Here is My Question:
Is it ok to take Tecfidera for protection as I am rapidly moving into "secondary progressive MS" and Ocrevus is not an option as I have breast cancer history! Any advice from you would be much appreciated.

Answer:
There are many options for people in the late relapsing phase of multiple sclerosis, including Tecfidera. We do not provide specific prescribing advice on this site but the following general guidance may be used to help with your decision.

1. There are no current DMTs approved for established secondary progressive MS. All current therapies are approved for 'relapsing forms' of MS, including those patients with superimposed worsening of their disease AND relapses. This is also called secondary progressive MS with relapses or early secondary progressive MS. These are all confusion designations. Distinguishing between different stages of MS is more art than science, and many experts would disagree on the designation in any individual patient. Most MS experts use a combination of age, risk factors, clinical characteristics, and medical co-morbidities to determine the most appropriate DMT or to determine if DMTs should be used at all. Almost all clinical trials restrict enrollment to those people under the age of 60 (if not 55), so little is known about the benefits or risk of treatment in people over the age of 60.
2. It is important to establish short- and long-term goals for starting a DMT: what are you trying to accomplish and what risks are you willing to take to achieve those goals? This is something to discuss with your doctor
3. Once you decide to start a therapy you need to monitor your condition regularly to make sure you are achieving your goals and not developing complications. This monitoring may include collecting functional performance measures on a regular basis and noting them for doctor in a journal, and getting regular monitoring blood tests or MRI scans, if appropriate. For instance, it is particularly important to monitor your lymphocyte count while taking Tecfidera.

Good luck

Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego

Here is My Question:
Can a person with MS have his tattoo removed by laser?

Answer:
There is no MS related contraindication to tattoo removal.

Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego

Here is My Question:
Is it safe to change from Tecfidera to Ocrevus, I’ve read they are seriously interactive?

Answer:
It is possible to transition from Tecfidera to Ocrevus.  The clinician can evaluate through blood testing the status of the patient’s immune system to safely transition.

A. Scott Nielsen MD MMSc
Neurologist and MS Specialist at Kaiser Permanente

Here is My Question:
Three weeks ago today I got the Moderna vaccine, had chills that afternoon and sweating that night. All was well until this week, Tues. (which was 2 weeks and 4 days after the shot) I had chills in the afternoon and much worse sweating the middle of that night. Again on Thurs. of this week, more chills, but no sweating, and today more chills. I phoned my Dr. and was told it probably wasn't related to the vaccine, maybe a low grade infection, but if it keeps up to get blood work, etc. done. Could the vaccine trigger a flare or something to do with the immune system? Has anyone else had the same problem?

Answer:
About 10% of individuals can get the injection site swelling, rash, and various symptoms.  I, in fact, had this reaction with the first dose. The second dose has been reported as more difficult for some individuals.  Again, I too had that reaction with Moderna.  I would interpret this as your immune system reacting to the vaccine, producing cytokines (protein chemical messengers) that lead to these various symptoms.  Some MS patients understand the relationship between cytokines and similar symptoms because they’ve been treated with interferon-beta disease modifying therapies.

While I can’t say that you didn’t have another cause such as an infection of some sort, I would first consider this being vaccine related (or rather your immune response to the vaccine).  I also would look at this as evidence that the vaccine is stimulating your immune system in a positive way.  

There is no evidence that the vaccine triggers new MS inflammation (we also have lots of experience vaccinating our patients over the years and haven’t seen that concern).  However, when your core body temperature rises, that can influence nerve signal conduction which could bring out old symptoms of your MS.  Some consider this a “pseudo-relapse” because it isn’t new MS inflammation but simply the influence of heat on nervous system function for a period of time.

