Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar

Farzad Fatehi; Kamyar Moradi; Ali Asghar Okhovat; Ghazaleh Shojatalab; Behnaz Sedighi; Reza Boostani; Payam Sarraf; Bahram Haghi Ashtiani; Majid Ghasemi; Soussan Moussavi; Nassim Anjidani; Shahriar Nafissi

doi:10.3389/fneur.2021.682622

Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar

Front Neurol. 2021 Aug 26:12:682622. doi: 10.3389/fneur.2021.682622. eCollection 2021.

Authors

Affiliations

¹ Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
² Neurology Department, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
³ Neurology Department, Shafa Hospital, Kerman University of Medical Sciences, Kerman, Iran.
⁴ Neurology Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
⁵ Neurology Department, Imam-Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Department of Neurology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
⁸ Department of Neurology, Kashani Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
⁹ Medical Student, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
¹⁰ Head of Medical Department, Orchid Pharmed Company, Tehran, Iran.

Abstract

Objectives: Myasthenia gravis (MG) is an immune-mediated neuromuscular disorder responsive to immunomodulatory treatments. 10-20% of MGs are not responsive to conventional first-line therapies. Here, we sought to investigate the efficacy and safety of rituximab therapy in the treatment of patients with refractory MG. Methods: In a 48-week, multicenter, open-labeled, prospective cohort setting, 34 participants with refractory MG were assigned to receive infusions of Zytux, which is a rituximab biosimilar, according to a validated protocol. Clinical, functional, and quality of life (QoL) measurements were recorded at baseline, and seven further visits using the Myasthenia Gravis Foundation of America (MGFA), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Activities of Daily Living profile (MG-ADL), and Myasthenia Gravis Quality of Life (MGQoL-15) scales. Besides, the post-infusion side effects were systematically assessed throughout the study. Results: The correlation analysis performed by generalized estimating equations analysis represented a significant reduction of MGC, MG-ADL, and MGQoL-15 scores across the trial period. The subgroup analysis based on the patients' clinical status indicated a significant effect for the interaction between time and MGFA subtypes on MG-ADL score, MGC score, and pyridostigmine prednisolone dose, reflecting that the worse clinical condition was associated with a better response to rituximab. Finally, no serious adverse event was documented. Conclusions: Rituximab therapy could improve clinical, functional, and QoL in patients with refractory MG in a safe setting. Further investigations with larger sample size and a more extended follow-up period are warranted to confirm this finding. Clinical Trial Registration: The study was registered by the Iranian Registry of Clinical Trials (IRCT) (Code No: IRCT20150303021315N18).

Keywords: clinical response; myasthenia gravis; refractory; rituximab; zytux TM.

Publication types

Case Reports