Okuda Darin T, Tardo Lauren M, Wright Crystal M, Munoz Shanan B, Punnen Tom G, Patel Mahi A, Moog Tatum M, Burgess Katy W
Department of Neurology, Neuroinnovation Program, Multiple Sclerosis & Neuroimmunology Imaging Program, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Peter O'Donnell Jr. Brain Institute, Dallas, TX 75390, USA.
The University of Texas Southwestern Medical Center, Department of Neurology, Neuroinnovation Program, Multiple Sclerosis & Neuroimmunology Imaging Program, Dallas, TX, USA.
Ther Adv Neurol Disord. 2024 Nov 21;17:17562864241300047. doi: 10.1177/17562864241300047. eCollection 2024.
An expansion in the availability of generic specialty disease modifying therapies (DMTs) for treatment of multiple sclerosis (MS) has increased recently. Generic specialty medications aim to provide greater access to molecules that alter the disease trajectory at lower costs. The US Food and Drug Administration requires generic products to contain between 90% and 110% of the stated active ingredient and an 80%-125% bioequivalence range. We present the clinical experiences and absolute lymphocyte counts (ALC) trends of six people with MS originally treated with Gilenya (fingolimod) 0.5 mg who were required to transition to generic fingolimod 0.5 mg by third-party administrators, and the medication content from recovered products. Six individuals with acute clinical exacerbations or disease advancement on MRI were identified during routine scheduled visits from a tertiary care center and consecutively included from January 2024 to August 2024. ALC trends were constructed for each individual during Gilenya and generic fingolimod treatment. These individuals experienced signs of disease advancement while on generic fingolimod 0.5 mg at approximately 1 year of treatment and elevations in ALC, a biological metric related to the mechanism of action of sphingsine-1-phosphate receptor modulation, were observed following the transition. High purity fingolimod for standardization tests, Gilenya 0.5 mg, and five recovered generic fingolimod 0.5 mg products were independently tested in an accredited laboratory. Gilenya 0.5 mg capsules had an average fingolimod content of 97.7% (standard deviation (SD) = 2.59%). Three recovered generic fingolimod 0.5 mg products used during relapses had an average content of 91.2% (3.25%), 81.6% (6.24%), and 72.5% (2.05%). Two generic fingolimod 0.5 mg products not associated with relapse activity revealed averages of 97.4% (1.82%) and 103.3% (3.77%). Subpotent generic specialty DMTs may not only result in greater risk for disease activity but may also expose individuals to the potential for disease rebound, depending on the mechanism of action.
近年来，用于治疗多发性硬化症（MS）的通用型疾病修正疗法（DMTs）的可及性有所增加。通用型专科药物旨在以更低的成本让更多人能够使用改变疾病进程的分子药物。美国食品药品监督管理局要求通用型产品所含活性成分在规定量的90%至110%之间，生物等效性范围为80%至125%。我们呈现了6例最初使用0.5毫克吉立安（芬戈莫德）治疗的MS患者的临床经验和绝对淋巴细胞计数（ALC）趋势，这些患者被第三方管理机构要求转换为通用型0.5毫克芬戈莫德，并报告了回收产品的药物含量。在一家三级医疗中心的常规定期随访中，识别出6例出现急性临床加重或MRI显示疾病进展的个体，他们于2024年1月至2024年8月被连续纳入研究。在使用吉立安和通用型芬戈莫德治疗期间，为每个个体构建了ALC趋势。这些个体在使用0.5毫克通用型芬戈莫德治疗约1年后出现疾病进展迹象，且在转换药物后观察到ALC升高，ALC是一种与1 -磷酸鞘氨醇受体调节作用机制相关的生物学指标。用于标准化测试的高纯度芬戈莫德、0.5毫克吉立安以及5个回收的0.5毫克通用型芬戈莫德产品在一家认可的实验室进行了独立检测。0.5毫克吉立安胶囊的芬戈莫德平均含量为97.7%（标准差（SD）=2.59%）。在复发期间使用的3个回收的0.5毫克通用型芬戈莫德产品的平均含量分别为91.2%（3.25%）、81.6%（6.24%）和72.5%（2.05%）。2个与复发活动无关的0.5毫克通用型芬戈莫德产品的平均含量分别为97.4%（1.82%）和103.3%（3.77%）。效力不足的通用型专科DMTs不仅可能导致疾病活动风险增加，还可能使个体面临疾病反弹的可能性，具体取决于其作用机制。
