Low dose naltrexone in multiple sclerosis: Effects on medication use. A quasi-experimental study

Low dose naltrexone (LDN) has become a popular off-label therapy for multiple sclerosis (MS). A few small, randomized studies indicate that LDN may have beneficial effects in MS and other autoimmune diseases. If proven efficacious, it would be a cheap and safe alternative to the expensive treatments currently recommended for MS. We investigated whether a sudden increase in LDN use in Norway in 2013 was followed by changes in dispensing of other medications used to treat MS. We performed a quasi-experimental before–and–after study based on population data from the Norwegian Prescription Database (NorPD). We included all patients that collected at least one LDN prescription in 2013, and had collected at least two medications with a reimbursement code for MS, or collected a medication with MS as the only indication in 2009 or 2010. Outcomes were differences in cumulative dispensed doses and incidence of users of disease modifying MS therapies, and medications used to treat MS symptoms two years before and two years after dispensing the initial LDN prescription. The eligible 341 patients collected 20 921 prescriptions in the observation period. Apart from changes in line with general trends in MS therapy in Norway, there was no difference in neither dispensed cumulative doses or number of prevalent users of MS specific medication. Initiation of LDN was not followed by reductions of other medications used to treat symptoms associated with MS.

低剂量纳曲酮（Low dose naltrexone, LDN）已成为多发性硬化症（multiple sclerosis, MS）领域备受关注的超适应症治疗手段。数项小型随机对照研究表明，LDN或对多发性硬化症及其他自身免疫性疾病具有有益效应。若被证实有效，它将成为当前临床推荐的多发性硬化症昂贵治疗方案的廉价且安全的替代选择。

本研究旨在探究2013年挪威LDN使用量骤增后，其他多发性硬化症治疗药物的配药情况是否出现变化。本研究基于挪威处方数据库（Norwegian Prescription Database, NorPD）的人群登记数据开展类实验性前后对照研究。研究纳入了2013年至少配取1张LDN处方，且在2009年或2010年期间，至少配取2种带有多发性硬化症报销编码的药物，或以多发性硬化症为唯一适应症药物的所有患者。

研究结局指标为初始LDN处方配取前后两年内，多发性硬化症疾病修正治疗药物（disease modifying MS therapies）的累计配药剂量差异、使用者发生率，以及多发性硬化症症状治疗药物的使用变化。最终纳入的341例患者在整个观察期内共计配取20921张处方。除与挪威多发性硬化症治疗的整体趋势相符的变化外，多发性硬化症特异性药物的累计配药剂量与现患使用者数量均未出现显著差异。初始使用LDN后，并未出现多发性硬化症相关症状治疗药物用量减少的情况。