JAMA：干扰素β治疗多发性硬化症与患者伤残进展减少无关

芝加哥–据7月18日刊《美国医学会杂志》JAMA上的一项研究披露，在罹患复发-缓解型多发性硬化症（MS）的病人中，用广泛使用于治疗MS的处方药干扰素β进行治疗与患者的较少的伤残进展无关。

加拿大温哥华英属哥伦比亚大学的Afsaneh Shirani, M.D.及其同事开展了一项研究，旨在调查接触干扰素β与复发-缓解型MS的伤残进展之间的关系。这项研究包括了来自英属哥伦比亚的前瞻性收集的数据（1985-2008）。接受干扰素β治疗的复发-缓解型MS患者(n = 868)与未接受治疗的现今的人群组(n = 829)及过去的人群组（即在干扰素β获得批准之前的人群组）(n = 959)进行了比较。主要的检测结果为从合格接受干扰素β治疗（基线）至确认且持续地在扩展的伤残状态量表上（EDSS）（范围在0-10，较高的评分表明较严重的伤残）的评分为6（需要用手杖走100米；在超过150天时证实没有可检测的到的改善）的时间。

对患者的跟踪时间（首次至末次EDSS检测的时间）因组而异，过去未经治疗的群组（中位数[中点]，10.8年）的跟踪时间要长得多， 这些人按定义进入该研究的时间要比现今人群组要早得多。现今人群组的中位跟踪时间在治疗组为5.1年而在未经治疗组为4.0年。

所观察到的达到某种持续性EDSS评分为6的结果百分比在治疗组为10.8%；在现今的未经治疗组为5.3%；在过去的未经治疗为23.1%。

研究人员写道：“在对潜在的基线混淆因素（性别、年龄、患病时间及EDSS评分）进行校正之后，无论是考量现今的对照群组或是过去的对照群组，接触干扰素β与EDSS评分达到6的危险性的统计学上的显著差异之间没有联系。”对并存的疾病及社会经济状况在可能的情况下做进一步的校正没有改变对数据的解读。

“总之，我们没有发现有证据显示，给予干扰素β与复发-缓解型MS患者的伤残进展的减少有关。治疗MS的最终目标是为了防止或延缓长期的伤残。我们的发现对常规性使用干扰素β药物来达到在MS中的这一目标提出了质疑。然而，有可能某个亚组的患者会得益于干扰素β的治疗，而这种关系在我们的综合性“现实的”的研究中无法被看到。还需要做进一步的研究来发现这些潜在的患者；也许通过药物基因组学或生物标记研究可为某种量身打造的个性化的医疗方法铺平道路。我们的发现还鼓励人们对MS的新型疗法进行研究。”

doi:10.1001/jama.2012.7625
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Association Between Use of Interferon Beta and Progression of Disability in Patients With Relapsing-Remitting Multiple Sclerosis

Afsaneh Shirani, MD; Yinshan Zhao, PhD; Mohammad Ehsanul Karim, MSc; Charity Evans, PhD; Elaine Kingwell, PhD; Mia L. van der Kop, MSc; Joel Oger, MD, FRCPC; Paul Gustafson, PhD; John Petkau, PhD; Helen Tremlett, PhD

Context Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. Objective To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Design, Setting, and Patients Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. Main Outcome Measures The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. Results The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta–treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0.77; 95% CI, 0.58-1.02; P = .07) were considered. Further adjustment for comorbidities and socioeconomic status, where possible, did not change interpretations, and propensity score adjustment did not substantially change the results. Conclusion Among patients with relapsing-remitting MS, administration of interferon beta was not associated with a reduction in progression of disability.