Here is My Question:
Hello. I'm in a bit of a pickle! I just tested positive for Covid 19 and have my first rituximab infusion in a week. Should I ask to delay the infusion or proceed?

Answer:
You should discuss this further with your MS specialist as I am providing general information but only your specialist should be helping you make this decision. In general, I would delay the rituximab infusion until it was clear you were recovered from the COVID19 infection. This will also allow your body to develop excellent immunity to the most recent strain of viruses before starting rituximab.

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

Here is My Question:
Can I safely stop my DMT (tysabri) after age 65? I’m tired of the monthly infusions. It’s been 8 years on this particular drug and I’m doing well.

Answer:
Stopping certain multiple sclerosis disease modifying therapies has been associated with reactivation of disease. However, this risk is not shared evenly among users of these medications. For purposes of further discussion the treatments most commonly associated with this risk are the Sphingosin-1-phosphate modulators (S1P modulators)- Fingolimod (Gilenya), Siponimod (Mayzant), Ozanimod (Zeposia) and Ponesimod (Ponvory)- and the adhesion molecule inhibitor class, which at present only includes Natalizumab (Tysabri). 

The overall risk of reactivation and relapse after stopping these medications is between 30 to 50 % and depends primarily on your disease activity prior to starting the medication, your disease type and your age. People with more than 1 relapse in the year prior to starting Tysabri, relapsing remitting disease and a younger age all have a higher risk. When the relapses occur after stopping treatment will depend on how quickly the effect of the drug wears off; peak relapses occur 3-4 months after stopping tysabri but can occur for up to a year. For S1P modulators, relapses may occur more rapidly after discontinuation; the time interval between stopping the S1P modulator and the onset of relapse likely depends on the washout rate of the medication. This means that relapses potentially occur more quickly after stopping Ponesimod (Ponvory) and SIponimod (Mayzant), both of which are cleared more rapidly from the body than Fingolimod (Gilenya) and Ozanimod (Zeposia).

Now let's return to your situation. You are definitely an outlier at age 65. You started Tysabri at age 57 which is an unusually late age to start this medication. Most MS clinical trials do not even allow people over age 55 to enter the study. If you look at published studies of people relapsing after stopping Tysabri the mean age is usually around 38 with a standard deviation of 5-10 years. Therefore, when these studies report a lower risk of relapse in older individuals you are definitely in this group. If you were experiencing progressive disease before starting Tysabri and none or only one definite relapse in the year prior to starting, your risk of relapse after stopping is even lower.

One way to reduce the risk of relapse after stopping Tysabri, regardless of your risk factors, is to give a single infusion of an anti-CD20 monoclonal antibody like rituximab (500 mg) or ocrelizumab (300 mg). For the SIP modulators, this infusion is given after it is clear that your lymphocyte counts are rising; for both Natalizumab and S1P modulators, this infusion is given after your doctor insures you do not have presymptomatic PML on imaging. In all circumstances there is no evidence that more than one infusion is required to prevent these relapses from occurring.

As always, please discuss these issues with your MS specialist. Only he or she knows the details of your individual case and can provide the best recommendation.

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

Here is My Question:
I was diagnosed with MS four years ago. The first medication I took was dimethyl fumarate and after two years I still had disease progression. So I did one round of almetuzumab/Lemtrada afterwards.
then I suddenly had ITP so I didn't do round 2. I took IVIG for ITP 3 times and then took rituximab because my platelets would go as low as 0. While on rituximab turned out that I had hep B virus antibodies from an old injury so I started taking antivirals (Vemlidy). What do you think is the most suitable medication would be? Would I be able to take mavenclad?

Answer:
You pose a very important question for which we currently have incomplete answers. Immunosuppression in patients with chronic active Hepatitis based on serology and the presence or absence of viral DNA replication is associated with Hepatitis B viral reactivation. This can be quite serious. While anti-CD20 therapies (rituximab, Ocrelizumab and Ofatumumab) are most strongly associated with Hep B viral reactivation, this can also theoretically happen in people on other forms of immunosuppression including alemtuzumab, or even Mavenclad. This is particularly true of an individual, such as yourself, who has received multiple therapies associated with this risk. 

There are studies currently planned or underway to determine if co-treatment with Vemlidy reduces this risk but no definite answers yet.

Given this information, it could be appropriate to remain on both Rituximab and Vemlidy, if the rituximab is effective at treating your MS and your risk of Hep B viral reactivation is relatively low (defined as only Hep B core antibody positive). You should definitely see a hepatitis specialist (ID doctor or hepatologist) to determine your overall risk of Hep B viral reactivation. If there is no evidence of DNA replication (Hep B DNA negative and Hep B Surface Ag negative), your risk is lower. However, they will need to monitor your labs for viral reactivation, if you continue treatment with Rituximab and vemlidy.

Hope this helps.

​PLEASE NOTE: This information/opinions on this site should be used as an information source only.  This information does not create any patient-HCP relationship, and should not be used as a substitute for professional diagnosis and treatment.  Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition.

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

Here is My Question:
Are there people with MS that live normal life with minimum symptoms? From what Ive seen in the groups or forums, it looks like everyone lives with certain pains or disabilities and can’t live a normal life.

Answer:
A normal life for anyone requires adaptions to all of life's burdens including injuries, common ailments, and aging, not to mention psychological stress, anxiety and depression. It is no different for those with MS, although those afflicted may experience further burdens over time. With this in mind, I can say that there are many people with MS that experience a relatively benign course, accumulating little impairment or disability over their life. It is hard to give you a number since everyone experiences MS differently; even those whom others may consider disabled in a wheelchair may report a higher quality of life than others still standing. I believe it is not just the level of measure impairment that dictates how we experience disease; it is the ability to adapt and remain positive, usually with the help of a great social supports (friends and family), that allow people to do well over time.

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

Here is My Question:
My daughter started on Sept 15 with tingling in her arm and has had muscle weakness and is not able to walk. She has pins and needles, sweating, no appetite/nausea, and bladder issues. She has had 3 good days total but its not getting better. Her MRI spine is clear. Brain faint hyperintensity. No Size or shape noted.
Ideas?

Answer:
Please direct your query to your primary physician or neurologist. It is not possible for me to comment without the benefit of further information and examination findings.

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:
Is the effect of 'regression to the mean' taken into account to determine efficacy of DMTs/diet/lifestyle,... with RRMS? If so, how? (both in research, and by the treating individual neurologist)

Answer:
The best way to control for, "regression to the mean" is to use a contemporaneous control group in all clinical investigations. Of course, the best controls are randomized and blinded to treatment assignment if you are conducting an interventional study.

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

Here is My Question:
I’ve read elective abortion can cause increased relapse. Is this true if the patient is on and remains on Tysabri? Also, do you think medical verses surgical abortion is safer?

Answer:
Amazingly, there is very little written on this subject. Most of the literature is based on outcomes of pregnancy after certain drug exposure or relapse risk post-partum.

There is one study from Italy in 2018 looking at 188 pregnancy terminations/abortions mostly in the first trimester. Risk of relapse and new MRI activity was mildly increased after pregnancy termination, particularly in those who stopped disease modifying therapy or with disease activity (relapses or MRI activity) in the year prior to pregnancy termination.

I would expect people with MS to do very well if they continue Tysabri before and after pregnancy terminations.

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