​Here is My Question:
Should I start Tysabri with JCV index of 2.21?

I am 30 yr old caucasian male, I was diagnosed sept 2016 with MS. I had JC index of 1.82 and declined to start Tysabri or any meds. Jan 2017 2 new T2 lesions on brain, 4 total T2, now a JC index of 2.21.

I am willing to start meds now, Tysabri for 12 months is what's being recommended by my nuero. Her argument against other meds are that they are not as effective and we need to stop new lesions.

Are there any other meds you could recommend that are effective but not as risky for PML??

Thank you!!

Answer:
I agree with the decision to treat your MS (there are multiple blog posts on this site that detail the benefits of treating and treating early for MS).

The choice of disease modifying therapy (DMT) can be a little complicated and comes down to how aggressive your MS really is (which you allude to in your question).  Other considerations depend on certain prognostic factors of your MS.  Male gender tends to have a more difficult disease course than women (on average).  Other considerations include a history of motor attacks (ie, weakness or clumsiness), frequent and recurrent attacks early on, presence of spinal cord or brainstem lesions, etc.  These are poorer prognostic factors which can argue for use of a highly effective therapy such as tysabri.  However, your risk for PML is higher than an individual with negative JC virus antibody titers.

Because I do not know you and haven't had the opportunity to examine your or review your imaging, I cannot realistically suggest a different course for your MS than what has been suggested by your neurologist.  If you are a candidate for a highly effective therapy, the off label use of rituximab 500mg would be an option for you.  This is very similar to the soon to be approved medication called ocrelizumab.  The estimated risk of PML is ~1:25,000 (based on treatment of rheumatoid arthritis patients on rituximab).  Your risk with Tysabri for PML is much higher than this.  I'd suggest reviewing options with your neurologist as there are 15+ FDA approved therapies now.

A. Scott Nielsen MD MMSc
Neurologist and MS Specialist at Kaiser Permanente
KP Fontana and Riverside Medical Centers

Here is My Question:
I am a 43 year-old female and was recently diagnosed with MS just last month. Late December 2015, I suffered from an attack of optic neuritis and spent three days in the hospital for IV steroid treatment and other diagnostic tests. Other than the IV steroids and a three week taper of oral prednisone, I have never been on any other DMTs or immunosuppresants. The ON has been my only symptom, as well as some minor facial tingling. My MRIs showed approximately 3-4 active lesions and 3-4 inactive lesions. None on C or T spine. I take medication for hypertension and hypothyroidism.

My MS specialist neurologist is recommending Rutixan as my first form of treatment for MS. I am JC positive, not sure of exact level. I know there have been no reported cases of PML in MS patients treated with Rituxan, and that the risk is about 1 in 25,000. Is Rituxan normally used as a front line treatment for MS? It seems very aggressive to me, but my neuro said that he wants to treat it aggressively, as I am so young and have so little disability at this point. He wants to keep it that way. Do the benefits of this treatment outweigh the risks of PML?

​How long could I safely take Rituxan before having to consider switching to another DMT? I've read that patients can only take Rituxan for 2 years max.? I have ruled out Tysabri, Tecfidera, and Gilenya due to PML risk. How small or large is the PML risk in Gilenya as compared to Rituxan? Is Aubagio more effective than the interferon drugs in regards to delaying disease progression, number of relapses, and number of MRI lesions? Not looking for recommendations, just a little guidance. =) 

Answer:
Being JC Ab positive has only been shown to a significant predictor of risk for PML in patients taking natalizumab (Tysabri) and it has not been shown to be a valid predictor of PML in patients on other MS therapies.

Because there are only a handful of cases of PML in patients taking Gilenya (five patients) or Tecfidera (three patients), there are no recommendations for screening patients with the JC Ab test to guide therapy choices. 

No one knows the actual risk of PML with the oral medications but it appears to be significantly lower when compared to natalizumab.  While Aubagio has not had any reported cases of PML yet, I would not be surprised if a case or two is eventually reported over the next several years.

As you mentioned, the risk of PML with rituximab is also very low.  Rituximab is sometimes used as an option for treating relapsing MS patients but it is not commonly used as the first medication.
You will need to discuss with your neurologist how much “risk” you are willing to take in being aggressive in the treatment of your MS for the future potential benefits (decreased disability, decreased relapses, decreased MRI lesions).  Once you decide how much risk you are willing to take you will be better prepared to choose which medication to start. 

