Here is My Question:
Where can I find the paper for the phase II trials for Kesimpta and the lower dose given every 12 weeks? I was also wondering are their any trials going on with less frequent less B cell depletion and response assessment in MS?

Answer:
The phase II Ofatumumab (Kesimpta) clinical trial published in the Journal of Neurology is attached. This can also be found as a free access journal through a google search or PubMed.

Here is My Question:
Should patients taking Tysabri get a booster shot for COVID-10? Thanks!

Answer:
​All people, with or without MS, over the age of 12 will require COVID19 booster shots. Starting in September all states will provide boosters to anyone over the age of 12 if it has been at least 8 months since their second vaccine dose with either the Pfizer or Moderna COVID19 vaccines. There is still no consensus in the US for boosters in those who received the single dose J&J vaccine, but it is reasonable to obtain a booster with another vaccine if you are immunosuppressed and received the J&J vaccine.

COVID19 vaccine boosters should be given as soon as possible (as early as 28 days after your second COVID19 vaccine shot) to the following people with MS :

1. Older individuals (most states will define the cut of age as > 65) 
2. Immunosuppressed individuals . This includes people with solid organ transplants, Bone marrow transplants (also called hematopoietic stem cell transplants), chronic steroids and those on chemotherapy
3. People with MS on certain disease modifying therapies . This includes those who received alemtuzumab (Lemtrada), Cladribine (Mavenclad) or anti-CD20 therapies (Ocrevus, Kesimpta, rituximab and biosimilars) in the past 3 years and those currently taking a S1P modulator (Gilenya, Mayzant, Zeposia and Ponvory). This also applies to people on a fumarate (Tecfidera, Vumerity or Bafiertam) with absolute lymphocyte counts less than 600.

Special considerations for COVID19 vaccine booster timing in people on intermittent lymphocyte depletion therapies (Lemtrada, Mavenclad, Ocrevus, Kesimpta, Rituximab and biosimilars): 

1. Improved COVID19 vaccine antibody responses were observed in people on anti-CD20 therapies who received a vaccine at least 3 months after their last treatment (infusion or injection). While this data mostly applies to Ocrevus and Rituximab, it is likely to apply to treatment with Kesimpta. We do not have data on those who received Mavenclad or Lemtrada will also experience decreased responses to COVID19 vaccines or boosters for at least 3-6 months after their last treatment. For these reasons if you are between doses of any of these specific disease modifying therapies (DMTs), which are all administered intermittently, or if you are about to start one of these DMTs, it is reasonable to obtain your COVID19 booster shot before your next treatment, or in some cases, before your first dose of the disease modifying therapy. If you received treatment with any of these DMTs in the last 3 months, you should discuss the pros and cons of delaying your booster vaccine with your doctor depending on your situation. In most cases we will encourage that you get the booster and follow additional precautions to avoid exposure to COVID19.  

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

Tecfidera is an oral fumarate approved for relapsing forms of multiple sclerosis. It is taken twice a day with a relatively short duration of action. If you stop taking it, any benefit you were receiving from this medication will wear off over time. Good reasons to stop taking it include the following:

1. You don't tolerate Tecfidera
2. Your blood monitoring tests show a persistent abnormality, such as a low lymphocyte count.
3. You continue to experience evidence of disease activity (relapses or MRI activity) >3 months after starting treatment
4. You MS continues to progressively worsen for 6 months despite taking tecfidera and your MS specialist can verify this worsening on exam
5. Your doctor has decided for other reasons that you know longer require a disease modifying agent. This is common in people with MS over 55 with no evidence of disease activity for many years

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

Here is My Question:
I had a spinal tap done and it came back with oligoclonal bands (OCBs) band number matching and negative for oligoclonal bands. Do I have MS?

Answer:
Spinal fluid Oligoclonal bands (OCBs) are immunoglobulins (also called antibodies) usually of the IgG subtype, although some labs also measure IgM Oligoclonal bands. They are called "bands" because of their stained appearance (colored stripes or bands in a row)  on an agarose gel electrophoresis plate. For assisting in the diagnosis of MS, we look for Oligoclonal bands in a spinal fluid sample that are not observed in a matching serum sample obtained from a blood draw at the time of your lumbar puncture. Those bands that are seen in both the serum and CSF sample are not unique to your nervous system. They simply represent immunoglobulin that leaked into your spinal fluid from the blood stream. For instance, you could have 14 OCBs in your spinal fluid sample and 10 of them could match OCBs observed in your serum sample. This would mean you have 4 spinal fluid oligoclonal bands (14-10=4), each produced by plasma cells residing in your nervous system. Some labs consider an abnormal result as 2 or more unique spinal fluid OCBs whereas others consider 4 or more as abnormal.

Oligoclonal bands are not diagnostic of MS and can be seen in people with many different inflammatory and degenerative conditions. People can also have forms of MS without Oligoclonal bands in the CSF.  The presence of absence of spinal fluid OCBs are just one of the pieces of information we used to help establish a diagnosis of MS.

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

Here is My Question:
Is there any reason for a person with MS having knee replacement surgery not to have spinal anesthesia instead of general anesthesia? Spinal anesthesia is the norm at the hospital where I get care and seems to me to be generally safer. But my surgeon said anesthesia might be reluctant to use spinal anesthesia due to my MS. I have “ mild” MS that has not caused any significant mobility impairments….which is more than I can say for the osteoarthritis in my knees.

