CIDP Has a Complex Pathophysiology and Path to Diagnosis

March 31, 2021
Joanna Lewis, PharmD, MBA

Joanna Lewis graduated from MUSC in 2007. Since then, she has held a variety of pharmacy practice roles, most recently a leadership position in the Department of Pharmacy at Duke University Hospital. Some of her responsibilities included medication safety, quality improvement, oversight of the financial charge capture process, and coordinating the implementation of a new technology system. She is passionate about precepting and mentoring new practitioners, as well as making the practice of pharmacy better.

Health-System Edition, Health-System Edition March 2021, Volume 10, Issue 3

Early recognition and treatment, along with a coordinated approach and multidisciplinary team, are important to limit disease progression.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a form of peripheral neuropathy thought to have autoimmune origins.1,2

CIDP is considered the most common treatable neuropathy worldwide, but it is still a rare disease. Approximately 30,000 individuals in the United States have CIDP. Although it can be difficult to recognize, early diagnosis is important to prevent long-term nerve damage or permanent disability in patients.

The classic presentation of CIDP is symmetrical weakness in both distal and proximal muscles that progressively increases for a period of more than 2 months.2,3

CIDP also has electrophysiological or pathological evidence of peripheral nerve demyelination and responds to immunosuppressive or immune-modulating treatments. CIDP has been referred to as the chronic equivalent of Guillain-Barre syndrome because their clinical presentations are similar, according tot he European Federation of Neurological Societies and Peripheral Nerve Society.3

CIDP presents with symptoms of distal or proximal limb weakness, fatigue, numbness, and/or pain.4-6 Although CIDP is caused by the body attacking the myelin sheath around the nerve, what causes that to happen is unclear. CIDP can occur at any time throughout life, but it is most often in the sixth or seventh decade, with men being twice as likely as women to develop the condition.4,5 No clear genetic or predisposing factors have been identified.

TREATMENT

Treatment requires individual strategies focused on increasing mobility, reversing sensory loss, and maintaining remission. Considerations for therapy include adverse effects, availability, comorbid conditions, cost, severity of the disease, and venous access. First-line therapy usually consists of corticosteroids, immunoglobulins, and plasma exchange.4,6 Of the first-line therapies, intravenous (IV) immunoglobulins (IVIg) are the most extensively studied, with their effects thought to be a result of reducing proinflammatory responses responses by upregulating FcγRIIB on effector macophages. When immunoglobulins are used, up to 75% of patients will improve, and up to one-third will experience a cure or remission.4

When choosing IVIg, the typical dose is a 2.0-g/kg loading dose, followed by a 1.0-g/kg maintenance dose every 3 to 4 weeks.6 Guidelines recommend titrating the maintenance dose and frequency based on individual needs.3,4 There are 4 IG therapies approved for CIDP: 3 intravenous and 1 subcutaneous.

The IVIg product Gamunex-C holds an FDA-approved indication for CIDP based on a trial showing improvement of certain motor symptoms as measured by the standard Inflammatory Neuropathy Cause and Treatment (INCAT) scale for up to 48 weeks following initial treatment compared with a placebo.7,8 Privigen gained FDA approval in 2017 for adults with CIDP to improve neuromuscular disability. The approval was based on results from 2 phase 3 studies that showed improvement on the INCAT scale: at 13 weeks, the Polyneuropathy and Treatment with Hizentra (PATH) trial; and at 25 weeks, the PRIMA trial.9,10

A subcutaneous immune globulin (SCIg), Hizentra received FDA approval in 2018 based on data from the PATH study that showed CIDP relapse or withdrawal for any reason was significantly lower with high- or low-dose Hizentra than the placebo: 38.6% with low-dose (0.2 g/kg weekly) and 32.8% with high-dose (0.4 g/kg weekly) Hizentra than with the placebo (63.2%).10

Most recently, the FDA approved Pfizer's immunoglobulin Panzyga (immune globulin intravenous [human] - ifas 10% liquid) for adults with CIDP.11 The approval was based on the findings of a prospective, double-blind, multicenter study (PROCID) that looked at 2 different maintenance dosages of 0.5 g/kg or 2 g/kg every 3 weeks compared with the standard maintenance dose of 1 g/kg every 3 weeks. These maintenance doses were all studied after a 2 g/kg loading dose. Results showed that at 24 weeks, 64.7%, 79.7%, and 91.7% were considered responders based on their INCAT scores in the 0.5, 1.0, and 2.0 groups.11,12

