Safety of tapering tacrolimus dose in patients with well‐controlled anti‐acetylcholine receptor antibody‐positive myasthenia gravis

Abstract

Background and purpose Tapering immunosuppressants is desirable in patients with well‐controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction‐associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction‐associated exacerbation when tacrolimus is tapered in stable patients with anti‐acetylcholine receptor antibody‐positive MG, and to determine the factors that predict exacerbations. Methods We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction‐associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction. Results Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction‐associated exacerbation than in those without exacerbation. The cut‐off values determined in a receiver‐operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction. Conclusion Tapering of tacrolimus was possible in most patients with well‐controlled anti‐acetylcholine receptor antibody‐positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late‐onset disease.

Immunotherapy choice and maintenance for generalized myasthenia gravis in China

“…Our study indicated that steroid‐sparing tacrolimus showed superior efficacy as well as lower incidence of adverse events compared with azathioprine or mycophenolate mofetil. Indeed, consistent with prior reports, many patients could taper tacrolimus or even stop concomitant steroids 22‐24 . In light of limitations in treatment duration of mycophenolate mofetil as monotherapy or steroid‐sparing agent, patients who failed were more likely to switch to tacrolimus treatment.…”

Long-Term Improvement in a Chinese Cohort of Glucocorticoid-Resistant Childhood-Onset Myasthenia Gravis Patients Treated With Tacrolimus

“…Even when the symptoms had been adequately controlled, most patients in our study were hesitant to stop taking tacrolimus because of the protracted illness course and significant chance of relapse ( 37 ). Tacrolimus dosage was successfully tapered in 24 (21.2%) of the 113 well-controlled patients in our cohorts without exacerbating their condition.…”

Remission and relapses of myasthenia gravis on long-term tacrolimus: a retrospective cross-sectional study of a Chinese cohort

“…In this study, relapses occurred in nearly half of the patients with well-controlled MG after tapering tacrolimus, which is considerably higher than the 4% relapses in the series of Nishida et al . 6 This could be because the latter limited definition of exacerbations to 3 months after tacrolimus reduction. In addition, relapses typically occurred within 6 months of dose reduction (mean 2.1 ± 1.6 months), indicating that the improvement induced by tacrolimus does not usually last after tapering off.…”