Ask the Doctor: Should I Consider Stopping Treatment?
By Dr. Jack Burks
Chief Medical Officer for MSAA
Q: When should someone stop a disease-modifying therapy (DMT)? I have not had a relapse for several years, but my doctor has mentioned that I may have progressed from relapsing-remitting MS (RRMS) to secondary-progressive MS (SPMS), in which case I might not experience relapses anyway. If this is true, I would not need to go to the expense or trouble of taking injections every-other day. However, if Betaseron is contributing to my recent lack of relapses, should I risk stopping it?
A: My advice is to weigh that decision very carefully. By stopping your medication, you would be taking a gamble, which could result in an increase in disease activity. AND (in my experience and not addressed in any scientific way), some patients who go off their successful DMT may develop a more rapid progression of their disease. Even worse, when they return to their original treatment, they do not respond as well as before. My feeling is: “if it ain’t broke, don’t fix it.”
In trying to understand this difficult disease, it appears that SPMS has an earlier, relapsing phase, as well as a later, degenerative stage, without relapses. Betaseron has been shown to be effective in the relapsing phase. Therefore, you may still be benefitting from Betaseron, since the treatment may be responsible for your lack of relapses. I feel the same about other DMTs for other patients.
In other words, Betaseron may still be reducing inflammation, which may be why you are no longer having relapses. If so, your relapses may return if you stop your medication. Unfortunately, we do not know that for certain, but why take a risk? In general, I believe that the effects of DMTs may be keeping patients healthier over the long run. Recent long-term data on Betaseron supports my opinion.
Therefore, I usually do not recommend stopping DMTs if my patients are doing reasonably well. However, if the patient cannot tolerate the DMT or is doing worse than I had expected, I recommend a switch of therapies. Of course, we cannot always predict the outcome of any MS treatment. Your doctor is your best guide. He or she may want you to get an MRI to check for the rate of disease progression. Or your doctor may suggest a second opinion from another MS expert.
Q: In your column in the last issue of The Motivator, one reader wrote about their chronic bout with diarrhea. You did not mention celiac disease, so I wanted to ask if this individual and any other person with MS who has unresolved, chronic diarrhea should be checked for celiac disease. I have MS and was often sick with symptoms of celiac, including headaches that required going to the ER. My husband happened to read an article about celiac disease, and this eventually led to my diagnosis, along with two other family members. We are grateful to know about this disorder and are able to resolve our symptoms through a gluten-free diet.
A: You make a good point. While celiac disease is responsible for a very small percentage of diarrhea in MS patients, it is more likely found in individuals with MS, as with other autoimmune diseases, than in the general population. A recent study suggests that celiac disease is five to 10 times higher in MS patients versus the general population. Diarrhea can be caused by any one of a great number (potentially hundreds) of factors, and to list all of these would not likely have been of help to the individual who wrote (mainly) about her vaginal problem. The specific cause is best evaluated by one’s doctor or by a specialist in gastrointestinal (GI) diseases, which I noted in my answer. We need to be careful that we don’t run the risk of people self-diagnosing their diarrhea as celiac disease when something else may be responsible. It is best to ask an expert in that field.
Celiac disease has a genetic basis, as do most immunological diseases. It is under-recognized in general, and is treatable by reducing gluten in the diet. The workup by a GI doctor includes getting blood tests, and the evaluation may require an upper-GI tract workup, including barium swallow and endoscopy, a barium enema, etc.
Q: Can you advise the role of hormonal therapy for women with MS who are menopausal? In my case, I recently had a hysterectomy. Please let me know if taking hormones is safe and if it can have any potential negative effect on my MS.
A: As with any treatment decision, we weigh the benefits versus the risks, which vary with each medication and with each patient. Exercise, diet, smoking (versus not smoking), and recreational drugs and alcohol are all important when discussing menopause with a doctor.
Menopause has short- and long-term consequences. Short-term issues include hot flashes, night sweats, emotional stress, vaginal dryness and pain, decreased libido, bladder problems, and changes with skin and hair. Long-term issues include osteoporosis (bone thinning) and an increased risk of cardiovascular events (heart attack and stroke).
To some extent, these issues may be addressed through symptom-management strategies. Various remedies and products are available to reduce several of the short-term symptoms, such as hormonal and non-hormonal creams for dryness. For the long-term consequences, medications, Vitamin D, and calcium supplements are often used to reduce bone thinning; diet, exercise, and when needed, medications, are useful in reducing the risk of cardiovascular events.
