Comparison between mono-tacrolimus and mono-glucocorticoid in the treatment of myasthenia gravis

Abstract

Objective: Use of tacrolimus in mild to moderate myasthenia gravis (MG) is generally limited to glucocorticoid-refractory cases; the advantage of mono-tacrolimus over mono-glucocorticoids is unknown.

Methods: We included mild to moderate MG patients treated with mono-tacrolimus (mono-TAC) or mono-glucocorticoids (mono-GC). The correlation between the immunotherapy options and the treatment efficacy and side effects were examined in 1:1 propensity-score matching. The main outcome was time to minimal manifestations status or better (MMS or better). Secondary outcomes include time to relapse, the mean changes in Myasthenia Gravis-specific Activities of Daily Living (MG-ADL) scores and the rate of adverse events.

Results: Baseline characteristics showed no difference between matched groups (49 matched pairs). There were no differences in median time to MMS or better between the mono-TAC group and mono-GC group (5.1 vs. 2.8 months: unadjusted hazard ratio [HR], 0.73; 95% CI, 0.46-1.16; p = 0.180), as well as in median time to relapse (data unavailable for the mono-TAC group since 44 of 49 [89.8%] participants remained in MMS or better; 39.7 months in mono-GC group: unadjusted HR, 0.67; 95% CI, 0.23-1.97; p = 0.464). Changes in MG-ADL scores between the two groups were similar (mean differences, 0.3; 95% CI, -0.4 to 1.0; p = 0.462). The rate of adverse events was lower in the mono-TAC group compared to the mono-GC group (24.5% vs. 55.1%, p = 0.002).

Interpretation: Mono-tacrolimus performs superior tolerability with non-inferior efficacy compared to mono-glucocorticoids in mild to moderate myasthenia gravis patients who refuse or have a contraindication to glucocorticoids.

Figure 1

Flowchart of the participants included in the current study. Based on the inclusion and exclusion criteria, mono‐TAC group and mono‐GC group were identified for testing the association between immunotherapy choice and clinical outcomes. The factors associated with treatment response to tacrolimus were assessed in mono‐TAC group. MG, myasthenia gravis; TAC, tacrolimus; GC, glucocorticoids; MG‐ADL, Myasthenia Gravis‐specific Activities of Daily Living scale; QMG, quantitative MG score; IVIG, intravenous immunoglobulin; PE, plasma exchange; MGFA class, Myasthenia Gravis Foundation of America clinical classification.

Figure 2

(A) Kaplan–Meier estimates of time to MMS or better in matched mono‐TAC group and mono‐GC group, plotted for subgroups by site of immunotherapy choice. There were 72 events recorded in 98 participants. Patient numbers at each follow‐up period are listed. (B) Kaplan–Meier estimate of relapse in matched mono‐TAC group and mono‐GC group, plotted for subgroups by site of immunotherapy choice. There were 17 events recorded in 98 participants. Patient numbers at each follow‐up period are listed. (C) Change in MG‐ADL scores from baseline to the end of the third month treatment in matched mono‐TAC and mono‐GC groups. Significant changes in MG‐ADL scores from baseline to the end of the third month treatment were observed in matched mono‐TAC and mono‐GC groups. There was no significant between‐group difference in favor of immunotherapy choices for MG‐ADL scores. (D) The receiver‐operating characteristics (ROC) curve represents the area under the curve (AUC) and 95% confidence interval (CI) are 0.88 and 0.80–0.97, respectively. The optimal cut‐off value of ΔMG‐ADL percentage was 50% (sensitivity, 80.5%; specificity, 93.8%).