Induction versus Escalation – Which is the More Promising Regime

With the availability of cell-depleting antibodies such as alemtuzumab or ocrelizumab, the question arises more and more frequently whether we need to change our strategy for treating MS.Currently, most patients are treated with a so-called escalation concept. This means that therapy is started with a drug that has only a moderate effect but is very safe, i.e., it hardly has any serious side effects. If the effect is insufficient, the therapy is optimized by switching to a more effective drug – for the higher effect one is then also willing to accept more serious side effects. This approach is driven primarily by the desire for high patient safety, which is absolutely understandable and desirable.

On the other hand, the escalation concept has the disadvantage that sometimes a lot of time is lost until the decision to switch to a more effective, but also “potentially more dangerous” substance is made. Time that many MS patients do not have due to a rather active course and that can cost a lot of functionality.

Therefore, the question is repeatedly discussed whether it would not be much more sensible to start treatment as efficiently as possible at the time of diagnosis of multiple sclerosis – i.e., to start therapy from the outset with a highly effective drug and to accept the “more dangerous” side effects in favor of high effectiveness. Such an approach is also referred to as induction therapy.

Alemtuzumab or the recently approved cladribine are drugs that are suitable for such induction concepts. They are very effective, are given only briefly at the beginning of a treatment year, and contain the promise of a long treatment-free interval. However, potential serious side effects and associated frequent laboratory controls are opposed to this. Overall, however, the side effects are rather rare – hence the question is justified, what actually fundamentally speaks against treating MS patients at the beginning with an induction concept?

Well, first and foremost there is certainly the fear of over-treating too many patients. Indeed, there are plenty of patients who manage well with a moderately effective and low side-effect basic therapeutic (interferons, glatiramer acetate).

Another argument that is often mentioned is that MS turns out to be benign in the course of time. The term “benign MS” is debatable. I admit that I personally don’t like it at all. I think you can only speak of a benign course if you can actually look back on a patient’s entire life – i.e., only if an MS patient is over 70 years old and is doing well in all respects. In a 25-year-old, at least I would never use the term “benign MS” because in such a case no one can predict what is yet to come, as there are no clear prognostic factors. And often a supposedly benign disease has changed its appearance.

Also against the background that many patients feel physically fit, but already have to accept cognitive restrictions due to MS, the term “benign MS” is relativized.

However, to be fair, data from a London cohort with a first demyelinating event were shown at the last ECTRIMS meeting in Paris, from which many individuals have had a relatively benign course even without therapy. In view of such data, it would probably be exaggerated to recommend induction therapy to every patient.

A “hit hard and early” strategy remains interesting in any case if it is possible to identify those patients at the beginning who have a high risk of severe disease with the help of biomarkers. In the future, the determination of neurofilament from serum could possibly be such a biomarker. As long as we do not yet have definitive tests here, we should at this point in time primarily use MRI images and the progression of lesion load in MRI as markers and decision aids for an appropriate therapy strategy.

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