Most patients with myasthenia gravis (MG) and resistance to glucocorticoids have a good prognosis after adding tacrolimus to their therapy regimen. a study recently published in Frontiers in Neurology suggests.  

Current maintenance treatment of MG includes pyridostigmine, glucocorticoids, and immunosuppressants; nevertheless, about a quarter of patients with MG do not respond or become resistant to glucocorticoids, and with time, patients may suffer from adverse drug reactions (ADRs) due to long-lasting immunotherapy.

Researchers conducted a retrospective, observational cohort study that evaluated the outcome of administering 2 to 3 mg of tacrolimus for at least 6 months to childhood-onset MG patients with inadequate response to 2 months of prednisone therapy, assessing factors associated with a positive response. Primary outcomes included prednisone dose, Quantitative MG (QMG) score, and MG-Activities of Daily Living (ADL) score. The improvement or lack thereof in MG patients took changes in QMG score into account.

The results showed that 75.8% of the 149 MG patients positively responded to tacrolimus treatment. The authors reported improvements in prednisone dose, QMG score, and MG-ADL score 1 month after initiating tacrolimus, and these continued to improve throughout the study. Notably, 78.8% of patients eventually stopped prednisone treatment.

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The thymus type and preintervention status were independent risk factors for predicting tacrolimus efficacy after controlling confounding factors in the multiple logistic regression analysis, with odds ratios of 3.156 and 0.284, respectively. 

“The thymus is thought to play an important role in the pathogenesis of MG. Our data showed that concomitant thymus hyperplasia was an independent risk factor for poor efficacy of tacrolimus in children with steroid-resistant MG, even in a situation when thymectomy therapy had been used,” the authors noted.

Furthermore, although the literature reports a high incidence of ADRs for tacrolimus (42.5% to 87.5%), the authors revealed an incidence of less than 7.5% after 3 years of follow-up, perhaps because lower doses were used. All of the ADRs appeared within 10 months and resolved after discontinuing tacrolimus; therefore, the authors suggest that tacrolimus is relatively safe to use in the long term for glucocorticoid-resistant MG patients. 

The authors concluded, “Although tacrolimus improved symptoms in the majority of steroid-resistant [childhood-onset MG] patients with few adverse effects, some patients still did not react well to tacrolimus. Clinically independent factors affecting tacrolimus efficacy include thymus hyperplasia and pre-intervention status.”

They added that they “are currently working on a follow-up study to explore the underlying immunological mechanism of therapeutic failure in patients who haven’t responded to steroids or tacrolimus.”

Reference

Bi Z, Cao Y, Lin J, et al. Long-term improvement in a Chinese cohort of glucocorticoid-resistant childhood-onset myasthenia gravis patients treated with tacrolimusFront Neurol. 2022;13:820205. doi:10.3389/fneur.2022.820205