Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital, Boston, MA, USA.
The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mult Scler. 2021 May;27(6):922-932. doi: 10.1177/1352458520936934. Epub 2020 Jul 7.
Reduction in absolute lymphocyte count (ALC) is expected with fingolimod treatment.
To evaluate the effect of fingolimod 0.5 mg versus intramuscular interferon β-1a (30 μg) on ALC and its relationship with infections in paediatric-onset multiple sclerosis (POMS) up to 4 years.
We assessed ALC at baseline, monthly till 3 months, and every 3 months (core phase) and with variable periodicity (extension phase) of Phase 3 PARADIG study ( = 215). Incidence rates (IRs) of infection-related adverse events (AEs)/100 patient-years were analysed by on-study nadir ALC.
With fingolimod, ALC rapidly reduced to 29.9%-34.4% of baseline values within 2 weeks and remained stable thereafter; no relevant changes observed with interferon. IRs of AEs were 67.6 with fingolimod and 61.8 with interferon; IR ratios with respect to interferon, overall: 1.09, by nadir ALC 0.2-0.4 × 10/L: 1.13 and >0.4 × 10/L: 0.91. Three patients had a single episode of ALC <0.2 × 10/L (core phase). No opportunistic infections were observed and infection risk did not increase during the extension phase.
In paediatric patients, the overall incidence of infections was comparable between fingolimod and interferon. No association was observed between nadir ALC and infections in POMS, although sample size may have been too small to rule an association.
接受芬戈莫德治疗时，预期会出现绝对淋巴细胞计数（ALC）降低。
评估芬戈莫德 0.5mg 与肌内注射干扰素β-1a（30μg）对儿科发病多发性硬化症（POMS）患者 ALC 的影响及其与感染的关系，随访时间长达 4 年。
我们评估了 PARADIG 研究 3 期（n=215）的基线、前 3 个月每月以及核心期每 3 个月和扩展期（定期）的 ALC。采用研究期间最低 ALC 分析感染相关不良事件（AE）/100 患者年的发生率（IR）。
接受芬戈莫德治疗，ALC 在 2 周内迅速降低至基线值的 29.9%-34.4%，此后保持稳定；干扰素治疗则未见相关变化。接受芬戈莫德治疗的 AE 发生率为 67.6%，接受干扰素治疗的为 61.8%；与干扰素相比，IR 比值，整体为 1.09，最低 ALC 为 0.2-0.4×10/L 时为 1.13，>0.4×10/L 时为 0.91。3 名患者出现单次 ALC<0.2×10/L（核心期）。未观察到机会性感染，且在扩展期感染风险未增加。
在儿科患者中，芬戈莫德与干扰素治疗的感染总发生率相当。虽然可能由于样本量太小而无法排除关联，但在 POMS 中，最低 ALC 与感染之间未观察到相关性。
