Restabilization treatment after intravenous immunoglobulin withdrawal in chronic inflammatory demyelinating polyneuropathy: Results from the pre‐randomization phase of the Polyneuropathy And Treatment with Hizentra study

Abstract

In patients with chronic inflammatory demyelinating polyneuropathy (CIDP), intravenous immunoglobulin (IVIG) is recommended to be periodically reduced to assess the need for ongoing therapy. However, little is known about the effectiveness of restabilization with IVIG in patients who worsen after IVIG withdrawal. In the Polyneuropathy And Treatment with Hizentra (PATH) study, the pre‐randomization period included sudden stopping of IVIG followed by 12 weeks of observation. Those deteriorating were then restabilized with IVIG. Of 245 subjects who stopped IVIG, 28 did not show signs of clinical deterioration within 12 weeks. Two hundred and seven received IVIG restabilization with an induction dose of 2 g/kg bodyweight (bw) IgPro10 (Privigen, CSL Behring, King of Prussia, Pennsylvania) and maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks. Signs of clinical improvement were seen in almost all (n = 188; 91%) subjects. During IVIG restabilization, 35 subjects either did not show CIDP stability (n = 21, analyzed as n = 22 as an additional subject was randomized in error) or withdrew for other reasons (n = 14). Of the 22 subjects who did not achieve clinical stability, follow‐up information in 16 subjects after an additional 4 weeks was obtained. Nine subjects were reported to have improved, leaving a maximum of 27 subjects (13%) who either showed no signs of clinical improvement during the restabilization phase and 4 weeks post‐study or withdrew for other reasons. In conclusion, sudden IVIG withdrawal was effective in detecting ongoing immunoglobulin G dependency with a small risk for subjects not returning to their baseline 17 weeks after withdrawal.

Mind the gap: acute bilateral vocal cord palsy in CIDP after extending the IVIG treatment interval?

“…In a stable patient, the discontinuation or delay of IVIG-therapy under clinical monitoring is a legitimate method to ascertain whether this expensive therapy is still efficient and needed at the given treatment frequency or if a longer therapy interval can be chosen in the current state of disease activity [11] . However, Mielke et al [12] have previously shown that the majority of patients deteriorate after sudden withdrawal of IVIG, but after restart of IVIG therapy, almost all patients show signs of improvement. Moreover, there is evidence from the literature that IVIG target doses can be titrated individually during the course of the disease but infusion frequencies are fixed in each patient [13] .…”

Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in chronic inflammatory demyelinating polyradiculoneuropathy: protocol of an international, randomised, double-blind, placebo-controlled trial (OPTIC)

“…The primary outcome, remission at 52 weeks, is measured using the I-RODS and the adjusted INCAT-DS. We chose to include both outcome measures to assess disability as relevant changes may be missed in patients if only one of these is used, as was shown in both the IVIg withdrawal as well as subsequent restabilization phase of the PATH study, which used a combination of both outcome measures to assess relevant changes [ 32 , 33 ]. Combining two outcome measures and using a(n individual) MCID-based approach, we hope to limit potential delay when treatment is required in the event of a relapse.…”

Systematic literature review of burden of illness in chronic inflammatory demyelinating polyneuropathy (CIDP)

“…Treatments further need to be reviewed on an ongoing basis to ensure that treatments are appropriate and avoid unnecessary burden. For example, it is recommended that IVIG is periodically reduced or withdrawn to avoid excessive costs, while corticosteroids should be reviewed or withdrawn to avoid AEs [15,39]. CIDP subtype and varied diagnostic criteria may also be important in treatment decisions; however, the evidence is unclear.…”

“…IVIG generally achieved high rates of response to treatment (44-91% response rate, across 11 studies), relative to placebo [12,[30][31][32][35][36][37][38][39][40][41][42][43]. Where comparative data were reported, IVIG increased the proportion of patients with CIDP who responded to treatment, relative to comparators, including corticosteroids and plasma exchange [12,29,31].…”

“…Subcutaneous immunoglobulins (SCIG) provide an alternative route of administration that may ameliorate some of the challenges associated with intravenous administration of immunoglobulins [14,[44][45][46][47][48]. Three studies reported on the clinical stability of patients with CIDP after commencing SCIG, with all studies finding that the majority of patients were clinically stable or improved (83-100%; n = 13-245) [39,47,48]. The largest trial on SCIG treatment (PATH, n = 172, placebo-controlled) found the proportion of patients with a CIDP relapse or who were withdrawn from the trial for any other reason which was 63% for patients in the placebo group, 39% for patients in the low-dose SCIG group, and 33% for patients receiving high-dose SCIG [46].…”