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

Abstract

Purpose: To evaluate the efficacy and safety of low dosages of rituximab (RTX) in the treatment of MuSK-antibody-positive MG patients.

Patients and methods: We retrospectively analyzed the data of MuSK-antibody-positive MG patients who were treated with low dosages of RTX from January 2018 to October 2021. The long-term treatment response to RTX was assessed by Myasthenia Gravis Foundation of America (MGFA) post-interventional status (PIS), Myasthenia Gravis Status and Treatment Intensity (MGSTI), dosage of steroid, MG-related activities of daily living (MG-ADL) and myasthenic muscle score (MMS) at the end of follow-up.

Results: Clinical improvement was observed in all eight patients with follow-up for 8 to 29 months after treatment. At the last visit, complete stable remission had been achieved in one patient, pharmacologic remission in three patients, minimal manifestations status in three patients and improved in one patient based on the MGFA-PIS criteria. MGSTI level 2 or better had been reached in six (75%) patients at the last visit. The steroid dosage decreased from 60 mg at baseline to 15 mg at the last follow-up (p = 0.011). The average MG-ADL score decreased from 11 (range 7 to 15) to 0 (range 0 to 3; p = 0.011), and the MMS improved from 38.5 (range 24 to 60) to 100 (range 90 to 100; p = 0.012). These differences were all statistically significant. During RTX treatment and subsequent follow-up, 1 patient reported minor post-infusion malaise.

Conclusion: Low-dose RTX is effective and safe for treating anti-MuSK antibody positive MG patients. A long-term response is observed after treatment. Larger prospective studies are required to provide further evidence.

Keywords: low-dose; muscle-specific kinase; myasthenia gravis; rituximab.

Figure 1

Distribution of weaknesses among the eight MuSK myasthenia gravis patients at baseline.

Figure 2

Low-dose RTX reduced the daily dose of prednisone along with clinical improvement in MuSK-MG patients. (A) Distribution of MGFA disease severity grades at baseline and last visit. (B) Changes in MGFA-PIS at the last visit. (C) Change in daily dose of steroids before and after RTX treatment. (D) Distribution of MGSTI categories at baseline and last visit. *P<0.05, vs baseline.

Figure 3

Changes in MG-ADL and MMS in MuSK-MG patients after treatment with low-dose rituximab during follow-up period. (A) The MG-ADL was significantly declined from 11 (7–15) before rituximab treatment to 0 (0–3, p= 0.011) after treatment. (B) MMS was 38.5 (24–60) at baseline and was improved to 100 (90–100, p=0.012) at last follow-up. *P<0.05; **P<0.01, vs baseline.

Figure 4

Changes in CD19⁺ and CD19⁺CD27⁺ B lymphocytes in MuSK-MG patients after treatment with low-dose rituximab at 1, 3, and 6 months. (A) CD19⁺ B cells were depleted by rituximab and remained <1% at 6 months. (B) CD19⁺CD27⁺ B-cell counts were decreased from 5.88 (4.00–16.48%) at baseline to 0.11% (0.00–0.22%) at 6 months. The difference is statistically significant. The upper and lower short black lines represent the maximum and minimum values, respectively. The long black line in the middle represents the median values. *P<0.05; **P<0.01, vs baseline.

Figure 5

Time of disease onset, time of clinical relapse and last follow-up visit are displayed. The vertical line at 0 crossing the x-axis indicates the initiation of low-dose RTX treatment. ○indicates time of disease onset. ◆indicates times from the first RTX infusion to clinical relapse. ▽indicates times from the first RTX infusion to last follow-up visit.