RE: Natalizumab vs fingolimod study of efficacy with unknown safety: A story which ended at interval
David A.Laplaud, MD, PhD, Inserm U1064, Nantes, France[email protected]
Y. Foucher, Nantes University, France
Submitted June 02, 2016
We thank Drs. Bhatia and Puri for the comment on our article. [1] The randomized clinical trial (RCT) remains the design of reference to evaluate theoretical effect of treatments. When the sample size is sufficient, a RCT ensures comparability of both treated and control groups. An additional advantage is marginal causality estimation (i.e. treatment effect of an entire treated population vs an entire control population). Nevertheless, it is well established that RCTs are performed during optimal circumstances (over-representation of treatment-adherent patients, low frequency of morbidity, etc.), resulting in non-representative conclusions for real-life practices. [2] Observational studies can closely represent real-life treatment effect, but treated and control patients are often non-comparable due to lack of randomization.
We compared fingolimod- vs natalizumab-treated patients with clinical and radiological outcomes at 1 and 2 years. [1] No other study has compared such outcomes in these patients, making the work original and strengthening the perceived impression of natalizumab's clinical superiority (at least for patients with the most aggressive disease). We agree safety and compliance data would have strengthened our research, but such data were unavailable. As we concluded in our article, [1] a RCT is needed to objectively compare natalizumab and fingolimod.
1. Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimodvsnatalizumab: A French multicenter observational study. Neurology 2016;86:117-778.
2. Zwarenstein M, Treweek S. What kind of randomized trials do we need? CMAJ 2009;180:998-1000.
For disclosures, please contact the editorial office at [email protected].
We thank Drs. Bhatia and Puri for the comment on our article. [1] The randomized clinical trial (RCT) remains the design of reference to evaluate theoretical effect of treatments. When the sample size is sufficient, a RCT ensures comparability of both treated and control groups. An additional advantage is marginal causality estimation (i.e. treatment effect of an entire treated population vs an entire control population). Nevertheless, it is well established that RCTs are performed during optimal circumstances (over-representation of treatment-adherent patients, low frequency of morbidity, etc.), resulting in non-representative conclusions for real-life practices. [2] Observational studies can closely represent real-life treatment effect, but treated and control patients are often non-comparable due to lack of randomization.
We compared fingolimod- vs natalizumab-treated patients with clinical and radiological outcomes at 1 and 2 years. [1] No other study has compared such outcomes in these patients, making the work original and strengthening the perceived impression of natalizumab's clinical superiority (at least for patients with the most aggressive disease). We agree safety and compliance data would have strengthened our research, but such data were unavailable. As we concluded in our article, [1] a RCT is needed to objectively compare natalizumab and fingolimod.
1. Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimodvsnatalizumab: A French multicenter observational study. Neurology 2016;86:117-778.
2. Zwarenstein M, Treweek S. What kind of randomized trials do we need? CMAJ 2009;180:998-1000.
For disclosures, please contact the editorial office at [email protected].