The advent of these powerful drugs poses yet another MS treatment dilemma: when should the approach be induction or escalation therapy?
Induction or escalation therapy?
Escalation is a familiar concept, Emmanuelle LePage, MD, wrote last spring in the French journal, Revue Neurologique (Rev Neuro 2018; 174: 449-457). Treatment starts with the safest disease-modifying drugs (glatiramer, beta interferons, teriflunomide, and fingolimod) and progresses upward through the monoclonal antibodies, finally landing – if necessary – at autologous bone marrow transplants and high-dose cyclophosphamide.
“The advantage of an escalation scheme is to allow many patients to have satisfying control of the disease while receiving relatively safe drugs and never escalating to more aggressive therapy” unless that becomes necessary, wrote Dr. LePage, a neurologist at University Hospital Pontchaillou, Rennes, France. The trade-off is that this approach may not adequately control relapses that irreversibly accumulate disability.
Induction, on the other hand, begins with a short-term course of highly-effective treatment, hitting the disease hard and early with the goal of extinguishing disease activity and, hopefully, benefitting long-term outcomes. “The aim of this strategy is to prevent early structural damage related to inflammatory-mediated demyelination and axonal loss,” Dr. LePage wrote. “This induction treatment strategy may also be a useful and conservative way to use these highly effective therapies while minimizing exposure and the subsequent safety risks.”
Once a patient achieves remission during induction, treatment can de-escalate to a long-term maintenance therapy with some of the safer agents. This approach is conceptually similar to the induction therapy approach to rheumatoid arthritis, in which aggressive treatment can modify disease progression if given during an early window of opportunity before joint damage occurs.
But while the therapeutic theory may be similar, the clinical picture is not, Dr. Rinker said.
“With RA there is more of this window of opportunity where you can see how things are going, and even have a chance to play catch-up because there can be some natural healing of the joints. In the central nervous system, the capacity for repair is much less. Patients who experience vision loss after a relapse may never have normal visual acuity again in that eye. The cost of disease activity in early MS is much higher, much sooner than it is in RA.”
The comparatively brief exposure time to the induction agent is a central feature of this approach, Dr. LePage noted. “The key to the success of induction is to use (these drugs) for the minimum amount of time needed to gain adequate control over disease activity … Considering the potentially serious side effects of the therapeutic candidates for an induction, this strategy has generally been reserved for patients with very active or aggressive disease at onset. In these patients, it is recognized that the risk of early disability is high, and that once neurological function is lost it cannot be restored. In such patients, this disease-inherent risk of poor outcomes can be considered to outweigh the risk of potentially serious side effects of powerful drugs.”