Clinical Challenges: Aggressive or Cautious When Treating Relapsing MS?

SAN DIEGO — The central question when starting treatment for a newly diagnosed relapsing remitting multiple sclerosis (RRMS) patient is essentially this: do you come out swinging, or do you take a more step-wise approach?

With 15 disease-modifying therapies available — ranging in impact from the old staple of interferon injections to more potent oral drugs and powerful infusion therapies, to chemotherapy-like alemtuzumab — the choice isn’t an easy one. Add to that the heterogeneity of the condition itself, with each patient being different from the last, and the picture is extremely complicated.

The debate is often thought about in terms of “induction” versus “escalation” therapy, although those terms have evolved away from their initial meaning to some extent, experts said here. Rather than seeing “induction” specifically as something that completely re-sets the immune system, it has become synonymous with starting patients on more aggressive therapies. Escalation, then, refers to the more step-wise approach of trying older, more milder agents first and then moving on when patients no longer respond.

“Most physicians do not like the terminology ‘escalation’ versus ‘induction,'” Edward Fox, MD, of Central Texas Neurology Consultants, told MedPage Today. “They don’t feel like the treatments need to be divided into two groups. Instead, we’re trying to look at individualized treatments, balancing the risks of ongoing disease versus the risks of therapy. We believe there are more highly efficacious drugs than others. Some medicines are better at controlling the disease process, but that comes at the price of decreased immune surveillance.”

Jacqueline Nicholas, MD, MPH, of OhioHealth in Columbus, Ohio, agreed that the terminology isn’t the most appropriate, but used those terms for lack of better ones. One of the criticisms of the escalation model, she said, is that treatment failure means the patient may have lost something they may not get back.

“Each time a patient fails a treatment, they’ve accumulated more brain damage or spinal cord damage, and that’s something you can’t get back. It’s already done,” Nicholas told MedPage Today. “The newer wave of thought in the field is that you should consider, in appropriate individuals, using something like induction therapy, to hit the disease hard early when we know we can have the greatest impact.”

Fox said traditional induction strategies like alemtuzumab or mitoxantrone are rarely used as first-line therapies; indeed, the indication on alemtuzumab requires the patient to fail two other drugs first. The question, he said, is more about whether more aggressive therapies are the right way to start.


Stephen Krieger, MD, of Mount Sinai Hospital in New York, said he prefers an escalation strategy, with a caveat: “It’s escalation, but it’s not complacent,” he said. For instance, he talks to patients about the injectables like interferon and glatiramer acetate (Copaxone), and then about oral medications. But he said it’s rare that he’d use an infusion therapy as a first-line agent.


“That said, if the patient has numerous worrisome signs, like stacked relapses and early disability, I’ll do a prompt escalation to an oral or infusion therapy,” he told MedPage Today.
The older therapies, which are often referred to as “platform” therapies, do have one advantage over newer, more aggressive drugs: evidence of safety, said Brian Weinshenker, MD, of the Mayo Clinic in Rochester, Minn.



The original injectables like interferon beta-1b (Betaseron) have been accumulating data for more than 20 years and have proven safe and effective. Weinshenker noted that in long-term data from those original trials, interferon beta-1b has shown an impact on disability, and reductions in causes of death that could be attributable to MS.


“As a patient, I might not ask, what is the newest and hottest drug? I would say, which one has been around a long time that we have good safety on, knowing I’m going to be on this drug for the next 10 or 20 years or longer,” Weinshenker said.


While the newer therapies have shown good evidence of protecting the brain in the short term, the long-term safety and efficacy data just aren’t available yet, he noted.


“On the surface, it makes sense [to treat aggressively], but the evidence supporting that it offers the desired long-term outcomes is limited,” he said. “Yet we can’t wait to treat patients until we have answers after 25 years. That’s why we’re having some difficulty figuring out what to do.”



Nicholas said the decision comes down to the patient being treated at the moment: “It’s very individualized. Most of us use our knowledge of prognostic factors in MS. If an individual comes in and has multiple poor prognostic factors — someone whose disease may be more aggressive — that’s someone we recommend starting on a higher efficacy agent, or perhaps induction with an agent like alemtuzumab. But if someone comes in and their first symptom was a sensory symptom and they’re female and they’re young, those are favorable prognostic factors. Certainly many of us would recommend that she go on a more effective agent, but it wouldn’t be wrong if she felt she wanted to start an injectable, knowing its safety profile and knowing she probably has a less aggressive course of MS.”


Article source found on Medpage Today