In this study they look at the effect of combining fludarabine with beta interferon and compare this with a combination of interferon beta and steroids (methylprednisolone) in people with breakthrough disease.
In the study they suggest that the action of fludarabine may be synergistic when used with beta interferon. Synergistic is a word used by many but seldom really show. Synergism occurs when the the action of two drugs is better than their additive effect alone. However when you use a non linear scale to assess efficacy it is very difficult to to show true synergy over a simple additive effect so addition is 2 + 2 = 4 where as synergy is 2 + 2 = 5.
People were first given steroids for a week then went on to fludarabine 5 times in a month for 3 months of steroids once a month for 3 months whilst taking interferon once a week and assessors were not blinded and if neutrophil numbers became low you could have cytokine therapy to increase this and people on steroids could have more steroids if they relapsed.
The study however only involved only 18 people and it is impossible to draw any real conclusions about efficacy or safety for that matter. There appeared to less However, the study was not based on any real sample size studies and not surprisingly in the end because the trial was so small them there was no differences to be seen, so more trials need to be done. A few people continued to relapse
If fludarabine was as good cladribine, one may expect that it could be better than beta interferon and you could simply do fludarabine by itself. In the cladribine verses beta interferon trial presented at the AAN 2013, I believe Cladribine was better than interferon beta.
However in this study they use a trickle dose of repeated injections and I wonder if this is the way to take these types of drugs, as it may drip feed side effects/infection risk and maybe best to get larger dose for the drug to do its stuff.
Prof G has questioned about whether people and neurologists are risk adverse and will "wait and see". This clearly shows there is some truth to be had and people are relapsing on treatment.
So the question one can have if people are failing beta interferon is, is it a good idea to carry on trying to treat people with interferons when they are relapsing or should they be switched onto a more effective treatments.