A. Scott Nielsen MD MMSc
Neurologist and MS Specialist at Kaiser Permanente

Here is My Question:
I had been diagnosed with MS in 2011, and since then I had been on Avonex with minimal side effects (like fever lasting for approximately 12-18 hours). Then I switched to Plegridy in November 2019. I thought the prolonged duration of fever (3-4 days) would subside after the initial few months, but it has not. My questions are:
1. Is it okay to switch back to Avonex?
2. Is Avonex equally effective as Plegridy?

P. S. I have had no relapse episode since 2011, and no visual symptoms apart from fatigue, though MRI had a one new lesion of activity three years back.

Answer:
Your question reflects the normal parsing of responsibilities in any doctor-patient relationship; you, the patient, are the only one who can decide what type of treatment is acceptable and whether any side effects you experience are manageable; we, the physicians, provide information and guidance on the relative efficacy and risks of these treatments. As a corollary, we also advise people on how to maximize the efficacy and minimize the risks. 
In your case I will hazard the guess that you've already decided you want to stop Plegridy and restart Avonex; this, in fact, is a good decision given the enhanced side effects you've experienced with Plegridy. To help you with this decision, without actually making the decision, let me tell you that both Plegridy and Avonex are the same active substance, Interferon Beta-1a. There is no evidence that Plegridy offers enhanced benefits other than the convenience of less frequent injections. Neutralizing antibody formation seems to lower with Plegridy but you did not have any problems with Avonex previously and I doubt this would be an issue now.
So, feel confident and make the decision you want to make, and free yourself from 3 days of side effects.

Revere P (Rip) Kinkel, MD
​Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
For 11 year's I been suffering from Chronic Migraine and 2019 I started difficulty walking, sensitivity to humidity, pins and needle, pain, blurred vision, electrical shock pain along spinal cord. Recent MRI showed white matters, other blood tests were negative for other conditions. One neurologist told me it is PPMS and the only treatment he gave was Fampyra. How can I be sure if I have PPMS. I don't have a neurologist. Thanks

Answer:
You need to see a neurologist, preferably one specializing in MS, for a detailed history, neurological examination, review of MR imaging studies of the brain and spine and spinal fluid analysis. A diagnosis of primary progressive MS requires spinal fluid analysis in most cases. Misdiagnosis is high if the specialist is not methodical in their evaluation.

​Revere P (Rip) Kinkel, MD
​Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
I take Ocrevus, and if there's less of an antibody response to the Covid vaccine because of this, will a third shot make a difference?

Answer:
Vaccine responses are complicated and depend on many environmental (such as exposure to B cell depleting agents like Ocrelizumab, rituximab and ofatumumab to name a few) and intrinsic factors (such as age, genetics).  One hypothesis is that the effectiveness of a vaccine response results from a race between the reactivation of immune memory and the spread of the virus after exposure. Now this is where it gets a little complicated, so I will try to simplify things.

B cells ( the cells destroyed by Ocrevus, rituximab and ofatumumab )are essential for early vaccine effectiveness, particularly against viruses and other pathogens that are outside of your cells and spreading throughout the body early in an infection ( so call incubation phase).  Some B cells turn into plasma cells after vaccination. Only plasma cells produce the antibodies that halt the initial spread of a viral infection. T cells are essential for destroying pathogens inside of cells or an established infection. Therefore, T cells are more important later in the stage of viral infection. Both cell types work together to create a maximal and rapid response. 

Interestingly, the plasma cells, that produce the antibodies measured in blood tests which check for your immunity against viruses, are not destroyed by Ocrevus and other medications that target the CD20 protein. This is because Plasma cells do not express CD20 on their cell surface. Unfortunately, plasma cells created by an initial vaccination (what is called priming) are short lived. This is one reason you typically need a second vaccine shot.