Please type in "PML" or "JC" in the search box in the upper right hand corner of this page and you will find many questions and answers about these topics.

Benjamin J. Osborne, MD
Department of Neurology
MedStar Georgetown University Hospital

PLEASE NOTE:  The information/opinions on this site should be used as an information resource 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.

Question:
What are the signs of PML? 

Answer:
PML causes subacutely progressively (developing over weeks) neurological symptoms and findings that can be quite similar to an MS relapse. Some common symptoms of PML that are less often observed in MS included large visual field deficits and language deficits. PML does not create spinal cord problems so a “relapse” confined to the spinal cord (which is common in MS) is unlikely to be caused by PML.

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

Here is My Question:

I am concerned of the risk of the onset of progressive multifocal leukoencephalopathy (PML) over the long-term. I was prescribed Tysabri for 8 months, than stopped after a flare-up which lead me to be hospitalized & a round of steroids. 

I was than switched to Tecfidera & after a year, the standard blood work resulted in "concerns" by my specialist. 

Additional blood work after the JCV test, I was found positive. So no new generation DMDs will be prescribed by my specialist due to these concerns. My concern is even though I have stopped using such, given the fact I am positive for the JCVirus, is there a risk that has been put into action which could lead to PML down the road? 

I was told once by my specialist once that these new DMDrugs could put these "side effects" into play either on the 1st dose or the 20th - no one knows for sure, as they are new drugs & not in use long enough to know the long-term impacts.
​
I know I may get back the same answer but maybe others may have researched this further. I know the prognosis is not good if you do get such, but how long must one consider this hurdle & continue to watch for signs. Should I continue to have my blood work monitored?

Thanks for any help!


Answer:
​​I would really encourage you to read some of information on our website concerning the risk of PML (just type in "PML" in the search box in the upper right corner on this page), because most of the statements and assumptions mentioned in your question are incorrect. Let me briefly summarize for you.

1. A positive JCV antibody test is a risk factor for the development of PML on Tysabri therapy ONLY. It is not a risk factor for PML on other disease modifying therapies, probably because the risk of PML on other disease modifying therapies is so low.

2. No one has developed PML more than 6 months after stopping Tysabri. It is assumed, for good reason, that most people diagnosed with PML after stopping Tysabri probably developed the PML during the Tysabri treatment period. The PML in these cases was only detected several months later when it became symptomatic.

3. The risk of PML on Tysabri therapy does not become significant until a person has been on Tysabri for more than 2 years. This risk is partly dependent on the titer or amount of JCV antibodies measured in your testing. Those with a JCV antibody index > 1.0 have a higher risk of PML after 2 years of therapy. Remember, the risk of PML in the highest risk patient after 2 years of therapy is still only 1 in 100 or 1 percent. This is a pretty low risk, and a risk that many highly active MS patients will take if other options have not been effective. It is increasingly recognized that diligent clinical and MRI monitoring in high risk patients can detect PML early (presymptomatic) with very good outcomes after stopping Tysabri.

4. The risk of PML on Tecfidera and other DMTs is exceedingly low. There are fewer than 10 reported cases of PML on tecfidera or related compounds over the past 20 years. The only known risk factor for PML on Tecfidera is a sustained lowering of the absolute lymphocyte count below 500 to 600. This is why we recommend discontinuing Tecfidera if blood testing over several months reveals a sustained lowering of the absolute lymphocyte count to these low levels. As with Tysabri, it takes a long time for PML to develop while receiving therapy with tecfidera unless your are immunocompromised when you start on treatment. Within several weeks or months of stopping tecfidera, your lymphocyte count should return to normal and your risk of PML should become negligible.

Ultimately, the best therapy for you will depend on the stage of your disease and your risk factors for disease progression. If you are considered a person at high risk for significant MS disease progression over the next 5 years, you require highly active therapy. These therapies have some risks but these risks often pale in comparison to the risks associated with progressing disease.

Your MS doctor may consider you a low risk for getting significantly worse in the next 5 years. If this is the case your may simply benefit from an injectable therapy or Aubagio . If he considers you high risk, then you should consider an intermediate (Tecfidera or Gilenya) or highly active (Tysabri, Lemtrada, Rituximab) therapy. If you have a difference of opinion on this subject, you may benefit from a second opinion to clarify your situation.

