Corticosteroids for Myasthenia Gravis: Can Immunoglobulin Therapy Reduce Use?

Treatment with IVIG-C is not more effective than placebo in lowering the daily dose of corticosteroids among patients with MG.

Patients with myasthenia gravis (MG) receiving immunoglobulin therapy did not reduce corticosteroid use any more than patients receiving placebo treatment, according to study findings published in Neurology.

Long-term use of corticosteroids correlates with potentially serious side effects despite its use as a first-line immunosuppressive therapy in patients with MG. Decreasing corticosteroid use without worsening MG symptoms is a primary goal of MG management.

Researchers conducted a multicenter, randomized, double-blind, placebo-controlled trial (Efficacy and Safety of IGIV-C in Corticosteroid Dependent Patients With Generalized Myasthenia Gravis; ClinicalTrials.gov Identifier: NCT02473965) to assess whether intravenous administration of human immunoglobulin 10% caprylate/chromatography purified (IGIV-C) could reduce the need for corticosteroids in 60 patients with MG (MGFA class II-Iva; AChR+). They conducted this study at 24 centers across 8 countries in North America and Europe.

The researchers randomly allotted 30 patients to the IGIV-C treatment group and 30 patients to the placebo group. Of the 60 patients, 38 (63.3%) completed all study follow-up visits while 12 patients in the treatment group and 10 in the placebo group discontinued due to adverse events, MG worsening, withdrawal of consent, and researcher decisions to discontinue the study.

These results suggest that effects of IGIV-C and [corticosteroids] are not synergistic and may be mechanistically different.

The initial loading dose of IGIV-C consisted of 2 g/kg infusions followed by 12 maintenance doses at 1 g/kg every 3 weeks. Corticosteroid tapering began after 3 administrations of IGIV-C or equivalent saline placebo infusions.

The researchers analyzed the percentage of patients in each group that achieved a 50% or greater reduction in corticosteroid use after 39 weeks of treatment compared with baseline use.

They found no significant differences in percentage of patients who achieved a 50% or greater reduction in corticosteroid use after 39 weeks between the intervention and placebo groups (60.0% vs. 63.3%, respectively; P =1.00).

Although not statistically significant (P =1.00), patients taking higher baseline doses of corticosteroids (>20mg/day) were more likely to achieve the 50% or greater reduction after 39 weeks compared with those on lower doses (≤20mg/day) in both the intervention and placebo groups (IGIV-C group: 70.0% vs. 55.0%; placebo group: 66.7% vs. 60.0%).

Treatment-emergent adverse events occurred at similar rates in both groups (IGIV-C: 90.0%; placebo: 93.3%). The most common events in the treatment group included headache, MG worsening, upper respiratory tract infections, and nausea, while the most common events in the placebo group included arthralgia, back pain, and nasopharyngitis.

Serious adverse events occurred in 4 out of 30 patients in the treatment group and 6 out of 30 patients in the placebo group with 2 deaths in the placebo group and 1 in the IGIV-C group. Causes of death included an MG exacerbation, sepsis, and cardiac arrest.

“The data from this study suggested no benefit of IGIV-C treatment over placebo in the reduction of daily [corticosteroid] dose,” the researchers noted. “These results suggest that effects of IGIV-C and [corticosteroids] are not synergistic and may be mechanistically different…and cannot be compensated for by the immunomodulatory properties of IVIG,” they concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Bril V, Szczudlik A, Vaitkus A, et al. A randomized, double-blind, placebo-controlled trial of the corticosteroid-sparing effects of immunoglobulin in myasthenia gravis. Neurology. Published online October 21, 2022. doi:10.1212/WNL.0000000000201501