Natalizumab superiority seems more evident on MRI than clinical endpoints
RobertaLanzillo, researcher, Federico II University, Naples, Italy[email protected]
Marcello Moccia, Nasples, Italy
Submitted March 17, 2016
We read with interest the multicenter observational study by Barbin et al. comparing the efficacy of natalizumab and fingolimod, [1] both licensed as second line therapies for multiple sclerosis (MS) in Europe. [2,3] However, we are concerned about the interpretation of the results showing overall natalizumab superiority on relapses in the first year of therapy.
The results of logistic regression on relapses in the two studied groups are difficult to account as evidence of natalizumab superiority since the lower confidence interval was 1.0, whereas the results on MRI activity were much more robust in favor of natalizumab (although calculated in a subgroup of the study population). In addition, Cox regression analyses are generally viewed as the gold standard for comparing drug efficacy, with estimates of hazard rates for different study endpoints. Thus, the absence of these models might be perceived as a tremendous bias.
Furthermore, the application of the propensity score method is unclear. In particular, it might be hypothesized that only a proportion of patients were included in the analysis, but no numbers were supplied. Considering the number of covariates included in the model, it is possible that main analyses have been conducted on a reduced sample size, limiting the reliability of present findings.
Results on disability progression are rowing against any differences, and we cannot underestimate the main goal of therapies in MS clinical practice: avoid disability accrual. In fact, it seems that the EDSS score improved during the first year of the study (in spite of relapses), and remained stable during the second year. [1] However, data were not clearly shown in text, tables, or supplementary material.
In conclusion, Barbin et al. must be acknowledged for great efforts in recruiting a large population and in evaluating different MS outcomes, including MRI. Nevertheless, the study had several limitations, and further evidence is required before determining whether natalizumab is superior to fingolimod or not.
1. Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimodvsnatalizumab: A French multicenter observational study. Neurology 2016;86:771-778.
2. Gajofatto A, Bianchi MR, Deotto L, Benedetti MD. Are natalizumab and fingolimod analogous second-line options for the treatment of relapsing- remitting multiple sclerosis? A clinical practice observational study. Eur Neurol 2014;72:173-180.
3. Kalincik T, Horakova D, Spelman T, et al. Switch to natalizumab versus fingolimod in active relapsing-remitting multiple sclerosis. Ann Neurol 2015;77:425-435.
For disclosures, please contact the editorial office at [email protected].
We read with interest the multicenter observational study by Barbin et al. comparing the efficacy of natalizumab and fingolimod, [1] both licensed as second line therapies for multiple sclerosis (MS) in Europe. [2,3] However, we are concerned about the interpretation of the results showing overall natalizumab superiority on relapses in the first year of therapy.
The results of logistic regression on relapses in the two studied groups are difficult to account as evidence of natalizumab superiority since the lower confidence interval was 1.0, whereas the results on MRI activity were much more robust in favor of natalizumab (although calculated in a subgroup of the study population). In addition, Cox regression analyses are generally viewed as the gold standard for comparing drug efficacy, with estimates of hazard rates for different study endpoints. Thus, the absence of these models might be perceived as a tremendous bias.
Furthermore, the application of the propensity score method is unclear. In particular, it might be hypothesized that only a proportion of patients were included in the analysis, but no numbers were supplied. Considering the number of covariates included in the model, it is possible that main analyses have been conducted on a reduced sample size, limiting the reliability of present findings.
Results on disability progression are rowing against any differences, and we cannot underestimate the main goal of therapies in MS clinical practice: avoid disability accrual. In fact, it seems that the EDSS score improved during the first year of the study (in spite of relapses), and remained stable during the second year. [1] However, data were not clearly shown in text, tables, or supplementary material.
In conclusion, Barbin et al. must be acknowledged for great efforts in recruiting a large population and in evaluating different MS outcomes, including MRI. Nevertheless, the study had several limitations, and further evidence is required before determining whether natalizumab is superior to fingolimod or not.
1. Barbin L, Rousseau C, Jousset N, et al. Comparative efficacy of fingolimodvsnatalizumab: A French multicenter observational study. Neurology 2016;86:771-778.
2. Gajofatto A, Bianchi MR, Deotto L, Benedetti MD. Are natalizumab and fingolimod analogous second-line options for the treatment of relapsing- remitting multiple sclerosis? A clinical practice observational study. Eur Neurol 2014;72:173-180.
3. Kalincik T, Horakova D, Spelman T, et al. Switch to natalizumab versus fingolimod in active relapsing-remitting multiple sclerosis. Ann Neurol 2015;77:425-435.
For disclosures, please contact the editorial office at [email protected].