Eculizumab effective in adolescents with refractory generalized myasthenia gravis

Key takeaways:

• Eleven adolescents were given weight-based and maintenance doses of eculizumab.
• Treatment led to significant change from baseline at week 1 in QMG and MG-ADL scores, with steady improvement through week 26.

BOSTON — Eculizumab significantly reduced disease severity and improved quality of life at 26 weeks in adolescents with refractory generalized myasthenia gravis, according to a presenter at the American Academy of Neurology annual meeting.

“[It is important] to boost the knowledge of the community to have interventional data in a targeted myasthenia therapy,” John F. Brandsema, MD, a pediatric neurologist at Children’s Hospital of Philadelphia, stated in his presentation.

Brandsema and colleagues aimed to examine the safety, efficacy, pharmacokinetics and pharmacodynamics of eculizumab — a terminal complement C5 inhibitor approved for adults with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis — as a treatment for adolescents with the same condition.

They conducted a phase 3, open-label, multicenter study of 11 individuals aged 12 to 17 years, six of whom were receiving chronic IV immunoglobulin. Participants were given eculizumab on a weight-based dosing regimen, with weekly induction of one to two doses of 600 mg or four doses of 900 mg followed by biweekly maintenance doses of 300 mg to 1,200 mg. The primary outcome of interest was change from baseline to week 26 in Quantitative Myasthenia Gravis (QMG) total score, while secondary outcomes included change from baseline to weeks 12 and 26 in MG-Activities of Daily Living (MG-ADL) total score.

According to results, 10 patients completed the primary evaluation period. Mean changes from baseline at week 26 were –5.8 (standard error [SE] = 1.2) for QMG total score and –2.3 (SE = 0.6) for MG-ADL total score. Similar changes were reported among participants, regardless of treatment with Ig. Overall, researchers reported statistically significant improvements in primary and secondary efficacy endpoints at week 1, which continued through week 26. Treatment-emergent adverse events were mild to moderate and mostly unrelated to drug administration. Three participants experienced six serious adverse events, which included three instances of MG worsening, an MG crisis, peritonsillar abscess and pyrexia. No deaths or meningococcal infections were reported, and no participants developed anti-eculizumab antibodies.

“The treatment was generally well-tolerated with minimal safety considerations,” Brandsema said. “We’d like to thank all the families of the participants in this study.”