Here is My Question:
I am 41 years old and was recently diagnosed with RRMS. My symptoms were tingling in my hands and feet. My MRI showed three lesions (one on the brain stem). My neurologist wanted to give me Tysabri but I am JC + with a titer of 3.4. My doctor suggested Copaxone or Tecfidera. How worried should I be about PML on Tecfidera. My recent blood work shows lymphocytes at 1.1. Is Copaxone a better option.
This is an excellent question; You seem to be a typical low risk early onset MS patient (you do not even satisfy current diagnostic criteria for definite MS if the information provided is correct). There are several, important missing pieces of information, so I will make several assumptions in my initial response. These assumptions are as follows:
1. There is no significant evidence of brain atrophy on your MRI scan
2. You only experienced sensory symptoms and have no limitations in function
3. There are no enhancing lesions on any MRI scans or new lesions on repeat MRI scans (these features would give you definite MS)
4. Your MRI findings are typical of MS. If not typical, sampling your spinal fluid would be the next step
If these assumptions are correct, you would be considered a low risk patient with many treatment options. I would list these options as follows
1. Start on High dose Vitamin D3 (5,000 to 10,000 IU a day depending on your 25 hydroxy vitamin D3 level) and repeat MR imaging 6, 12 and 18 months after the initial scan. If you should experience a relapse at any time or new MR activity on follow-up imaging, then initiate Disease modifying therapy. Rationale for this approach: In the CHAMPS and CHAMPIONS follow-up studies (these were part of a series of studies to determine if it is better to start treatment with an injectable at the onset of symptoms or after a person experiences recurrent disease activity), only 25 % of patients had less than 9 lesions on their initial MRI scan (you would fall into this group with 3 lesions). These patients did well over 10 years even if they received a placebo until their disease flared up again or there was new activity on an MRI scan. Many of these patients either never started a disease modifying therapy or stopped after several years of treatment and remained stable. It is reason to start high dose vitamin D3 therapy since it is safe in most people and there is mounting evidence it has some beneficial effect on disease activity. There is certainly no evidence of harm
2. Start on Tecfidera or Copaxone now: The downside of this approach is that you have no idea of your anticipated disease activity over the next few years in the absence of a disease modifying therapy. We do know that over the long term, starting treatment will reduce disease activity on a population basis but on an individual level only 20-25 % of patients with your characteristics will even experience a relapse in the first 2 to 3 years. Many people a concerned that without treatment their next relapse may be severe and they will not recover. In fact this is quite rare in people with your characteristics. This being said, many people with your characteristics are more comfortable with starting therapy now. This is certainly reasonable and the drugs are approved for this indication. So how do you decide? Primarily based on short term side effects, long term risks, convenience, tolerability and insurance restrictions. Assuming there are no insurance restrictions, options include the following in no particular order:
A. Copaxone: This is a partially effective drug with a long safety history that can be injected 3 days a week. The main side effects are injection site pain and lipoatrophy (loss of subcutaneous tissue at injection sites with divots developing in the skin)
There are no long term safety issues
B. Interferon: These are partially effective drugs with similar effectiveness to copaxone in patients like yourself. You would probably use a once a week (Avonex) or once every 2 week (Plegridy). Both are associated with flu like symptoms after injections that lessen with time and can be partially blocked by premedicating with tylenol or motrin. There are other minor risks but generally the interferons have an excellent long term safety profile. The advantage over copaxone would be fewer injections but only if you are one of the individuals who does not experience significant side effects.
C. Tecfidera: This is a great drug with almost 200,000 people with MS taking it worldwide. There is evidence that it is more effective than Copaxone. This a twice a day oral medication. The main side effects are flushing and GI side effects (nausea, lack of appetite, upper abdominal discomfort, cramping or diarrhea); these side effects are generally manageable and lessen considerably within 8-12 weeks of starting treatment. The main long term risk is a lowering of absolute lymphocyte count. This may be associated with the development of rare infections like PML but the incidence is very low (so far about 2 per 100,000 patients treated). JCV antibody index values have not been shown to be associated with risk of PML in patients on tecfidera. In your case, I might consider this drug second line along with Gilenya
D. Aubagio is an excellent choice as well: It is certainly as effective as any of the injectible treatments and all you take is a single pill very few side effects once a day. There are some concerns about using this in pregnancy but this is probably not an issue in your age group. The FDA recommends monitoring liver enzymes on this drug, but in my experience it is very rare to see significant liver enzyme elevations. Less than 10 % of patients experience some temporary hair thinning (usually not noticeable to others) on this drug, but this tends to reverse after 3-6 months of treatment. Generally, there have been very few short or long term risks with this drug, and I have not figured out why it is not used more often in early relapsing MS.
Tysabri is not a reasonable option; although a great treatment, your risk of PML after 2 years of treatment would be greater than 1 in 100
Hope this information helps.
Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Director of Hillcrest Neurology
Professor of Clinical Neurosciences
University of California San Diego
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