Does Teriflunomide as a DMT warrant discussion?

D

Speaking as a clinician who goes by the mantra ‘treat early, treat hard’, platform therapies as a whole receive less attention from me than highly-active treatments. However, I know that they have a place in the MS armamentarium and admittedly, I have a more than few patients on Teriflunomide. Some of whom have been stable on it for many years, whilst others I’ve had to transfer to another DMT within a few months of commencement. The same can be said for dimethyl fumarate (or DMF). I’m also cognisant of the fact that research that non-adherence is the biggest contributor to treatment failure in MS. For example, adherence to DMTs in MS varies between 41-93%, whilst by comparison the adherence rates in diabetics taking insulin for Type 2 SM varies between 62-64%. So it is important to get the treatment right from the start.

If we take a look at teriflunomide it has roughly 30% annual relapse rate reduction, it is an oral tablet taken once a day, and it’s side effects to consider before starting treatment is hair thinning and frequent blood tests for liver function monitoring. The long-term safety analysis (9 years follow up) suggests that it is largely well tolerated (see Figure below).

Figure: Patient disposition in Teriflunomide Multiple Sclerosis Oral (TEMSO) and the TEMSO extension study . a The major reason for screening failure was failure to meet inclusion criteria (n = 155 [62.0%]); b 2 patients (1 each in the 14-mg and 7-mg teriflunomide groups) were not exposed to study medication because of protocol violation; c did not give consent to continue in extension study; d 2 patients in the 14-mg/14-mg group were randomized but not treated: 1 did not wish to continue and the other 1 prematurely discontinued study treatment and did not take any double-blind medication in the extension.

In a new questionnaire based observational study from Australia, investigators studied treatment satisfaction with teriflunomide at 24 and 48 weeks.

In roughly, more than a half of the patients surveyed, teriflunomide was their first MS DMT. The average treatment satisfaction was >60% (see Figure below).

Figure: TSQM treatment satisfaction scores at week 24 and week 48: individual scatter plots by TSQM domain. TSQM, Treatment Satisfaction Questionnaire for Medication

Convenience in particular seems to be in favour of teriflunomide. Treatment satisfaction was also found to be correlated with the number of missed tablet doses; with a decrease in satisfaction as the number of missed doses increased.

It is important to realise the setting of this study. In Australia for relapsing-remitting MS (RRMS) there are 14 licensed therapies:  five injectables (glatiramer acetate, interferon beta-1a, interferon beta-1b, peg interferon beta-1a, ofatumumab), six oral (cladribine, dimethyl fumarate, fingolimod, ozanimod, siponimod, teriflunomide) and three administered via infusion (alemtuzumab, natalizumab, ocrelizumab). There is no pre-mandated hierarchy to their DMTs or a guidance as to which therapies are prescribed first or to follow on from beyond what is stated on the label (i.e. the drugs licensed indication). Therefore, pretty much you have your pick of treatments. In situations such as these, satisfaction with treatments plays a huge role.

BMJ Neurol Open 2022 Jul 4;4(2):e000315.

Abstract

Treatment satisfaction in patients with relapsing-remitting multiple sclerosis initiated on teriflunomide in routine clinical practice: Australian observational data

Todd A Hardy John Parratt Heidi Beadnall Stefan Blum Richard Macdonell Roy G Beran Neil ShueyAndrew Lee William Carroll Cameron Shaw Richard Worrell Jana Moody Mamdouh Sedhom Michael BarnettSteve Vucic 

Background: Adherence and persistence are critical to optimising therapeutic benefit from disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). This prospective, open-label, multicentre, observational study (AubPRO), conducted in 13 hospital-based neurology clinics around Australia, describes treatment satisfaction in patients newly initiated on teriflunomide (Aubagio) and evaluates the use of an electronic patient-reported outcome (PRO) tool.

Methods: Patients (≥18 years) newly initiated on teriflunomide (14 mg/day) were followed up at 24 and 48 weeks. Patients completed questionnaires and pill counts electronically using MObile Data in Multiple Sclerosis. The primary endpoint was treatment satisfaction, measured by the Treatment Satisfaction Questionnaire for Medication (TSQM, V.1.4), at week 48. Secondary endpoints included treatment satisfaction at week 24, other PRO scales, clinical outcomes, medication adherence and safety.

Results: Patients (n=103; 54 (52.4%) treatment naive) were mostly female (n=82 (79.6%)), aged 49.5 (11.8) years, with MS duration since symptom onset of 9.1 (11.8) years and a median Expanded Disability Status Scale score of 1.0. Mean treatment satisfaction scores were high (≥60%) across all domains of the TSQM V.1.4 at week 24 and at week 48. Compared with week 24, week 48 treatment satisfaction increased for patients who were treatment naïve and for those previously on another oral or injectable DMT. Over 48 weeks, PROs remained stable across a range of measures including disability, physical health, emotional health and mobility, and there were improvements in work capacity and daily life activity. Adherence was high throughout the study with mean compliance (pill counts) of 93.2%±6.26%, and 98 of 103 (95.1%) patients remained relapse-free.

