Need info on MS treatments - Beta interferon not working
My husband was diagnosed with MS in May and has been taking Rebif since July. His most recent MRI shows new immunological activity in his brain and he seems to have developed pretty severe arthritis in his fingers that he never had before. His joints are alarmingly swollen. I called MS Lifelines but they told me that the Dr. has to call to speak to a researcher that might have more information on the less common side effects. I've also noticed a progressive increase in his level of fatigue since he started taking the Rebif. The doctor thinks that all the symptoms indicate that the Rebif is not working and wants him to switch to Tysabri so I've been trying to find out exactly how Tysabri works. It's a monoclonal antibody so it has to have a specific antigen that it's neutralizing but I can't find what the antigen is or type of cell (T Cell/B Cell, subtype of T Cell etc.) it affects most. I'm also totally freaked about the possibility of PML. I was also wondering why Rituximab is not being used to treat MS. Rituximab also causes PML but it resulted in complete remission of the disease in a high percentage of patients tested in a small clinical trial. If both drugs can cause PML but Rituximab is more effective and requires fewer treatments, why isn't it used instead of Tysabri? I've asked my husbands neurologists these questions but he doesn't seem to know. Also there is a study at John's Hopkins where they induced remission of MS using cyclophosphamide (nasty stuff that) which effectively "reboots" the immune system. Does anyone know anything about that - if it could be a viable option anytime in the future? If anyone can give me some answers to all my questions, I would greatly appreciate it.
Hi, Jois, you have asked questions that could keep MS researchers and experts busy for months or years.
In all of my reading of the professional medical literature I have never heard anything about Interferon-beta-1a or 1b causing a true arthritis. This makes me think that the swollen and painful fingers are due to something else and NOT MS. This raises the question of the presence of another condition like Rheumatoid Arthritis, RA, which can happen concurrently with MS in really unlucky people. Also, garden variety Osteoarthritis can occur and come on quite rapidly. OA is a non-inflammatory arthritis while RA is an immune inflammatory type.
Don't make the immediate assumption that this is related to MS or the Rebif. See your doc and have a referral made to a Rheum or even just get Xrays. OA will show classic degenerative signs very early. I make this point, because my OA came on very quickly and quite severely in my hands when I was in my forties - my hands looked like an 80 year old's on xray.
In OA the classic joints to be affected are the last two knuckles and all three of the joints of the thumbs. In something like RA, the more typical joints are the joints at the base of the fingers, the wrists, and then the second knuckles. Blood tests that can help are an ESR, CRP, RA and ANA.
The Rebif should be kicking in now at 5 months, so it does appear that it is worsening rather than stabilizing or improving. The other DMD unrelated to Rebif is Copaxone and the Interferon that is at a higher dose is Betaseron.
How Tysabri works is a whole other topic and I'm not sure if it is known for sure how it works, beings that they do not even know the critical sequences of the pathology of MS.
The studies are not far enough along to determine long-term safety and efficacy in MS.
The cyclophosphamide bone marrow ablation is indeed a nasty procedure. In a study of 7 patients, one died from the procedure, but the others appear to have had a reversal of disease. That kind of chemotherapeutic attack on the immune system has up to a 20% mortality rate (all things considered). Some people are claiming a !% mortality rate, but that is not the average, and I view them with suspicion. At this point it should be reserved for the patients who are quickly deteriorating and facing complete disability after failure of all more safe treatments. My opinion. This kind of procedure takes many weeks, and the patient can suffer horribly from pain and infection. At certain points in the procedure death can occur from an IV site infection or a simple cold.
Compare that with a 0.1% (if that) chance of PML and the answer seems much clearer why Tysabri is being used over Cytoxan, even if Cytoxan had been studied sufficiently and approved. PML might freak you out, but it has to be viewed side by side with the risk of severe disability of the MS.
There is also Mitoxantrone which is also approved for RRS unresponsive to the firstline meds. My quarrel with this med is that it is directly cardiotoxic and it can only be used up to a certain dose before the heart shows unacceptable damage. In my mind, there would be NO "acceptable" amount of heart damage. Because from there on, if the MS is not arrested, then you have the effects of MS PLUS the damaged heart muscle.
A small study result is enough to call for other research, but it is very common that large studies either do not show the same results, show opposite results or show unacceptable side effects not seen in the initial small trial. If a "Hail Mary" play is needed then sometimes doc will go for the unproven, but promising treatment, but often the risks are huge. That, of course, is weighed against someone who is losing the ability to breathe or swallow on their own along with rapidly advancing spasticity and/or paralysis.
Those are my quick thoughts on your questions. I am very sorry to hear about your husbands ongoing progression.
Just a correction - the cyclophosphamide treatment at Johns Hopkins, called HiCy, is not the bone marrow ablation procedure. In the Hopkin's procedure, the white blood cells are eliminated, but the bone marrow cells are left intact. The hope is a new immune system, which does not attack the body's own cells, will grow back without the need for stem cell transplantation. Significantly more than 7 people have undergone this treatment, and I am not aware of any deaths. With this procedure, infection is a risk, but the Hopkins' protocol calls for patients to remain near the hospital for a week following, so they can be closely monitored.