So, it is reasonable to expect that medications depleting circulating B cells will decrease vaccine associated antibody responses. How much this happens will depend on how long you've been receiving the B cell depleting drug and how recently you've received a dose, as well as many other factors such as your age. The end result is that antibody responses to a vaccine, the type of response required for early elimination of the virus after exposure, will be lower and it will be more difficult for people exposed to the virus to clear an infection rapidly. This is possibly one of the reasons that immunosuppressed people do not clear the COVID19 virus rapidly and may spread the infection to other people for a longer period of time. How much B cell depletion will affect T cell responses to the virus, the responses required to combat an active infection after it is established and you are sick, is still unclear and being sorted out.  We suspect that diminished vaccine responses will require some people receiving B cell depleting therapies to receive subsequent booster vaccines in the future. Stay tuned for more information.

Revere P (Rip) Kinkel, MD
​Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
Is it important to know definitively if a person has ‘mild’ MS? For example, if it has been suspected for a number of years, but has not caused significant problems, does it really matter? Could a neurologist make a case for not diagnosing unless treatment is warranted? What is the benefit of knowing for sure?

Answer:
Our ability to predict the future severity of relapsing remitting (RR) MS is limited during the 5 to 10 years that follow an initial diagnosis, which can itself take several years.
A good rule of thumb for RR onset MS is the following.

1. At the time of MS diagnosis, the risk of significant motor disability (e.g., significantly impaired walking) within 30 years if untreated is approximately 75 %
2. An untreated patient who has minimal disability 10 years after the diagnosis of MS has only a25 % chance of developing significant motor disability during the first 30 years of their disease

This rule of thumb does not apply to people with primary progressive MS (PPMS). People with PPMS often have significant difficulty walking shortly after the onset of the disease and worsen more rapidly.

Revere P (Rip) Kinkel, MD
​Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
After being diagnosed with Open Angle Glaucoma for 10 years, I've recently found out that I do not have it. There is a situation with my optic nerves, that a Glaucoma Specialist seems to think it's an affect from multiple sclerosis. I was told years ago that I had MS but never sought treatment for it. I went to a neurologist and he scheduled an MRI. He also did blood work. I couldn't proceed with the MRI, so I'm waiting to obtain an appointment with open MRI. In the meantime, my labs are back and I tested positive for JCV ANTIBODIES. My level is 3.45. Can you explain this information to me? I am in a panic and very nervous as to what this means.. Thank you.

Answer:
You have asked several different questions which I will try to address:

1. Regarding the optic nerve disease you have, the most common cause of optic nerve damage worldwide is glaucoma. However, if your ophthalmologist feels you do not have glaucoma then the MS would be the most likely explanation for your optic nerve damage.  MS effects the central nervous system which includes the brain, spinal cord and the optic nerves.
2. The positive JC antibody test means you have been exposed to the JC virus. You do not have an infection, however.  50-60% of the world has been exposed to the JC virus and it does not cause any health problems unless you have been exposed to certain risk factors.  In rare cases the JC virus can cause a brain infection (called PML). The most common risk factor for patients with MS for getting PML is if they go on a medication called Tysabri (natalizumab) AND they are JC antibody positive. This means your neurologist will probably recommend that you do not take the medication Tysabri.
3. Once you are diagnosed with MS it is important to start treatment as soon as possible. So you should follow up with your neurologist as soon as possible to discuss treatment options for your MS.  Fortunately there are a large number of medications approved by the FDA for treating MS so your doctor can recommend he/she thinks  is best for you.

Benjamin Osborne, MD
Director, Neuromyelitis Optica (NMO),Neuro-Ophthalmology Clinics and MS/Neuro-immunology Fellowship Director
Associate Director of the NIH/Georgetown Neurology Residency Program
Medstar Georgetown University Hospital

Question:
Can I take the morning-after pill while I'm on Tecfidera?

Answer:
There are no drug interactions between Plan-B and Tecfidera

A. Scott Nielsen, MD MMSc
​Neurologist and MS Specialist at Kaiser Permanente

Here is My Question:
I’ve been stable on Copaxone since my diagnosis about 5 years ago, my latest MRI a few weeks ago showed 2 new lesions. I then changed doctors after finding a practice that seems to treat the whole person and not just the condition, and as this has ramped up my anxiety it seems to be more of the type of care I need. This new doctor is a big believer in Tysabri extended interval dosing and seems to have much success with it (several hundred patients, majority 8+years, many with high JCV titers) and feels this would be the beet route, with Vumerity as a second option but not nearly as favored.

