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.
- low efficacy – laquinimod
- moderate efficacy – interferon-beta, glatiramer actetate, teriflunomide
- intermediate efficacy – BG12
- high-efficacy – natalizumab, fingolimod, cladribine
- 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.
Other clinic speak posts of interest:
05 Sep 2013
“The motor, cerebellar and bladder systems are the three I am referring to. These systems are the so called efferent, effector or motor systems and characterised by their length and complexity. Motor or effector systems tend not …
31 Aug 2013
Are you depressed? Do you have executive dysfunction? #MSBlog #MSResearch #ClinicSpeak “For those us who see a lot of MSers we aware that there is strong link between depression and cognitive dysfunction and that …
26 Aug 2013
Pain and sleep problems in MSers explained. #MSBlog #Clinicspeak “The following YouTube video from the National MS Society is worth watching. If you have any queries on issues raised please do not hesitate to ask.” …
24 Aug 2013
“Are there any anatomists out there? The following is for you. A particular type of cerebellar tremor is one that affects the nerve fibres that leave the cerebellum in the so called superior cerebellar peduncles and pass through …
25 Aug 2013
Tube map: an holistic approach to MS, version 3.1 #MSBlog #MSResearch #ClinicSpeak “I have finally updated my tube map on my holistic approach to MS; thank you all for giving me feedback and advice about adding new …
26 Aug 2013
Sleep, Where art thee? Sleep cycle disorders in MS. #MSBlog #MSResearch #ClinicSpeak ‘O Sleep, O Gentle Sleep, Natures Soft Nurse, How Have I Frighted Thee, That Thou No More Wilt Weigh my Eye-Lids Down And …
23 Aug 2013
“The reason why MS causes seizures is because it is also a gray matter disease and can irritate nerve cells to fire spontaneously that results in seizures and hence epilepsy. The superficial gray matter is on the surface of the …
21 Aug 2013
Are you sure I have MS? 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 …
14 Aug 2013
“In this study more than half of MSers reported headache. Wow! This is a much higher self-reported prevalence of headache than I would have expected from my own clinical experience. What is your experience?”
16 Aug 2013
Bladder dysfunction; is it a problem for you? #MSBlog #MSResearch #ClinicSpeak. Clinical problem: I am 36 years of age and I have developed urinary frequency and urgency. Apart from this I am well and very active.
13 Aug 2013
“In general I try and avoid high-dose steroids to treat acute relapses simply because of the potential complications. This case report is a reminder of one of the rare complications of this treatment; i.e. a clot in one of the venous …
29 Jul 2013
Question: Relapsing/remitting MS for 7 years; 4.5 years on interferon-beta (Rebif) until pregnancy, no medication for 2.5 years, mild symptoms once a year. I have been offered Copaxone by my consultant. Should I start …
10 Aug 2013
“Several MSers have expressed their concerns about the long-term effects of alemtuzumab on their immune systems. Why? Alemtuzumab works by depleting your immune system and allowing it to recover spontaneously.
04 Aug 2013
There are a lot of questions being asked about disability and cognition. It is clear that there is a misunderstanding about disability. Before attempting to clarify these issues I need to explain to you what the EDSS or Expanded …
27 Jul 2013
“Whilst lying on the beach and getting my vD levels up I have been thinking about MS and our blog and how it should evolve. My beach think has become an annual ritual; but more on this later when I highlight our research …
06 May 2013
Do you have night-time bladder problems? This post is for you. #MSBlog #MSResearch “Recently I have focused on sleep problems in MS. One particular problem is bladder overactivity at night that results in you having to get …
14 Feb 2013
“One of the issues that I have under estimated is the psychological impact that MS has on you and your families. This is compounded by disappointment when science and medicine, which promises so much, fails to deliver.