled trial in patients with CIDP requiring IVIG or glucocorticoids found no significant benefit for oral methotrexate (15 mg weekly) on any of the primary or secondary outcome measures [77]. However, there was a remarkably high placebo effect, suggesting that the design of the trial may have contributed to the inability to find benefit from the drug. Thus, the role of methotrexate in CIDP remains unproven.

In the rare circumstance that plasma exchange is the only effective therapy, it can be used chronically. However, the treatment brings with it the added risks of sepsis and clotting due to the risk of indwelling catheters.

PATIENTS IN REMISSION — In general, the treatment should be continued until improvement is complete and patients have stabilized (with possible residual deficits). At that point, the treatment can either be tapered or stopped, and clinical surveillance for resurgence of disease activity should continue periodically for several years.

In many cases, appropriate treatment of CIDP with intravenous immune globulin or glucocorticoids leads to improvement or remission within a few months of starting therapy; approximately 30 percent of patients will achieve cure (five years or greater stability off treatment) or remission [35,88,89]. Reinstitution of treatment with therapy that had been effective is indicated if the disease becomes active.

PATIENTS WITH REFRACTORY DISEASE — For patients with severe CIDP (eg, unstable active disease with a progressive or relapsing course) who are refractory to treatment with intravenous immune globulin (IVIG), glucocorticoids, and plasma exchange, alternative immunosuppressant treatment options include cyclosporine, methotrexate, azathioprine, mycophenolate, and cyclophosphamide (see 'Alternative therapies' above). The choice among these is dependent on a number of factors that include the comfort level of the treating center and clinician with specific agents, side effect profiles of the alternative treatments, disease severity, age and sex of patient, and concurrent medical conditions.

We recommend that patients who are refractory to initial treatment be evaluated at a center with particular expertise in CIDP. The GBS/CIPD Foundation International has a number of designated Centers of Excellence that are available for consultation.

●Cyclosporine – For patients with moderately severe disease, our preferred alternative treatment is cyclosporine, which appeared effective in one case series of patients with refractory CIDP [66]. Keeping plasma trough levels between 100 and 150 ng/mL may help ensure a therapeutic response [66,67]. Improvement with cyclosporine therapy may occur within three months. However, the side effect profile for cyclosporine is greater than for the other agents. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Side effects'.)

●Methotrexate – Another alternative treatment for patients with no contraindications is oral methotrexate (7.5 to 15 mg once a week). Methotrexate was not beneficial for CIDP in a small placebo-controlled randomized trial but the trial had many limitations [77], and methotrexate has appeared to benefit some patients with refractory CIDP [76,78]. It is unclear whether a response to methotrexate occurs within three or four months or takes longer. We suggest at least a four-month trial, if the clinical condition allows.

Patients treated with methotrexate should receive folic acid 1 mg daily, or leucovorin 2.5 mg weekly, to prevent hematologic and other side effects. (See "Therapeutic use and toxicity of high-dose methotrexate", section on 'Overview of adverse effects'.)

●Rituximab – Rituximab appears to be effective in patients with refractory CIDP. Additionally, patients with CIDP associated with IgG4 antibodies to neurofascin or contactin may be refractory to IVIG and glucocorticoids but responsive to rituximab [90-92]. Some data also suggest that patients with nodal and paranodal antibodies or hematologic malignancies have a more robust response to treatment [92,93]. Even though this needs further study, rituximab remains a consideration in patients with refractory CIDP. We would consider its use prior to using more aggressive treatments discussed below. (See "Rituximab: Principles of use and adverse effects in rheumatoid arthritis", section on 'Adverse effects'.)

●Cyclophosphamide – Pulse intravenous (IV) cyclophosphamide can be effective for patients with severe refractory disease and can lead to long-term remission [30,59,60,62,63]. The usual dosing is 1000 mg/m² infused monthly for six months. Alternatively, very high-dose (eg, 50 mg/kg administered over one-hour IV for four days) cyclophosphamide regimen may induce a remission of the disease. A systematic review concluded that the available observational studies suggest that cyclophosphamide treatment may be beneficial [55]. These studies included IV pulse regimens and oral daily regimens of cyclophosphamide for patients who failed other therapies. Some of the responses were quite remarkable and sustained [63].

However, cyclophosphamide treatment is associated with potentially life-threatening side effects and should therefore be carefully considered and performed only at specialized centers. (See "General toxicity of cyclophosphamide in rheumatic diseases".)

●Autologous hematopoietic stem cell transplantation (AHSCT) – AHSCT has been used as a treatment of last resort for patients with CIDP that is refractory to other therapies, with reported benefit in some cases [86,87]. The main risk associated with AHSCT is infection related to immune suppression; therefore, caution is urged in considering this therapy. Whether AHSCT is more effective than a lower-dose cyclophosphamide regimen is not known. (See "Overview of infections following hematopoietic cell transplantation".)

SPECIAL CIRCUMSTANCES

Pregnancy — The treatment of CIDP in pregnancy is similar to that used for other patients [94]; additional considerations include the following:

●Glucocorticoids are frequently used in pregnancy and are considered safe for the fetus.

●Plasmapheresis is also considered safe for use in pregnancy, although not without potential complications. (See 'Plasma exchange' above.)

●Intravenous immune globulin (IVIG) is generally safe but is associated with potential side effects that might be of particular concern during pregnancy. (See 'Intravenous immune globulin' above.)

The choice among these therapeutic options should be coordinated with the obstetrician. The risks and benefits of these treatments appear to be finely balanced, and the decision is influenced by local availability, clinical expertise, and patient preferences.