Last I checked, Hopkins was still doing the HiCy as an off-label treatment, with patients (or their insurance) responsible for the cost. I believe they wanted to start a phase III clinical trial, but are having trouble with the funding. The main criteria for being eligible for this treatment was clear evidence that the MS was still in the inflammatory stage, i.e. Gd-enhancing lesions seen on MRI.
Actually I don't think your memory is that faulty or your data is wrong. There are studies happening like the one you described, where chemo is used to destroy the immune cells, and then stem cells are transplanted; just not at JH. Dr. Richard Burt at Northwestern has treated a small number of patients with his method. And, (now I'm going from memory, so this could be wrong), at least one patient died in a similar study. Like you pointed out, this is an intense procedure.
Thank you so much for all this information. I'll watch out for progress on the Rituximab and HiCy research. The funding situation is very disturbing.
I have a few more questions that maybe you could help me with?
My husband currently works in conditions that I worry are aggravating the MS. He spends several hours per day in an extremely hot steamy room and gets completely drenched in sweat practically daily.
The doctor said something about not getting over-heated, that it can bring on a flair. He specifically mentioned 103 degrees but could high frequency exposure for several hours at a time of lower temps - not sure exactly how high but I'd guess >90 - I'll have to check on that. Could this be initiating the flairs?
Also, he is severely allergic to certain animals and currently works in animal care. He wears protective clothing and masks but occasionally something will splash him or touches his skin between the gloves and lab coat or his neck that gives him a pretty bad reaction, rashes/hives which can spread to other areas besides the exposure site.
About 7 years ago he worked in a very poorly ventilated animal facility where he had regular and extreme reactions requiring high doses of benedryl several times per month. Could severe allergies be the original cause of his MS and is it possible that his current animal exposures are aggravating it?
Once again, your thoughts are greatly appreciated.
This is really just my informed opinion, as I am not in any way a medical professional. Others might chime in with better info.
For your second question, right now it's impossible to say what caused the MS, whether it's allergies or anything else, since the cause is unknown. However, I think the consensus opinion would be that the allergies did not cause this. I think the generally accepted theory is that something earlier in life (exposure to infection, lack of Vitamin D, etc). sets people up to develop MS later on. As for the allergies aggravating it, I could see this. In general, anything that makes me feel bad (cold, sinus problems, etc), seems to feel worse, added to the MS symptoms. Also, I think allergic reactions are a kind of immune response. So (and this is just speculation on my part), it would seem the allergies could aggravate MS symptoms, similar to what happens when someone gets infections.
The heat problem is pretty common with MS. To be honest, I've had only modest problems with heat - a buzzing feeling or feeling a little more fatigued. But, I think many people have more trouble with the heat. As I understand it, the nerves conduct more slowly when exposed to higher temperatures, so this becomes a problem for people with MS. Also, for most people any problems will resolve when the temperature goes down. There's no clear cut-off temperature for when problems might appear, and it probably varies with each person. A neuro once told me that being exposed to high temperatures (like sitting in a hot tub) can be a risk factor for an actual relapse. I don't know if this is true or not.
Oh, in regard to the HiCy, doctors at Johns Hopkins were able to use this because cyclophosphamide (or Cytoxan) is already approved for other uses, and has actually been used for MS for many years - but in lower doses. So, JH was able to prescribe it "off-label" for MS, and they used it in much higher doses, in an attempt to re-boot the immune system. It was this high-dose approach which they hope to try in phase III trials and get FDA approved. Not that I am recommending the treatment, but I believe they have treated many patients, and did release one study. And the patients who did receive this were able to get the costs covered by insurance.
patientx and jois - Heat can be devastating to someone with MS. The explanation is correct. As the myelin-damaged nerve attemps to conduct signals the signal is delayed or even blocked. Even a small fraction of an elevation in core temp will have these effects. So, warm seasons, an overwarm room, bath, shower, fever, and even moderate exercise can markedly increase one's symptoms. I become weak, irritable and can't think in mild heat.
Your husband should look into requesting accomodations under the ADA. Here is a Health Page on it.
Other possibilities are a fan, definitely a need for cooling garments like a cooling vest.
About the consequences of becoming overheated. Usually, the increased symptoms resolve when the body cools enough. BUT - it can lead occasionally to a true relapse and cause permanent problems. In the days before the MRI, one of the diagnostic tests for MS was a hot bath. The patient would be put in a hot bath and if their symptoms recurred, especially visual ones (called the Uhthoff's Phenomenon) then the test was "positive" for MS. This test fell into disfavor after a patient became paralyzed permanently (ya think?!)
One of our own, Sarahsmom (Julie), had a devastating relapse after an luxurious soak in a hottub. She was unable to get out of the tub on her own and had to be helped out by a stranger. That caused symptoms that lasted for months. I'm not sure if all of them ever resolved.
Heat can be tuly dangerous and not just obnoxious.
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