Here is My Question:
My question is about Ocrevus and the timing of a COVID vaccine.

A few days ago MedPage Today wrote:
"Patients taking ofatumumab (Kesimpta), alemtuzumab (Lemtrada), cladribine (Mavenclad), ocrelizumab (Ocrevus), or rituximab (Rituxan) may need to coordinate vaccination timing with the timing of their DMT dose."

I've read similar elsewhere, with guidance from neurologists recommending taking the vaccine at least six weeks before or after an Ocrevus infusion.

What is your advice?

Answer:
The appropriate timing of viral vaccination, specifically vaccination against COVID19, is a subject of significant concern to specialists treating people with immune subset depleting therapies, including the disease modifying therapies listed in your question. 

Immune depleting therapies are given infrequently because it takes many months or years for the immune cells to be replenished by bone marrow derived stem cells. The time course of individual immune cell subset repletion varies with different treatments and how they are administered: dose, frequency and route of administration can affect the repletion timecourse. 

Anti-CD20 monoclonal antibody treatments (e.g., Rituximab, Ocrelizumab and ofatumumab) are a case in point. These treatments specifically target and destroy B cells expressing the CD20 'target' on their cell surface. This includes both naive B Cells and memory B cells.  As these names imply naive B cells are important for learning about new viral infections and are required to mount strong antibody responses to viral vaccination. Memory B cells are created by exposure to vaccinations or native viruses; these cells allow you to respond quickly to eliminate a virus and other pathogens before they make you sick. Memory B cells, however, are a two-edged sword; they are also involved in autoimmunity, and their depletion by these therapies may be the main beneficial mechanism of action in diseases like Multiple Sclerosis or Neuromyelitis Optica. 

Naive B cells will return much earlier than memory cells and we can take advantage of this differential repopulation of B cell subsets in our vaccination protocols by vaccinating people after naive B cells return but before they are repopulated with memory B cells that can trigger autoimmunity. 

How do you know the sweet spot for vaccination after receiving B cell depleting therapies? One way is to measure B cells subsets after treatment with simple blood tests. For instance, after treatment with Rituximab and Ocrelizumab, naive B cells often start to return within 6 months, but memory B cells can take more than 12 months to start to return. If your doctor is unable to measure B cell subsets, he or she can simply measure total CD19+ B cells every 3 months after a treatment. Initially, there will be no CD19+ B cells detected at all but once the lab begins to see CD19 + B cells in your blood sample, the cells will only be naive B cells.

In practice it is almost impossible to time your treatments precisely for vaccination. You should take comfort in several facts about the immune system response to viruses before this worries you too much. First, cytotoxic CD8+ T cells, which are not even targeted by anti-CD20 monoclonal antibodies, are created by vaccination and are the main line of defense, along with cells of the innate immune system, against respiratory virus like COVID19. In fact, it is the impaired innate immune response in the elderly that is partly responsible for the severity of COVID19 infections in older people. Second, we know that people receiving anti-CD20 therapies can mount antibody responses to vaccines; although these antibody responses tend to be muted, they are often strong enough to be protective.

You should also take comfort in the fact that retreatment with immune depleting therapies can often be delayed for long intervals without your MS getting worse. It is a little trickier to delay these treatments with other conditions like Neuromyelitis Optica but some delay is still possible.

So at present we are delaying anti-CD20 therapies whenever possible to allow for COVID19 vaccination during a period of naive B cell repletion. If this is not possible, we are not recommending any significant delay in vaccination (no more than 8-12 weeks) but do recognize that people vaccinated after an anti-CD20 therapy will likely require booster vaccines in the future.

Please remember that regardless of your vaccination status, your main line of defense against COVID19 is wearing a mask and staying away from people who may be infected, especially in enclosed spaces like homes or restaurants, for more than a few minutes.

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:
Do you have any experience with plasma exchange (plasmapheresis) for progressive MS, and if so, do you believe that it can be helpful for some patients (even if it is difficult to predict which ones)? To be clear, I am NOT asking about using plasma exchange for an acute relapse. I have secondary progressive MS, have tried all of the latest and greatest DMTs (currently on Ocrevus), and my mobility continues to decline at an increasing rate. Thank you.