Other immunosuppressant drugs discussed above are not recommended for use in pregnancy, particularly early in pregnancy. (See 'Alternative therapies' above.)

Acute infection — Patients with CIDP on chronic immunosuppressive therapy are at an elevated risk of infection. In CIDP patients with severe infection (eg, hospitalized or receiving parenteral antimicrobial therapy), we favor delaying immunosuppressive therapy until infection has come under control. Ideally, such decisions regarding the resumption of therapy are made in consultation with infectious disease specialists.

In general, glucocorticoid therapy should be continued throughout the infection to prevent adrenal insufficiency. (See "Pharmacologic use of glucocorticoids", section on 'HPA axis suppression'.)

Perioperative issues — No high-quality data or guidelines are available to guide management of CIDP treatment in the perioperative period. Patients with active disease are at risk for clinical worsening in the setting of perioperative systemic stress or exposure to neuromuscular-blocking anesthetic agents. Specific decisions for an individual patient with CIDP undergoing elective surgery are based on disease severity and medical comorbidities and should be planned with the treating surgical team. General principles guiding these decisions include:

●For patients with severe or active disease, an escalated dose or timing of current CIDP therapy to pretreat patients prior to elective surgery may be useful.

●For patients stable on maintenance therapy, we try to reduce immunosuppressive doses prior to elective surgeries to reduce risks of infection and wound healing issues.

●We avoid neuromuscular-blocking agents in these patients. In one retrospective review of 17 patients with CIDP undergoing general anesthesia (including use of succinylcholine in 5 cases and nondepolarizing muscle relaxants in 11 cases), two patients required postoperative mechanical ventilation and three others had clinical worsening [95].

The medical management of glucocorticoids during the perioperative period is discussed separately. (See "The management of the surgical patient taking glucocorticoids".)

PROGNOSIS — Data are limited regarding the long-term prognosis of CIDP. Approximately two-thirds of patients with CIDP will initially respond to any single standard therapy (intravenous immune globulin [IVIG], glucocorticoid, and plasma exchange), while approximately 10 to 15 percent of patients are resistant to all of these [88,89]. Approximately 30 percent of patients with CIDP will achieve cure or remission.

A study of 38 Japanese patients with CIDP assessed functional status at five-year follow-up. Patients had been treated with various regimens, including glucocorticoids (89 percent), IVIG (45 percent), and plasma exchange (34 percent). Complete remission was reported in 10 patients (26 percent), partial remission in 23 (61 percent), and ongoing relapses or severe disability in 5 (13 percent). In the partial remission group, there were 13 patients who had stopped immune-modulating treatments, and 10 patients who required intermittent or continuous therapy, mainly glucocorticoids [96].

In a retrospective review of 106 patients with a consensus diagnosis of CIDP and a mean follow-up of 6.4 years who were blindly classified by experts using the CIDP Disease Activity Status (CDAS), the proportion of patients in each category was as follows (table 2) [88]:

●Cure (five or more years off treatment): 11 percent

●Remission (less than five years off treatment): 20 percent

●Stable active disease (one or more years on treatment): 44 percent

●Improving (three months to less than one year on treatment): 7 percent

●Unstable active disease: 18 percent

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neuropathy".)

SUMMARY AND RECOMMENDATIONS

●Early, effective treatment is important in chronic inflammatory demyelinating polyneuropathy (CIDP) in order to stop the immune attack against the myelin sheath of peripheral nerves so that secondary axonal degeneration and long-term disability is minimized. (See 'Goals and course of treatment' above.)

●For treatment-naïve patients with CIDP who are more than mildly affected or for mildly affected patients who are rapidly worsening, we recommend initial immune-modulatory treatment using either intravenous immune globulin (IVIG), plasma exchange, or glucocorticoids (Grade 1B). Each is an effective treatment. (See 'Intravenous immune globulin' above and 'Plasma exchange' above and 'Glucocorticoids' above.)

•When rapid response is desired, we suggest initial treatment with IVIG (if available) (Grade 2C). IVIG is usually easier to administer than plasma exchange; both plasma exchange and IVIG may have a more rapid response than with glucocorticoids.

•For patients with more insidious CIDP, we suggest initial treatment with glucocorticoids (Grade 2C). In these patients, a rapid treatment response may be less critical, and glucocorticoids appear to be more effective at achieving long-term remission. We prefer the use of pulse glucocorticoids, either oral or intravenous, rather than daily prednisone, for initiation and titration of dosing.

●The success or failure of a treatment regimen should be judged using objective methods using the results of a disability scale and a quantitative grip measure both before and during treatment to quantify clinical changes. (See 'Assessing response to therapy' above.)

●For patients who fail to respond to the initial mode of therapy or respond suboptimally, an escalated dose or different therapy should be substituted. For patients who relapse (during taper or after stopping therapy) after responding to initial therapy, the initially successful treatment modality is repeated or escalated. (See 'Inadequate response to initial therapy' above and 'Managing and preventing relapse' above.)

For most patients who experience ongoing relapses with IVIG or other maintenance therapy, we suggest starting glucocorticoids (Grade 2C). Glucocorticoid therapy is more likely to produce a clinical remission than either IVIG or plasma exchange. Other immunosuppressants may be an alternative but have been less well studied in patients with CIDP. (See 'Maintenance glucocorticoids' above.)

●The prognosis of CIDP is generally favorable, but data are limited. Approximately 30 percent of patients achieve cure or remission, while approximately 18 percent have unstable active disease with a progressive or relapsing course. (See 'Prognosis' above.)