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:
I have 3 lesions on my spinal cord. What could cause this? Does this mean I have JC virus or PML?

Answer:
I have always hated the term, “lesions”, because it so non-specific. The literal translation is something structurally abnormal. In the context of Multiple sclerosis, a lesion usually refers to a white spot (T2 hyper intense) on MRI. These T2 hyper intensities or white spots are common in both the spinal cord and brain. In fact it is extremely rare for a person to have MS without these white spots on MRI. The good news is that PML does not typically involve the spinal cord so you do not have to be concerned about that diagnosis. If you have MS, then that is the most likely cause of the white spots on your MRI can.

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

Here is My Question:
I have been on Gilenya for 3yrs. Several months ago I was diagnosed with breast cancer. My neurologist took me off Gilenya while I was going through treatments for cancer (lumpectomy and radiation). I'm now cancer free. My neurologist said I shouldn't go back on Gilenya because of my previous cancer diagnosis. He put me on another drug but the side effects bothered me so he took me off it. He now wants to put me back on Gilenya. I also tested positive for JC virus. I just read about the concern of Gilenya and the possibility of causing PML. Should I be concerned about going on Gilenya since I've had cancer and tested JC virus positive? 

Answer:
The incidence of PML in MS patients receiving Gilenya since its approval in 2010 is extremely low. There is no evidence that JC virus antibody studies predict the risk of PML on Gilenya or any therapy other than Tysabri. There is also no clinical evidence from post marketing studies that Gilenya interferes with the ability of your immune system to provide adequate surveillance against the recurrence of cancer, although this remains a theoretical concern with this treatment. 

Risks are always relative and must be interpreted in the context of what makes you comfortable or uncomfortable.  Although I know nothing about your MS, it is quite likely that your risk of  MS worsening without effective treatment is much higher than your risk of  developing PML or experiencing a recurrence of cancer as a result of treatment with Gilenya. You and your doctors have a better idea of the following information that is needed to help you with this decision:

1. What is the severity of your MS and your risk of becoming significantly disabled in the near term (i.e. next 5 to 10 years)?  The higher the near term risk the greater the importance of initiating treatment with a highly effective treatment now. However, if you are already significantly disabled with problems walking and classified as either secondary or primary progressive MS, there is little evidence that Gilenya will be beneficial. In this situation the risk:benefit ratio may be reversed. A good way to think about this is to consider the last time you experienced your age, the last time you experienced a typical relapse and the manner in which MS has worsened over time; generally, if you are over 50, have not experienced a typical relapse in more than 2 years and have noticed slow worsening of you condition over a period in excess of 6 months, you have either secondary or primary progressive MS. 

2. How effective was Gilenya during your prior three years of treatment with this drug? If it was only partially effective, perhaps another therapy is more appropriate at this time

3. What is your risk of cancer recurrence? If it is considered a very small risk based on cancer type, stage and treatment then there is less concern?

Hope this helps 

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

Here is My Question:
I was on Tysabri for two years and then switched to Tecfidera. After 7 months on Tecfidera my WBC count dropped to lymphocyte 3500; absolute 795; cd3 562; cd4 508; cd8 55. All LOW as in half of the lowest number on the scale. My doctor said to stop Tecfidera and that I NEED to be back on Tysabri. If the cd8 number is the wbc that holds off the JC virus, then wouldn't it mean that the barn door is now wide open? Why would he put me back on a drug know to have a greater risk of PML with prior immunosuppressant especially when my blood test reflect a major suppression? Plus being on Tysabri for 2 years and feeling like I dodged the PML and rebound by exiting the drug at the appropriate time. He retested my JC virus. Waiting for results. He feels that being off Tecfidera for 30 days will give my immune system time to get normal and I can restart Tysabri with no risk of PML pending a negative or low number on JC virus test. I don't want to start Tysabri again, but I'm not seeing any other options?? Forget CRABS. Made me very ill. Hoping for a long term solution without PML risk. 

Answer:
This is a common concern facing patients and physicians, so let me take some time to address it today. As I have stated in previous responses, there is really no way to totally eliminate the risk of PML. 

There are or I suspect there will be reports of PML with all highly active therapies for MS, although the risk varies dramatically between different treatments. The highest risk occurs in JC virus antibody positive people with MS receiving Tysabri for over 2 years. Within this group, the risk appears to be higher in those with JCV antibody index values greater than 1.5. 

