Changes in therapy are frequent. In addition to the substance, the application also plays a role, as comparisons of clinical trial results and real-world data show.
Randomized controlled trials (RCTs) remain the gold standard for testing various clinical questions. But when it comes to clinical practice, real-world data collection is essential. Real-world evidence studies inform not only rare side effects, but also mediation efficacy, residual disease activity, and reasons to change therapy. The basis is a large, heterogeneous patient collective that corresponds to real-life conditions.
At a press conference held by Sanofi Genzyme in Cologne, Germany, Univ. Prof. Dr. med. Luisa Klotz, senior physician at the Department of Neurology at Münster University Hospital, explained just such Real World data against the background of the results of clinical studies on teriflunomide. Teriflunomide is an immunomodulator with anti-inflammatory properties that is administered orally once daily. As Prof. Klotz pointed out, it is precisely this oral application that is important for many patients. This was also shown by the analyses of Sacca and colleagues, who investigated reasons for a change in therapy in 3025 MS patients at 24 sites. In three years, about half switched to a different therapy, with application playing a role in addition to the active ingredient. “A change in therapy, for example, occurred more often with injection therapy than with oral application,” Prof. Klotz specified.
Clinical studies on teriflunomide
The pivotal TEMSO and TOWER studies demonstrated a significant reduction in disability progression compared to placebo. In a post-hoc analysis of pooled data from both studies, the placebo comparison also showed a significant 53% reduction in the annual relapse rate with residuals. In terms of preventing relapses, teriflunomide is comparable to dimethyl fumarate, which is also given orally. The long-term efficacy and safety of teriflunomide have been demonstrated by long-term data from the pivotal studies and the Phase II extension study, which showed a low annualized relapse rate and stable EDSS (“Expanded Disability Status Scale”) over 12 years.
And in practice?
A prospective, multicenter, industry-independent observational study tested how many patients achieved NEDA (“No Evidence of Disease Activity”) status under real-world conditions with teriflunomide or dimethyl fumarate. Included were 468 patients with relapsing-remitting MS at therapy initiation with teriflunomide or dimethyl fumarate. Over an observation period of twelve months, both drugs proved to be comparable. However, teriflunomide was significantly better tolerated: patients treated with dimethyl fumarate had side effects more often than those taking teriflunomide (26.5% vs. 12%). This finding is quite relevant in practice, especially since side effects are a frequent reason for changing therapy.
Another observational study (TAURUS-MS-I; n=1128) over two years also indicates good practicality of teriflunomide. About three-quarters of participants had been pretreated at baseline and had switched to teriflunomide because of injection fatigue or flu-like side effects. Under this therapy, relapse rates decreased significantly and FSS (“Fatique Severity Scale”) scores stabilized. Patient satisfaction increased. The side effect profile was consistent with the results of the clinical trials, with increased ALT, headache, diarrhea, nausea, and decreased hair density being the most common, most of which were reversible. The reason for the increased patient satisfaction could be the ease of oral use and good tolerability with sustained efficacy, the study leader said.
Prof. Klotz summarizes: “The current real-world data on MS therapy with teriflunomide confirm the positive efficacy and safety profile from the pivotal and long-term studies and give no indication of unexpected side effects”.
InFo NEUROLOGY & PSYCHIATRY 2019; 17(3).
