The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (38 page)

Under the new diagnostic criteria, a woman who experiences a single MS attack can be started right away on injectable or oral medications that have been shown to slow the progression of the disease—in many cases preventing permanent disability. Early treatment also benefits patients with CIS, who have a very high risk of developing MS.

Interferon beta-1b (Betaseron),
The first disease-modifying drug for MS, was approved by the FDA back in 1993, and there are now a dozen more approved for treating relapsing-remitting MS, secondary progressive MS, and progressive-relapsing disease.

Betaseron works like natural human interferon to inhibit immune system activity and reduces MS relapses by about 30 percent in active MS and by 50 percent in patients treated at the onset of their first symptoms. It is injected under the skin every other day. Betaseron slows the progression of physical disability and reduces exacerbations in relapsing-remitting MS and in CIS.
¹⁷

Interferon beta-1a (Avonex)
also works like natural human interferon to dampen immune system activity. It is also given after a single MS attack and reduces the frequency and severity of exacerbations in people with relapsing-remitting MS. The drug is given by self-administered injection (using either a prefilled syringe or an auto-injector pen) once a week into the large muscles of the thigh (or the hip or upper arm muscle). Avonex reduces relapses by about 18 percent, slows MS progression, and studies show it may help cognitive impairment in relapsing MS.

Avonex can cause liver damage, so liver enzymes must be monitored carefully.
¹⁸

Avonex and Betaseron both can cause menstrual irregularities in about 15 percent of women.

Extavia (interferon beta-1b)
is identical to Betaseron but delivered by a different company (made in the same plant). It’s administered by
subcutaneous injection every other day to treat relapsing MS and individuals with CIS. The side effects and safety profile of Extavia are also identical to Betaseron.
¹⁹

Interferon beta-1a (Rebif)
reduces the frequency of MS exacerbations, reduces disease activity seen on MRI, and slows progression of disability. A study comparing Rebif to Avonex showed it produced a 32 percent reduction in relapses compared to Avonex. Another trial showed Rebif could delay MS development after a first MS-like attack.
²⁰

Rebif is prescribed in prefilled syringes and given by self-injection three days a week at the same time of day, with each injection 48 hours apart. There can be reactions at the injection site (soreness, redness, pain, bruising), so you’re advised to pick a different spot each time to lessen the chance of an infection or other problem.

Plegridy (PEGylated interferon beta-1a)
is a new interferon drug for relapsing forms of MS.
PEGylation
is a chemical alteration of the interferon beta-1a molecule that allows the drug to be given under the skin with a prefilled autoinjector every two weeks, rather than the more frequent injections required by other interferons. In clinical trials, Plegridy reduced relapses by about 36 percent and new brain lesions by 67 compared to a placebo after a year.
²¹

Betaseron and other interferon drugs cause flu-like symptoms (fatigue, fever, chills, muscle aches), which lessen after a while. (Note: Influenza infections cause the body to produce interferons, which causes those “flu-like” symptoms.) In addition, interferon drugs may cause elevated liver enzymes and low red and white blood cell counts that can increase the risk of infection, changes in thyroid function, and allergic reactions. Periodic blood testing is needed to monitor liver or blood changes. There can also be reactions at the site of the subcutaneous injections, which can be serious and require medical attention in about 5 percent of cases.

These medications cannot be used during pregnancy.

Glatiramer acetate (Copaxone)
is a synthetic protein that looks like myelin to the immune system. It seems to block attacks on myelin by T cells, apparently acting as a decoy for myelin, but it may also change the immune system to suppress inflammation. Copaxone is approved for relapsing-remitting MS. A 12-year clinical trial among patients with relapsing-remitting MS found that most of those who stayed on Copaxone had an improvement in their
neurological status or remained unchanged. Another study found that Copaxone stopped new brain lesions caused by MS flares and reduced the amount of damaged brain tissue over time, with the protective effects appearing three to four months after treatment began.
²²

Copaxone is available in prefilled syringes and given by injection once a day. It can cause reactions at the injection site. In rare cases, there may be anxiety, chest tightness, shortness of breath, and flushing right after an injection, but there do not seem to be any long-term consequences.
²³
A generic version of
glatiramer acetate
is also available.

