Two renowned multiple sclerosis (MS) specialists shared their opposing views regarding the use of escalation or induction treatment for newly diagnosed MS patients. The debate was at the Hot Topic 1 Session of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2016 Congress, now taking place in London through Sept. 17.
The two treatment strategies differ in their use of more potent immunosuppressant drugs. Escalation therapy is the standard approach used today, where new patients with relapsing MS are treated with less potent, but relatively safe, drugs such as interferon-beta drugs Avonex and Rebif, or Copaxone (glatiramer acetate).
The main idea behind this approach is that treatment side effects should be proportional to the disease state. If this treatment is not able to control the disease, more potent immunosuppressant drugs, such as Gilenya (fingolimod), Tysabri (natalizumab), Novantrone (mitoxantrone), or other biologics, are introduced.
This treatment can, in turn, be replaced by even more potent immunosuppression, such as stem cell transplants or high-dose cyclophosphamide, if patients keep relapsing despite treatment. As treatments become more aggressive, the severity of potential side effects rises accordingly.
Induction treatment is virtually the opposite approach. It starts early on with an induction phase of aggressive immunosuppressant drugs, followed by maintenance treatment with somewhat more benign immunomodulatory medicines. The idea is to “shock” the disease in its earliest stages to retard or prevent progression, but to keep the induction phase as short as possible to minimize side effects.
Today, induction treatment is used only in patients with very active or aggressive disease, where the risk of early disability is deemed to be higher than the risk of side effects.
In his talk, “The initial treatment of early active relapsing remitting MS should be with a potent induction therapy rather than standard immunomodulation then escalation,” Gilles Edan from the Central University Hospital of Rennes in France argued that early induction treatment may prevent the loss of neurological function.
He backed up his claim by citing a randomized clinical study showing that induction with Novantrone, followed by maintenance treatment, controlled disease better than interferon-beta treatment.
Edan said Tysabri is also effective as an induction treatment, but it has been seen to trigger rebound inflammation when stopped. A more recent study of Lemtrada (alemtuzumab) showed that only five days of intravenous treatment with the drug had durable benefits for relapsing patients in early disease stages.
Emmanuelle Waubant from the University of California, San Francisco, presented a more cautious view of the concept in her talk, “Against potent induction early.”
She stated that the increased risk of infections that hit immunocompromised people can sometimes have fatal consequences. Since most of these more aggressive immunosuppressant drugs are fairly new, there is little safety data on long-term use, meaning we basically do not know if other side effects of the treatments will emerge.
Also, treatments such as stem cell transplant have often been conducted in studies without control groups, making it difficult to compare side effects.
Waubant also argued that few randomized studies of the more potent immunosuppressant drugs have explored their early use compared to placebo or to standard treatment, and that no large trial of induction treatment has been performed. In other words, there now is very little data supporting the use of an induction treatment approach.
In final remarks, she said that only a few of the highly potent treatments change the immune system in a way that would extend disease remission, and concluded by saying that with the levels of knowledge available today, induction therapy early in the disease course is not suitable for the majority of patients.