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

Here is My Question:
I have SPMS and my condition is declining rapidly even though I am on Ocrevus. I have seen recommendations for long-term pulse therapy to treat SPMS (stand-alone or as adjunct to DMT) that call for 3 to 5 days of IV steroids anywhere from 3 to 6 times per year. Specifically, the National Clinical Advisory Board to the NMSS suggested every 3 to 4 months in a 2008 report and the Cleveland Clinic currently suggests every 8 weeks. Do you recommend long-term pulse therapy for treatment of SPMS, and if so, how often would you recommend? I would like to do everything possible to arrest my decline. Thank you.

Answer:
Many years ago, Donald Goodkin and I did a study at the Cleveland clinic using bimonthly (every 8 weeks) intravenous methylprednisolone pulses (also called high dose steroid pulses; uses 500 to 1000 mg IV x 3 days) to treat patients with what was then called relapsing progressive MS, but is now called secondary progressive MS. The treatment group did experience a slower rate of progression over 2 years, but the treatment never caught on in the MS community for two main reasons; first, steroids even when given as infrequent high dose pulses can be difficult for some people to tolerate and many physicians were unwilling to use this treatment based on their prior negative experience with the use of regular daily doses of steroids to treat MS ; second, the treatment effect from our study was modest. Many people now feel that combining pulse high dose steroid treatment with other disease modifying therapies could provide more meaningful benefits than using pulse bimonthly steroids alone. While combination treatments have been studied and found useful in relapsing remitting MS, this has not yet been done with secondary progressive MS.

We currently have several patients doing well on combined treatment with Ocrelizumab and every 2-to-3-month pulses of high dose steroids but we really have too little data to support generally recommending this treatment strategy.

​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 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