Whats Lost is Lost, Why CRAB can sometimes mean CRAP

This German studies shows real life data that dimethyl fumarate is better than the CRAB drugs plus teriflunomide......So why are we still using them?

Comparative effectiveness of delayed-release dimethyl fumarate versus interferon, glatiramer acetate, teriflunomide, or fingolimod: results from the German NeuroTransData registry. Braune S, Grimm S, van Hövell P, Freudensprung U, Pellegrini F, Hyde R, Bergmann A; NTD Study Group.J Neurol. 2018 Oct 16. doi: 10.1007/s00415-018-9083-5. [Epub ahead of print]
BACKGROUND:Comparative effectiveness (CE) research allows real-world treatment comparisons using outcome measurements important to physicians/patients. This German NeuroTransData registry-based analysis compared delayed-release dimethyl fumarate (DMF) effectiveness with interferons (IFN), glatiramer acetate (GA), teriflunomide (TERI), or fingolimod (FTY) in patients with relapsing-remitting multiple sclerosis (RRMS) using propensity score matching (PSM).
METHODS:Data from registry patients aged ≥ 18 years with RRMS, ≥ 1 relapse, and Expanded Disability Status Scale (EDSS) assessment(s) after index therapy initiation underwent 1:1 PSM to match DMF with comparator populations baseline characteristics. Primary outcome measurement was time to first relapse (TTFR). Secondary outcome measurements included annualised relapse rate (ARR), proportion of patients relapse free at 12 and 24 months, time to index therapy discontinuation (TTD), and reasons for discontinuation. Exploratory analyses included time to 3- and 6-month EDSS confirmed disability progression (CDP). Non-pairwise censoring was the primary analysis method; pairwise censoring was the main sensitivity analysis method.
FINDINGS:Post-matched cohorts were well-balanced. By non-pairwise censoring, TTFR and ARR were significantly lower in DMF populations versus matched IFN, GA, and TERI, but there was no evidence of difference between DMF and FTY. TTD was similar between DMF and IFN, GA, and TERI, but significantly shorter versus FTY. Time to CDP generally showed no evidence of difference between DMF and comparator populations. Pairwise censored analysis results confirmed the non-pairwise censoring results.
INTERPRETATION:These results support previous CE studies in demonstrating relative improvement in real-world effectiveness with DMF versus first-line agents IFN, GA, and TERI, and similar effectiveness versus FTY.

OK I accept that there are merits for each agent and perhaps in Germany it means that the Neuros doesnt have to do any monitoring if people are on a certain drug, but looking at the ocrelizumab extension trial data presented at ECTRIMS and at the Ammerican Academy (see post two days ago) where they put people on beta interferon on ocrelizumab two years after other people started on ocrelizumab and when they looked at confirmed disability progression the damage was done. 

People on ocrelizumab did better during the trial and when switched they both progressed at the same rate saying that you can get the benefit still,  but what was lost in the first two years whilst on beta interferon, stayed lost. Why do we need more evidence to treat early and effectively?

CoI Multiple

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