Treatment with tacrolimus improves clinical symptoms and modulates plasma levels of soluble costimulatory molecules and their ligands in patients with refractory myasthenia gravis (MG), a recent study suggests.

Significant reductions in clinical scores, including the Quantitative MG score (QMG), the MG-specific manual muscle test (MMT), the MG-related activities of the daily living score (MG-ADL), and the 15-item MG-specific quality of life score (MG QOL-15), were observed in patients with MG after receiving daily oral doses of tacrolimus for 12 months (P <0.0001), reported Hui Wu, Jing’an District Centre Hospital of Shanghai, in China, and colleagues.

“In this study, we identified that 3 mg tacrolimus daily can significantly improve the clinical symptoms of patients with refractory MG within one year, reflecting by significant score reduction of QMG, MMT, ADL, MG QOL-15, as well as tapering of daily oral PSL dose,” the authors wrote.

The results were published in the Journal of Neuroimmunology.

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The study’s cohort consisted of 32 patients with refractory MG. The average disease course was 4.9 years. Mean age at disease onset was 37.8 years.

QMG score decreased from 10 to 6, MMT reduced from 11 to 4, MG-ADL scores declined from 4.5 to 2, and MG QOL-15 dropped from 10.5 to 7. Roughly 33% of the patients achieved minimal manifestation status after the year of treatment, and another 16 were improved. Tacrolimus treatment also allowed patients to taper their daily prednisone use from 32 mg to 13.75 mg.

The results also showed that levels of soluble programmed cell death protein-1 (sPD-1), inducible costimulator (sICOS), cluster of differentiation 40 (sCD40), the CD40 ligand (sCD40L), and interleukin-2 (IL-2) were significantly increased in patients with refractory MG at baseline compared to healthy controls. Levels of the sPD-1 ligand (sPD-L1), sICOS ligand (sICOSL), and cluster of differentiation 25 (sCD25) were also elevated in patients but not enough to reach significance.

Significant decreases in plasma levels of sPD-1, sICOSL, sCD40, sCD25, and IL-2 were also observed overall in the patients after 12 months of tacrolimus treatment. In the subset of patients who improved clinically over the 12 months, the levels of sPD-1, sICOSL, and sCD25 all significantly decreased from when the disease was more severe.

Correlation analysis between clinical and laboratory results showed a negative relationship between sCD25 and clinical severity scores, including QMG score and MMT. The levels of sCD40 and IL-2 were negatively correlated with the MG-ADL score.

Several costimulatory molecules and their ligands were positively correlated, as well, including IL-2 with sPD-1, sPD-L1, sICOS, sICOSL, and sCD40. Positive correlations were also found between sPD-1 and sPD-L1, sICOS, and sICOSL.


Wu H, Chen L, Zhou X, et al. Effect of tacrolimus on soluble costimulatory molecules in patients with refractory myasthenia gravis. J Neuroimmunol. 2022;372(577955):577955. doi:10.1016/j.jneuroim.2022.577955