What is the correct therapy strategy for MS? This discussion was also in focus at this year’s ECTRIMS Meeting. Given the significant pathological changes and their associated effects on brain function, which are already present in the first years after diagnosis, a growing faction of MS specialists currently believe that MS should be treated from the beginning with the most effective drugs/therapy strategies possible.The availability of drugs that enable so-called (pulsed) immune reconstitution therapy has promoted this discussion. Therefore, it was intensively discussed whether an early effective approach (under the slogan “hit hard and early”) might not be a better strategy than the currently used escalation therapy, in which the therapy is adjusted depending on the response to the chosen drug.
The escalation therapy is primarily safety-driven, i.e. treatment starts with a moderately effective, but relatively safe drug (often with interferon preparations or glatiramer acetate) and this medication is then adjusted depending on therapeutic success. This strategy often takes a relatively long time until patients are treated with highly effective therapies. Accordingly, this strategy means under-treatment of very active patients, while on the other hand it prevents over-treatment, i.e. the administration of very effective, but also side-effect-rich drugs to patients who do not necessarily need highly effective medication.
Prof. Gavin Giovannoni, London, made a very emotional plea for abandoning the escalation strategy in favor of a “hit hard and early” strategy. Too much time would pass with the currently used approach, too many patients with active MS would be under-treated in the first, decisive years and thus risk their brain health, which Gavin Giovannoni defines much more broadly than “no evidence of disease activity”, i.e. freedom from relapses, EDSS progression and MR activity.
He outlined the significant individual consequences that delaying effective therapy can have for an MS patient and advocated a bolder approach. Even though more effective drugs often have serious side effects, there are sufficient monitoring and safety measures that allow effective risk reduction and thus put the benefits and risks of such therapy in a reasonable relationship to each other.
However, Prof. Giovannoni also emphasized that such a “hit hard and early” strategy can only be decided upon within the framework of shared decision-making with the patient, as the patient ultimately has to bear the risk. In his opinion, however, an enlightened and informed patient will always prefer brain health.
In view of this discussion about the correct therapy strategy, the results of autologous stem cell transplantation (=HSCT, hematopoetic stem cell transplantation) are of great interest, as this measure currently represents the ultimate approach to “reset” the immune system. In the past, this measure was primarily used late in the course of MS with already very pronounced disability and showed only limited benefit. Only in recent years has it become clear that use in highly active patients early in the course of MS has considerable efficacy.
However, the measure was very invasive and originally had a mortality rate of almost 3 percent. Prof. Paolo Muraro, London, who has been dealing with HSCT for many years, reported that changing protocols and more targeted patient selection significantly reduced mortality with this method and is now at most 0.2%.
In the recently communicated randomized study MIST, in which 110 patients were either treated with HSCT or a conventional regime that was also performed with very effective therapies such as natalizumab or rituximab, no death occurred at all and it was reported that 60% of the patients were stable after HSCT, but only 6% by applying a conventional therapy – a highly significant result in favor of autologous stem cell transplantation.
It is clear that the future discussion about the “hit hard and early” strategy will also be a discussion about the role of autologous stem cell transplantation.