Unfortunately, the risk factors for the development of PML in patients on therapies other than Tysabri remain unclear. For instance, we do not yet know if JCV antibody results are a risk factor for PML in patients on therapies other than Tysabri. It is clear that prolonged lymphocyte depletion is a risk factor for PML in multiple clinical situations, but guidelines for the use of this information to monitor different treatments is not available, and will likely differ between treatments depending on their mechanism of action. 

For instance, Tecfidera actually depletes lymphocytes, particularly CD8 positive lymphocytes, and there is a general recommendation to stop treatment in individuals with prolonged depletion of absolute lymphocytes counts below 500 to 600. Yet, there is already a report of a patient on Tecfidera developing PML with a less severe reduction in lymphocyte count, prompting concerns related to the degree of lymphocyte reduction that should prompt patients to discontinue therapy. 

Lastly, lymphocyte depletion tends to persist for longer periods after discontinuation of Tecfidera compared to other agents. 

So how can you use this information to make your treatment decision?

1. Given your reduction in absolute lymphocyte count (795) and CD8 count (55) and your elevation in CD4/CD8 ratio (> 5.0) you should consider stopping Tecfidera if the reductions worsen over the next few months. It is probably too early to determine if it is necessary to stop Tecfidera now. It is the persistence of lymphocyte reduction over time that should be a concern.

2. Restarting Tysabri treatment depends on a number of factors but should probably be avoided if you are JCV antibody positive (esp with an index > 1.5) and if your absolute lymphocyte count and subsets have not returned to normal after stopping Tecfidera.

3. Gilenya may be a reasonable treatment option for you. The risk of PML is exceedingly low and the drug itself only sequesters lymphocytes without actually depleting them. For instance, it is very common for the measured lymphocyte count to drop below 500 in patients on Gilenya, but this drop is not associated with a significant increase in the risk of any infection. I would certainly consider a trial of Gilenya before returning to Tysabri, if you are JCV antibody positive. Again, I would not start Gilenya until your absolute lymphocyte count returns towards normal (over 1000).

4. Depending on your prognostic features, Aubagio may be an alternative.  This is generally well tolerated and to my knowledge there has not been a report of PML developing in a patient on this treatment.

I am not recommending any particular treatment, but aim to inform you of your options so that you can discuss what is best for you with your physician.

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


PLEASE NOTE:  The information/opinions on this site should be used as an information resource 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.

Question:
My daughter has had MS for 20 years. She has been on Tysabri for almost 5 years. She was diagnosed with JVC granular cell neuropathy of the cerebellum in September 2014. Her spinal copies were 267. As of feb 2015 they were at 58. Could someone please explain to us in plain English how do we know when this infection is gone? My daughter is tired all the time. How hard should she push herself to do everyday things? Her symptoms are numerous and she doesn't seem to be improving. Does the cerebellum once compromised repair itself? Are their symptoms that indicate we need to be even more worried that something is really wrong or that we could be facing death if not treated? Right now my daughter is on no maintance drugs for her MS. I am really concerned about this but should I be? Lastly is there any layman phamplets or literature you could direct me to. We do have an excellent MS doctor but he is not an expert on this mutant gene of JVC and therefore consults with other doctors. My daughter is on her 7th month of this virus and we are all concerned. Thank you.

Answer:
We are very sorry to hear about your daughter's diagnosis. You seem very knowledgeable about her particular condition but let us provide some general information that may benefit other readers and answer your specific question.

The John Cunningham Virus (JCV) is ubiquitous (meaning it exists everywhere in the world), only infects humans and does not appear to cause any primary illness when a person gets infected. The number of people infected with this virus varies from study to study, but most studies suggest that more than 80 % of all people are infected with this virus. Following infection the JCV remains asymptomatic in the bone marrow and kidneys (whether or not you have MS).  Some people produce detectable antibodies after infection with the JC virus infection, whereas others do not. The present or absence of antibodies to the JC virus using the current assay available for MS patients, does not indicate whether you have a latent or prior infection with the JC virus, but it does indicate your risk of developing a productive JCV infection of the nervous system, if you are receiving treatment with Tysabri.

