Subcutaneous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy

Abstract & Commentary

By Norman Latov, MD, PhD, Professor of Neurology and Neuroscience, Department of Neurology and the Brain and Mind Research Institute, Weill Cornell Medical College. Dr. Latov has served a consultant to Grifols, Novartis, CSL Behring, Baxter Biotherapeutics, and Merck, and owns stock in Therapath LLC.

Synopsis: Subcutaneous immunoglobulin appears to be an effective treatment alternative to intravenous immunoglobulin for patients with chronic inflammatory demyelinating polyneuropathy.

Source: Markvadsen LH, et al, for The Danish CIDP and MMN Study Group. Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy. Eur J Neurol 2013;20:836-842.

The authors of this study tested the efficacy of subcutaneous immunoglobulin (SCIG) as maintenance therapy in chronic inflammatory demyelinating polyneuropathy (CIDP). Twenty-nine patients on maintenance therapy with intravenous immunoglobulin (IVIG) for CIDP were randomized to either the same total dose of SCIG or to subcutaneous saline as placebo, administered once or twice weekly for 12 weeks. In the SCIG group, there was significant improvement compared to baseline in the isokinetic muscle strength (IKS), the primary outcome measure, as well as in several secondary outcome measures including the Overall Disability Sum Score, 40-M walking test, and grip strength. In the placebo group, the same outcome measures showed a decline. At the completion of the study, 20 of the 29 study subjects preferred subcutaneous infusions to IVIG due to increased flexibility, more stable muscle performance, milder side effects, and time saving. The authors conclude that SCIG treatment is a safe and effective alternative to IVIG in patients with CIDP.

Commentary

SCIG is administered weekly, and absorbed into the bloodstream more slowly than IVIG, with maximal serum concentrations achieved at 4-6 days, resulting in less variability in serum concentrations and lower trough levels. Given its tissue distribution, however, an additional 20-50% is required to deliver the same amount of immunoglobulin into the intravascular space.1,2 As such, SCIG treatment may be beneficial in patients whose symptoms worsen toward the end of the IVIG treatment cycle, although higher doses may be required in some patients with otherwise borderline therapeutic serum levels. Accordingly, in the current study, the SCIG-treated patients did better as a group compared to their baseline on IVIG therapy, although three of the 14 experienced a deterioration in their IKS score after switching from IVIG to the same dose of SCIG. As is the case with IVIG therapy,3 the dose of SCIG would require optimization in individual patients, based on the clinical response.

IVIG remains the preferred treatment for initiating therapy, as therapeutic levels can be reached more quickly by intravenous than subcutaneous administration. Furthermore, in a study of patients with Kawasaki disease, a single dose of 2 g/kg was superior to 0.4 g/kg over 5 days,4 suggesting that peak concentrations may also be a factor in the initial treatment response. Dyck et al, however, reported that slower induction with weekly infusions of 0.4 g/kg over 3 weeks was as effective as plasmapheresis in patients with CIDP.5

In addition to convenience, SCIG can be self-administered at home,6 potentially eliminating the need for home nursing care or infusion centers. The resulting cost savings would be considerable, providing further incentive for SCIG therapy.

References

1. Bonilla FA. Pharmacokinetics of immunoglobulin administered via intravenous or subcutaneous routes. Immunol Allergy Clin North Am 2008;28:803-819.

2. Berger M, et al. Pharmacokinetics of subcutaneous immunoglobulin and their use in dosing of replacement therapy in patients with primary immunodeficiencies. Clin Immunol 2011;139:133-141.

3. Rajabally YA, et al. Dose of intravenous immunoglobulins in chronic inflammatory demyelinating polyneuropathy. J Peripher Nerv Syst 2006;11:325-329.

4. Sato N, et al. Selective high dose gamma-globulin treatment in Kawasaki disease: Assessment of clinical aspects and cost effectiveness. Pediatr Int 1999;41:1-7.

5. Dyck PJ, et al. A plasma exchange versus immunoglobulin infusion trial in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol 1994;36:838-845.

6. Nicolay U, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunodeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin Immunol 2006;26:65-72.