Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: interim analysis of post-marketing surveillance

Abstract

Background: Eculizumab, a humanized monoclonal antibody targeted to terminal complement protein C5, is approved in Japan for treatment of patients with anti-acetylcholine receptor antibody-positive (AChR+) generalized myasthenia gravis (gMG) whose symptoms are difficult to control with high-dose intravenous immunoglobulin (IVIg) therapy or plasmapheresis.

Methods: This interim analysis of mandatory post-marketing surveillance in Japan assessed the safety and effectiveness of eculizumab at 26 weeks after treatment initiation in patients with AChR+ gMG.

Results: Data were available for 40 adult patients in Japan [62.5% (25/40) female; mean age at eculizumab initiation, 51.0 years]. Fifteen patients had a history of thymoma. Six patients were excluded from the effectiveness analysis set due to participation in the open-label extension part of the phase III, randomized, double-blind, placebo-controlled REGAIN study [ClinicalTrials.gov identifier: NCT02301624]. After 26 weeks' follow up, 32 patients (80%) were continuing eculizumab treatment. Adverse drug reactions were reported by seven patients [most frequently headache (n = 3)]. One death was reported during eculizumab treatment (relationship unclear as determined by the treating physician) and there was one death 45 days after the last dose (considered unrelated). No meningococcal infections were reported. Mean (standard deviation) changes from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores were -3.7 (2.61) (n = 27) and -5.6 (3.50) (n = 26), respectively, at 12 weeks, and -4.3 (2.72) (n = 26) and -5.6 (4.02) (n = 24), respectively, at 26 weeks. Improvements in MG-ADL and QMG scores were generally similar in patients with/without a history of thymoma. Frequency of IVIg use decreased following eculizumab initiation.

Conclusion: In a real-world setting, eculizumab was effective and well tolerated for the treatment of AChR+ gMG in adult Japanese patients whose disease was refractory to IVIg or plasmapheresis. These findings are consistent with the efficacy and safety results from the global phase III REGAIN study of eculizumab.

Keywords: eculizumab; effectiveness; myasthenia gravis; safety; thymoma.

Figure 1.

Patient disposition. Patients may be counted for more than one reason for discontinuation. AE, adverse event; CRF, case report form; OLE, open-label extension.

Figure 2.

Total scores for (a) MG-ADL and (b) QMG at eculizumab initiation and after 12 and 26 weeks of treatment in all patients with generalized myasthenia gravis and in subgroups of patients with and without a history of thymoma (effectiveness analysis set). Data in graphs have been offset for clarity. MG-ADL, Myasthenia Gravis Activities of Daily Living score; QMG, Quantitative Myasthenia Gravis score; SD, standard deviation.

Figure 3.

(a) MG-ADL responders^a and (b) QMG responders^b after 12 and 26 weeks of eculizumab treatment in all patients with generalized myasthenia gravis and in subgroups of patients with and without a history of thymoma (effectiveness analysis set). ^a⩾3-point improvement in MG-ADL total score after eculizumab initiation. ^b⩾5-point improvement in QMG total score after eculizumab initiation. MG-ADL, Myasthenia Gravis Activities of Daily Living score; QMG, Quantitative Myasthenia Gravis score.

Figure 4.

Proportion of patients receiving no/one/two/three/four/at least five IVIg treatments before and after eculizumab initiation (effectiveness analysis set). IVIg, intravenous immunoglobulin.