Due to reasons that are not entirely clear, people who are immunosuppressed and people who are receiving certain treatments, particularly natalizumab, may experience a productive infection of the central nervous system by the JC virus. For this to occur, one or more genes expressed by the virus must become mutated to cause the infection in the brain. What causes the mutations, allows the virus to be transported to the nervous system so that an infection may develop, and allows the virus to enter brain cells not normally infected by the original virus (called the archetypal strain) and reproduce remains unclear at this time.

The most common central nervous system infection by a mutated JC Virus is called Progressive Multifocal Leukoencephalopathy (PML). This is an infection of the oligodendrocytes that make myelin in the brain. It is this same myelin that is the target of inflammation in MS. Therefore, the initial symptoms of PML can be confused with worsening of MS and the diagnosis of PML requires a high degree of vigilance. Less commonly, the mutated virus can infect the granule cell neurons in the cerebellum and cause a condition called JCV granule cell neuronopathy. This condition does not directly affect oligodendrocytes or myelin and  can be very difficult to detect since patients experience a progressive shrinkage of the cerebellar cortex without the white matter changes typically associated with PML on MRI scans. MRI is very good at detecting changes in the white matter of the brain (such as MS and PML) but not as good at detecting changes in the cortex or gray matter (such JCV granule cell neuronopathy). In some cases people present with both typical PML and Granule cell neuropathy of the cerebellum making it easier to establish a diagnosis. The symptoms of JCV granule cell neuronopathy usually include progressive unsteadiness walking (called ataxia or walking like a drunk), slurred slow speech with loss of normal rhythm (called dysarthria) and incoordination of movements. While these same symptoms can be caused by MS, their development or worsening in an otherwise stable MS patient on long term Tysabri therapy is reason to suspect JCV granule cell neuronopathy.

To date, there have been over 130,000 individuals throughout the world that have been exposed to Tysabri. The overwhelming majority of patients with JCV related nervous system infections are reported as PML although it is likely that other JCV related conditions like JCV granule cell neuronopathy may go undetected or misdiagnosed. 

Once a Tysabri treated patient develops PML, there is a 23% mortality rate, and the other 77% of patients survive the infection but are left with varying levels of disability.  In some cases the virus is eliminated and no longer detected after the immune response is restored (read below). In other cases like your daughter, the virus remains detectable in low amounts for variable periods of time because of partial viral clearance by the immune system response.  In this case the condition becomes chronic much like the underlying multiple sclerosis. Physical/Occupational therapy may be indicated to help facilitate some functional recovery.  Your doctors can help direct this when it is most appropriate. We know far less about the outcomes of people with MS who develop JCV granule cell neuritis as there are very few reported cases.

When PML occurs on Tysabri treatment, the generally accepted strategy to manage this situation is to remove the Tysabri from the patient by using plasma exchange (this is a procedure that filters the blood, removing the Tysabri).  This is done in a hospital setting.  The rationale for this is to remove the blockade of white blood cells from the nervous system (so they can get into this space and fight off the infection).  Following plasma exchange the patient often develops a strong inflammatory response against the infected brain that worsens their condition and is usually controlled with steroid treatment. This is call an Immune Response Inflammatory Syndrome or IRIS. Unfortunately, there is no proven additional therapy that can eradicate the virus.  Therefore, we rely on the strength of the immune system to clear the virus.  Periodic testing of the spinal fluid is important to prove that the immune system has successfully cleared the virus. 

To answer your question about a disease modifying therapy to treat your daughter's MS:  we would agree with your daughter's treating physician not to treat at this point in time as she still has copies of the virus in her spinal fluid. From your message, we suspect that the MS doctor appropriately has an infectious disease specialist helping in the medical care of your daughter and her PML. The world’s expert on your daughter’s condition (JCV granule cell neuronopathy) is a former colleague at Beth Israel Deaconess Medical Center in Boston, Dr Igor Koralnik. I would suggest that your daughter's doctor contact Igor for advice on management, if they have not already done so.

Revere Kinkel MD and A. Scott Nielsen MD MMSc

Here is My Question:
My latest JCV came back positive at a level of 2.93 - I have been on Tysabri since the phase 3 trials (minus the year they took it off the market in 2005?) - I have done and am doing really well on Tysabri...my level has been around that for the last several blood draws...as I am doing so well - and am probably the healthiest I have ever been in my life - should I consider "Rituxan"? Doesn't it also carry a slightly lower risk of PML?

