Subcutaneous IVIG for Chronic Inflammatory Demyelinating Polyneuropathy

Abstract & Commentary

By Michael Rubin, MD

Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Rubin reports no financial relationships relevant to this field of study.

Synopsis: Compared to intravenous immunoglobulin, subcutaneous administration of immunoglobulin appears to have equal efficacy with more patient convenience.

Source: Markvardsen LH, et al. Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol 2013; Jan. 7, 2013. DOI: 10.1111/ene.12080; [Epub ahead of print].

Is the subcutaneous administration of immunoglobulin (SCIG) as safe and effective as intravenous immunoglobulin (IVIG) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as it is for multifocal motor neuropathy and primary immune disorders? To answer this question, 30 IVIG-responding, CIDP patients were recruited for a randomized, double-blind, placebo-controlled trial to receive subcutaneous injections, 2-3 times weekly for 12 weeks, of either their prestudy IVIG dose or saline. Injection volume was never more than 20 mL per injection site, and patients received anywhere from 30-300 mL per week, over 30-120 minutes per infusion period. All patients had previously received IVIG every 3-10 weeks. Exclusionary criteria included age younger than 18 years or older than 80 years, malignancy, pregnancy, coagulopathy, or drug allergy. No patient had previously received SCIG. Muscle strength, measured by the same neurologist and performed by isokinetic dynamometry using four pre-selected muscle groups individualized to each patient’s weakness, was the primary endpoint, with secondary endpoints encompassing muscle strength of nine bilateral muscle groups using a modified Medical Research Council (MRC) scale and a grip strength test averaged over three attempts for each hand. Patients were evaluated 2 weeks pre-study initiation, at study initiation, and at 10 and 12 weeks. At the first and last evaluation, additional measurements obtained included an Overall Disability Sum Score (ODSS), grading arm and leg disability on a scale of 0 (normal) to 12 (total disability), a nine-hole-peg test (9-HPT), and a 40-m-walking test (40-MWT). Statistical analysis included the paired and unpaired t-test, with significance achieved at P < 0.5.

Of 40 patients screened, 30 fulfilled entry criteria and 29 were allocated to treatment, 14 to SCIG and 15 to saline, with one patient withdrawing prior to informed consent. Both groups were comparable with respect to duration of CIDP, weekly immunoglobulin dose, degree of disability, MRC score, grip and isokinetic strength, and functionality as measured by 9-HPT and 40-MWT. Compared to the saline group, which deteriorated over the course of the 12-week study, SCIG treatment resulted in significant improvement of all parameters except for 9-HPT, including ODSS, isokinetic strength, MRC and grip strength, and 40-MWT. Redness at the injection site was reported in six SCIG and two saline-treated patients, with rash and itching in two and one SCIG patients, respectively. No patient reported any generalized symptoms. At study end, when asked which was preferred, 20 of 29 enrollees stated a preference for SCIG over IVIG due to improved flexibility with daily life, enhanced strength stability, milder side effects, and shorter infusion times. SCIG appears to be a safe, efficacious, and attractive alternative to IVIG for the treatment of CIDP.


SCIG may be as effective as IVIG, with improved patient convenience and lower cost, but its mechanism of absorption is incompletely understood. Uptake through blood and lymphatic capillaries, transport through the extracellular matrix, and pre-systemic elimination influence its absorption, which is also impacted by the anatomic site of injection. Rat studies investigating the slow subcutaneous infusion of rituximab suggest that in addition to the site and dose of injection, neonatal Fc receptor-mediated transport is also a major determinant of subcutaneous absorption of monoclonal antibodies.1


  1. Kagan L, Mager DE. Mechanisms of subcutaneous absorption of rituximab in rats. Drug Metab Dispos 2013;41:248-255.