Eculizumab versus rituximab in generalised myasthenia gravis

Abstract

Objective: Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction. However, evidence shaping treatment decisions, particularly for treatment-refractory cases, is sparse. Both rituximab and eculizumab may be considered as therapeutic options for refractory MG after insufficient symptom control by standard immunosuppressive therapies.

Methods: In this retrospective observational study, we included 57 rituximab-treated and 20 eculizumab-treated patients with MG to compare the efficacy of treatment agents in generalised, therapy-refractory anti-acetylcholine receptor antibody (anti-AChR-ab)-mediated MG with an observation period of 24 months. Change in the quantitative myasthenia gravis (QMG) score was defined as the primary outcome parameter. Differences between groups were determined in an optimal full propensity score matching model.

Results: Both groups were comparable in terms of clinical and demographic characteristics. Eculizumab was associated with a better outcome compared with rituximab, as measured by the change of the QMG score at 12 and 24 months of treatment. Minimal manifestation of disease was more frequently achieved in eculizumab-treated patients than rituximab-treated patients at 12 and 24 months after baseline. However, the risk of myasthenic crisis (MC) was not ameliorated in either group.

Interpretation: This retrospective, observational study provides the first real-world evidence supporting the use of eculizumab for the treatment of refractory, anti-AChR-ab positive MG. Nonetheless, the risk of MC remained high and prompts the need for intensified monitoring and further research effort aimed at this vulnerable patient cohort.

Keywords: myasthenia; neuroimmunology; neuromuscular.

Figure 1

Flow chart detailing patient recruitment. Seventy-seven patients were included in the final study for rituximab (n=57) and eculizumab treatment (n=20). ab, antibody; AChR, acetylcholine receptor; MuSK, muscle-specific tyrosine kinase.

Figure 2

Changes to baseline QMG score. QMG scores were assessed at 6, 12 and 24 months. Baseline is defined as start of rituximab or eculizumab therapy. (A) Change to baseline QMG score after 12 months of treatment. (B) Change to QMG score at baseline after 24 months. Differences between groups were assessed in a model of optimal full propensity score matching. The propensity scores were calculated for each patients using a logistic regression model. Patients were matched for QMG score at baseline, sex, age at diagnosis, age at baseline and thymoma. Error bars display mean (95% CI). QMG quantitative myasthenia gravis. ***p<0.001, **p<0.01, *p<0.05, p≥0.05, not significant.

Figure 3

Time to myasthenic crisis after baseline. (A) Kaplan-Meier curve displaying time to myasthenic crisis after baseline. Baseline is defined as start of rituximab or eculizumab therapy. Differences between groups were assessed by logrank test. (B) Number of patients achieving minimal manifestation after 12 and 24 months of treatment according to treatment. (C) Number of rescue therapies per patient in the 24 months observation period. Differences between groups were assessed by two-sided Student’s t-test. (D) Change to cortisone dose at baseline at 12 and 24 months of treatment. Error bars display mean (95% CI). **p<0.01, *p<0.05, p≥0.05, not significant.