Updated Review Highlights Efficacy of Intravenous Immunoglobulin for Chronic Inflammatory Demyelinating Polyradiculoneuropathy

In an update to a 2013 review, newly published findings showed that treatment with intravenous immunoglobulin (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) increased the number of patients who significantly improved disability scores after 2 to 6 weeks of treatment compared with placebo.^1,2 Additionally, findings suggested that IVIg is equally effective as intravenous methylprednisolone (IVMP) and oral prednisolone during this treatment timeframe for this patient population.

Among 5 trials with high-certainty evidence (patients, n = 269), findings showed that IVIg treatment resulted in an increased probability of significant improvement in disability after 6 weeks relative to placebo (risk ratio [RR], 2.40 [95% CI, 1.72-3.36] number needed to treat for an additional beneficial outcome [NNTB], 4 [95% CI, 3-5]). In 3 trials with high-certainty evidence (patients, n = 90), IVIg improved disability 2 to 6 weeks after the start of treatment compared with placebo, as demonstrated on modified Rankin Scale (mean difference [MD], -0.26 points; 95% CI, -0.48 to -0.05). In 1 trial with moderate-certainty evidence (patients, n = 117), investigators noted that IVIg “probably” improved disability, as measured on the Inflammatory Neuropathy Cause and Treatment (INCAT) scale, after 24 weeks (MD, 0.80 points; 95% CI, 0.23-1.37) in comparison with placebo.

Top Clinical Takeaways

IVIg demonstrates a significant increase in the probability of disability improvement in patients with CIDP in 2 to 6 weeks, comparable with other treatments.
Variability in disability scales and improvement definitions among trials makes it challenging to establish the clinical relevance of the pooled effects.
Despite positive indications, additional research is essential to evaluate the long-term benefits and potential harms of IVIg compared with alternative treatments for CIDP.

“We are confident that immunoglobulin compared with placebo increases the likelihood of improved disability scores after 2 to 6 weeks of treatment. However, we have moderate confidence in most other results, because statistical analysis suggested that the effect of immunoglobulin could be beneficial or harmful,” senior author Filip Eftimov, MD, PhD, medical specialist in neurology at Amsterdam UMC, and colleagues wrote.¹

In this review, investigators assessed the efficacy and safety of IVIg in patients with CIDP among studies from the Cochrane Neuromuscular Specialized Register, CENTRAL, MEDLINE, Embase, and 2 trials registers up until March 2023. The selected RCTs and quasi-RCTs tested IVIg versus placebo, plasma exchange, or corticosteroids in patients with definite or probable CIDP. Published in Cochrane Database of Systematic Reviews, the primary outcome was improvement in disability in 6 weeks following the initiation of treatment. The secondary outcomes included change in mean disability score in 6 weeks, change in muscle strength in 6 weeks, change in mean disability score at 24 weeks or later, frequency of serious adverse events, and frequency of any adverse events.

Researchers gathered data from 9 RCTs with 372 participants (men, n = 235) from Europe, North America, South America, and Israel. Five of the trials (patients, n = 235) compared IVIg with placebo, one trial (20 participants) compared IVIg with plasma exchange, 2 trials (patients, n = 72) compared IVIg with prednisolone, and one trial (patients, n = 45) compared IVIg with IVMP. Authors noted that 1 new trial was included for the current update but did not contribute any data to the meta-analyses.

“Since each trial used a different disability scale and definition of significant improvement, we were unable to evaluate the clinical relevance of the pooled effect,” Eftimov et al noted.¹ “There was low statistical heterogeneity between the trial results, and the overall risk of bias was low for all trials that contributed data to the analysis.”

Among 3 trials (patients, n = 315), investigators observed probably little or no difference between IVIg and placebo in the frequency of serious adverse events (SAEs)(RR 0.82, 95% CI 0.36 to 1.87; moderate-certainty evidence). Authors noted that the investigation comparing IVIg with plasma exchange reported none of the main outcomes. In addition, IVIg compared with prednisolone probably had little or no effect on the probability of significant improvement in disability 4 weeks after the start of treatment as observed in 1 trial (RR, 0.91; 95% CI, 0.50-1.68; patients, n = 29; moderate-certainty evidence), and little or no effect on change in mean disability measured on mRS from another trial (MD, 0.21 point; 95% CI, -0.19 to 0.61; patients, n = 24; moderate-certainty evidence).

In 1 cross-over trial with moderate-certainty evidence (patients, n = 32), authors noted potentially little or no difference between IVIg and prednisolone in frequency of SAEs (RR, 0.45; 95% CI, 0.04-4.69). Another trial of moderate-certainty evidence (patients, n = 45) showed that IVIg probably increased the likelihood of significant improvement in disability 2 weeks after starting treatment compared with IVMP (RR 1.46; 95% CI, 0.40-5.38).

In a single trial, IVIg in comparison with IVMP was shown to probably have little or no effect on change in disability measured on the Rankin scale 2 weeks after the start of treatment (MD, 0.24 points; 95% CI, -0.15 to 0.63; patients, n = 45; moderate-certainty evidence) or on change in mean disability, as measured with the Overall Neuropathy Limitation Scale, 24 weeks after the start of treatment(MD, 0.03 points; 95% CI, -0.91 to 0.97; participants, n = 45; moderate-certainty evidence). In that study, the frequency of SAEs appeared to be higher with IVIg compared with IVMP (RR, 4.40; 95% CI, 0.22-86.78; n = 45; moderate-certainty evidence).

“Each study defined improvement in its own way, and the studies used different measurement scales, so it is difficult to relate them to changes in the clinical condition of people with CIDP. Further research is needed to assess the long‐term benefits and harms of immunoglobulin compared with other treatments,” Eftimov et al noted.¹