van der Voort Laura F, Gilli Francesca, Bertolotto Antonio, Knol Dirk L, Uitdehaag Bernard M J, Polman Chris H, Killestein Joep
Department of Neurology, VU Medical Center, de Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
Arch Neurol. 2010 Apr;67(4):402-7. doi: 10.1001/archneurol.2010.21. Epub 2010 Feb 8.
To confirm that neutralizing antibodies (NAb) to interferon beta can persist after therapy withdrawal and to evaluate whether persisting NAb are associated with a worse clinical disease course in multiple sclerosis (MS).
Retrospective study.
Tertiary referral center in The Netherlands.
A total of 71 patients with relapsing-remitting multiple sclerosis treated with interferon beta in the past.
Persisting NAb after therapy withdrawal were tested using the cytopathic effect assay. Patients with and without persisting NAb were compared on several outcomes: the change in annualized relapse rate from prior to interferon beta treatment initiation to after cessation of treatment, time to sustained disability on the Kurtzke Expanded Disability Status Scale, and the use of disease-modifying treatments after cessation of treatment with interferon beta.
Seventeen of 71 patients (24%) tested NAb positive after a median interval of 25 months (interquartile range, 10-51 months) after interferon beta treatment cessation. Eleven of these 17 patients (15%) were high-titer NAb positive (>150 10-fold reduction units per mL). Persisting NAb were associated with an increase in the annualized relapse rate (P = .04) and a reduction in time to reach a sustained Expanded Disability Status Scale score of 6.0, ie, the need for unilateral assistance to walk 100 m (P = .02). Moreover, NAb-positive patients were treated with second-line therapy significantly more often, especially mitoxantrone (P = .006).
Anti-interferon beta NAb can persist after interferon beta treatment withdrawal and are associated with overt clinical disease activity. This is made apparent by an increase in relapse rate and faster disability progression and is supported by the observed need for more aggressive therapy after interferon beta treatment cessation. Prospective studies are warranted to confirm these results.
确认抗干扰素β中和抗体（NAb）在治疗停药后是否会持续存在，并评估持续存在的NAb是否与多发性硬化症（MS）更差的临床病程相关。
回顾性研究。
荷兰的三级转诊中心。
共有71例既往接受过干扰素β治疗的复发缓解型多发性硬化症患者。
停药后使用细胞病变效应试验检测持续存在的NAb。比较有和没有持续存在NAb的患者在几个结果上的差异：从开始使用干扰素β治疗前到治疗停止后的年化复发率变化、达到Kurtzke扩展残疾状态量表持续残疾的时间，以及停止使用干扰素β治疗后使用疾病修饰治疗的情况。
71例患者中有17例（24%）在停止使用干扰素β治疗后的中位间隔25个月（四分位间距，10 - 51个月）检测出NAb呈阳性。这17例患者中有11例（15%）高滴度NAb呈阳性（>150个10倍减少单位/毫升）。持续存在的NAb与年化复发率增加（P = 0.04）以及达到扩展残疾状态量表评分6.0（即行走100米需要单侧辅助）的时间缩短相关（P = 0.02）。此外，NAb阳性患者接受二线治疗的频率明显更高，尤其是米托蒽醌（P = 0.006）。
抗干扰素β NAb在停止干扰素β治疗后可持续存在，并与明显的临床疾病活动相关。这表现为复发率增加和残疾进展加快，并且在停止干扰素β治疗后观察到需要更积极的治疗也支持了这一点。有必要进行前瞻性研究以证实这些结果。
