Riley Nicholas, Drudge Christopher, Nelson Morag, Haltner Anja, Barnett Michael, Broadley Simon, Butzkueven Helmut, McCombe Pamela, Van der Walt Anneke, Wong Erin O Y, Merschhemke Martin, Adlard Nicholas, Walker Rob, Samjoo Imtiaz A
Novartis Pharmaceuticals Australia, Sydney, NSW, Australia.
EVERSANA, Value and Evidence, Burlington, ON, Canada.
Ther Adv Neurol Disord. 2024 Mar 23;17:17562864241239453. doi: 10.1177/17562864241239453. eCollection 2024.
Evidence from network meta-analyses (NMAs) and real-world propensity score (PS) analyses suggest monoclonal antibodies (mAbs) offer a therapeutic advantage over currently available oral therapies and, therefore, warrant consideration as a distinct group of high-efficacy disease-modifying therapies (DMTs) for patients with relapsing multiple sclerosis (RMS). This is counter to the current perception of these therapies by some stakeholders, including payers.
A multifaceted indirect treatment comparison (ITC) approach was undertaken to clarify the relative efficacy of mAbs and oral therapies.
Two ITC methods that use individual patient data (IPD) to adjust for between-trial differences, PS analyses and simulated treatment comparisons (STCs), were used to compare the mAb ofatumumab the oral therapies cladribine, fingolimod, and ozanimod.
As IPD were available for trials of ofatumumab and fingolimod, PS analyses were conducted. Given summary-level data were available for cladribine, fingolimod, and ozanimod trials, STCs were conducted between ofatumumab and each of these oral therapies. Three efficacy outcomes were compared: annualized relapse rate (ARR), 3-month confirmed disability progression (3mCDP), and 6-month CDP (6mCDP).
The PS analyses demonstrated ofatumumab was statistically superior to fingolimod for ARR and time to 3mCDP but not time to 6mCDP. In STCs, ofatumumab was statistically superior in reducing ARR and decreasing the proportion of patients with 3mCDP compared with cladribine, fingolimod, and ozanimod and in decreasing the proportion with 6mCP compared with fingolimod and ozanimod. These findings were largely consistent with recently published NMAs that identified mAb therapies as the most efficacious DMTs for RMS.
Complementary ITC methods showed ofatumumab was superior to cladribine, fingolimod, and ozanimod in lowering relapse rates and delaying disability progression among patients with RMS. Our study supports the therapeutic superiority of mAbs over currently available oral DMTs for RMS and the delineation of mAbs as high-efficacy therapies.
网络荟萃分析（NMA）和真实世界倾向评分（PS）分析的证据表明，单克隆抗体（mAb）比目前可用的口服疗法具有治疗优势，因此，对于复发型多发性硬化症（RMS）患者，有必要将其视为一类独特的高效疾病修饰疗法（DMT）进行考虑。这与包括支付方在内的一些利益相关者目前对这些疗法的看法相悖。
采用多方面间接治疗比较（ITC）方法来阐明mAb与口服疗法的相对疗效。
使用两种利用个体患者数据（IPD）来调整试验间差异的ITC方法，即PS分析和模拟治疗比较（STC），来比较mAb奥法妥木单抗与口服疗法克拉屈滨、芬戈莫德和奥扎莫德。
由于有奥法妥木单抗和芬戈莫德试验的IPD，因此进行了PS分析。鉴于有克拉屈滨、芬戈莫德和奥扎莫德试验的汇总数据，在奥法妥木单抗与每种口服疗法之间进行了STC。比较了三个疗效结局：年化复发率（ARR）、3个月确诊残疾进展（3mCDP）和6个月确诊残疾进展（6mCDP）。
PS分析表明，奥法妥木单抗在ARR和达到3mCDP的时间方面在统计学上优于芬戈莫德，但在达到6mCDP的时间方面并非如此。在STC中，与克拉屈滨、芬戈莫德和奥扎莫德相比，奥法妥木单抗在降低ARR和减少3mCDP患者比例方面在统计学上更具优势，与芬戈莫德和奥扎莫德相比，在减少6mCP患者比例方面也更具优势。这些发现与最近发表的NMA基本一致，后者将mAb疗法确定为RMS最有效的DMT。
互补的ITC方法表明，奥法妥木单抗在降低RMS患者的复发率和延缓残疾进展方面优于克拉屈滨、芬戈莫德和奥扎莫德。我们的研究支持mAb相对于目前可用的口服DMT对RMS的治疗优势，并支持将mAb划定为高效疗法。
