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.

Keywords: Privigen; chronic inflammatory demyelinating polyneuropathy (CIDP); inflammatory neuropathy cause and treatment (INCAT); intravenous immunoglobulin (IVIG); polyneuropathy and treatment with Hizentra (PATH).

Figure 1

Study design. Abbreviations: CIDP, chronic inflammatory demyelinating polyneuropathy; IgPro10, 10% intravenous immunoglobulin preparation; IgPro20, 20% subcutaneous immunoglobulin preparation; IVIG, intravenous immunoglobulin. Note: “Stop” indicates that subject was discontinued from the study after all study completion assessments were performed

Figure 2

Subject disposition. Per investigator, one additional subject met the criteria to enter the IgPro10 restabilization period (N = 208), but the subject withdrew consent and did not receive any IgPro10 (treated count N = 207). A total of 13 subjects were rescreened. Abbreviations: CIDP, chronic inflammatory demyelinating polyneuropathy; IgPro10, 10% intravenous immunoglobulin preparation; IgPro20, 20% subcutaneous immunoglobulin preparation; IVIG, intravenous immunoglobulin; N, number of subjects; PP‐PSDS, per‐protocol pre‐randomization safety data set; PSDS, pre‐randomization safety data set. ^*An additional subject did not return to at least the inflammatory neuropathy cause and treatment (INCAT) score at screening, but was randomly allocated in error. ^†Reasons for exclusion of 12 subjects from the PSDS: five subjects did not demonstrate CIDP deterioration during the IVIG withdrawal period, but were transitioned to the IgPro10 restabilization period; five subjects took prohibited concomitant medication during the pre‐randomization phase; one subject received an increased loading dose during pre‐randomization phase; one subject took prohibited concomitant medication (nonstudy IVIG) during pre‐randomization phase and received an increased loading dose during pre‐randomization phase

Figure 3

Primary efficacy outputs (PSDS population). Abbreviations: INCAT, inflammatory neuropathy cause and treatment; I‐RODS, inflammatory Rasch‐built overall disability scale; MRC, Medical Research Council; N, number of subjects; PSDS, pre‐randomization safety data set. Mean and SE are plotted