The most common adverse effects of IVIg include dermatitis, fever, headache, and increased blood pressure. Contraindications for IVIg are a history of severe systemic hypersensitivity reactions, such as anaphylaxis, to human immunoglobulin and for patients who are IgA-deficient with antibodies against IgA and history of hypersensitivity. IVIg also carries a black box warning of acute renal failure, renal dysfunction, and thrombosis.8-11

Research results show that up to 20% of patients become refractory to first-line CIDP therapy.13 Additional therapies to be considered if first-line therapy is not successful are other immunotherapies; antiepileptics, such as gabapentin; tricyclic antidepressants, such as amitriptyline; and other drugs often used to treat peripheral neuropathy, such as duloxetine (Cymbalta) or pregabalin (Lyrica). Several biologic response modifiers have also been considered for treating CIDP, including the monoclonal antibody alemtuzumab and interferon β-1a, which was effective for treatment-resistant CIDP in a placebo-controlled trial. In rare cases, a stem cell transplant may be warranted. Physical therapy also may help improve motor function.

CIDP can have a complex pathophysiology and path to diagnosis. Early recognition and treatment are important for limiting disease progression. Treatment requires a coordinated approach with a multidisciplinary care team, including pharmacists who can help guide treatment strategies by staying informed of the clinical research.

REFERENCES

1. Vallat JM, Sommer C, Magy L. Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition. Lancet Neurol. 2010;9(4):402-412. doi:10.1016/S1474-4422(10)70041-7

2. Gelinas D, Katz J, Nisbet P, England JD. Current practice patterns in CIDP: a cross-sectional survey of neurologists in the United States. J Neuro Sci. 2019;397:84-91. doi:10.1016/j.jns.2018.11.031

3. Van den Bergh PYK, Hadden RDM, Bouche P, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision. Eur J Neurol. 2010;17(3):356-363. doi:10.1111/j.1468-1331.2009.02930.x

4. Ryan M, Ryan SJ. Chronic inflammatory demyelinating polyneuropathy: considerations for diagnosis, management, and population health. Am J Manag Care. 2018;24(suppl 17):S371-S379.

5. Fisse AL, Motte J, Grüter T, Sgodzai M, Pitarokoili K, Gold R. Comprehensive approaches for diagnosis, monitoring and treatment of chronic inflammatory demyelinating polyneuropathy. Neurol Res Pract. 2020;2:42. doi:10.1186/s42466-020-00088-8

6. Köller H, Kieseier BC, Jander S, Hartung HP. Chronic inflammatory demyelinating polyneuropathy. N Engl J Med. 2005;352(13):1343-1356. doi:10.1056/NEJMra041347

7. Gamunex-C. Prescribing information. Grifols Therapeutics Inc; 2020. Accessed Feb 20, 2021. https://www.gamunex-c.com/documents/27482625/27482925/Gamunex-C+Prescribing+Information.pdf/9258bd0f-4205-47e1-ab80-540304c1ff8e

8. Hughes RAC, Donofrio P, Bril V, et al. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory de myelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008;7(2):136-144. doi:10.1016/S1474-4422(07)70329-0

9. Léger JM, De Bleecker JL, Sommer C, et al. Efficacy and safety o f Privigen in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, openlabel phase III study (the PRIMA study). J Peripher Nerv Syst. 2013;18(2):130-140. doi:10.1111/jns5.12017

10. van Schaik IN, van Geloven N, Bril V. Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (the PATH Study): study protocol for a randomized controlled trial. Trials. 2016;17(1):345. doi:10.1186/s13063-016-1466-2

11. Cornblath DR, Hartung HP, Katzberg HD, Merkies ISJ, van Doorn PA. A randomised, multi-centre phase III study of 3 different doses of intravenous immunoglobulin 10% in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ProCID trial): study design and protocol. J Peripher Nerv Syst. 2018;23(2):108-114. doi:10.1111/jns.12267

12. U.S. FDA approves PANZYGA for the treatment of adults with chronic inflammatory demyelinating polyneuropathy (CIDP). News release. Pfizer. February 12, 2021. Accessed February 21, 2021. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-panzygar-treatment-adults-chronic

13. Cocito D, Grimaldi S, Paolasso I, et al; Italian Network for C IDP Register. Immunosuppressive treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy. A nationwide retrospective analysis. Eur J Neurol. 2011;18(12):1417-1421. doi:10.1111/j.1468-1331.2011.03495.x

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