Answer:
PLEX isn't accepted as a disease modifying strategy for relapsing or progressive forms of MS.  You are correct that is can be beneficial for those with a steroid-refractory relapse.  More to your point, there is very little published data on use of PLEX in progressive forms of MS; however, those that are published suggest that if PLEX is helpful, it seems to skew towards younger patients with less MS disease duration.  This isn't altogether surprising since approximately 30% of PPMS patients show signs of subclinical inflammatory disease activity (ie, new lesions showing up on a brain MRI).  In fact, these patients seem to be the ones that benefit from immunotherapy (such as ocrevus, rituximab, siponimod, etc).  Those without signs of inflammation tend not to show a response.  

Also, it is important to remember that there appears to be an independent neuro-degenerative ("progressive") phase of MS.  In other words, the progressive phase in many respects appears to be independent of inflammation.  So, even on a proven therapy such as Ocrevus, the data do not show a cessation of progression, but rather, a slowing of the rate of progression.

At present, Ocrevus is likely a good option to maximize immunotherapy to benefit progressive MS (assuming you are still in the inflammatory phase as well), but given PLEX in addition does run the risk of removing the Ocrevus (monoclonal antibody) from your circulation and rendering it relatively ineffective.

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

Here is My Question:
Kesimpta is offering for the first time the possibility not to travel to an infusion centre twice a year in order to get a B-cell therapy (Ocrevus). Self administration at home sounds like more "freedom“.

However - What about traveling under Kesimpta? As far as I know, it must continously be cooled. When traveling intercontinentally this can be difficult to achieve depending on the destination.

Are there any guidelines or ideas how to manage this? Would it be a solution to take an additional "shot“ just before leaving for a three weeks trip? Or would it be safe to delay the next injection till returned home?

Answer:
According to the data provided in the package insert, Kesimpta does need to be continuously cooled at a stable refrigeration temperature (2ºC to 8ºC (36ºF to 46ºF)) until the time of use. It would be possible to maintain this in certain types of travel but not others as you mention. 

The best way to navigate travel and the injection schedule will be determined on an individual basis. 

Some predictions can be made based on how the drug works in the body and how long those effects last. Kesimpta binds to the CD20 cell surface antigen on certain B cells and destroys these cells. We are able to measure the depletion of these B cells using blood tests. The clinical trials for Kesimpta measured B cells to determine the optimal dosing for their product. Early dose finding trials showed a significant effect of treatment (on MRIs) even when dosed every 12 weeks (doses ranged from 3mg to 60mg). They also found that when people stopped treatment, the median time to B cell repletion was 40 weeks. This suggests that people can go at least 12 weeks between injections without a return of MRI disease activity.

Assuming that a person has been on the treatment for 12 weeks (the point at which over 99% of patients in clinical trials had B cells below the lower limits of normal) then it would be safe to assume that the majority of people would be okay delaying their dose until they return home. 

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 need advice. I have a unusual story, Six years ago I had unusual episode. Numbness, tremor, mostly on right side. It all resolved in a month. For the next five years I had stiffness in legs. My right leg would be weak if I walked too much. My rightt arm would be weak if I reached high for something. I saw doctors over the years and had MRIs that were all normal.

Last Christmas my arms felt like 50lb weights were on them and I couldn’t use them as much. I keep having episodes like this but my MRIs are always normal.

I've been tested for lupus, B12, ALS...I've had every test you can think of. I am 52 years old, can I have PPMS? This mimics MS I have so many same symptoms plus I feel like I have had flares.

Where do I go from here I am getting worse and scared to have another episode. In November I was on a rowing machine working on my arm strength to get it back and a treadmill. I can’t even lift my arms well or lift my ankle up . Please help me I need help!

