背景:COVID-19大流行引起了临床医生的关注,特别是抗CD20单克隆抗体(mAb)和芬戈莫德,可能会使多发性硬化症(pwMS)患者的COVID-19恶化。这项研究旨在检查DMT在大流行发作前后的处方趋势。
方法:对来自MSBase的8,771名参与者进行了一项多中心纵向研究。定义了两个时间段:大流行前(2018年3月11日至2020年3月10日)和大流行后(2020年3月11日至2022年3月11日)。使用多变量混合效应逻辑回归分析时间和处方趋势之间的关联。DMT启动是指任何DMT的首次启动,而DMT开关表明在最后一次使用后6个月内改变方案。
结果:大流行发作后,DMT开始/转换为那他珠单抗和克拉屈滨的显着增加[(那他珠单抗开始:OR1.72,95%CI1.39-2.13;转换:OR1.66,95%CI1.40-1.98),(克拉屈滨起始:OR1.43,95%CI1.09-1.87;转换:OR1.67,95%CI1.41-1.98)]。抗CD20mAb启动/转换在大流行的年份减少,但是在第二年恢复了,这样,大流行后的总体几率略有增加(开始:OR1.26,95%CI1.06-1.49;转换:OR1.15,95%CI1.02-1.29。芬戈莫德的启动/切换,干扰素-β,和阿仑单抗显着降低[(芬戈莫德开始:OR0.55,95%CI0.41-0.73;转换:OR0.49,95%CI0.41-0.58),(干扰素-γ起始:OR0.48,95%CI0.41-0.57;转换:OR0.78,95%CI0.62-0.99),(阿仑珠单抗起始:OR0.27,95%CI0.15-0.48;转换:OR0.27,95%CI0.17-0.44)]。
结论:大流行发作后,临床医生优先使用那他珠单抗和克拉屈滨,而不是抗CD20单克隆抗体和芬戈莫德,可能保持疗效,但降低感知的免疫抑制风险。这可能对pwMS中的疾病进展有影响。我们的发现强调了全球公平的DMT准入的重要性,以及循证决策在全球卫生挑战中的重要性。
BACKGROUND: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset.
METHODS: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use.
RESULTS: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)].
CONCLUSIONS: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.