The importance of considering differences in study and patient characteristics before undertaking indirect treatment comparisons: a case study of siponimod for secondary progressive multiple sclerosis

Abstract

Adlard (2020) The importance of considering differences in study and patient characteristics before undertaking indirect treatment comparisons: a case study of siponimod for secondary progressive multiple sclerosis,

Indirect comparisons of siponimod with fingolimod and ofatumumab in multiple sclerosis: assessing the feasibility of propensity score matching analyses

“…The importance of conducting a detailed assessment of cross-trial heterogeneity when undertaking ITCs was recently demonstrated by Samjoo et al for trials in SPMS patients 35 . In this case, the feasibility assessment highlighted the appreciable cross-trial heterogeneity that would have caused biased results if traditional ITCs, such as Bucher ITCs or NMA were conducted.…”

“…Instead, population-based ITC methods that accounted for disparities in clinical covariates by leveraging IPD were found to be a more valid approach to examining comparative efficacy. Previous studies in MS and several other therapeutic areas have provided insights into the impact of adjustments on the validity of ITCs [35][36][37][38] . In these examples, the clinical interpretation of the comparative efficacy of interventions was altered when accounting for differences in clinically relevant covariates.…”

“…Supporting the findings of this study, the importance of MS phenotype as a determinant of ITC feasibility has been noted in other recently published ITCs and feasibility assessments for ITCs. Samjoo et al 35 concluded that ITCs were not feasible between the EXPAND siponimod trial in SPMS patients and the OPERA I/II ocrelizumab trials in RMS patients 6 in part because the patient populations were too dissimilar. Substantial differences in baseline patient characteristics between EXPAND and OPERA I/II were noted for age, EDSS score, time since onset of MS symptoms, exposure to prior DMTs, prior relapse history, and MRI lesion measures.…”

Siponimod for active secondary progressive multiple sclerosis

“…NICE recommendation of siponimod for active SPMS relied on the results of a single clinical trial, known as the EXPAND trial 4 . In common with most trials evaluating DMTs, the EXPAND trial outcomes were difficult to interpret 5 . Patients were recruited from 31 countries for the trial.…”

“…4 In common with most trials evaluating DMTs, the EXPAND trial outcomes were difficult to interpret. 5 Patients were recruited from 31 countries for the trial. As the definitions of the different subtypes and stages of MS can differ from one country to the other, NICE had to examine the equivalence of the trial's subjects to establ i s h i f t h e c o n c l u s i o n s a n d s u b s e q u e n t recommendations could apply to UK standard practice.…”