Trial (TEMSO) of Teriflunomide


Background:The Teriflunomide Multiple Sclerosis
Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled
phase III study, demonstrated that teriflunomide significantly reduced
annualized relapse rate (ARR), disease progression and magnetic
resonance imaging (MRI) activity, with a favorable safety profile in
relapsing multiple sclerosis
(RMS) patients.
Objective:The purpose of this study was to report the
effects of teriflunomide on ARR and disability progression in
pre-specified subgroups.
Methods:RMS patients (n=1088) were randomized to
placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks.
Subgroup analyses were performed for ARR and disability progression by
baseline demographics (gender, race, age), disease characteristics
(Expanded Disability Status Scale (EDSS) strata, relapse history, multiple sclerosis
(MS) subtype), MRI parameters (gadolinium-enhancing lesions, total
lesion volume) and prior use of MS drugs. A generalized estimating
equation method and Cox regression model were used to assess consistency
of the treatment effect across subgroups, utilizing a
treatment-by-subgroup interaction test for each factor
Results:Reductions in ARR and disability progression were
consistent across subgroups in favor of teriflunomide, with no
treatment-by-subgroup interaction test reaching statistical
Conclusion:The positive effects of teriflunomide were
demonstrated consistently across subgroups in TEMSO.

The TEMSO study was reported as a news flash where it was claimed that teriflunomide was benefical in most MSers and the full trial has been published and showed that both 7 mg and 14 mg once-daily oral doses of teriflunomide significantly reduced the annualized relapse rate (ARR) (relative risk reductions: 31.2% (p=0.0002) and 31.5% (p=0.0005)) and 12-week confirmed disability progression (hazard ratio reductions: 23.7% (p=0.0835) and 29.8% (p=0.0279)) compared with placebo .

We have reported on the TOWER teriflunomide study and other studies involving teriflunomide. In TOWER, a double-blind, multi-center trial enrolled 1,169 MSers and compared once-daily treatment with either 7 mg (There was a 22% reduction in relapse) or 14 mg (there was about a 35% reduction in relapse) oral teriflunomide against placebo, with a modest reduction of relapses at the 14mg dose.

The objective of current report was to determine whether the effects of both doses of teriflunomide on ARR and disability progression were demonstrated consistently in a range of pre-specified patient subgroups from the TEMSO study related to demographic and disease characteristics at baseline.

                                   Teriflunomide structure

Although there was no difference in relapse rate between placebo and secondary progressive MSers this would be expected as the number of relapses in SPMS is reduced. However there was some influence in the rate of progression in this group.

This study shows there is not one group of MSers (based on sex, age, EDSS status, Location, number of relapses etc.) who benefit over another group it works as well, or not, in all groups.

This drug is being positioned to compete against beta interferons and glaterimer acetate as it as about as safe and effective as the compounds mentioned but has the advantage of been oral.

CoI: None. Prof G multiple

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  • It's as safe and effective as the injectables, but it's oral- no more flu like symptoms, no more injection site reactions etc.
    It's not as effective as nataluzimab, but then it's safer

  • Which reasonable patient would give away a drug twice as effective (Tysabri, assuming low-PML risk).

    Is the convenience of a pill v.s. a monthly hospital visit so valuable that one is willing to relapse twice more?

    I find it disgraceful that more money is going into funding lesser quality drugs. (again, this rant excludes any benefit to SPMS as there is nothing in the market for these guys)

  • For me the ideal MS treatment would be one that requires at least 24 hours of hospitalisation. That is because most insurance policies here in India do not cover outpatient expenses (except for pre- and post-hospitalisation).

    Most of the population doesn't have any medical insurance. But insurance is not much help for MS.

  • "24 hours of hospitalisation"

    This is more of a regulatory and public policy concern.

    I can't see how it relates to our debate hereby!!

    To conclude: I want to see much more public money going in stem cells away from these dead-end drugs. Stem cells procedures are not patentable, that's why I emphasize on *public* money.

    The MS Society ought to wake up to this reality.

  • Well, I guess, it's easier to optimise existing drugs than finding new ones for SPMS. However, from a financial perspective it could be very valuable since a single effective drug for SPMS could easily become a market leader – let's hope the CEOs of Biogen Idec and Co. know that and are testing new compounds.

    It's quite interesting to watch – 5 years ago there were only a few RRMS and now they're growing like mushrooms.

  • Where insurance does not cover outpatient treatment, it means that oral drugs and even injected treatments are hard to afford. This is private insurance and has nothing to do with public policy.

    Intravenous treatments are more affordable, because doctors can help patients get around the 24-hour requirement (by keeping them longer in hospital). But it would be nice (more straightforward) if the treatment officially required overnight observation or if it took a whole day to infuse.

  • "how is this drug better than existing DMDs for RRMS"

    It is a pill and not an injectable…therefore ease of use

    Anon 10.25 says it all

  • Is the convenience of a pill v.s. a monthly hospital visit so valuable that one is willing to relapse twice more?

    This is risk benefit and cost excerise. Some people are risk
    averse what if you are JC virus positive. What if Genzymne prices it below the interferons it is half the cost of tysabri and does not have the PML risk. This gives MSers more choice

  • "I want to see much more public money going in stem cells away from these dead-end drugs. Stem cells procedures are not patentable, that's why I emphasize on *public* money. The MS Society ought to wake up to this reality".

    Procedures are not patentable….where there is a will there is sometimes a way, e.g. methods of production et al.

    The MS Society is awake…it is putting a lot of its research resource into stem cell and has funding commitments to Cambridge and Edinburgh and other places. However it has not an endless pot of cash.

    There is a worldwide effort in stem cells a few years ago it was gene therapy..where is that now?…so putting all eggs in one basket has its risks.

    In many lesions in MS there are lots of progenitors there but they are not maturing and doing what they should. So should be be trying to add more stem cells into a situation where the stem cells are not doing what they should be doing or should be be developing "drugs" that change the environment to make existing stem cells do what they should do. Stem cells mean different things to different people.

    If those dead end drugs do not put the fire out then it is like throuwing logs onto a fire

  • It's quite interesting to watch – 5 years ago there were only a few RRMS and now they're growing like mushrooms.

    This is because we know how to do studies to show an effect for RRMS drugs, we do not know how to do the studies to best show an effect for SPMS. In history lots of potentially useful drugs for RRMS were effectively thrown away because they were used in trials where they could never work.

  • Lamotrigine trial failed..wrong MRI outcome measure.

    CUPID has just failed…wrong MSer group?..Wrong dose? so it is back to drawing board..

  • Initial trials in MS with new immunosuppressive agents were actually done in secondary progressive MS rather than RRMS.

    This is because doctors were risk averse. They did not want to treat early MS because 30% would do well (so-called benign MS) and they did not want to tip the balance away from that. Likwise historically they did not have MRI to aid diagnosis and because there were no treatments diagnosis may have not been made early.

    This (progressive) phase of disease responds poorly to immunosuppressive drugs, therefore trials failed and the drugs were destined for the scrapheap. However the drugs were unlikely to work in this phase of disease because they just don't so the trial design was flawed.

    By moving treatment earlier and earlier one is seeing better and better levels of efficacy

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