LAUSR

We read with interest the recently published review article in CNS Drugs by Dr. Papadopoulos and Dr. Mitsikostas comparing the absolute differences in benefit-to-risk ratios of oral disease-modifying therapies in multiple sclerosis [1]. However, we noticed several inaccuracies in the figures and tables in the article, which inevitably raise important questions about the methodology of data extraction, analysis validity, and result robustness. Although we believe that the inaccuracies presented in Table 2 are innocent arithmetical errors, they unfortunately affect the calculations provided in both Tables 3 and 4, as well as in Fig. 1 (a figure highlighting the conclusions of the study of Drs. Papadopoulos and Mitsikostas) [1]. For comparison, we provide the correct proportions of patients reported to have no evidence of disease activity (NEDA) and safety outcomes, as reported in the original randomized clinical trials [2–7] or additional post-hoc analyses (Table 1). [8–11] Furthermore, in Table 3 of the article by Drs. Papadopoulos and Mitsikostas, the provided total numbers of patients for cladribrine, dimethyl-fumarate, and fingolimod are also inaccurate [1]. As according to the relevant publications these numbers should have corresponded to 781, 692, and 1556, respectively [2–7], it becomes evident that the risk ratios and number-need-to-treat (NNT) values for the aforementioned disease-modifying therapies presented in Table 3 have all been accordingly miscalculated. In addition to the numerical miscalculations of the number-needed-to-harm values presented in Table 4, as a result of the use of incorrect denominators for the safety population as highlighted above, we were also not able to reproduce several of the likelihood to help or harm (LHH) ratios presented in Fig. 1. Using the number-needed-to-benefit and number-needed-to-harm values provided by Drs. Papadopoulos and Mitsikostas and in the same statistical calculator (graphpad.com/quickcalcs), we were unable to independently verify the numbers reported by Drs. Papadopoulos