Since my diagnosis, from what I’ve read online in my panic-googling moments, Tysabri has always felt like the scariest option and when he named it my heart sank. Due to Covid vaccine concerns, he doesn’t suggest now is the time for Ocrevus or Kesimpta, which is what I was leaning towards.

I am JCV+ with a titer of 2.8 (when tested 4 years ago) and I’m terrified of PML. The new Dr, and again my panic-googling, show that the EID of Tysabri significantly reduces the risk, and the doctor said they would do bloodwork and MRIs every 3 months along with me reporting any issues as soon as I notice them. Does this then keep me in a safe place for moving forward with Tysabri or should I require more monitoring, or a different med altogether. So many have a PML risk.
​
It seems to be a very effective med to help freeze any progression and maintain my quality of life. The studies I’ve read all seem to show greater increase risk if staying on the med for more than 2 years, and it seems to me it’s difficult to safely switch to another effective DMT after this one without triggering progression.
​
I just don’t know how to know what’s best to make these decisions, any insight is greatly appreciated!

Answer:
So much information can be overwhelming to anyone, so let's take apart your question and answer it logically.

1. The overall risk of PML in Tysabri treated patients (300 mg IV every 28 days) with a JCV index > 1.5 is 1/1000 (a reasonable risk) during the first 2 years of treatment and then 1/100 (an unreasonable risk if other treatments are available) after 2 years of treatment. The risk in the first 12 to 18 months of treatment is much less than 1/1000.
2. Extended interval dosing does decrease the risk of PML substantially (> 90 %) but we do not specifically know the reduction of risk in those with a JCV index > 1.5, the highest risk group.
3. Anti-CD20 agents (Ocrevus, Rituximab and Kemsimpta) are excellent therapies for individuals who need to stop taking Tysabri because of the risk of PML. They are very effective at preventing rebound after stopping Tysabri.
4. Tysabri does not appear to affect your ability to mount a good response to vaccination . This has been demonstrated with the influenza vaccine. Anti-CD20 agents do appear to diminish vaccination responses.

With this information in mind, we often make the following recommendation to people with MS who need to switch to a more highly active disease modifying therapy.

1. It is okay to begin treatment with Tysabri even if your JCV index is > 1.5 if you monitor with MRI scans every 6 months during the first year of treatment. After 6 months to a year of treatment, you must switch to extended interval dosing or switch to an anti-CD20 therapy.
2. Get your COVID 19 vaccination during the time you are receiving Tysabri to protect you from COVID19.
3. Do not wait longer than 2 months to start anti-CD20 therapy after stopping Tysabri, but make sure you get an MRI of the brain after stopping Tysabri and before starting anti-CD20 therapy to make sure you do not have pre-symptomatic PML.

​
Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
Does Kesimpta give you hair loss?

Answer:
We have not observed any hair loss with Kemsimpta. Some people report mild transient hair thinning with Ocrevus but this is because it is co-administered with steroids to prevent infusion reactions. Steroids are well known to cause hair thinning

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
Which drug is better, Ocrevus or Kesimpta? I don't know which one to choose...

Answer:
Ocrelizumab (Brand name Ocrevus) and Ofatumumab (Brand name Kemsimpta) are the two currently approved anti-CD20 monoclonal antibodies for the treatment of multiple sclerosis. Both treatments are FDA approved for relapsing forms of multiple sclerosis. They are both humanized monoclonal antibodies (IgG1 subtype) that bind to a protein called CD20- a marker for all B cells beginning at the pre-B cell stage - and destroy these cells. Once destroyed these cells are gradually replenished over time by stem cells in the bone marrow. The extent and duration of B cell depletion depends on the method of administration, the dose administered, the interval between administered doses and several host factors (e.g. age, weight, prior immunosuppression).

