Centonze Diego, Amato Maria Pia, Brescia Morra Vincenzo, Cocco Eleonora, De Stefano Nicola, Gasperini Claudio, Gallo Paolo, Pozzilli Carlo, Trojano Maria, Filippi Massimo
Department of Systems Medicine, Tor Vergata University, Via Montpellier, 1, 00133 Rome, Italy.
IRCCS Neuromed, Pozzilli, Italy.
Ther Adv Neurol Disord. 2023 Jul 8;16:17562864231183221. doi: 10.1177/17562864231183221. eCollection 2023.
Multiple sclerosis (MS) is a chronic, progressive neurological disease involving neuroinflammation, neurodegeneration, and demyelination. Cladribine tablets are approved for immune reconstitution therapy in patients with highly active relapsing-remitting MS based on favorable efficacy and tolerability results from the CLARITY study that have been confirmed in long-term extension studies. The approved 4-year dosing regimen foresees a cumulative dose of 3.5 mg/kg administered in two cycles administered 1 year apart, followed by 2 years of observation. Evidence on managing patients beyond year 4 is scarce; therefore, a group of 10 neurologists has assessed the available evidence and formulated an expert opinion on management of the growing population of patients now completing the approved 4-year regimen. We propose five patient categories based on response to treatment during the first 4-year regimen, and corresponding management pathways that envision close monitoring with clinical visits, magnetic resonance imaging (MRI) and/or biomarkers. At the first sign of clinical or radiological disease activity, patients should receive a highly effective disease-modifying therapy, comprising either a full cladribine regimen as described in regulatory documents (cumulative dose 7.0 mg/kg) or a comparably effective treatment. Re-treatment decisions should be based on the intensity and timing of onset of disease activity, clinical and radiological assessments, as well as patient eligibility for treatment and treatment preference.
多发性硬化症（MS）是一种慢性进行性神经疾病，涉及神经炎症、神经退行性变和脱髓鞘。基于CLARITY研究中良好的疗效和耐受性结果（这些结果在长期扩展研究中得到了证实），克拉屈滨片被批准用于高度活动性复发缓解型MS患者的免疫重建治疗。批准的4年给药方案预计累积剂量为3.5mg/kg，分两个周期给药，间隔1年，随后进行2年的观察。关于4年后患者管理的证据很少；因此，一组10名神经科医生评估了现有证据，并就如何管理目前已完成批准的4年治疗方案的患者群体不断增加的情况形成了专家意见。我们根据前4年治疗方案中的治疗反应提出了五类患者，以及相应的管理途径，这些途径设想通过临床就诊、磁共振成像（MRI）和/或生物标志物进行密切监测。在出现临床或放射学疾病活动的第一个迹象时，患者应接受高效疾病修正治疗，包括监管文件中描述的完整克拉屈滨治疗方案（累积剂量7.0mg/kg）或同等有效的治疗。重新治疗的决定应基于疾病活动发作的强度和时间、临床和放射学评估，以及患者的治疗资格和治疗偏好。