Answer:
This is an excellent question but difficult to answer. You have a number of options. First, your risk of PML if you remain on monthly treatment with Tysabri is approximately 1 in 100 or 1 %. You and your doctor know more than I do about the benefits you have received from Tysabri treatment for the past 9-10 years and your risk factors for MS disease progression, so the two of you need to decide if your treatment should be modified based on your overall assessment.

There are several factors that may affect your decision. First, people with a low body mass index or weight accumulate more Tysabri over time and may be at increased risk of PML. This is particular true of people less than 60 kg. If you are relatively thin I would strongly consider increasing the interval between Tysabri infusions to every 8 weeks instead of every 4 weeks. There is accumulating evidence that this is beneficial in all JCV antibody positive (high titer) patients but particularly in those who are thin. I currently treat monthly for the first 18 treatments and then every 8 weeks in all MS patients with a JCV antibody index > 0.6. With few exceptions this interval works well but in some cases we need to infuse every 6 weeks to avoid a return of annoying MS symptoms. 

Another strategy would be to switch to another disease modifying therapy that you are likely to tolerate. This strategy can be beneficial, depending on your prior treatment experiences before starting Tysabri and your disease risk factors but is not without risk. Some people experience significant MS relapses after stopping Tysabri, even if another treatment is started immediately. Furthermore, some of the treatments you may consider could be associated with PML as well, including Gilenya, Tecfidera and Rituximab. The safest drugs to switch to would be the inteferons or Copaxone, but these may not be as well tolerated or as effective. Aubagio has not yet been associated with PML but this may just be due to too little experience. We do not recommend drugs on this site, but are simply providing you with information to discuss with your physician to make the best decision for you.

Revere Kinkel MD
Director of the UCSD Multiple Sclerosis Program

Here is My Question:
After years on Tysabri, my JCV was higher than was considered safe so I switched to another med. Does that JCV level go down over time? Does is stay at that high(er) level?

Answer:
There is no evidence at present that the amount of JCV antibodies (i.e. the JCV antibody index value) when you are tested is related to being on or off treatment with Tysabri. JCV antibody index values will fluctuate over time and can either go up or drop to undetectable levels ( i.e a Negative JCV antibody result in a person previously positive).  Generally, index values tend to stay within a certain range, either negative or low (< 1.5) or high (> 1.5) with repeat testing; but this is not always the case and requires continuous monitoring while on treatment.

The important thing to remember is that we have no knowledge of a person developing PML more than 6 months after stopping Tysabri, regardless of JCV antibody index values or treatments used after stopping Tysabri.

Rip Kinkel, MD

Here is My Question:
What is the carryover risk of PML when transitioning a patient from Tysabri to Rituximab? Does that change how you transition?

For example, can you stop Tysabri and then start Rituximab in less than 30days (in an attempt to prevent or reduce likelihood of rebound?) OR because of lingering PML risk do you wait a certain number of days? THANKS (A neuro pharmacist)

Answer:
First, this is great that specialists treating people with MS are starting to ask questions on this site.  We want this to be a learning forum for all of us to share and learn, so there is no reason for only those with MS to ask questions here, so thanks for your question! 

To answer your question, there is really no single answer for every case. It depends on the individual's risk of a relapse after stopping Tysabri, their JCV antibody index, their prior history of immunosuppression and their duration of Tysabri therapy.

I personally do not wait more than 60 days to treat with Rituximab so as to minimize the risk of relapse after stopping Tysabri, but this wait is often dictated by insurance authorization delays more than anything else. Most relapses after stopping Tysabri occur between 3 and 6 months following the last dose, so treating with Rituximab within 60 days is prudent. You may wait up to 3 months in a person with a lower risk of relapse and a higher risk of PML. You will definitely wait longer if there is any  concern of early pre symptomatic PML at the time of stopping Tysabri. I think it is important to repeat another MRI and possibly check CSF before starting Rituximab to make sure there is no new activity suspicious for PML.

These are of course just my thoughts on the matter. Many others in the field wait far longer than 3 months in all cases before using Rituximab after stopping Tysabri.

If you search this site for PML, you will find a lot of information about it. http://www.healthcarejourney.com/apps/search?q=PML

-Rip Kinkel, MD

PLEASE NOTE:  The information/opinions on this site should be used as an information resource 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.