Intravenous versus subcutaneous immunoglobulin – Authors' reply

We thank Ravi Uniyal and colleagues for their comments on our results from the PATH trial1van Schaik IN Bril V van Geloven N et al.Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Neurol. 2018; 17: 35-47Summary Full Text Full Text PDF PubMed Scopus (163) Google Scholar on subcutaneous immunoglobulin (SCIg) for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). They express concern about the relapse rates in the treatment groups and hypothesise the cause being the pharmacokinetics of SCIg. CIDP is a disease with a relapsing-remitting or progressive course. A patient with CIDP has an intrinsic chance of relapsing and treatment will reduce this chance. In the ICE trial (intravenous immune globulin [10% caprylate-chromatography purified] for the treatment of CIPD),2Hughes RA Donofrio P Bril V et al.Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial.Lancet Neurol. 2008; 7: 136-144Summary Full Text Full Text PDF PubMed Scopus (517) Google Scholar the absolute risk reduction for relapse with intravenous immunoglobulin (IVIg) versus placebo was about 29% during the second period (randomised withdrawal phase). Relapse rate with IVIg was 13% and with placebo was 42%. In a sensitivity analysis of the PATH trial (the best comparison with the ICE trial), the absolute risk reduction was 23% for the lower dose (0·2 g/kg/week) and 37% for the higher dose (0·4 g/kg/week). The higher dose is the highest absolute risk reduction in a randomised controlled trial of CIDP and we cannot conclude that the relapse rates in PATH trial are of concern. All patients had similar baseline IgG concentrations after IVIg treatment and before random allocation to SCIg or placebo. IgG trough concentrations in patients receiving the lower SCIg dose were nearly stable throughout the study, whereas those receiving the higher SCIg dose showed an increase of 4 g/L (appendix). This pattern was observed in patients who relapsed and in those who did not, implicating factors other than IgG concentrations. With the use of serum IgG data from all patients entering the restabilisation phase in the PATH trial, bioavailability of SCIg was estimated to be approximately 82%. Compared with 1 g/kg/3 weeks IVIg treatment (area under the curve [AUC] 0–21 days 431·1 g*L/day), exposure was equivalent with 0·4g/kg/week SCIg (AUC 0–21 days 451·3 g*L/day) and about 20% lower with 0·2g/kg/week SCIg (AUC 0–21 days 358·4 g*L/day). Both SCIg doses prevented CIDP relapse compared with recommended IVIg regimens. IVIg dose in CIDP should be individualised; similarly, the choice of SCIg dose should be based on patients' individual needs. INvS chairs a steering committee for CSL Behring and received departmental honoraria for serving on scientific advisory boards for CSL Behring and Baxter. He received departmental research support from The Netherlands Organization for Scientific Research and from the Dutch Prinses Beatrix Fonds. All lecturing and consulting fees for INvS were donated to the Stichting Klinische Neurologie, a local foundation that supports research in the field of neurological disorders. INvS serves on the editorial board of the Cochrane Neuromuscular Disease Group, is a member of the organising committee of the Inflammatory Neuropathy Consortium, a standing committee of the Peripheral Nerve Society, and is a member of the Scientific Board of the Kreuth III meeting on the optimal use of plasma-derived medicinal products, especially coagulation factors and normal immunoglobulins organised under the auspices of the European Directorate for the Quality of Medicines and HealthCare. OM is a CSL employee and programme director for the PATH study. We thank Michael Tortorici for the insights in the pharmacokinetic modeling and simulations. Download .pdf (.51 MB) Help with pdf files Supplementary appendix Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trialThis study, which is to our knowledge, the largest trial of CIDP to date and the first to study two administrations of immunoglobulins and two doses, showed that both doses of SCIg IgPro20 were efficacious and well tolerated, suggesting that SCIg can be used as a maintenance treatment for CIDP. Full-Text PDF Intravenous versus subcutaneous immunoglobulinWe read with interest the Article by Ivo van Schaik and colleagues1 about the use of weekly subcutaneous immunoglobulin (SCIg) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). After an IgG dependency test, the investigators randomly assigned 172 patients to low-dose SCIg (0·2 g/kg), high-dose SCIg (0·4 g/kg), or placebo. Relapse or withdrawal rate was significantly higher in the placebo group (63%) than in the high-dose SCIg group (33%) or low-dose SCIg group (39%). Full-Text PDF