I do not want to have general anesthesia for a number of reasons and feel like this would be second rate care based on superstition since *I* can’t find any data to support increased risk with spinal anesthesia. Do you know of any?

Answer:
Epidural and spinal anesthesia is widely accepted in most countries for people with Multiple Sclerosis. Most of the studies published concern the use of these forms of anesthesia at childbirth for cesarean section, but there is little reason to believe this form of anesthesia would expose additional risks for other procedures where this form of anesthesia is utilized in people without MS.

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

Here is My Question:
After much consideration, I have made the decision to switch from Ocrevus to Tysabri. The options I am weighing are to either go to Kesimpta or Tysabri. Since Kesimpta is similar to Ocrevus I have decided to go with Tysabri due to the decline (clinically) that I was seeing with Ocrevus.

Anyway, I have seen a lot of postings from people going from Ocrevus to Tysabri but not many the other way around. Is this a change that you see often?

Also, in reading about Tysabri, I am wary of a couple of things:

1)PML- Although my JCV level is relatively low, 0.34, I would be lying if this does not worry me.
2)I know that due to the PML risk, Tysabri is usually not a drug that one is on for many years; I am concerned about "AFTER TYSABRI," as I have read, even on this site, "there is an increased risk of relapsing, usually within 6 months of stopping Tysabri."

My MS has declined clinically in the last few years; going from walking normally to using a cane sometimes due to leg weakness, and also much more spasms and spasticity, but my MRIs have remained stable.

I guess my main concern is since I have been so “stable,” with minimal decline, is going on Tysabri “worth the risk” of both PML as well as relapsing after stopping.

Please let me know your thoughts on this.
Thanks!

Answer:
Those are a lot of good questions. First let me eliminate some misinformation included in your question about the use of Tysabri

1. Tysabri can be used for many years, and we have many people who have taken this medication for more than 10 years
2. The risk of PML is 20 times higher if your JCV index is > 1.5 compared to a JCV index < 0.9. This is a very low risk that can be managed

This being said, Tysabri is only effective for definite relapsing forms of MS; This is a form of MS generally confined to younger people (Less than 45). Someone with no MRI activity or relapses, like yourself, who is experiencing continued worsening of their disease is better characterized as secondary progressive MS. Tysabri is not effective for secondary progressive disease in the absence of relapses or MRI disease activity. There are no approved therapies for secondary progressive MS without relapses or MRI disease activity and we are encouraging people in this stage of the disease to participate in clinical trials of newer DMTs, such as the selective Bruton Tyrosine Kinase (BTK) inhibitors 

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

Here is My Question:
Are those of us on Rituxan/Ocevrus considered immunocompromised?

Answer:
People on anti-CD20 monoclonal antibodies (rituximab or Ocrelizumab) are selectively immunocompromised because of partial depletion of a subset of lymphocytes called B cells. B cells comprise approximately 20-25 % of circulating lymphocytes. The most common lymphocytes are CD3 positive T cells (70-75 %) and the least common at Natural Killer (NK) cells. Lymphocytes (T cells, B cells and NK cells), in turn, represent 20-40 % of total white blood cells in circulation.

True old-fashioned immunosuppression drugs (often called chemotherapy) tend to suppress or deplete many different types of white blood cells. For instance, cyclophosphamide (cytoxan) , a form of chemotherapy, kills off many types of lymphocytes as well as other types of white blood cells (neutrophils) in a dose dependent manner. This can cause a broad array of infectious and even neoplastic complications depending on the duration of use

Selective B cell depletion, at least with short term use, tends to be associated with far fewer infectious complications than more traditional immunosuppressants.

 

Here is My Question:
I have pain nearly every day. My doctor said it is Levator Ani Syndrome pain due to my MS. Can I do anything to help relieve this pain? It is getting me down and every time I use my bowels it hurts even more. I am on CBD and THC oil and have been for 3 weeks but don’t feel any better. Have you got any suggestions about what I can do? Thank you kind regards.

Answer:
Levator Ani Syndrome is another term for chronic pelvic floor muscle pain, a syndrome almost entirely unique to women. Pelvic floor physical therapy (PT) is the therapeutic modality most effective for this disorder but requires perseverance given the chronicity of Levator Ani Syndrome in most people. You can start by looking for physical therapists trained in Pelvic Floor PT.

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:
Are eosinophils and absolute eosinophils typically high in MS pediatric patients at the age of 13?

Answer:
Eosinophilia is not a hallmark of MS.  However this can be seen on specific therapies (such as Tysabri).

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

Here is My Question:
I have a cough that won't go away. I used to smoke cigarettes and stopped about 8 months ago. For three months I have not not been able to breathe, I can barely walk when I stand or walk (not even a long distance) I'm out of breath. What could it be?

The cause of your breathing difficulty and shortness of breath is not clear from your description but it is important that your primary care physician or a pulmonary specialist (lung doctor) evaluate this problem as soon as possible. If you cannot get in to see your doctor, you may need to be evaluated in an emergency room or urgent care center. 

Your difficulty standing and walking may be directly or indirectly related to your breathing difficulty and will also require an assessment after your doctors make sure your ability to breath normally is safe guarded. 

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