Hormone replacement therapy (HRT) adds lost estrogen and sometimes progesterone, with the goal of minimizing both the short-and long-term consequences of menopause. Certain risks exist with HRT – regardless of whether someone has MS – and these need to be discussed with your doctor.
Estrogen does not appear to have any negative effects on MS. Does estrogen help MS? Some preliminary data show encouraging evidence that estrogen may decrease MS relapses. This theory was developed from the fact that women who are pregnant (and have high estrogen levels) rarely experience MS relapses, but relapses commonly occur shortly after giving birth (when estrogen levels decrease). Definitive studies are underway to observe the effects of estrogen on a woman’s MS. Estrogen does not appear to have any negative effects on disease-modifying therapies (DMTs), so this factor should not be a concern.
The final decision is between the physician and the patient. Additional risks and benefits should be discussed. If a patient and her gynecologist decide on using HRT, as a neurologist, I would have no problem with that decision.
NOTE: The following questions were not included in the print edition of this issue due to space constraints.
Q: I was diagnosed with MS in 2004. The only symptoms I had were two separate bouts of numbness and a bout with optic neuritis, which led to my diagnosis of MS. I have been on Copaxone now for eight years and have not had a relapse since starting the medication. My MRIs have been stable and I am doing very well.
My first neurologist told me that it may be possible to discontinue my medication if I did not have a relapse for 10 years. I have since moved and my second neurologist said it’s actually 15 years, but he did not recommend stopping my medication because I could eventually relapse and it might be more aggressive.
I’ve done a little research on my own and came across a research paper written in August 2004 by Moses Rodriguez, MD, at Mayo Clinic in Rochester, MN. His research shows “the longer the duration of MS and the lower the disability, the more likely a patient is to remain stable and not progress to a greater level of disability.” Obviously, this is very encouraging to me and I am interested in your opinion on this.
A: First, let me say that I am very pleased that your MS is doing so well on Copaxone. Dr. Rodriguez’s statement was a general comment related to a large population of MS patients. As you know, each MS patient is different and your neurologist is in the best position to judge your risks of getting worse. He is likely to be concerned about what may happen to you, if you stop your medication (Copaxone) that has been associated with your “good years.” Unfortunately, as your doctor points out, you are still at risk of getting worse.
What to do? You might get a “third opinion” from an MS center in your area. Recognizing that every patient is different, generally my advice to my patients is: until we know more about who will remain stable and who will get worse, I recommend “covering your bets” and staying on treatment. The long-term risks of Copaxone are negligible. If Copaxone is contributing to your MS stability, this benefit may wane after you stop. Therefore, why take a chance, if you are tolerating the treatment well?
Q: My husband was diagnosed in December 2011. The doctor he is seeing is great, the only thing is, he writes on all of my husband’s papers that he has relapsing-remitting MS (RRMS), but he is on home healthcare, and his nurses and family doctor say that he has progressive MS. I was wondering if you could give us any insight as to whether or not he does.
It took me three years after he started having major problems to get him to go see a doctor and it took another year for a diagnosis. He never went into what we know as a remission stage. He has continually gotten worse. He has little mobility and many symptoms, including problems with speech, swallowing, memory, vision, and numbness. He takes Copaxone, plus his other medicines for his extreme pain and muscle spasms. I just don’t know what to do or say to the doctor. Things are very difficult for us and our three boys. I am unable to work because he must have someone with him at all times. Please give us any insight that might be useful for the doctor and our family.
A: Your question points out one of the difficulties in differentiating a diagnosis of RRMS from SPMS (secondary-progressive MS) and PPMS (primary-progressive MS). More confusing is the fact that SPMS is divided into a relapsing form as well as a non-relapsing form. This is further complicated by the fact that individuals with PPMS typically have good days and bad days, but do not have actual verified relapses.
However, a few people with PPMS may start having relapses, in which case the disease course name would then be changed to PRMS (progressive-relapsing MS). I can’t blame anyone for being confused at this point! Fortunately, your neurologist is well aware of these issues. He is likely to believe that you are continuing to have inflammation, which may be helped by Copaxone.
Aside from the academic issue, why the fuss? It is very important because insurance only covers treatments for “relapsing” forms of MS. Therefore, your doctor’s diagnosis of RRMS assures that your Copaxone is covered by insurance (assuming that your husband receives his medication through insurance). If still concerned, you can discuss my answer with your doctors.
