Copaxone vs Beta Interferon - Meta-Analysis

[SuzE-Q]

Cochrane Database Syst Rev.

2016 Nov 24;11:CD009333. [Epub ahead of print]

Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis.

La Mantia L1, Di Pietrantonj C, Rovaris M, Rigon G, Frau S, Berardo F, Gandini A, Longobardi A, Weinstock-Guttman B, Vaona A.
Author information

BACKGROUND:
Interferons-beta (IFNs-beta) and glatiramer acetate (GA) were the first two disease-modifying therapies (DMTs) approved 20 years ago for the treatment of multiple sclerosis (MS). DMTs' prescription rates as first or switching therapies and their costs have both increased substantially over the past decade.

As more DMTs become available, the choice of a specific DMT should reflect the risk/benefit profile, as well as the impact on quality of life.

As MS cohorts enrolled in different studies can vary significantly, head-to-head trials are considered the best approach for gaining objective reliable data when two different drugs are compared.

The purpose of this systematic review is to summarise available evidence on the comparative effectiveness of IFNs-beta and GA on disease course through the analysis of head-to-head trials.This is an update of the Cochrane review 'Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis' (first published in the Cochrane Library 2014, Issue 7).


OBJECTIVES:
To assess whether IFNs-beta and GA differ in terms of safety and efficacy in the treatment of people with relapsing-remitting (RR) MS.

SEARCH METHODS:
We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (08 August 2016) and the reference lists of retrieved articles. We contacted authors and pharmaceutical companies.

SELECTION CRITERIA:
Randomised controlled trials (RCTs) comparing directly IFNs-beta versus GA in study participants affected by RRMS.

DATA COLLECTION AND ANALYSIS:
We used standard methodological procedures as expected by Cochrane.

MAIN RESULTS:
Six trials were included and five trials contributed to this review with data. A total of 2904 participants were randomly assigned to IFNs (1704) and GA (1200). The treatment duration was three years for one study, two years for the other four RCTs while one study was stopped early (after one year).

The IFNs analysed in comparison with GA were IFN-beta 1b 250 mcg (two trials, 933 participants), IFN-beta 1a 44 mcg (three trials, 466 participants) and IFN-beta 1a 30 mcg (two trials, 305 participants). Enrolled participants were affected by active RRMS. All studies were at high risk for attrition bias. Three trials are still ongoing, one of them completed.

Both therapies showed similar clinical efficacy at 24 months, given the primary outcome variables (number of participants with relapse (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.87 to 1.24) or progression (RR 1.11, 95% CI 0.91 to 1.35). However at 36 months, evidence from a single study suggests that relapse rates were higher in the group given IFNs than in the GA group (RR 1.40, 95% CI 1.13 to 1.74, P value 0.002).

Secondary magnetic resonance imaging (MRI) outcomes analysis showed that effects on new or enlarging T2- or new contrast-enhancing T1 lesions at 24 months were similar (mean difference (MD) -0.15, 95% CI -0.68 to 0.39, and MD -0.14, 95% CI -0.30 to 0.02, respectively). However, the reduction in T2- and T1-weighted lesion volume was significantly greater in the groups given IFNs than in the GA groups (MD -0.58, 95% CI -0.99 to -0.18, P value 0.004, and MD -0.20, 95% CI -0.33 to -0.07, P value 0.003, respectively).

The number of participants who dropped out of the study because of adverse events was similar in the two groups (RR 0.95, 95% CI 0.64 to 1.40).The quality of evidence for primary outcomes was judged as moderate for clinical end points, but for safety and some MRI outcomes (number of active T2 lesions), quality was judged as low.

AUTHORS' CONCLUSIONS:
The effects of IFNs-beta and GA in the treatment of people with RRMS, including clinical (e.g. people with relapse, risk to progression) and MRI (Gd-enhancing lesions) measures, seem to be similar or to show only small differences.

When MRI lesion load accrual is considered, the effect of the two treatments differs, in that IFNs-beta were found to limit the increase in lesion burden as compared with GA. Evidence was insufficient for a comparison of the effects of the two treatments on patient-reported outcomes, such as quality-of-life measures

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[Catdancer]

Worse decision I ever made, to stop the Betaseron. I'm on tecfidera now, but haven't noticed any significant improvement I can relate to it specifically.

