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Eur J Neurol. 2019 Jul 15. doi: 10.1111/ene.14039. [Epub ahead of print]
Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis.
Nishida Y1, Takahashi YK1, Kanai T2, Nose Y1, Ishibashi S1, Sanjo N1, Uzawa A2, Oda F2, Ozawa Y2, Kuwabara S2, Noguchi E3, Suzuki S3, Nakahara J3, Suzuki N3, Ogawa T4, Yokoyama K4, Hattori N4, Konno S5, Fujioka T5, Kawaguchi N6, Hatanaka Y7, Sonoo M7, Kaneko J8, Ogino M8,9, Nishiyama K8, Nomura K10, Yokota T1.
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 has not been known.
To clarify the frequency of reduction-associated exacerbation when tacrolimus is tapered in stable patients with anti-acetylcholine receptor antibody (anti-AChRAb)-positive MG, and to determine the factors that predict exacerbations.
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 less than 3 months after the reduction.
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 one 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 cutoff 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.
Tapering of tacrolimus is possible in most patients with well-controlled anti-AChRAb-positive MG. Early age at onset and a large reduction from maintenance dosage are associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late-onset disease.
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