Chronic inflammatory demyelinating polyneuropathy (CIDP) results in disability through immune-mediated nerve injury, which can lead to irreversible deficits after the inflammatory component of CIDP is treated.
The for CIDP diagnosis and treatment from the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) strongly recommends initial treatment for both typical and variant CIDP forms with intravenous immunoglobulin (IVIG) or corticosteroids, followed by plasma exchange if that is ineffective. Some patients are refractory to initial treatments and may require a different approach.
Overall, relapses requiring additional treatment have been estimated to occur in 20% to 35% of people with CIDP, and CIDP-associated disability may be severe.
"Disability in CIDP is significant both in the short run and long term," said Richard Lewis, MD, of Cedars-Sinai Medical Center in Los Angeles.
"If treated early, long-term axonal damage and permanent disability can be avoided," Lewis stated. "Treatment decisions need to be based on the severity of the disability and how aggressive the disorder is."
Early treatment hinges on early diagnosis, and delayed diagnosis is very common in CIDP, noted Jeffrey Allen, MD, of the University of Minnesota in Minneapolis.
"The time from symptom onset to diagnosis of CIDP is 10 months or more for most patients," Allen said.
"There are many reasons that misdiagnosis and delayed diagnosis occur," he continued. "More common errors include failure to interpret nerve conduction studies correctly, an overreliance on mild or moderately elevated cerebrospinal fluid protein or using a test-of-treatment -- for example, response after starting IVIG -- as a diagnostic test and relying only on subjective perception of benefit."
CIDP variants, especially distal, multifocal, sensory, and motor CIDP, are especially challenging to diagnose accurately, Allen added.
Initial Treatment
Managing CIDP involves both addressing abnormal immune activity and managing residual symptoms. Initial CIDP treatment is guided by evidence-based therapies that escalate depending on the response, Lewis and Allen noted in a .
First-line treatments need to be personalized to find the ideal dose for a particular patient and determine whether long-term treatment is needed at all, they stated. Although many immunosuppressive agents may be used in patients who don't respond, all are unproven and the risk, cost, and unknown likelihood of benefit must be balanced, they added.
"There is no reliable disease activity biomarker that can be used to guide treatment -- a reality that makes it very challenging to optimize treatment to individual patient needs," Lewis and Allen pointed out.
The EAN/PNS treatment guideline calls for IVIG or corticosteroids as initial treatment in all CIDP types, with IVIG as the first-line treatment in motor CIDP. The choice of IVIG versus corticosteroid treatment is rooted in patient considerations, the guideline authors noted.
IVIG induction treatment is typically a total dose of 2 g/kg, divided over 2 to 5 days. Two to five repeated doses of 1 g/kg IVIG every 3 weeks may be needed in some patients before improvement or ineffectiveness can be determined.
Observational studies and clinical experience strongly suggest that corticosteroids are effective in CIDP, the guideline authors wrote. The best corticosteroid regimen is not known, and pulsed high-dose corticosteroid treatment with oral dexamethasone or IV methylprednisolone may be considered as an alternative to daily oral prednisone/prednisolone or dexamethasone, they added. Treatment response usually starts after several weeks or months, and a dose reduction of corticosteroids should be attempted regularly to minimize doses and determine whether a patient is in remission.
If IVIG or corticosteroids are ineffective, the EAN/PNS guideline strongly recommends plasma exchange, using peripheral veins if possible. "Plasma exchange requires good vascular access and specialized equipment," the guideline authors noted. "These drawbacks make plasma exchange, despite its effectiveness and relative safety, the third option for chronic treatment after corticosteroids and IVIG."
Maintenance Treatment
Corticosteroids, IVIG, and plasma exchange are also used as maintenance therapies to help prevent relapses.
"Although up to 30% of CIDP patients can go into remission off treatment, only about 10% can remain off treatment for 5 years," Lewis said. "Tapering treatments can be done but must be weighed over risk for relapse."
In 2018, the study showed benefit for subcutaneous immunoglobulin (SCIG) as maintenance treatment, leading to the of SCIG (Hizentra) in CIDP.
In 2024, (Hyqvia) became another maintenance treatment option. In the phase III trial, facilitated SCIG led to a CIDP relapse rate of 9.7% versus 31.5% with placebo (difference -21.8%, P=0.0045). Like other immunoglobulin products, facilitated SCIG contains a for thrombosis. The treatment also is approved for primary immunodeficiency.
Maintenance CIDP treatment may be required with other therapies if IVIG, SCIG, plasma exchange, or corticosteroids are ineffective or require problematically high doses. used in the maintenance role include azathioprine and cyclophosphamide, among others.
EAN/PNS guidance about other agents includes a weak recommendation against methotrexate or fingolimod (Gilenya) and a strong recommendation against interferon beta-1a. Guideline authors also cited significant morbidities and mortality risk for hematopoietic stem cell transplantation and concluded it should be considered only as a last-resort option in specialized CIDP centers.
The sparse evidence base for CIDP maintenance therapies has led to an ongoing search for alternative treatments. Efgartigimod combined with hyaluronidase (Vyvgart Hytrulo), a subcutaneous drug approved for myasthenia gravis, inhibits recycling of circulating immunoglobulin G and is one treatment being studied. The investigational agent riliprubart, a complement C1s inhibitor, is another. A comparing riliprubart and IVIG as maintenance CIDP therapy will be underway soon.
Disclosures
The 2021 EAN/PNS guideline task force was supported by the European Academy of Neurology, the Peripheral Nerve Society, the GBS/CIDP Foundation International, and the GAIN Charity U.K.
Lewis reported relationships with Argenx, CSL Behring, Sanofi, Grifols, Roche, Alexion, Boehringer Ingelheim, and Alnylam.
Allen reported relationships with Argenx, CSL Behring, Takeda, Grifols, and Alexion.