IVIg Plus IV Methylprednisolone Does Not Improve Remission Rates in CIDP, Study Shows

Adding intravenous methylprednisolone (IVMP) to intravenous immunoglobulin (IVIg) induction therapy did not significantly increase remission rates among patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), according to results from a randomized controlled trial. The study was stopped early after investigators identified thromboembolic events in the combination therapy group, raising concerns about the safety of this treatment strategy.¹

At 52 weeks, remission occurred in 38% of patients treated with IVIg plus IVMP compared with 28% of those receiving IVIg plus placebo, a difference that did not reach statistical significance (difference, 10%; 95% CI, −11% to 31%; P = .47).¹ Senior investigator Filip Eftimov, MD, PhD, a medical specialist at UMC Amsterdam, and colleagues, concluded that the combination regimen should not be used with the goal of increasing remission rates until its safety profile is better understood.

Testing a Combination Induction Strategy

CIDP is an autoimmune neuropathy characterized by progressive or relapsing motor and sensory dysfunction lasting at least two months. Intravenous immunoglobulin and corticosteroids are both effective first-line therapies, though many patients require ongoing maintenance treatment to prevent relapse.^2-4

IVIg typically produces relatively rapid clinical improvement, whereas corticosteroids may take longer to show benefit but have been associated with sustained remission in some patients. Investigators designed the trial to evaluate whether combining IVIg with IVMP could provide both rapid symptom control and improved long-term remission rates.

The randomized, double-blind, placebo-controlled study enrolled adults with probable or definite CIDP at neuromuscular centers in the Netherlands and the United Kingdom. Eligible participants included treatment-naïve patients, those who relapsed after at least one year of remission, or individuals who deteriorated following an initial IVIg loading dose.¹

Participants were randomly assigned to receive either IVIg plus IVMP (1000 mg every three weeks) or IVIg plus placebo during an 18-week treatment period. All patients received an IVIg loading dose of 2 g/kg followed by maintenance infusions of 1 g/kg. The primary endpoint was remission at 52 weeks, defined as sustained improvement on disability measures without the need for additional CIDP treatment.

Remission Rates and Clinical Outcomes

A total of 77 participants were randomized before the trial was halted by the data safety monitoring board. Among these patients, 14 of 37 (38%) in the IVIg/IVMP group and 11 of 40 (28%) in the IVIg/placebo group achieved remission at 52 weeks.¹

After adjustment for country of enrollment and treatment status, the odds ratio for remission was 1.7 (95% CI, 0.62–4.5), indicating no statistically significant difference between groups.¹

Secondary outcomes showed a similar proportion of participants improving during the treatment phase. Disability improvement at 18 weeks occurred in 73% of patients receiving IVIg plus IVMP compared with 68% receiving IVIg alone.¹

The median time to improvement was 6 weeks with combination therapy versus 12 weeks with IVIg alone, though this difference was not statistically significant. Investigators also reported that among patients who responded to treatment, those receiving the combined regimen often experienced greater overall improvement in disability and impairment scores.

The authors suggested that these findings may indicate that some patients treated with IVIg alone are undertreated, noting that magnitude of improvement may be a clinically meaningful measure beyond minimal thresholds used to define response.

Safety Findings Prompt Early Trial Termination

Recruitment was stopped after investigators observed four thromboembolic events in the IVIg plus IVMP group, including three pulmonary embolisms and one deep venous thrombosis. No thromboembolic events occurred in the IVIg-placebo group.¹

These events occurred despite mitigation strategies such as limiting IVIg infusion rates. Patients recovered after treatment with anticoagulants and did not experience long-term complications.

Across the study overall, 296 adverse events were reported, with similar numbers between treatment groups. Most events were mild, although severe adverse events occurred in two participants in the combination therapy group and included pulmonary embolism requiring hospitalization.¹

Both IVIg and systemic corticosteroids have independently been associated with thromboembolic risk, and investigators noted that the combination may increase this risk in certain patients.

“The occurrence of four thromboembolic events in the IVIg/IVMP group needs to be emphasized,” the study authors wrote.¹

Implications for Future Research

Investigators acknowledged that the trial was underpowered because enrollment stopped before the planned sample size of 96 participants was reached. However, even under optimistic assumptions, the study would likely not have detected the large remission difference originally anticipated.

Overall, the findings suggest that adding corticosteroids to IVIg induction therapy does not meaningfully improve remission rates in CIDP using the dosing regimen studied.

“Combined treatment did not lead to significantly more frequent remissions than IVIg alone,” the authors concluded.¹

Future studies may explore whether alternative corticosteroid regimens, lower doses, or preventive anticoagulation strategies could reduce thromboembolic risk while preserving potential benefits in disability outcomes.

REFERENCES
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2. Van den Bergh PYK, et al. European Academy of Neurology/Peripheral Nerve Society guideline on CIDP. Eur J Neurol. 2021. https://doi.org/10.1111/ene.14642
3. Hughes RA, et al. Intravenous immunoglobulin for CIDP. Cochrane Database Syst Rev. 2017. https://doi.org/10.1002/14651858.CD001797.pub3
4. Eftimov F, et al. Corticosteroids for CIDP. Cochrane Database Syst Rev. 2013. https://doi.org/10.1002/14651858.CD002062.pub3