Clinic speak: fingolimod and natalizumab are just as good as each other when used 2nd-line

Which is best; fingolimod or natalizumab? Does it matter? #MSBlog #MSResearch #ClinicSpeak

"All Pharma companies would like us  to think that their drug is best. It is not that simple. At present we have three highly-effective DMTs licensed in Europe; mitoxantrone, natalizumab and fingolimod. And soon we will have alemtuzumab. Which is better and does it matter? Until randomised head-2-head studies are done comparing these drugs with each other we won't know which is the most effective. Using their relative effects on relapse and disability progression data to rank them is not appropriate as these drugs were tested in different populations and at different times. What we do know is that there has been a tendency for MSers entering contemporary trials have less active disease, i.e. fewer relapses, which makes it more difficult to show a treatment effect compared to placebo. For example, a 50% reduction in relapse rate compared to placebo in a more benign group of MSers could represent a 70% reduction in relapse rate in a more active group of MSers.  Therefore I personally don't know which is the most effective drug and I don't think it matters either. I simply slot DMTs into zones of efficacy in relation to their impact on relapses; i.e.

  1. low efficacy - laquinimod
  2. moderate efficacy - interferon-beta, glatiramer actetate, teriflunomide
  3. intermediate efficacy  - BG12
  4. high-efficacy - natalizumab, fingolimod, cladribine
  5. very high-efficacy - alemtuzumab, mitoxantrone, bone marrow transplantation 

These zones are based on an average effect on relapses and don't necessarily tell you how the individual MSer will do on each drug. For example, you may go onto interferon-beta and be a good responder and be treated-2-target of NEDA (no evidence of disease activity). In comparison, you may choose fingolimod and don't respond to it and continue to have relapses. What these zones of efficacy tell you is that you are more likely to respond to the individual drugs the higher you move up the treatment ladder; in other words it is game of probabilities. This is why we have truly entered an era of personalized medicine where we have to help you choose a drug that suits you and addresses your needs."

"I am a firm believer in MSers choosing their own DMTs; each drug or class of drugs have their own risks and benefits and you need to weigh these up based on your disease profile and personal requirements. The following are a list of some of the questions you need to answer:

What type of MS do I have?
What prognostic group do I fall into?
Do I have active MS?
What is the risk of me not having any treatment?
Am I eligible for treatment with a DMT?
What DMTs are available to me?
What are the pros and cons of these treatments?

What is reassuring about this study below is that for MSers failing the so called 1st-line injectables is that they are as likely to respond to fingolimod or natalizumab. Am I surprised? No, both these DMTs are from the highly-effective group of DMTs and should on average have a similar impact on disease activity. Does it mean that fingolimod is as effective as natalizumab or is natalizumab as effective as fingolimod? No. To answer this question you have to do a randomised-controlled trial that is preferably double-blinded with a much larger number of MSers; 427 is simply too few MSers to answer a superiority or non-inferiority question. Hidden in the study below will be a lot of biases that cannot be excluded; for example MSers with more active disease could have been offered natalizumab more often than fingolimod based on the assumption that natalizumab may be more effective than fingolimod. All this study tells us that if you are failing 1st-line therapies and are offered fingolimod or natalizumab you are as likely to reach the target of relapse and disease-progression free with either drug."

"The elephant in the room is the question of how much damage was accumulated by these 427 MSers whilst on 1st-line therapy before going onto a more effective treatment? Would this group of MSers be better off if they were treated with fingolimod or natalizumab initially? How many would not have developed bladder or sexual dysfunction, walking difficulties or cognitive impairment if they had been offered treatment from the outset with a highly effective DMT? I am extremely concerned about this issue and care passionately about it. If you have an unfavourable disease profile why take the chance of accumulating more irreversible damage when we have more effective treatments that will reduce the chances of this happening. Please note reduce, and not eliminate, the chance of this happening."

"I hope there will come a time when all MSers are offered the option of starting on a high-efficacy DMTs from the outset. When this occurs I think we will make a big difference to the burden of disease at a population level."


Epub: Braune et al. Second line use of Fingolimod is as effective as Natalizumab in a German out-patient RRMS-cohort. J Neurol. 2013 Sep 6.


Background: Although Fingolimod is registered as a second-line drug in RRMS in Europe there are no clinical studies available comparing Fingolimod (Fingo) and Natalizumab (Nz). 

Objectives: This observational cohort-study used health data routinely collected in outpatient neurology practices throughout Germany completing a treatment period of 12 months included 237 MSers starting on Nz and 190 patients on Fingo because of failure of the first-line treatment. 

Results: Mean relapse rate drastically decreased in both treatment groups within three months of therapy in a similar degree and remained on a low level. Both treatment groups saw a similar proportion of MSers with unchanged and improved EDSS (80.53 % in Fingo, 79.32 % in Nz). There was no statistically significant difference between the proportion of MSers being relapse free (75.79 % in Fingo, 71.73 % in Nz), progression free (87.39 % in Fingo, 82.70 % in Nz) or relapse and progression free (71.05 % in Fingo, 62.03 % in Nz) at 12 months in both strata. 

Conclusions: Clinical efficacy of Fingo and Nz in RRMS second-line-therapy was similar during the first 12 months of treatment.

CoI: Multiple

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