Both drugs are highly effective in relapsing forms of MS; although it is difficult to directly compare efficacy or safety without head-to-head clinical trials the reductions in annualized relapse rates, sustained disability progression and MRI measures of disease activity were similar for both drugs compared to the comparator drugs for each study, Rebif for the Ocrevus phase III clinical trials and Aubagio for the Kemsimpta Phase III clinical trials. 

So how do you decide between these different treatments? I've attached a table summarizing the pros and cons of each treatment, at least relative to the other treatment. To understand this table it is important to first understand several important concepts

1. It is NOT necessary to deplete (destroy) totally or continually circulating B cells to control Multiple Sclerosis. For instance, we know that a single course of intravenous rituximab, another anti-CD20 monoclonal antibody, will suppress relapses and MRI activity for over a year and well after naive B cells repopulate. We also know from the phase II Kemsimpta trial that robust treatment effects were observed with doses as low as 3 mg every 12 weeks (note that the approved dose is 20 mg every 4 weeks) despite only partial depletion of total B cells.
2. B cells are very important cells in your immune system . They mount responses against foreign invaders like virus and help regulate other essential immune functions. Persistent depletion of B cells can and often does have negative consequences especially after several years. Persistent depletion of B cells, especially naive B cells,also makes it more difficult to develop a good immune response to vaccines; this would include the COVID19 vaccine

In summary both Ocrevus and Kemsimpta are outstanding treatments for MS. The main differences are the mode of administration (intravenous for ocrevus and subcutaneous for Kemsimpta) and the duration of B cell depletion after a single treatment (much longer for Ocrevus). Of course, Ocrevus has an obvious advantage for primary progressive patients, since it is the only medication approved for this indication as well as relapsing forms of MS.

You can open the file below to see the pros and cons of each drug.

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
Can you have gastric sleeve surgery if you have multiple sclerosis

Answer:
Gastric sleeve surgery is not contraindicated in MS.  

​A. Scott Nielsen MD MMSc
Neurologist and MS Specialist at Kaiser Permanente

Here is My Question:
Is ‘stable’ a good MRI result 18 months post-aletizumab? Is it the same as NEDA?

Answer:
We prefer explicit descriptions in our MRI reports. Words like "large", "numerous", or "small" are vague and of no meaning. "Stable" on the other hand means there are no changes, for better or worse, compared to a prior study. "Stable" would be equivalent to 'No Evidence of Disease Activity' (NEDA3), if there are no new or enlarging T2 hyperintensities and no enhancing lesions.

Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego

Here is My Question:
I have RRMS according to my prior MS specialist but new doctor things it’s possibly PPMS. I’ve been on Ocrevus for about 2 years. He said that according to research and conferences that they are recommending that Ocrevus patients be switched to Zeposia due to new evidence that say Ocrevus may increase severity and frequency of COVID-19. Have you heard anything about this advice or recommendations?

Answer:
I’d suggest another opinion before deciding to transition therapies (especially if you’ve been stable on Ocrevus). At this time, there simply isn't compelling data to firmly conclude a b-cell biological is riskier than a S1P receptor modulator in context of covid infection. Moreover, distinguishing relapsing MS from Primary Progressive MS is not typically a difficult one to make so it seems odd to me that the possibility was communicated to you. Of those two therapies, Ocrevus was approved for PPMS. Another consideration is covid vaccines. It is reasonable to assume that both therapies can limit your response to a covid vaccine, but becoming vaccinated after enough time has elapsed from a b-cell biological treatment is possible since delaying infusion to receive a vaccine is not fraught with concerns about rebound disease activity which is not the case with S1P modulators. I’d request another opinion by a fellowship trained neuro-immunologist who can consider your entire history and response to treatment before making the switch.

A. Scott Nielsen MD MMSc
Neurologist and MS Specialist at Kaiser Permanente