Answer:
It is very difficult to establish a diagnosis based on the history of symptoms you provide. I can tell you that it is rare for MRI scans to remain normal for over 6.5 years in people with MS of any type. There are many causes of waxing and waning weakness and fatigue including disorders of the muscle, neuromuscular junction, and peripheral nerves. I would begin by getting a second or third neurological evaluation, perhaps at an academic  neurology clinic.
Good luck

​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:
My neurologist is suggesting I get the Ocrevus infusion now and then get the Covid vaccine when it becomes available. I am 73 years old and have PPMS.; What do you think?

Answer:
Opinions on this matter differ, primarily because of the lack of information. Let's break down the information we know so that you can make an informed decision.

1. The Ocrevus primary progressive MS (PPMS) clinical trial excluded people over the age of 55. Therefore, there is no evidence of benefit in someone who is 73. The benefit observed in the Ocrevus PPMS clinical trial and in trials of other anti-CD20 monoclonal antibody therapies in PPMS, was observed in younger patients with evidence of active brain inflammation on MRI. Active inflammatory disease is uncommon as people age and certainly once people reach the age of 73
2. Age is a significant risk factor for both severe COVID infections and death due to COVID infections. 8 out of 10 people dying from COVID19 are over age 65. These are the most important people to get immunized after health care workers and those residing in nursing homes.
3. We are in a phase of the pandemic when infection rates are rising exponentially and hospitals in some areas like southern California may run out of hospital beds soon. It is more important than ever to prioritize staying healthy and getting your vaccine as soon as it is made available to you.
4. We do not know if responses to the COVID vaccine will be as strong in someone who has received Ocrevus in the prior 6 months

I hope this information helps when you discuss this topic with your MS specialist

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:
My fiancee has RRMS. She is currently experiencing chronic insomnia, depression and memory loss. I love her and I am doing my best to be patient and supportive. The mood swings are constant and I need help because it is seriously affecting our relationship. I am seeking advice and assistance. Thank you in advance.

Answer:
The symptoms of depression, insomnia and forgetfulness are very common in people with Multiple sclerosis (MS), even during early stages when individuals are not showing many visible manifestations of the disease. The symptoms are often interrelated and primarily a result of underlying depression or anxiety disorder. Depression itself is often considered a primary symptom of MS by many MS specialists.

These symptoms affect both those afflicted by the disease and those close to them, as you've aptly described in your message. Both of you would benefit from further education and couples counseling to support your efforts to effectively manage these symptoms. Your fiancé needs to address these symptoms with her MS specialist, and seek an evaluation by a psychologist or psychiatrist knowledgeable about the psychiatric manifestations of MS. Good luck and try to be patient.

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 am currently taking Gilenya. I've been on it since before it got approved. I was in a clinical trial. I'm facing hip replacement surgery in the next couple of months. I'm getting mixed information about the necessity to stop Gilenya a month before the surgery. I don't want to stop it as I don't want the risk of the relapse. What is the latest recommendation?

This question was posed see you in May of 2017 and I want to know if there's any new or different information and/or recommendation.

Answer:
I can think of no reasons to discontinue Gilenya before or after a hip replacement. Stopping Gilenya a month prior to surgery would require you to undergo another first dose observation period when you restart it post operatively and would put you at risk for a rebound relapse. There is a black box warning in the package insert about stopping Gilenya without an alternative treatment to prevent rebound relapses.

You've been on Gilenya for over a decade without complications. It makes no medical sense to stop it except for the day of surgery when you are NPO.

Gilenya will not affect healing or your ability to form clots. There is no evidence it increases the risk of post-operative infections.
Hope this information helps

