Oral Disease-Modifying Treatments for Relapsing Multiple Sclerosis: A Likelihood to Achieve No Evidence of Disease Activity or Harm Analysis

Dimitrios Papadopoulos, Dimos-Dimitrios D. Mitsikostas

The likelihood to help or harm (LHH) is an absolute measure of the benefit versus risk profile of a medication, which can be used to assess the potential for benefit versus harm of different disease-modifying treatments (DMTs) for relapsing multiple sclerosis (R-MS) and facilitate clinical decision-making. The objective of this study was to assess absolute differences in benefit:risk ratios of oral DMTs for R-MS, using LHH analysis with no evidence of disease activity (NEDA) as beneficial outcome. The number needed to treat for a paient to achieve NEDA (NNTBNEDA) was used as an effect size metric of efficacy and the number needed to treat for a patient  to experience  an adverse event (NNTHAE), a serious adverse event (NNTHSAE), or treatment discontinuation due to an adverse event (NNTHAE-D) were used as measures of risk. The LHH-which is the ratio of NNTH:NNTB-values were calculated from published phase III trial data for oral DMTs. The values for likelihood to achieve NEDA than experience any AE ratio (LHH(AE/NEDA)) were 3.9, 6.8, 12.5 and 3.7, the likelihood to achieve NEDA than experience a SAE ratio (LHH(SAE/NEDA)) values were 3.5, 15, 23.5 and 2.8, and the likelihood to achieve NEDA versus discontinue treatment (LHH(AE-D/NEDA)) values were 20.3, 4.3, 3.9 and 3.1 for cladribine, dimethyl-fumarate, fingolimod, and teriflunomide, respectively. With all of the oral DMTs examined, R-MS patients are more likely to achieve NEDA than experience any adverse event.