My drug is better than low hanging fruit. Rituximab better than CRAB

Spelman T, Frisell T, Piehl F, Hillert J.Comparative effectiveness of rituximab relative to IFN-β or glatiramer acetate in relapsing-remitting MS from the Swedish MS registry. Mult Scler. 2017 Jun 1:1352458517713668.

OBJECTIVE:To compare treatment effectiveness and persistence in relapsing-remitting multiple sclerosis patients who initiated rituximab versus glatiramer acetate (GA) or interferon-beta (IFN-β).
METHODS:A total of 461 patients from the Swedish MS registry in the rituximab arm were propensity score matched on a 1:2 basis with 922 patients from the IFN-β/GA comparator, between April 2005 and November 2015. Annualised relapse rate (ARR) was compared using the Poisson method. A marginal Cox model was used to analyse time to first relapse, 3-month confirmed disability progression and treatment discontinuation in the matched sample. A signed-rank test was used to compare Expanded Disability Status Scale (EDSS) change from baseline.
RESULTS:Rituximab was associated with a reduction in ARR (0.003; 95% confidence interval (CI) = 0.001, 0.009) relative to IFN-β/GA (0.026; 95% CI = 0.020, 0.033) ( p < 0.001). Rituximab was associated with an 87% reduction in the relapse rate (hazard ratio (HR) = 0.13; 95% CI = 0.04, 0.41) and an 85% reduction in the discontinuation rate (HR = 0.15; 95% CI = 0.11, 0.20) relative to IFN-β/GA. EDSS regression from baseline was greater in the 

rituximab group at 12 and 24 months.
CONCLUSION:Rituximab appears to be superior to first-generation disease-modifying treatments (DMTs) with respect to relapse control and tolerability, whereas superiority on disability outcomes is less clear.


I tear my hair out when a DMT is tested against a placebo, meaning in this day and age it is oK to give someone nothing, when you have nearly twenty active treatments. 

The next worse thing is that you test your agent against placebo-plus. 

No disrespect to people taking beta interferon or copaxone as they are the Worlds most popular treatments, but we know their level of efficacy. It is not high and to test rituximab against beta interferon or copaxone is a non-contest. 

Howeve,r it may lose if we look at the  side -effects  as the outcome as the CRAB drugs are well tolerated

We can do an off-label assessment against a CRAB, but why not do the rituximab against fingolimod, or alemtuzumab and give the drug a run for its money.

The ethics committees/funders need to get some jajce (eggs) to stop these practice of placebo controlled relapsing MS trials. I know it makes it easier to get a result  

However, if this particular case it was not a trial of one verses the other it was assessing in real life. For every one rituximab pwMS they selected to control it with 2 people taking CRAB

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