The earlier the better; even non-highly effective DMTs have benefit

Are we throwing the baby out with the bathwater? Does interferon-beta have life left in it as a treatment for MS? #MSBlog #MSResearch

Epub: Nagtegaal et al. Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome. Mult Scler. 2013 Jul 10.

BACKGROUND: MS is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for MSers.

OBJECTIVE: To evaluate whether IFNB-1b in CISers prevents persisting T1 hypointensities on MRI (persistent black holes (PBHs)).

“Black holes left behind are and indication or loss of nerves and axons. Lesions that cause black holes on MRI are more destructive than lesions that don’t leave black holes.”

METHODS: In the placebo-controlled phase, CISers (n = 468) were initially randomised to IFNB-1b (n = 292) or placebo (n = 176) for two years or clinically definite MS (CDMS). In the open-label phase (n = 418), both groups were offered IFNB-1b for up to five years. Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan (minimum time one year).

RESULTS: A total of 435 CISers were evaluable for analysis. The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases (0.42 vs 0.71, p = .0102 and .70 vs 1.17, p = .0121). Exploratory analyses identified baseline characteristics that affected rate of conversion.

CONCLUSIONS: Although the rate of lesions that converted to PBH showed no significant differences between groups, the numbers of PBHs per CISer out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo. 

“Maybe we shouldn’t throw the baby out with the bathwater. If interferon-beta works why replace it with the newer agents? The problem is that the majority of MSers will ultimately fail interferon therapy. It is a great pity we don’t have predictive markers to help us decide which MSers is going to be a responder or a non-responder. At the moment we put you on interferon beta and watch and see what happens. If you have relapses , or progress, or develop new lesions on MRI, or develop NABs we say you are a non-responder and if you remain stable we say you are a responder. The problem with this is that while we wait 12, 24, 36 or more months MS may continue to cause damage, or shred, your brain that is irreversible. This is why a lot of neurologists who have access to more effective treatments early are using them as first-line agents. Then there is also the issue of side effects and tolerance issues; some MSers don’t like to inject themselves and don’t like the flu-like side effects and skin reactions. It is all very complicated, which is why DMT decisions have to be personalised. 

“The message from this study is clear; interferon beta when used as early as possible in CISers works and reduces black holes or tissue destruction. This is reassuring to know. The problem we have in the UK is  that NICE and the Department of Health won’t allow us to use interferon beta after the first clinical event; we have to wait until the second attack and we can only start interferon if that second attack occurs witin 2 years of the first attack. While we wait for the second attack to happen MS may be active and continue to damage or shred your brain. No wonder MSers and neurologists in the UK feel let down.”

CoI: multiple

12 thoughts on “The earlier the better; even non-highly effective DMTs have benefit”

  1. Prescribing Beta-interferon after the first attack seems too early. It is a big decision to start this treatment. Professor McDonald once said to me after I refused ACTH, "we would have thought you improved because of the treatment" after I improved with no drugs. I can't be confident that early intervention is the correct path.

    1. But everyone is different. Just because you improved with no drugs doesn't mean it will be the same for everyone. Access to effective treatments to those who want it and are clinically justified should be as early as possible. All the data is pointing this way.

    2. I agree, everyone is different, I have friends with MS and not one of us is affected in the same way. Probably, if the treatment was there when I was in my twenties I would have grabbed it with both hands. I was very scared. I had quite a few attacks. I was told by a Neurologist I was doing something right, but he couldn't tell me what.I really wish he could. I now have SPMS, but this followed a few unrelated operations. Wouldn't it be wonderful if there was a genetic test, that told us which drugs would be effective for every patient.

    3. Anon 5:54 – hearing stories like yours bring into focus the very human strife that comes with MS. It's a disease that hits the young and mercilessly abuses them from the inside out.We need more stories like yours to remind of the human cost of this disease: how it isn't some entity that exists in labs and conferences, but a insidiously cruel plight that has an effect on the sufferer, their family and society at large.

  2. It wasn't a big decision for me. I was having relapses every 2 or 3 months. I was diagnosed and then hit with another and went onto Rebif immediately. I was too scared not to try something. It's been 13 years and yes, I've had more relapses, but no obvious progression. For me, a relapse is like breaking a leg or a wrist. It happens, it heals and I recover and move on. But – and this is a big wobbly but, there is no way to determine progression prior to diagnosis in RRMS. I have the type of RRMS that responds well to beta-interferon. Had I been able to take Campath (didn't get on the trial), I'd have had that as a first choice. Okay, my story is a little more complicated than that, but Rebif was right for me and still works, although if I was to be offered Campath (or whatever it is called now) I'd take it. I relapse on average, once every 3 years. Not bad, but I'd like something that stops the damn things once and for all.I think it's important to point out that as with the 'MS as Dementia' 'Brain shredding' ain't necessarily going to happen to everyone. In the West Wing, the President seems to go into SPMS (with relapses) in series 7, but he still functions well at the end. Don't forget that. Abby was worried, but the brain shredding didn't happen.

    1. thanks for mentioning that study. from what i've read there are a few camps, no? : 1) was anyone surprised? 2) study was flawed 3) silencei've seen a few who were disappointed and i keep looking

  3. This study would be important if black holes were predictors of progression. They are not, so it isn't.

  4. My son was diagnosed with MS in his early 20's 5 years ago. He'd probably had it for at least a year before that. He had rebif but continued to relapse. He was offered tysabri, but was concerned about PML. He managed to find a neurologist who would prescribe campath. He had that 3 years ago, and has not had a relapse since. He used to be very sporty as a boy, but couldn't manage most post diagnosis- he still went to the gym. This year he tried ski ing again, he plays golf and 5 a side football. His bladders not great and he's still a bit wobbly, but campath has transformed the way his life was going. I just can't say how much early effective treatment has meant. It absolutely must be offered to all new MSers

    1. I wish there was a 'like' button. Anon 9:42 I agree with you. I wonder if there's a chance of it being trialled for PwMS who have had it a while. Most post-beta interferon MSers get offered Gilenya or Tysabri, but why not Lemtrada (Campath)? Surely it will still work? I'm not progressing, but I do have disease activity and I'd like stop that activity dead in its tracks.I know Professor G is passionate about stopping progression, I wish he'd come up with a better term than brain shredding. How about brain damage? It's what it really is.

    2. Damage is too passive, shredding tells it how it is. If it makes the nihilists change their mind I am all for MS being called the shredder. Do you know if your shredder is active?

  5. Your right brain damage is too passive. Shredding , although uncomfortable to admit, it is what's going on .

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