“I like to think that these drugs give the brain a ‘breather,’ allowing more of the normal remyelination to occur,” says Dr. Reder, who also serves as director of clinical neurology trials at the University of Chicago.

Natalizumab (Tysabri)
is one of a new class of therapeutics called
alpha 4 integrin inhibitors
. It’s a monoclonal antibody designed to prevent the migration of inflammatory cells from the blood to other sites in the body. (In MS, it would block adhesion molecules that attach T cells to cells lining the blood vessels in the brain pulling them across the blood-brain barrier.)

According to the Multiple Sclerosis Association of America (MSAA), recent data also suggest that it may also enhance remyelination and stabilize damage to the myelin sheath.
⁷
Studies show it slows relapse rates by as much as 66 percent, reduces lesions seen on MRI by 80 percent, and produces sustained improvement in disability in patients with RRMS. (It’s also approved for Crohn’s disease.)

Like other drugs in this class, Tysabri carries a “black box” warning that it can cause
progressive multifocal leukoencephalopathy
(
PML
, see
page 254
), a potentially fatal viral infection, so it’s only available only through a “restricted distribution” program for physicians (the TOUCH
^®
Prescribing Program, see
Appendix A
).
²⁴

There are now three oral disease-modifying MS drugs:
fingolimod (Gilenya)
,
teriflunomide (Aubagio)
, and
dimethyl fumarate (Tecfidera)
, all in capsule form.

Gilenya (fingolimod)
is the first of a new class of drugs called
sphingosine 1-phosphate (S1P) receptor modulators
. It keeps potentially damaging T cells from exiting lymph nodes, so there are fewer of them in blood and tissues. By doing so, it may reduce damage to the central nervous system (CNS) and allow or enhance nerve repair within the brain and spinal cord; Gilenya may also have neuroprotective effects.

Gilenya capsules are taken once a day, with or without food. The adverse side effects include an initial reduction in heart rate; infrequent changes in the conduction of electricity in the heart (
atrioventricular [AV] block
); macular edema (swelling behind the eye, which can affect vision); and infections, including reactivation of herpes infections.

FDA labeling recommends that all patients have an
electrocardiogram (
ECG
)
before taking their first dose of the drug and a second ECG six hours after the first dose. New patients also are advised to take the drug in their doctor’s office the first time with hourly blood pressure and heart rate checks during a six-hour monitoring period.
²⁵

Aubagio (teriflunomide)
is a pyrimidine synthesis inhibitor, related to the rheumatoid arthritis drug leflunomide. It inhibits a key enzyme needed by activated lymphocytes to make DNA. This helps reduce proliferation of T and B immune cells that are active in MS and also blocks T cells from producing immune messenger chemicals. Clinical trials data indicate it reduces relapse rates by more than 30 percent in RRMS
²⁶
and reduces the size of MS brain lesions.
²⁷
The higher dose (14 mg/day) tested in the trials lessens disability. Aubagio capsules are taken in one (7 mg or 14 mg) dose, once a day with or without food.

Side effects include elevations in liver enzymes and severe liver problems (including liver failure). Women taking the drug need monthly blood tests for the first six months to monitor their liver enzymes and additional testing if symptoms of liver problems arise (such as nausea, vomiting, abdominal pain, unusual fatigue, loss of appetite, and yellowing of the skin or whites of the eyes). Aubagio can cause numbness and/or pain in the hands or feet (peripheral neuropathy) and transient elevations in blood potassium that can lead to kidney failure, so women must be monitored for both, as well as for high blood pressure. Aubagio can also trigger severe skin reactions.
²⁸

Aubagio cannot be taken during pregnancy, by women (or men) who want to conceive a child, or even by women of childbearing age who aren’t using an effective contraceptive method, since animal data indicate that it may cause significant birth defects.

