Per the 2021 updated European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), use of intravenous immunoglobulin (IVIg) is strongly recommended as initial treatment in typical CIDP and CIDP variants and should be considered as first-line treatment in motor CIDP (Good Practice Point). The usual total IVIg dose of 2 g/kg, divided over 2 to 5 days, is generally used for induction treatment, and two to five repeated doses of 1 g/kg IVIg every 3 weeks may be needed based on clinical responses to the initial treatment regimen. In the presence of end-of-dose deterioration before the next IVIg infusion, dose may need to be increased, or infusion interval may be shortened. [1]
For maintenance therapy, either IVIg or subcutaneous immunoglobulin (SCIg) are recommended, with no preference for one route over the other. While the most optimal dosing regimen for IVIg maintenance is not well-established, a dose of 1 g/kg every 3 weeks has been most commonly reported in clinical trials. Regardless, clinical practice should consider lower doses and longer treatment intervals maintaining maximal sustained improvement (e.g., 0.4-1 g/kg every 2-6 weeks). When switching patients from IVIg to SCIg, clinicians may start with the same mean dose (1:1) per week and adjust doses based on reliable outcome measures. Compared to IVIg, subcutaneous administration renders additional benefits of self-treatment at home, avoidance of intravenous cannulation, and possibly fewer systemic side effects; however, SCIg (subcutaneous swelling and pain) may lead to more local side effects and more frequent infusions, especially when a high-dose (>20-30 g/infusion) is required. [1]
A 2021 review discusses various treatment options for CIDP, including use of IVIg. Due to historical use and clinical data, including a Cochrane meta-analysis, the authors consider IVIg as a first-line treatment unless there is a contraindication. However, there is no agreement upon dosing or frequency for all CIDP patients, and the dose should be individualized per patient. Patients with severe and rapid conditions should receive more aggressive and higher doses compared to milder, slowly progressive cases. A common dosing schedule is every 3 to 4 weeks, but the amount needed may vary. Patients will require periodic monitoring by a neuromuscular physician to assist in individualized treatment. Based on early data, the authors typically initiated with a loading dose of 2 g/kg over 5 days, then 0.4 g/kg per week in severe cases. Milder cases may be exempt from the loading dose and only require 0.4 g/kg every other week. Adverse events from clinical studies suggest a risk of headaches, dermatological eruptions, and serious thromboembolic events. Therefore, use is cautioned in patients with cardiovascular conditions or history like recent thromboembolic events. Patients may receive pretreatment with antihistamines, corticosteroids, or NSAIDs to reduce risk of allergic reactions or headache. Periodic renal function monitoring may be considered for patients at risk (i.e., older age, diabetes, prior history of renal injury). When possible, low-osmolality formulations should be used as sucrose can worsen renal injury, and glucose can lead to hyperglycemia. [2]
A 2017 Cochrane overview summarized the evidence from Cochrane and non-Cochrane systematic reviews of any treatment for CIDP, including IVIg, and provided comparisons among different interventions. Compared to placebo, a 2013 Cochrane meta-analysis found more participants had improved after IVIg (78 out of 141; 53%) than after placebo (30 out of 28; 23%) based on 5 randomized trials involving 235 participants (risk ratio [RR] 2.40, 95% confidence interval [CI] 1.72 to 3.36), corresponding to a number needed to treat for an additional beneficial outcome of 3.03 (95% CI 2.33 to 4.55; high-quality evidence). Only one 2008 trial (N= 117) reported long-term disability outcome based on Inflammatory Neuropathy Cause and Treatment (INCAT) disability score at 24 weeks, observing mean improvement from baseline disability of 1.1 ± 1.8 and 0.3 ± 1.3 with IVIg and placebo, respectively (mean difference 0.8, 95% CI 0.23 to 1.37). Additionally, use of IVIg was associated with a higher risk of adverse events, such as headache, nausea, chills, and fever compared to placebo (49% vs. 18%; RR 2.62, 95% CI 1.81 to 3.78). No significant difference was noted in the incidence of serious adverse events. [3], [4]
Comparative data to corticosteroids or plasma exchange appeared to be less robust. Results from individual trials generally reported no significant differences between IVIg and oral prednisolone, IV methylprednisolone, prednisone, or plasma exchange in short-term improvement of impairment or disability, while one 2012 study reported less treatment discontinuation in IVIg group than intravenous methylprednisolone group (13% vs. 52%; RR 0.54, 95% CI 0.34 to 0.87). However, corticosteroids are generally more widely available, cheaper, and easier to use than IVIg. Future trials are needed to investigate the long-term benefits and cost-effectiveness of IVIg and other interventions. [3]
A 2017 meta-analysis compared the efficacy and safety of IV versus subcutaneous (SC) immune globulin for management of inflammatory demyelinating polyneuropathies. Patients with CIDP and/or multifocal motor neuropathy (MMN) were included with muscle strength assessed using the Medical Research Council sum score (MRC-SS). The effect size (ES) was used to measure the raw mean difference between the two formulations. A total of 8 studies (N= 138) were included in the meta-analysis, which found no significant difference in muscle strength outcome in patients with CIDP (ES 0.84; 95% CI -0.01 to 1.69). However, SCIg reported a 28% reduction in relative risk for moderate and/or systemic adverse events compared to IVIg (95% CI 0.11 to 0.76). Based on these findings, efficacy appears to be similar with SCIg conferring a greater safety profile. However, other measurements of muscle strength were excluded from the analysis, and the range of examined muscles varied between studies. Follow-up varied between 3.5 to 24 months, and the majority of patients were switched from IVIg to SCIg. [5]