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

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).

Efficacy and Safety of Low-Dose Rituximab in Anti-MuSK Myasthenia Gravis Patients: A Retrospective Study

“…RTX also has beneficial effects in refractory MG. 25 In a prospective study by Fatehi et al, 34 patients with refractory MG had significant decreases in Myasthenia Gravis Composite (MGC) and MG-ADL scores after treatment with Zytux, an RTX biosimilar. 26 In a retrospective study with a 10-year follow-up, sustained clinical remission was achieved in all 4 patients with refractory MG after RTX therapy. 27 These results demonstrate that RTX is effective not only as an induction therapy, but also for sustained remission in patients with MG.…”

New and emerging treatments for myasthenia gravis

“…12 A prospective open label multicentre study of 34 patients with refractory generalised myasthenia gravis treated with Zytux (a rituximab biosimilar) showed reduced disease activity and improved quality of life. 13 Although these data are encouraging, the BeatMG (B Cell Targeted Treatment in Myasthenia Gravis) study, a phase 2 randomised controlled trial designed to examine the safety and efficacy of rituximab in AChR+gMG, failed to show a significant steroid sparing effect compared with placebo, although the safety profile was favourable. 14 This study had some limitations, however, including a higher than anticipated response rate in the placebo group, low B cell counts from baseline immunosuppressive treatment, and a mild level of disease severity.…”

Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions

“…The presence of a small level of IgG4 might be associated with plasma cells. Thus, recent studies indicate that Rituximab is effective in improving the quality of life in severe as well as refractory MG [ 203 ]. In addition, Zytux, a biosimilar to Rituximab is also effective in providing therapeutic relief for refractory MG [ 203 ].…”

“…Thus, recent studies indicate that Rituximab is effective in improving the quality of life in severe as well as refractory MG [ 203 ]. In addition, Zytux, a biosimilar to Rituximab is also effective in providing therapeutic relief for refractory MG [ 203 ]. Another mAb known as Eculizumab can mitigate the autoantibody effect on C5 protecting neuromuscular junction [ 204 ], and therefore is now being considered a safer therapeutic candidate.…”