The goal of the induction model is to stop MS activity as soon as possible. This goal is based on the assumption that a window of opportunity early in the disease warrants the increased therapeutic risk despite an unclear prognosis. “If there’s no window of opportunity, we can wait to induce [patients] a few years down the road,” said Dr. West. “But if there is really a narrow window at the beginning … then the induction model makes a lot of sense.”
The idea of the window of therapeutic opportunity arose from studies of alemtuzumab in the late 1990s and early 2000s in patients with severe MS. In a 2006 article that examined EDSS change following alemtuzumab therapy, Coles et al found that while most patients with secondary progressive MS got worse, those in the relapsing-remitting arm achieved significant and striking improvement. “Not only did they stabilize … they actually gained multiple points on their EDSS score,” said Dr. West.
One caveat with the induction paradigm is that because one gets a variable response from available DMTs, clinicians can achieve NEDA with any of these medicines, but often at a high cost: they all raise significant safety and tolerability concerns. These concerns provided the rationale for the escalation paradigm.
Data indicate that a Caucasian patient with features such as monofocal onset, a low relapse rate in the first two to five years, or good recovery after the first relapse likely has a better prognosis than an African American or other nonwhite patient with features such as multifocal onset, a high relapse rate in the first two to five years, or poor recovery after the first relapse. A patient with a good prognosis may limit a clinician’s tolerance of risk and incline him or her toward the escalation model, said Dr. West.
“The idea here is: can we basically work through medicines in a quick way to get [patients] to a NEDA status while also limiting the risk? The assumption here is that sometimes the risk of treatment is greater than that of the MS.... We can define and identify what constitutes treatment failure … and then the next DMT might be more effective.
“We have a lot of tools with which to fight this disease,” Dr. West continued. “Our goal should be to stop the illness as soon as we can…. Both the escalation model and the induction model are trying to get to that goal—they’re just doing it a little bit differently.”
—Fred Balzac