TY - JOUR
T1 - Azathioprine
T2 - Tolerability, efficacy, and predictors of benefit in neuromyelitis optica
AU - Costanzi, C.
AU - Matiello, M.
AU - Lucchinetti, C. F.
AU - Weinshenker, B. G.
AU - Pittock, S. J.
AU - Mandrekar, J.
AU - Thapa, P.
AU - McKeon, A.
N1 - Funding Information:
Dr. Costanzi reports no disclosures. Dr. Matiello is supported by a postdoctoral fellowship grant from the National MS Society. Dr. Lucchinetti receives publishing royalties for Blue Books of Neurology: Multiple Sclerosis 3 (Saunders Elsevier, 2010); receives research support from the NIH, the National MS Society, and the Guthy-Jackson Charitable Foundation; and receives license royalties from RSR Ltd. for a patent re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica. Dr. Weinshenker serves on data safety monitoring boards for Novartis and Biogen Idec; serves on the editorial boards of Multiple Sclerosis , the Canadian Journal of Neurological Sciences , and the Turkish Journal of Neurology ; has received research support from Genzyme Corporation and the Guthy-Jackson Charitable Foundation; and receives license royalties from RSR Ltd. for a patent re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica. Dr. Pittock may accrue revenue for patents re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica and Aquaporin-4 autoantibody as a cancer marker; and has received research support from Alexion Pharmaceuticals, Inc. and the Guthy-Jackson Charitable Foundation. Dr. Mandrekar and Dr. Thapa report no disclosures. Dr. McKeon receives research support from the Guthy-Jackson Charitable Foundation.
PY - 2011/8/16
Y1 - 2011/8/16
N2 - Objective: To evaluate the efficacy, tolerability, optimal dosing, and monitoring of azathioprine in patients with neuromyelitis optica (NMO). Methods: This was a chart review and telephone follow-up study of 99 patients with NMO spectrum of disorders (NMOSD) treated with azathioprine (1994-2009). NMOSD were NMO (2006 diagnostic criteria) or partial NMO forms (NMO-immunoglobulin G seropositive). Wilcoxon signed rank test was used to compare pretreatment and postinitiation of azathioprine (posttreatment) annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) score, and visual acuity outcome. Linear regression was used to assess the effects of various factors on ARR change and disability. Results: The median duration of NMOSD symptoms prior to initiation of azathioprine was 2 years (range 1-27); 79 patients were women. Eighty-six patients had NMO and 13 limited NMO versions, including transverse myelitis in 8 and optic neuritis in 5. Median posttreatment follow-up was 22 months. Thirty-eight patients discontinued drug (side effects, 22; no efficacy, 13; lymphoma, 3). Among 70 patients with >12 months follow-up, 48 received ≥2.0 mg/kg/day (ARR: pretreatment, 2.20; posttreatment, 0.52); 22 received <2.0 mg/kg/day (ARR: pretreatment, 2.09; posttreatment, 0.82); 52 received concomitant prednisone (ARR: pretreatment, 2.20; posttreatment, 0.89) and 18 did not (ARR: pretreatment, 1.54; posttreatment, 0.23); p < 0.0001 for each comparison. EDSS was stable or improved despite ongoing attacks in 22 patients (31%). Twenty-six patients tolerated azathioprine and were relapse-free (37%, median follow-up 24 months; range 12-151). Mean corpuscular volume increase influenced ARR change (p = 0.049). Conclusions: Azathioprine is generally effective and well-tolerated. Early initiation, adequate dosing, and hematologic parameter monitoring may optimize efficacy. Classification of evidence: This study provides Class IV evidence that azathioprine is effective for reducing relapse rates and improving EDSS and visual acuity scores in patients with NMO spectrum of disorders.
AB - Objective: To evaluate the efficacy, tolerability, optimal dosing, and monitoring of azathioprine in patients with neuromyelitis optica (NMO). Methods: This was a chart review and telephone follow-up study of 99 patients with NMO spectrum of disorders (NMOSD) treated with azathioprine (1994-2009). NMOSD were NMO (2006 diagnostic criteria) or partial NMO forms (NMO-immunoglobulin G seropositive). Wilcoxon signed rank test was used to compare pretreatment and postinitiation of azathioprine (posttreatment) annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) score, and visual acuity outcome. Linear regression was used to assess the effects of various factors on ARR change and disability. Results: The median duration of NMOSD symptoms prior to initiation of azathioprine was 2 years (range 1-27); 79 patients were women. Eighty-six patients had NMO and 13 limited NMO versions, including transverse myelitis in 8 and optic neuritis in 5. Median posttreatment follow-up was 22 months. Thirty-eight patients discontinued drug (side effects, 22; no efficacy, 13; lymphoma, 3). Among 70 patients with >12 months follow-up, 48 received ≥2.0 mg/kg/day (ARR: pretreatment, 2.20; posttreatment, 0.52); 22 received <2.0 mg/kg/day (ARR: pretreatment, 2.09; posttreatment, 0.82); 52 received concomitant prednisone (ARR: pretreatment, 2.20; posttreatment, 0.89) and 18 did not (ARR: pretreatment, 1.54; posttreatment, 0.23); p < 0.0001 for each comparison. EDSS was stable or improved despite ongoing attacks in 22 patients (31%). Twenty-six patients tolerated azathioprine and were relapse-free (37%, median follow-up 24 months; range 12-151). Mean corpuscular volume increase influenced ARR change (p = 0.049). Conclusions: Azathioprine is generally effective and well-tolerated. Early initiation, adequate dosing, and hematologic parameter monitoring may optimize efficacy. Classification of evidence: This study provides Class IV evidence that azathioprine is effective for reducing relapse rates and improving EDSS and visual acuity scores in patients with NMO spectrum of disorders.
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U2 - 10.1212/WNL.0b013e31822a2780
DO - 10.1212/WNL.0b013e31822a2780
M3 - Article
C2 - 21813788
AN - SCOPUS:80055095675
SN - 0028-3878
VL - 77
SP - 659
EP - 666
JO - Neurology
JF - Neurology
IS - 7
ER -