Conclusion: This cohort of Australian patients with RRMS, newly initiated on teriflunomide, and treated in a real-world clinical practice setting, reported high treatment satisfaction and adherence at 24 and 48 weeks. Patient-reported measures of disability remained stably low, work capacity and daily life activity improved, and most patients remained relapse-free.

About the author

Neuro Doc Gnanapavan

18 comments

  • “There is no pre-mandated hierarchy to their DMTs or a guidance as to which therapies are prescribed first or to follow on from beyond what is stated on the label (i.e. the drugs licensed indication).”

    What??? Wait… You mean patients don’t have to have a third relapse, fail a second drug and have a specific increase or decrease of their EDSS in order to change to a medication that’s more effective but more expensive? You mean MS Specialist neurologists have free rein to recommend the treatment they deem to be most appropriate as professionals? But surely their system would collapse under the anarchy that ensues, no?

    I’m obviously being sarcastic. But isn’t it sad that in the United Kingdom we have MS specialist neurologists who are world experts, world authorities in the treatment and management of both MS and the side effects of its treatments. And they have to make choices and recommend treatments that they know not to be optimal, and where they know patients will decline permanently and irretrievably as a result of those treatments because they cannot prescribe stronger treatments “yet”, until certain boxes are ticked and hoops jumped through.

    I don’t even think we save money. What we gain in shaving off the cost of medication by denying it to those with neurological reserve, we more than lose in having to treat their premature disability and fund their premature retirement. It’s not just ridiculous is unethical.

    • Australia is unique in this respect, pretty much everyone else is in the same boat. Take the US for instance. When a new treatment comes in the inventing nation has to jump through several hoops. Those who adopt can modify the requirements. Wait until genetic therapy becomes the mainstay of treatment; the country that leads on this will be crippled with regulation. What should be written in is that everything should be reviewed at year 5.

  • Thanks NDG for this article, good info however I feel the title is not answered from long-term efficacy point of view. I’m also surprised to see it actually has a reasonable satisfaction score – I heard so much about its terrible day to day side effects. However the drop rate would be another aspect to comment for teri compared to other DMT’s? (drop and satisfaction should be looked at together).

    • Yes, you’re right. This needs to be done for many drugs. The drop outs from long term follow at least the reasons for it need to specify whether it is for disease breakthrough or for intolerance.

  • Teriflunomide is worth discussion as a maintenance therapy after hitting the disease hard with an induction therapy.

    • Well it’s effect on brain atrophy makes it a feasible option if you take end organ damage as the option. It needs to be a 5year study. If Sanofi is willing to do this I’m sure it won’t be that hard to set up!

  • I will be honest, the posts here have been pushing stronger DMTs as the first DMT of choice but I’ve been using Teri/Aubagio for 2 years now. I do feel that I am a tad slower cognitively in addition to mild spasticity but so far as a high risk demographic (Male) I have yet faced a second relapse. Here’s to hoping that I have been misdiagnosed or am a strong responder to Teri/Aubagio. Please don’t jinx me!

    • I agree I have been pushing the ATTACK-MS that we are doing….however as a non doctor I dont have to consider side effects just the response and I accept say 30% do well and hopefully you at 30%…for the high DMT it will be flipped and the 70% will do well

    • Don’t worry Steve there are patients of mine who are doing well on Teriflunomide/Tecfidera. The key is to treat early and then you’re doing neuroprotection. Some people need a lighter immunosuppressant than others, but this is all about personalised medicine. An NFL reading at diagnosis is very good at picking this out.

  • DOES TERIFLUNOMIDE AS A DMT WARRANT DISCUSSION?

    In my situation, yes. I was able to use Teri as a bridge between OCR and Clad. Teri was effective at keeping (modulating) my B-cells at a very low level, while I transitioned from OCR to Clad. No issues or relapses during the 11 month transition. B-cells remained well below baseline. Plus, I figured if any B-cells did come back, they should do so under a DMT with known anti-viral aspects.

    • Could you share your experiences as a Ocr. to cladribine switcher?
      When did you take your first cladribine dose?

      • Nonny- I am satisfied with Clad, a bit more fatigue during the treatment phases and you might find your B-cell may not repopulate as expected on Clad, because of taking OCR first.

        I became “allergic” to OCR after 4 cycles, so I had no choice but to switch.

        I took my first Cladribine dose 18 months after my last OCR infusion. My circulating CD19 b-cells began to repopulate around month 11, which is when I started taking Teri. The max CD19 b-cell level was 30/ul with Teri modulating.

        I had my neuro test the details of my lymphocytes monthly.

        Best of luck!

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