Dimethylfumarat (1) – Tecfidera®

• Clinical trials
  • In addition, the G-BA noted that the study 109MS302 (CONFIRM), submitted by the pharmaceutical company, included not only two study arms with different dimethyl fumarate administration frequencies and daily doses, and a placebo control arm, but also an active-controlled arm comparing the drug with glatiramer acetate.

Patients with relapsing-remitting multiple sclerosis (RRMS)

• An additional benefit compared with interferon beta-1a is not proven.
• Due to the aforementioned shortcomings regarding completeness, the inadequate verification of the basic assumptions of the network meta-analysis concerning similarity, homogeneity and consistency, and the unsuitable statistical model, the indirect comparison presented in the dossier did not allow for any valid conclusions to be drawn regarding the additional benefit of dimethyl fumarate compared with the selected appropriate comparator therapy, IFN β-1a.
• mortality
  • The information on deaths (1 death in the IFN β-1a group), also contained in the study report for the MSCRG trial, was not taken into account by the pharmaceutical manufacturer within the indirect comparison of dimethyl fumarate with IFN β-1a.
• morbidity
  • In the network meta-analysis from the statement, for most endpoints only the comparison of dimethyl fumarate and IFN β-1a, 44 μg s.c. (Rebif®), is considered, which means that this indirect comparison is also substantively incomplete.
• Side effects
  • Furthermore, no analyses of serious adverse events are presented, and only incomplete analyses of deaths are provided.
• Overall assessment
  • Due to the differences mentioned above, it cannot be assumed that the study populations included in the indirect comparison are sufficiently similar. Consequently, no valid conclusions regarding the additional benefit of dimethyl fumarate compared with the appropriate comparator therapy can be drawn on the basis of the presented network meta-analysis.
  • Consequently, the results from the presented network meta-analysis cannot be relied upon, as they are also based on an unsuitable statistical model and incomplete analyses.

Courtesy translation only, please refer to the German original.