Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis

Abstract

Background: The objective of this study was to evaluate the efficacy and safety of repeated low-dose rituximab treatment guided by monitoring circulating CD19+ B cells in patients with refractory myasthenia gravis (MG). Methods: Patients with refractory MG who had received rituximab treatment at two teaching hospitals between September 2013 and January 2017 were reviewed retrospectively. The treatment protocol consisted of an induction treatment with low-dose rituximab (375 mg/m2 twice with a 2-week interval), followed by retreatment (375 mg/m2 once). Retreatment was based on either circulating CD19+ B-cell repopulation or clinical relapse. Outcome measures included the MG Foundation of America (MGFA) clinical classification and postintervention status, prednisolone dose, CD19+ B-cell counts, clinical relapse, and adverse effects. Results: Of 17 patients, 11 (65%) achieved the primary endpoint, defined as the minimal manifestation or better status with prednisolone ⩽5 mg/day, after median 7.6 months (range, 2–17 months) following rituximab treatment. Over a median follow up of 24 months (range, 7–49 months), a total of 30 retreatments were undertaken due to clinical relapse without B-cell repopulation ( n = 6), on the basis of B-cell repopulation alone ( n = 16) and both ( n = 8). B-cell recovery appeared to be in parallel with clinical relapse on the group level, although the individual-level association appeared to be modest, with B-cell repopulation observed only at 57% (8/14) of clinical relapses. Conclusions: The repeated low-dose rituximab treatment based on the assessment of circulating B-cell depletion could be a cost-effective therapeutic option for refractory MG. Further studies are needed to verify the potentially better cost-effectiveness of low-dose rituximab, and to identify biomarkers that help optimize treatment in MG patients.

Efficacy and safety of rituximab in myasthenia gravis: a French multicentre real‐life study

“…Indeed, 86.2% of our patients achieved the primary outcome with an MGFA-PIS of 'improved' or better at 6 months. This efficacy is concordant with the literature [11,12,17,18]. The percentage in the present study is greater because we chose to consider that an 'improved' MGFA-PIS was a good response, contrary to other studies where a good response was 'minimal manifestations' or better.…”

“…This treatment has been used for 20 years in haematological disorders and more recently in autoimmune disorders, such as rheumatoid arthritis [25]. In patients with MG, AEs were present in 4.2%-14% [18,26]. In the present study, 42.8% of patients presented with AEs during the treatment.…”

“…Infections are frequently reported in the literature, but only 4% are severe in haematological disorders [25]. Furthermore, prolonged B-cell depletion may occur, even if rarely, and may promote infections [18]. Pre-therapeutic clinic and blood tests are necessary to detect infection before infusion.…”

Rituximab in AChR subtype of myasthenia gravis: systematic review

“…Online supplementary file 1 summarises data from selected studies on the use of RTX in AChR-MG. Thirteen studies have been selected, showing good safety 1 2 6 7 9 11–18. The data collected from each report included the number and regimen of infusions used for therapy with RTX, antibody type and titres pretreatment and post-treatment, follow-up duration, data on safety and postintervention status of MG.…”

“…The presence of thymoma in AChR-MG was specified in eight studies, accounting for 34 out of 165 overall patients with AChR-MG (online supplementary file 1). Some patients with thymoma did not respond at all to RTX, resulting unchanged or showing only a limited improvement7 14–16; others reported a significant improvement 7 9 11 12 15 16. However, the presence of thymoma has not been associated with a different response to RTX in AChR-MG 7 15 16…”