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:
Thank you for the opportunity; I do not currently have a primary care physician. At a very young age (3-4 I believe) I contracted a very serious case of meningitis. I know that I was close to death and had to be taken from Nor Cal to Anaheim. Without a background in medicine Google is a troubling source for self diagnosis. I do have a BA in Journalism and am at least able to filter BS. In short, my symptoms of left hemisphere weakening, numbness, spasticity, gait, etc sure sound like MS is slowly setting in over the past 8 years or so. I know my fever was extremely high when I was young. In short, am I likely correct (I know you can’t do much more than say ‘see a damn doctor already man!’ that the damage to demyelination from my 30 year old illness is a contributing factor to this motor control deterioration? I’ve tried yoga, Thai chi, etc abs still jog daily....Yet engaging/firing the correct muscles to support athletic and daily movement has become near impossible. It was therapeutic just to share that; so thanks. I have no health insurance and I hear constantly about early diagnosis abs therapy. I don’t want charity and I understand the pharmaceutical world more than most. Is there anything I can do (nutrition, supplements, style of exercise) to help slow my symptoms (assuming it is MS). Thank you! Ryan in Portland

Answer:
You’re right, Dr. Google isn’t an adequate substitute for the actual specialist. The assumption of MS is a big one and I remain unconvinced based on symptoms with a history of meningitis presented. However, I’ll play ball and simply say that in the case of confirmed MS—and in addition to a disease modifying therapy, a healthy/well-balanced diet, exercise, and potentially supplementing with vitamin D3 5,000 IU daily, may be helpful. Patients with MS are not exempt from other health issues that come with age. High blood pressure, diabetes, cholesterol problems, etc can also injure the nervous system and increase the rate of disability.  

Ultimately, however, a proper evaluation with an MS specialist is in order. Please be kind in response to this post. My knowledge and command of the English language is likely not up to par with a journalist.

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

Here is My Question:
What diet will help those with MS who are unable to take the medication?

Answer:
There have been many proposed MS diets over the years and many claim anecdotal evidence as proof of efficacy.  The fact is that there is no high level scientific evidence for these diets.

​Many have been packaged as “anti-inflammatory” diets which is a testable hypothesis for a well designed clinical trial.  It remains a challenge to carry out such a study because people, by nature, cheat on their diets (which make it difficult to confirm actual benefit).  You can certainly trial a diet yourself and gauge your response.  Of course, it would be best to review the selected diet with your PCP to ensure no contraindications to the diet based on your other health factors.

It remains advisable to follow recommendations for a general well-balanced diet.  Food choice affects other areas of health that MS patients are not excluded from.  For instance, high salt, carbohydrate, fatty, etc diets can accelerate cardiovascular disease that can also injure the nervous system.

As far as the inability to take an MS therapy, I have to question that statement.  There are so many available (and different) MS therapies that it would be hard to believe that ALL are contraindicated in one person.  Even if there was a religious or other exception of conscious to a specific type of therapy, there remains a variety of medication class/type/mechanism to find a suitable therapy for everyone who would otherwise qualify for a disease modifying therapy.

Use of one of these therapies is better than nothing for MS patients who remain in the inflammatory phase of their MS.

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

Here is My Question:
Which part of the spine should be considered to check for lesion in MS? Is the C and D spine enough or should we consider the L spine as well?

Answer:
Your physician should know the appropriate nervous system regions to evaluate you for MS using MR imaging. Remember, MS only affects the optic nerves (which is part of the central nervous system), brain and spinal cord. The spinal cord ends at the L2 vertebral body level, so imaging of the cervical and thoracic spinal cord usually covers the entire spinal cord region.

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:
Hi I have been on cellcept for 11 years now. For the first 6 years I did not have a relapse and my dosage was reduced. But 5 years ago got a relapse and have been back on the original dosage and now every year I get a small relapse. I have been advised to think about Ocrevus. I wanted to know if there will be some side effects and if it is possible to go back from Ocrevus to cellcept if needed. Thanks for the inputs.

Answer:
Yes, you could in theory go back to cellcept if you wanted to.  Ocrevus is a b-cell biologic to treat MS (and there are others including Rituximab and Ofatumumab).  These therapies are considered highly effective in the treatment of MS while cellcept has been used off label for more mild cases (although not used much now due to the myriad of approved therapies for this disease).  Cellcept is also used for MS mimicking conditions such as NMO.  I’d suggest speaking with your treating provider to better understand the recommendation to switch (is it due to confirmed new inflammatory disease or just because of various symptoms in the absence of inflammation on your MRI scans or confirmed by neurologic examination in the clinic?).

