Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial -

Subcutaneous immunoglobulin for maintenance treatment in chronic inflammatory demyelinating polyneuropathy (PATH): a randomised, double-blind, placebo-controlled, phase 3 trial
Information type: Randomised controlled trials
Source: The Lancet Neurology
Specialities: Neurological disorders
Summary
RCT (n=172, 24 week maintenance) found absolute risk reductions in relapse/withdrawal were 25% for low-dose (0.2g/kg) subcutaneous immunoglobulin solution 20% vs. placebo (p=0.007), 30% for high-dose (0.4g/kg) vs. placebo (p=0.001), and 6% for high-dose vs. low-dose (p=0.32).
UKMi comment

A commentary notes the weaknesses of the study, many inevitable, due to the variable course of chronic inflammatory demyelinating polyneuropathy (CIDP).

1.    Study was not designed, and did not generate any data, to assess whether subcutaneous immunoglobulin (SCIg) is as good as, better than, or preferable to intravenous immunoglobulin (IVIg) for CIDP maintenance therapy because no head-to-head comparison was done.

2.    IgG dependency test did not prove quite successful because 37% of patients in the placebo group remained stable and did not relapse.

3.    19% of patients on high-dose and 33% on low-dose SCIg relapsed, indicating that a switch of a stable patient on IVIg to SCIg carries a clinically calculable relapse risk. Furthermore, only 23 (70%) of 33 relapsed patients returned to baseline with IVIg rescue therapy, which is unusual and concerning.

4.    9 (16%) of 58 patients in the high-dose group and three (5%) of 57 in low-dose group withdrew for reasons unrelated to relapses, raising the possibility of frustration or discomfort with pumps, tubes, or injection-site reactions that might have contributed to the decision to withdraw; injection-site reactions occurred in 17 (29%) of 58 patients in the high-dose group.

The commentator suggests that the practical message from this study for neurologists is that “patients with CIDP who have stabilised with IVIg now have the option of switching to SCIg. Considering that, on the basis of results from the trial, 26% might relapse and several might withdraw, some patients might not feel comfortable switching, but others would prefer SCIg because of independence and convenience. For patients with poor venous access, cardiovascular risks, or systemic IVIg-related side-effects, switching to SCIg is likely to be an easy choice.” He acknowledges that questions relating to dose and cost remain, and a patient will need to weigh up 1 day per month IVIg infusion in outpatient centres or at home (as done currently) or four weekly home self-infusions (finger strength permitting) in two to eight parallel sites of 50 mL each, lasting 1–2 hours.
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