One of my patients (I'll call him "David") was a 35-year-old executive of a publishing company. While typing on his laptop at work one day, he suddenly lost vision in his right eye. His co-workers drove him to the emergency room, where an ophthalmologist did an eye exam, which revealed inflammation of the optic nerve, the nerve that transmits visual information from the retina to the brain.
Upon further questioning, David admitted to experiencing numbness and weakness in his legs in the past, but he was so busy he didn't bother to seek medical care. Given those symptoms, the doctor ordered a magnetic resonance imaging (MRI) scan, which showed lesions consistent with multiple sclerosis (MS). An autoimmune inflammatory disease of the central nervous system, MS is characterized by episodic flare-ups of symptoms such as weakness and numbness of the upper and lower limbs, poor balance, vision loss, and bladder problems. The course and severity of the disease are unpredictable, and treatment varies from case to case.
By the time he came to me, David feared he'd go blind. He was also worried that he might lose his job or jeopardize his marriage. With all that weighing on him, he wanted to start treatment immediately. But when we discussed the various medications, he felt overwhelmed.
David's feelings are not unusual. Given the array of options, it can be challenging for physicians and patients to select the best one. Here are some considerations to discuss with your neurologist.
While there is no cure for MS, there are at least 10 different disease-modifying treatments (DMTs) that can prevent flare-ups, and many more are in the pipeline: interferon beta-1a (Avonex, Rebif, Plegridy), interferon beta-1b (Betaseron), glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), fingolimod (Gilenya), teriflunomide (Aubagio), natalizumab (Tysabri), and alemtuzumab (Lemtrada). Each treatment has side effects, which you should discuss with your doctor.
To help my patients choose the appropriate therapy, I review three important factors with them: the formulation (whether the medication is available as a pill, an injectable, or by intravenous infusion), the side effects, and severity of the disease.
For patients who hate needles and want convenience and don't mind taking a daily medication, I suggest oral pills such as dimethyl fumarate, fingolimod, or teriflunomide. I also review the side effects. For example, side effects of dimethyl fumarate include flushing and itching, which can be treated with aspirin and Benadryl. Other side effects are abdominal pain, diarrhea, and some bloating. In addition, patients who take dimethyl fumarate must have their white blood cell count and liver enzymes monitored every three months the first year, and then every six months.
A side effect of teriflunomide is hair thinning, although most people recover their hair after a year or so. I advise women of reproductive age that teriflunomide can cause birth defects, and that it can affect sperm as well—for as long as two years after stopping the medication. If my patients opt for teriflunomide, I recommend at least two forms of contraception for men and women. The medication can have toxic effects on the liver and also decrease white blood cell counts, which help fight infections, so I also monitor white blood cell counts and liver function in patients taking this medication.
If my patients are considering fingolimod, I let them know they have to be hospitalized for at least six to eight hours after the first dose to monitor heart rate. I avoid prescribing fingolimod for patients with certain types of heart disease, as rare cases of sudden cardiac deaths have been noted. In general, I prescribe fingolimod for patients who have failed interferon therapy or who have more severe MS. I also monitor their white blood cell counts and liver functions.
For those who worry that they'll forget to take a daily pill, I might recommend an injectable. Injectables have been in use for more than 20 years so there are more data on their long-term side effects than there are for pills or infusions. Depending on the formulation, the shot may be administered into the skin (subcutaneous) or into the muscle (intramuscular). The frequency of the injection can vary with different formulations: glatiramer acetate is injected three times a week (daily if you use the 20mg/ml formulation), while interferon beta-1a (Avonex) is injected once a week and the subcutaneous peginterferon beta-1a (Plegridy) is dosed once every two weeks.
Injectables can cause flu-like symptoms for a day or two after they are administered. They may also cause redness, burning pain, a rash, or swelling at the injection site, which can be mitigated by rotating sites for the shots. Patients must also have their liver and blood counts monitored. Depression can also occur. Rarely, glatiramer acetate can cause an immediate reaction after injection, including anxiety, chest tightness, shortness of breath, and flushing. This reaction lasts five to 10 minutes and has no known long-term effects.
For my patients for whom oral or injectable medications don't work or whose MS is too severe (they have significant spinal cord damage and many brain lesions), I administer monthly infusions of intravenous natalizumab at a certified infusion center. If that doesn't work, I may recommend alemtuzumab, an infusion given twice a year that can be prescribed and administered by certified neurologists only. It is only recommended for patients who have failed at least two other drugs.
Natalizumab is fairly well tolerated, but I still monitor blood counts and liver functions. In addition, I inform my patients that progressive multifocal leukoencephalopathy (PML), a rare, fatal progressive brain infection for which there is no treatment, has been reported with natalizumab. But there are well-defined protocols to screen and monitor patients for these infections, and they are followed in close collaboration with the drug manufacturer.
I always discuss the risks and benefits of the drug before starting treatment. Alemtuzumab has a boxed warning for serious, sometimes fatal autoimmune conditions and life-threatening infusion reactions and an increased risk for malignancies, including thyroid cancer, melanoma and lymphomas.
So what did David choose? After a long discussion, we decided to start with the oral drug dimethyl fumarate as David was not fond of needles. He has been taking it for six months now without any significant side effects or MS flare-ups.