[Sunshine]

I missed part of your history, I knew you were on Beta for years and did well. Then doc had you stop. You went into a downward spiral off of it
Why couldnt they return you to Beta?

[Virginia]

BBS, even if they did return Cat to it there is no way of knowing if it will work again, as it did the first time. That is the reason I am so afraid to get off Rebif. If I start further down it might not work the second time around.

[Sunshine]

Any research that can address the issue of stopping a once effective med , and if restarting it ends up no longer effective?

[agate]

I'm pretty sure that you can restart Betaseron at any time but unfortunately the longer you wait to start it (or restart it), the less effective it will be, apparently.

It is important to note that all current MS therapies are preventative and not restorative. As the disease progresses, response to DMT typically declines. The key to successful treatment of MS is to slow the inflammatory process early in the disease. It is likely that the accumulation of irreversible tissue damage limits the potential for benefit from DMT as the disease progresses.

From Cleveland Clinic Center for Continuing Education article, "Multiple Sclerosis."

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[Catdancer]

I stopped the Betaseron after having almost 20 years of no real flares and just a slow decline . The doctor convinced me that "after a these years if is likely the MS has burned itself out; why keep doing this very costly and inconvenient drug??" He was NOT a neurologist. I should not have listened to him. Two years later, the bottom fell out, three years of near death, now w major disability.

My neurologist thinks the tecfidera is better. Taken orally twice a day, he thinks it stays more consist in my system. Who knows. Since taking it I don't think I've had any more flares. Now it's a matter of trying to regain some mobility. Unfortunately that may not be possible.

[Sunshine]

Never give up hoping and trying. The nervous system is so complex and has a complex interaction with the mind. One never knows what continual effort does on the cellular level.

I remember well how close to the end you were and I was and still am amazed at your courage.

[agate]

I'd like to echo what BBS said. You might surprise yourself one of these days as you keep up with the PT, good nutrition, and plenty of rest.

The nervous system seems to be so incomprehensible that no one knows which of these MS drugs is going to work on which person. Everyone and his/her neuro just pick a drug from the available assortment and they wait and see whether the MS gets worse. At least there is a good feeling in knowing you're doing what you can to feel as well as you can.

[stillstANNding]

SuzE,

I am trying to find out if the authors have anything to disclose and who paid for the study.
Just trying to keep them honest.

ANN

[agate]

stillstANNding, isn't the Cochrane Database a fairly standard source for meta-analyses? Would there be a question about authors who are in the pocket of drug companies or other commercial interests with a Cochrane study?

The Cochrane Database has been around for quite a while and is often referred to. This is what appears under "Who We Are" at its Website:

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Or maybe you meant the Cleveland Clinic link that I posted?

Anyway, thank you for being alert to the problem of finding out what researcher is in whose pocket.

[stillstANNding]

Thank you, Agate.
ANN

[agate]

I could be quite wrong about Cochrane Database. Maybe it's possible for researchers/authors to set up Cochrane studies that are skewed in favor of whatever drug company is supporting them....

[SuzE-Q]

I could be quite wrong about Cochrane Database. Maybe it's possible for researchers/authors to set up Cochrane studies that are skewed in favor of whatever drug company is supporting them....

The Cochane group don't do any actual experimentation, they just collect all existing research, eliminate any studies that don't fall within their methodological parameters, and tabulate the full results.

Scientific Method believes that study results must be replicated in order to feel comfortable with the validity of the results - the Cochrane Group attempts to do just that, by aggregating all study results together from various studies to determine the strength of the findings. It's also a way to weed out bias and poor methodologies and ensure study methods, etc. are sound.

Meta-analyses is when you can really get a sense of how a drug is performing.

[agate]

Back when I was on Copaxone I found a Cochrane study that ranked it lower in effectiveness than the interferons. That was the only place where I found this information.

In the years since, though, I've found a few other articles that state that--although it's apparently not a fact that the people at Teva (makers of Copaxone) want spread around.