You can read more about the b-cell biologics and efficacy, safety, side effects by searching under “Rituximab” which is the oldest such therapy, or “Ocrevus”.

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

Here is My Question:
I was just diagnosed with MS and was told I am at the early stages. Will medication actually slow progression or does this depend person to person? They prescribed Kesmipta, how well is this new injection?

Answer:
Catching the MS disease process early is important since all therapeutic options (called disease modifying therapies or DMTs) only help prevent new inflammatory damage to your nervous system.  At this point in time, there is no reparative therapeutics. Based on various prognostic factors, some patients may be at higher risk of significant disability in the years to come IF they are not started and maintained on a good DMT.  Kesmipta is the newest in a class of highly effective DMTs called the b-cell biologics.  These are very powerful therapies that have the potential to put the patient in a permanent remission state that is called “no evidence of disease activity”.  Kesmipta is given by injection (at home).  If you search this site for what the b-cell biologics can do for MS, it is best to search using Rituximab (or Rituxan) which was the first approved b-cell biologic.  The other b-cell therapuetics are given by infusion at infrequent intervals (ie, once semiannually or potentially annually).

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

Here is My Question:
Do we need to go for a spinal tap test to detect MS if the result of my brain and spine MRI came back negative?

Answer:
Analysis of the spinal fluid by way of a "spinal tap" or lumbar puncture is very useful when imaging studies do not clearly explain or diagnose a process that appears to be coming from the central nervous system or the lining (called the meninges) around the central nervous system.

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:
For the last year and a half I have felt a burning sensation in my right outer thigh intermittently that lasts for 15-20 seconds and goes away with little movement. It does not occur every day, and happens only for a particular standing position for more than 10 minutes. It subsides automatically when I sit down. I did the contrast spinal and brain MRI which came back normal, The result of the evoked potential test and nerve conduction test also came back negative. I am still having doubts of having MS, what's your thought on this?  

Answer:
The outer thigh is an area that transmits sensations to the brain through a peripheral sensory only nerve branch called the lateral femoral cutaneous nerve. This nerve is often compressed under the inguinal ligament or damaged by diabetes. There are of course many other reasons this nerve could be irritated or damaged, but these are the most common reasons. A neurologist would not normally ascribe your symptoms to a problem in the central nervous system- such as multiple sclerosis- unless you had other symptoms or findings on examination that pointed to a problem in the central nervous system. A problem involving the lateral femoral cutaneous nerve could be confirmed with nerve conduction studies, but this is usually a clinical diagnosis. It is typically called meralgia paresthetica.

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 MS people take Pfizer’s coronavirus vaccine?

Answer:
Yes, MS patients will be able to take the Pfizer COVID19 vaccine, since it is NOT a live vaccine

​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 had a stroke on 08/17/20.I had MRI’s which show a large lesion on my spinal cord L3-L4. Also my spinal tap shows higher protein levels in my CSF. Prior to stroke my balance was off and was falling. Since my stroke I have chronic weakness in left arm and limited mobility. I still have the problem and am now going on 3 months since the stroke. From what I’ve read it’s uncommon to be caused by my stroke. Both my legs are chronic with numbness which I’ve had for roughly over 12 months and I'm still weeks out from seeing my neurologist. Would so appreciate answers if I have MS. While in the hospital the neurologist said it’s likely that I do. I would just like to confirm it. Also, are flare ups mainly old symptoms that come back or do they mean a new lesion.

Answer:
I would like to be able to assist you with your questions, but much of the information you have provided does not make sense. For instance,

1. Is the thought that you either had a stroke , MS or both?
2. the spinal cord does not extend down to the L3/4 level so you could not have a spinal cord lesion at this site?
3. Slightly elevated CSF protein can be seen with various types of stroke and with MS

Sound like you need to see a good neurologist or MS specialist. Strokes are often confused with acute MS because the MRI scan will often show a pattern consistent with restricted diffusion in both conditions. We differentiate strokes from MS based on age, risk factors, history, exam and imaging features. 

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