Regarding side effects, there are both positive and negative effects in comparison with beta interferon 1a
Teriflunomide (trade name: Aubagio) has been approved in Germany since August 2013 for adults with relapsing remitting multiple sclerosis. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this new drug offers an added benefit over the appropriate comparator therapy specified by the Federal Joint Committee (G-BA).
This is not the case, however: Although certain side effects occur less frequently under teriflunomide than under beta interferon 1a, others are more frequent. Overall, IQWiG does not regard an added benefit as proven.
Drug manufacturer limited itself to a certain beta interferon preparation
Multiple sclerosis (MS) is a chronic, incurable, inflammatory disease of the central nervous system, which often has a relapsing course. If there is a remission of all or most symptoms after a relapse, this type of MS is called relapsing-remitting (RRMS).
The Federal Joint Committee (G-BA) specified beta interferons (1a or 1b) or glatiramer acetate as appropriate comparator therapy. The drug manufacturer chose beta interferon 1a as comparator therapy, but limited itself to one certain preparation from this drug group (Rebif). This did not influence the result of the assessment, however. Teriflunomide is taken as a tablet, whereas beta interferon 1a has to be injected.
Only data from an approval study were used
In its dossier, the manufacturer presented results from an approval study (TENERE), which directly compared teriflunomide with Rebif. In this study, patients were treated for 48 to 115 weeks. The study was unblinded, i.e. both patients and doctors knew which drug was administered.
In addition, the manufacturer used an indirect comparison based on three studies, all of which tested teriflunomide or Rebif against placebo. The placebo was used as what is known as the "common comparator". The manufacturer then combined the results of this indirect comparison with the results from TENERE. However, the indirect comparison was unsuitable to support the results from the direct comparison (TENERE). IQWiG therefore only included the data on the direct comparison in the assessment.
No relevant differences in morbidity and quality of life
No conclusions can be drawn on mortality because no patients died during the study. The study was not long enough and did not have enough participants anyway to be able to reveal any differences in mortality.
Regarding disability progression and relapses such as vision disorders, there were no statistically significant differences between the teriflunomide and the interferon group.
No statistically significant difference was observed for the outcome "health-related quality of life", either.
Opposing results for side effects
There were also no important differences found with regards to serious adverse events and the outcome "treatment discontinuation due to side effects".
The picture is more complex for non-severe or non-serious side effects, however: Flu-like symptoms were less frequent under teriflunomide than under beta interferon 1a. This was also the case for reactions at the injection site, but this side effect cannot occur with a tablet (teriflunomide). In contrast, diarrhoea and hair loss (alopecia) were more frequent in the teriflunomide group.
Reliability of conclusions is limited
Overall, regarding side effects, IQWiG sees a hint of a positive and a negative effect, in each case with a considerable extent. IQWiG regards the reliability of the conclusions of the study to be limited, so that it sees hints, but no indications. One of the reasons is that the study was unblinded.
Balancing the positive and negative effects regarding side effects, the Institute does not regard an added benefit of teriflunomide in comparison with beta interferon 1a as proven.
G-BA decides on the extent of added benefit
The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer's dossier and IQWiG's assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G-BA then decides on the extent of the added benefit, thus completing the early benefit assessment.
The G-BA website contains both general English-language information on benefit assessment pursuant to §35a Social Code Book (SGB) V and specific German-language information on the assessment of teriflunomide.
More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information here.