In addition, Aubagio remains in the blood for an average of eight months after it is stopped and may even linger in the blood for up to two years after the last dose is taken. If you become pregnant while taking the drug, it must be discontinued immediately and an accelerated elimination procedure will
be needed to decrease Aubagio to a safe level in the blood (less than 0.02 mg/L), according to the FDA. The medication can be eliminated from the body in 11 days with cholestyramine or active charcoal.
²⁸

Tecfidera
is approved for people with relapsing forms of MS. The starting dose is a 120 mg capsule twice a day. After a week, the dose is increased to 240 mg twice a day, a maintenance dose. While it can be taken with or without food, taking the capsules with a meal may reduce flushing (warmth, redness, itching, and/or burning sensation), a common side effect of the drug. Other side effects can include gastrointestinal upsets, such as nausea, vomiting, diarrhea, abdominal pain, and indigestion.
²⁹

Because it can lead to decreased white blood cell (
lymphocyte
) counts, it’s recommended that before starting the drug a complete blood count be done to detect preexisting lymphopenia.

Animal studies show adverse effects on a fetus during pregnancy and lactation, but there are few well-controlled studies in pregnant women. So the FDA recommends that Tecfidera be used during pregnancy only if the potential benefits outweigh potential risks to the fetus.
²⁹
The drug label also carries a warning about
PML
.
³⁰

Alemtuzumab (Lemtrada),
another injectable medication is a new MS drug. It’s a humanized monoclonal antibody (note the suffix
mab
) directed at CD52, a protein that sits on the surface of immune cells, of unknown function. The drug reduces suppressor T cells and increased autoreactive B cells. Because of these effects, it can trigger other autoimmune diseases.

Lemtrada is given by intravenous infusion for five consecutive days initially and for three consecutive days after 12 months. The Lemtrada label includes a boxed warning about a potential 30 percent risk of thyroid disease, immune thrombocytopenia, serious infusion reactions within 24 hours, and malignancies, including thyroid cancer and melanoma.
³¹
It’s only available from certified prescribers, and all patients must be enrolled in a “Risk Evaluation and Mitigation Strategy (REMS)” program so potential side effects can be periodically monitored and any adverse effects reported back to the FDA.
³²

More common side effects include rash, headache, dizziness, fever, nasal congestion, nausea, diarrhea, urinary tract infections, fatigue, insomnia, upper respiratory tract and fungal infections, herpes infections, hives, itching, and joint and back pain.
³²

Clinical trials reported in 2012, comparing Lemtrada with Rebif in patients not previously given any MS disease-modifying therapy (including Rebif), found a majority of those treated with Lemtrada were free of new brain lesions, had significant reductions in disease activity seen on MRI, and remained relapse-free for two years.
³²
The drug also slowed the loss of brain volume.
³³

Mitoxantrone (Novantrone)
is an anticancer drug that suppresses T cell, B cell, and macrophage activity and seems to lessen attacks on myelin. It is usually given intravenously every three months for up to two years (or up to a specific cumulative lifetime dose). A 2002 study from France, where it has been used for more than two decades, found that an initial “induction” course of more intense mitoxantrone therapy for six months significantly reduced relapse rates, and kept 43 percent of patients relapse free for a five-year period. More recent studies also suggest that combining Novantrone with Betaseron may reduce disease progression in people with aggressive relapsing-remitting disease, or with secondary progressive disease when MS isn’t well-controlled by Betaseron.
³⁴

Novantrone can affect the heart, raising the risk of congestive heart failure. So you must have normal heart function to take the drug, and tests of cardiac function are necessary before and during treatment. Novantrone also imparts an increased risk of developing leukemia and can cause permanent sterility. It is being used much less to treat MS currently with the advent of newer and safer medications.

All of these new MS drugs can be very costly, especially the oral medications. The wholesale price of Gilenya (with no discount) is a hefty $60,000 a year, Tecfidera costs almost $55,000 a year, and the annual price tag for Aubagio is $45,000. Out-of-pocket costs will depend on your insurance; some states have drug assistance programs, and drug manufacturers also have programs to provide MS medications at low or no cost (see
Appendix A
).