Starting treatment – what happens in the real world?
An MS drug’s ability to reduce the frequency of relapses and slow worsening disability is evaluated in clinical trials. The people who are studied in these trials are highly selected according to various criteria: the overwhelming majority are white (e.g. 97% in the TEMSO trial of Aubagio), haven’t lived very long with MS (about 3 years in the OPERA trials of Ocrevus) and have infrequent relapses (typically 1 per year). The advantage of a trial is that it allows for a more rigorous comparison of treatment effects against a placebo (or increasingly against another drug). The disadvantage is that the efficacy that’s shown won’t necessarily apply to people with MS living in the real world – people who are older or younger, with a more wide-ranging experience with MS, and living with other medical conditions.
That’s why real-world studies are done – to gain a sense of how a drug performs when given to the range of people who show up at a neurologist’s office. Such studies can reveal curious differences. For example, the TERI-PRO study found that the people taking Aubagio outside the U.S. were twice as likely to report hair loss as Americans taking Aubagio (Coyle and colleagues. Mult Scler Relat Disord 2019;31:157-164). We can only speculate why.
Most people now start treatment with an oral therapy (e.g. Aubagio, Tecfidera) rather than an injectable (e.g. Copaxone, Rebif, Avonex, Betaseron), or they switch to an oral because they’re tired of injecting or find their injectable drug isn’t working for them. U.S. surveys recently reported that only 1 in 6 people now start treatment with an injectable, and their first switch is most often to an oral therapy (Coyle PK. AAN 2020; P14.1018 and P14.1020). Oral drugs are equally popular as initial therapies in Canada and other countries (Setayeshgar and colleagues. Mult Scler Relat Disord 2018;25:57-60. Maniscalco and colleagues. Mult Scler Relat Disord 2020; epublished March 16, 2020. Maurer and colleagues. Ther Adv Neurol Disord 2019;12:1756286419892077). More potent drugs are available, but they are generally being reserved for the people with severe MS who really need them.
Real-world can provide some insights about how well these oral therapies perform. And since most trials don’t directly compare drugs, these studies can also give a sense of how one drug fares against another. This is important because many people will be taking that drug for a decade or more (Labauge P. AAN 220; P9.1022).
A recent real-world study of Aubagio was TAURUS-MS, which looked at over a thousand people in Germany who were on the drug (Kallmann and colleagues. Ther Adv Neurol Disord 2019;12:1756286419835077). About 75% had switched from another drug, often one of the injectables. In the 16 months after starting Aubagio, the average relapse rate was cut in half and there was a boost in treatment satisfaction (convenience, effectiveness), indicating that an oral therapy was the better option.
Similarly, in the PROTEC real-world study, 88% of people became relapse-free in the year after starting Tecfidera (Berger and colleagues. Mult Scler J Exp Transl Clin 2019;5:2055217319887191). People also reported significant improvements in the fatigue, daily living and work performance. This last measure – the ability to continue working – has become increasingly important in studies. Work ability provides a practical assessment of daily function and gives a global sense of a person’s physical and cognitive abilities. With this in mind, a separate real-world study found that people taking Tecfidera had better work productivity and quality of life compared to those taking Copaxone or one of the interferons (Lee and colleagues. Neurol Ther 2017;6:79-90), suggesting that an oral therapy is more effective and has less burdensome side effects.
Numerous real-world studies have looked at how oral drugs compare. A French study found that Tecfidera was better than Aubagio at reducing the risk of relapses (Conde and colleagues. Eur J Neurol 2019;26:460-467). Tecfidera also performed better than Aubagio with respect to relapses, disability and MRI lesions in an Italian study (D’Amico and colleagues. Ther Adv Neurol Disord 2018;11:1756286418796404). In addition, a newly-published study in Austria has reported that people taking Tecfidera had fewer relapses than those on Aubagio or Gilenya; the Aubagio group was more likely to experience treatment interruptions and less like to show disability improvement compared to Tecfidera or Gilenya (Guger and colleagues. J Neurol 2020; epublished April 3, 2020).
Efficacy is one consideration. Another is whether a person can remain on the regimen, which is largely determined by whether the drug is perceived to be effective and how tolerable its side effects are. Some studies have found that people are equally likely to stay on treatment with once-daily Aubagio or twice-daily Tecfidera (D’Amico and colleagues. J Neurol 2019;266:411-416). The two drugs appear to be well-tolerated and have similar side-effect profiles. Aubagio can cause hair thinning (O’Connor and colleagues. N Engl J Med 2011;365:1293-303); Tecfidera can cause flushing (Gold and colleagues. N Engl J Med 2012;367:1098-107). Both can be associated with nausea and diarrhea. Stomach upset may be more common with Tecfidera but these effects can be minimized if the drug is taken with food or with over-the-counter stomach remedies (Min and colleagues. Neurol Ther 2019;8:109-119).
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