De-escalation experience



Safety considerations may make patients or treating physicians reluctant to continue with chronic immunosuppressive MS therapy [1,2] and older age may add to this concern [3,4]. Indeed, experts have recommended thinking twice about using agents with potent immunosuppressive effects in people with MS when they become clinically more vulnerable [3-6]. But how should these patients be treated? For patients with MS who have been clinically stable for a prolonged period-of-time, treatment de-escalation has been suggested [7,8]. De-escalation approaches have been used in oncology or rheumatology, but almost no data are available in MS [8].


A small study from Germany (n=30) in which clinically stable patients with MS were de-escalated from mitoxantrone to either s.c. interferon beta-1a or placebo has been conducted [9]. De-escalation to interferon beta appeared favorable versus placebo although, given the small study size, statistical significance was not reached. In another small pilot study, patients were switched from natalizumab to Betaferon (n=9) for safety considerations (and not for disease stability) [2]. Treatment satisfaction assessments suggested that such a change in therapy is feasible, well-accepted and tolerated by patients.


In general, MS management is trending towards early highly effective therapy but the length of time patients should remain on these agents is not clear. How long their benefits outweigh their risks with longer exposure or with older age has yet to be established [7]. Of note within this context are the findings of a large meta-analysis of clinical studies involving more than 28,000 patients with MS that found that second generation therapies may lose their advantage on disability progression beyond the age of 40 [10].



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