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

Y. Nishida, Y. K. Takahashi, T. Kanai, Y. Nose, S. Ishibashi, N. Sanjo, A. Uzawa, F. Oda, Y. Ozawa, S. Kuwabara, E. Noguchi, S. Suzuki, J. Nakahara, N. Suzuki, T. Ogawa, K. Yokoyama, N. Hattori, S. Konno, T. Fujioka, N. KawaguchiY. Hatanaka, M. Sonoo, J. Kaneko, M. Ogino, K. Nishiyama, K. Nomura, T. Yokota

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalEuropean Journal of Neurology
DOIs
Publication statusAccepted/In press - 2019 Jan 1

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Myasthenia Gravis
Tacrolimus
Cholinergic Receptors
Safety
Antibodies
Age of Onset
Maintenance
Immunosuppressive Agents
ROC Curve

Keywords

  • anti-acetylcholine receptor antibody
  • calcineurin inhibitor
  • dose reduction
  • immunosuppressants
  • myasthenia
  • reduction-associated exacerbation
  • tacrolimus
  • tapering

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis. / Nishida, Y.; Takahashi, Y. K.; Kanai, T.; Nose, Y.; Ishibashi, S.; Sanjo, N.; Uzawa, A.; Oda, F.; Ozawa, Y.; Kuwabara, S.; Noguchi, E.; Suzuki, S.; Nakahara, J.; Suzuki, N.; Ogawa, T.; Yokoyama, K.; Hattori, N.; Konno, S.; Fujioka, T.; Kawaguchi, N.; Hatanaka, Y.; Sonoo, M.; Kaneko, J.; Ogino, M.; Nishiyama, K.; Nomura, K.; Yokota, T.

In: European Journal of Neurology, 01.01.2019.

Research output: Contribution to journalArticle

Nishida, Y, Takahashi, YK, Kanai, T, Nose, Y, Ishibashi, S, Sanjo, N, Uzawa, A, Oda, F, Ozawa, Y, Kuwabara, S, Noguchi, E, Suzuki, S, Nakahara, J, Suzuki, N, Ogawa, T, Yokoyama, K, Hattori, N, Konno, S, Fujioka, T, Kawaguchi, N, Hatanaka, Y, Sonoo, M, Kaneko, J, Ogino, M, Nishiyama, K, Nomura, K & Yokota, T 2019, 'Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis', European Journal of Neurology. https://doi.org/10.1111/ene.14039
Nishida, Y. ; Takahashi, Y. K. ; Kanai, T. ; Nose, Y. ; Ishibashi, S. ; Sanjo, N. ; Uzawa, A. ; Oda, F. ; Ozawa, Y. ; Kuwabara, S. ; Noguchi, E. ; Suzuki, S. ; Nakahara, J. ; Suzuki, N. ; Ogawa, T. ; Yokoyama, K. ; Hattori, N. ; Konno, S. ; Fujioka, T. ; Kawaguchi, N. ; Hatanaka, Y. ; Sonoo, M. ; Kaneko, J. ; Ogino, M. ; Nishiyama, K. ; Nomura, K. ; Yokota, T. / Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis. In: European Journal of Neurology. 2019.
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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.",
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author = "Y. Nishida and Takahashi, {Y. K.} and T. Kanai and Y. Nose and S. Ishibashi and N. Sanjo and A. Uzawa and F. Oda and Y. Ozawa and S. Kuwabara and E. Noguchi and S. Suzuki and J. Nakahara and N. Suzuki and T. Ogawa and K. Yokoyama and N. Hattori and S. Konno and T. Fujioka and N. Kawaguchi and Y. Hatanaka and M. Sonoo and J. Kaneko and M. Ogino and K. Nishiyama and K. Nomura and T. Yokota",
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T1 - Safety of tapering tacrolimus dose in patients with well-controlled anti-acetylcholine receptor antibody-positive myasthenia gravis

AU - Nishida, Y.

AU - Takahashi, Y. K.

AU - Kanai, T.

AU - Nose, Y.

AU - Ishibashi, S.

AU - Sanjo, N.

AU - Uzawa, A.

AU - Oda, F.

AU - Ozawa, Y.

AU - Kuwabara, S.

AU - Noguchi, E.

AU - Suzuki, S.

AU - Nakahara, J.

AU - Suzuki, N.

AU - Ogawa, T.

AU - Yokoyama, K.

AU - Hattori, N.

AU - Konno, S.

AU - Fujioka, T.

AU - Kawaguchi, N.

AU - Hatanaka, Y.

AU - Sonoo, M.

AU - Kaneko, J.

AU - Ogino, M.

AU - Nishiyama, K.

AU - Nomura, K.

AU - Yokota, T.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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KW - calcineurin inhibitor

KW - dose reduction

KW - immunosuppressants

KW - myasthenia

KW - reduction-associated exacerbation

KW - tacrolimus

KW - tapering

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