IVIG Given Prior Prednisone Safely Prevents Most MG Flares, Study Finds

Infusions of intravenous immunoglobulin (IVIG) given before high-dose prednisone safely prevents most of its associated exacerbations in people with generalized myasthenia gravis (MG), a study reports. 

The study, “Intravenous immunoglobulins may prevent prednisone-exacerbation in myasthenia gravis,” was published in the journal Nature Scientific Reports. 

Corticosteroids such as prednisone are a common treatment for MG, generally given as an add-on medication when anticholinesterase therapies such as Mestinon (pyridostigmine, by Bausch Health; generics available) do not control symptoms.

Clinical studies have shown that daily use of high-dose prednisone can significantly ease symptoms. But its use can also exacerbate MG symptoms, especially in the first weeks of treatment, for reasons not fully understood. These symptom flares can range from mild to severe.

IVIG is one way of controlling MG exacerbation. In IVIG, immune proteins collected from healthy donors are infused directly into the bloodstream to neutralize autoantibodies, or antibodies that attack the body’s own tissues. 

While an international consensus on MG management supports using IVIG before immunosuppressants to prevent exacerbations, data supporting this approach is lacking.

Researchers at Bellvitge University Hospital in Spain investigated whether a combination therapy with IVIG and prednisone is safe and effective in people with generalized MG using corticosteroids for a first time. 

Their analysis included 30 men and 15 women with generalized MG, ages 26 to 85. Forty participants were 50 or older at disease onset. Most patients (34, or 75.6%) had ocular symptoms as their first MG manifestations.

Forty-one patients had autoantibodies targeting acetylcholine receptors, and four had no detectable autoantibodies. The majority had mild MG, and one-third had had their thymus removed (thymectomy). 

Participants received 0.4 g/kg of IVIG daily for five days. Seven to 10 days later, they were started on a full dose of 1 mg/kg prednisone given daily (0.75 mg/kg per day in patients with comorbidities). 

Over the subsequent six weeks of follow-up, patients were assessed as better, worse, or the same as before starting prednisone, based on the Myasthenia Gravis Severity Scale (MSS) and the Quantitative Myasthenia Gravis (QMG). 

At week four, 39 people (86.7%) showed definite clinical improvement, with one (2.2%) demonstrating an MG exacerbation based on MMS criteria. Two additional patients showed significant deterioration, as identified using the more sensitive QMG criteria. 

These three patients experienced clinical improvements two weeks later, while a remaining study participant (2.2%) showed stable disease despite high-dose prednisone and a round of IVIG.

“Therefore, when analyzing the efficacy of combined therapy, 91.1% of patients responded to treatment at 6 weeks,” the researchers wrote. 

Notably, a study using the same MSS criteria found that not using pre-IVIG treatment was associated with a markedly higher rate of prednisone-associated exacerbations (42%).

Most patients in this study experienced mild side effects, with asymptomatic increases in liver enzymes being the most common. No patient with mild MG had severe adverse effects following IVIG. The majority had side effects deemed related to prednisone, including insomnia, irritability, high blood glucose, and hypertension.

“In conclusion, combined therapy with IVIG and prednisone in patients with generalized MG is safe and effective,” the scientists wrote. “The rate of prednisone-induced paradoxical exacerbation in our population was lower than that reported in previous literature, suggesting that IVIG could have a protective effect against such exacerbations.”

“Further prospective research in a larger cohort is needed to confirm this protective effect,” they added.