On March 28, 2017, the FDA approved a new, uniquely-acting drug for the treatment of multiple sclerosis (MS). They approved Ocrevus (oIcrelizumab)
for "relapsing forms of multiple sclerosis (MS) and primary progressive multiple sclerosis (PPMS)."
The wife of a friend of mine has MS and is currently doing well on one of the older medications. He asked me what I thought of this new medication.
After reviewing the medical literature, I shared with him what I learned. I thought my notes and thoughts might be of interest to some of the readers of Daily Kos as well
After some editing for inclusion on Daily Kos, here are my notes:
- When you see the letters “mab” at the end of a drug name, you know you are looking at a monoclonal antibody.
- OIcrelizumab is a monoclonal antibody which targets B-cells. Most immune-modulating drugs for MS target T-cells. T-cell and B-cells cause an immune response via different mechanisms.
- The initial Phase III clinical trials of ocrelizuma used patients with rheumatoid arthritis, hematological cancers, lupus and MS. They had to stop the trials in the RA, cancer and lupus patients because of an increase in progressive multifocal leukoencephalopathy and opportunistic infections. Many of these patients were on other immune suppressant drugs.
- In the MS patients, they saw a "pronounced decrease" in MRI activity (number needed to treat or NNT=20) and a "significant decrease" (NNT= 200) in relapse rate with ocrelizumab.
- In MS patients, side effects were mostly minor "infusion-related" events, although there was an non-significant increase in respiratory and urinary tract infections in those treated with the higher dose of ocrelizumab (NNT=20).
- There was one patient in the ocrelizumab high-dose group who died from acute-onset thrombotic microangiopathy "where a possible relation to the study treatment could not be excluded."
- A more recent Phase III study comparing ocrelizumab to interferon in relapsing MS showed a decrease in relapse rates after 96 weeks (NNT=700) and disability progression at 24 weeks (NNT=30). In other words, patients on ocrelizumab had fewer and less severe relapses compared to patients on interferon.
- A similar study comparing ocrelizumab to placebo in PPMS showed a decrease in disability progression at 12 weeks (NNT=16) . In other words, while ocrelizumab didn’t stop symptoms, it did slow down their progression in some patients.
- Ocrelizumab will have a list price of $65,000/year.
Keeping in mind that I am an internist and NOT an expert in the treatment of MS, here are my thoughts:
- It is important to note that ocrelizumab is only indicated for relapsing forms of MS and primary progressive multiple sclerosis (PPMS).
- The most impressive result was the decrease in MRI disease activity. Although MRI is a good surrogate for MS activity, we treat patients, not MRIs.
- The Phase III studies included a limited number of patients. It is possible that rare, but serious side effects will become apparent with more widespread clinical usage.
- Rule #1 of the art and practice of medicine; "If it works, keep doing it." In other words, if a medication is working for a patient with relapsing MS, I would be wary of changing it.
- If a patient with relapsing MS is not responding to older medications, ocrelizumab is worth a shot. Of course, it may be problematic whether insurance will cover it. The patient and physician should be prepared to jump through hoops to get it.
- Previously, there were no good treatments for PPMS. PPMS is such a devastating disease, ocrelizumab would be worth a shot. Once again, there will be hoops to jump through.
- I would watch carefully as we get more widespread experience with ocrelizumab.