Q: Besides the obvious, how bad is it to smoke while being treated with Betaseron every other day? Can you set me straight (and/or direct me to articles) on what happens when I smoke? I have been four days without one.
A: I feel for you – everyone knows how difficult it is to stop smoking – despite all of the serious warnings. It is important for your MS and for your general health to stop smoking. Data show that smoking increases the risk of MS and increases the risk of one’s MS becoming worse. The internet has several articles on this topic, many of which may be found just by doing a search for "smoking and MS."
This article on WebMD provides findings from a Harvard study, linking cigarette smoking to a more rapid progression of the disease (Boyles, S., "Smoking Tied to Multiple Sclerosis Progression," WebMD Health News, April 25, 2005).
In the article, the authors state that "…the risk of progressing from relapsing-remitting MS to secondary-progressive disease during roughly five years of follow-up was 3.6 times higher for current and past smokers than for patients who never smoked." The article does note that more studies need to be conducted in this area to confirm how much benefit is derived once someone stops smoking.
A far more detailed article may be found at the United States National Library of Medicine, National Institutes of Health’s website (Handel, A.E., et al, “Smoking and Multiple Sclerosis: An Updated Meta-Analysis,” PLoS One, 2011; 6(1): e16149). This article provides the results of an updated meta-analysis of the effects of smoking on MS.
Excerpts include, “Our meta-analysis includes data on a large number of MS cases and controls. It is firmly established that smoking cigarettes is associated with MS susceptibility… Our results are suggestive of an association between smoking and risk of secondary progressive MS, but the high level of heterogeneity between studies, both in design and statistical outcomes, limits the ability to draw firm conclusions. However, the demonstration of a dose-response effect [i.e., dependent upon the number of cigarettes smoked per day] on disease progression and disease severity is suggestive of a causal link.” At the conclusion of this online article is a listing of more than 50 articles, many of which focus on the potential risks of smoking and MS.
In addition to the negative effects that smoking may have on MS progression, I’m sure you are also well aware of the many other serious health risks associated with smoking. For all of these reasons, and to enjoy as healthy of a life as possible, I fully support your efforts to “kick the habit!”
Q: I was diagnosed with RRMS in 2009, but had symptoms for 10 years before a diagnosis was made. In 2011, after taking Avonex (interferon beta-1a) for one year, I was diagnosed with systemic scleroderma. I was told that a small trial was done with interferon beta-1b to determine if it could make scleroderma worse, but the results were inconclusive. Do you know if any of the interferons can cause or worsen scleroderma?
A: For the benefit of our other readers, scleroderma is a rheumatic disease with many forms that primarily affects women, ages 30 to 50. About 300,000 people in the United States are affected. It is a connective-tissue disease involving skin, joints, muscles, and collagen. Many individuals with MS have some overlapping symptoms with scleroderma, such as Raynaud’s phenomenon. This may cause symptoms such as cold and blue-appearing fingers, skin tightness, carpal-tunnel syndrome, and fatigue.
MS may occur with other autoimmune diseases, and a few patients have scleroderma along with their MS. We do not know the underlying mechanism of these diseases, but there may be some overlap. Additional information may be found in the following article: “Multiple sclerosis and systemic sclerosis: efficacy of interferon beta on skin lesions;” P B Carrieri, M Petracca, S Montella, M Delfino, C Sepe, A Gattoni; Ann Rheum Dis 2008;67(8):1192-1193. This article suggests that interferon may actually help the skin problems in scleroderma. I found nothing in the medical literature that demonstrates interferons might make scleroderma worse.
You may want to consider getting your scleroderma doctor and your neurologist to work closely together. They might refer you to a specialty center for consultation. This is not a simple issue and it requires specific advice based on your individual situation.
To Submit Questions to Ask the Doctor…
If you have a question that you would like to ask, please submit your question to:
MSAA
Questions for Ask the Doctor
c/o Dr. Jack Burks
375 Kings Highway North
Cherry Hill, NJ 08034
Readers may also send in questions via email to askdr@mymsaa.org. Please be sure to write “Ask the Doctor” in the subject line.
Jack Burks, MD is the chief medical officer for MSAA. He is an international MS neurologist, writer, lecturer, and researcher, who assists with
the development of new MS therapies.