Physicians
and researchers approach the treatment of MS in three ways:
Physicians
and researchers approach the treatment of MS in three ways:
The first approach is to treat an exacerbation, usually with a high-dose, short-term, powerful drug such as a corticosteroid. The goals are to (1) reduce the severity and duration of the relapse by decreasing inflammation, and (2) potentially minimize any permanent damage resulting from the attack.
The second approach is an attempt to slow or stop disease activity and progression. Trials in this area are normally conducted with drugs that affect the immune system and may be tolerated for prolonged periods of time. Surgical techniques and even complex alterations to the blood are also under investigation.
The third approach uses drugs and therapies to manage MS symptoms. These may be found in another MSAA booklet devoted entirely to this subject.
The ultimate goal is to cure the disorder and repair any damage to the myelin and axons. Trials are presently underway to study the potential of transplanted remyelinating cells to grow new myelin within MS lesions.
Without a definitive cause or cure, finding the best treatment for MS is challenging. Drug therapies available today for MS have limited efficacy, but they do show positive results. For the first time, individuals with MS may now choose from five different approved drug therapies.
In the past, these drugs were only available to those with RRMS, but
now people with progressive disease forms have
choices too. More options are anticipated in the near future, but trials
for MS treatments require several years to test dosages, side effects,
and overall success.
Drug treatments are usually administered either orally (by mouth) or by injection. Injections may be performed in one of four ways:
A new device for subcutaneous injection is now available for those who give themselves self-injections. The auto-injector is an enclosed needle and syringe that offers a number of benefits over the traditional style. Because it is fully enclosed, the needle is hidden and this helps to alleviate any discomfort one might have about needles. Additionally, the depth of the injection is controlled, the user may reach more difficult injection areas, and the drug is delivered with just a push of a button. Many drug companies now offer an auto-injector device for their medications that are injected subcutaneously.
Most people with MS experience exacerbations, which often last from one to three months. Acute neurologic and physical symptoms must be present for at least 24 hours – without any signs of infection or fever – before the treating physician can consider that it is a true relapse.
Pseudoexacerbations are temporary symptom flare-ups that are brought
on by external influences – such as infection, exhaustion, heat,
or depression. Checking for a fever is important, since even a minor
infection can cause old symptoms to reappear, or new ones to develop.
Urinary tract infection (UTI) is the most common illness to cause a
pseudoexacerbation. People with
"heat-sensitive" MS should also avoid situations – such as hot tubs or saunas – which
can raise the body's temperature. These too can cause a temporary flare-up.
During a relapse, gadolinium-enhanced MRI scans may show new active lesions. Sometimes older lesions become reactivated as well. Although most relapses remit without any drug intervention, most doctors will recommend treatment when the symptoms are severe enough to affect the person's ability to function normally.
Inflammation with damage to myelin appears to cause the exacerbation; conversely, reduction of the inflammation is thought to assist with recovery. By treating the inflammation, the exacerbation will hopefully be less severe, subside sooner, and possibly cause little or no permanent damage. Anti- inflammatory medications are used for this purpose.
Steroid (or corticosteroid) treatments are considered to be the most effective anti-inflammatory therapy at this time. Corticosteroids are natural or synthetic hormones associated with the adrenal glands. These include glucocorticoids, which are mentioned later in this section. These drugs decrease the production of cytokines and antibodies which in turn reduces inflammation. Through chemical changes, steroids may also improve the conduction of nerve impulses along demyelinated areas.
In addition to its anti-inflammatory properties, corticosteroid treatment also acts as an immunomodulator (this is an agent that alters one or more functions of the immune system). Corticosteroids have been shown to reduce the duration and degree of an exacerbation while bringing about recovery sooner. These agents are also thought to reduce defects in the BBB, reduce edema (swelling), and possibly promote remyelination, which in turn improves the conduction of nerve impulses. Despite all of these benefits, their long-term effects on the course of the disease are not yet proven.
Corticosteroids tend to have more dramatic results for people with newer cases of MS (less than five years). These drugs are usually more effective in alleviating visual difficulties, facial weakness, and spasticity, while having less influence on tremor, coordination problems, and loss of balance.
High-dose corticosteroids are typically given for periods that vary from three to 14 days. Following this high-dose course, a patient may need to be taken off the drug slowly to avoid withdrawal problems. Common side effects with short-term use (less than six weeks) include water retention, acne, increased appetite and weight gain, as well as anxiety and difficulty sleeping.
Less common side effects are associated with long-term use. These include excess hair growth, fragile bones and skin, severe acne, slower healing of wounds, joint problems, psychosis, convulsions, euphoria, cataracts, high blood pressure, peptic ulceration, and increased susceptibility to infections. "Cushingoid state" is an unusual condition which also may occur with long-term use. Symptoms of this condition include many of those mentioned, along with a reddening and swelling of the face and neck, raised blood sugar levels, and osteoporosis.
Synthetic adrenal glucocorticoids (betamethasone, cortisone, dexamethasone, methylprednisolone, prednisolone, and prednisone) are the most commonly used steroid treatments for acute exacerbations. In addition, adrenocorticotropic hormone (ACTH) is a protein hormone extracted from animal pituitary glands. It is given by intramuscular injection and has been used to treat MS for more than 30 years.
ACTH causes the release of glucocorticoid hormones by stimulating
the adrenal gland. These hormones can now be made synthetically and appear
to be stronger, have fewer side effects, and last longer than ACTH. Steroids
work by restricting or arresting an enzyme that is required for inflammation
after an injury. In addition to anti-inflammatory actions, these steroids
display immunosuppressive properties (traits which suppress or weaken
the immune system), and appear to affect the T-lymphocytes.
Often
nerve flow is temporarily increased in affected areas. A rise in energy
may be experienced by those taking these hormones, as well as a sense
of well-being or possibly even an exaggerated feeling of happiness. Some
individuals, however, may feel depressed while taking steroids.
High doses of methylprednisolone (Depo-Medrol®, Solu-Medrol®) given intravenously (IV) is now the treatment of choice among treating physicians. Compared to ACTH, methylprednisolone is more convenient and more consistent, while offering faster results with fewer side effects.
Preferred dose, duration, and even method of administration vary widely. Most prescribe 500 to 2000 mg given orally or via IV over two to 24 hours, for three to 10 days. IV steroids can be administered as an outpatient procedure or at the person's home if a hospital stay is not necessary for other reasons. This therapy may be followed with a short, tapering course of oral corticosteroids. The benefits of adding this oral taper are mixed, and some doctors do not prescribe it for their patients.
A rapid reduction in active lesions, as seen through gadolinium-enhancement
on an MRI, is associated with this type of high-dose corticosteroid therapy.
Some studies suggest that taking high-dose steroids orally is as effective
as IV administration. Steroids given orally are less expensive and more
convenient than those given intravenously, but comparative results are
not definitive.
Low-dose steroid treatment is controversial and believed to possibly
shorten the time between relapses. While studies suggest that low-dose
glucocorticoids may reduce symptoms, this therapy may also increase someone's
risk for subsequent relapses. Many doctors support the idea of keeping
a close eye on a patient who is only experiencing mild symptoms, while
immediately initiating a steroid treatment for a severe attack.
Although intravenous dexamethasone is not prescribed as often as methylprednisolone,
it does have many of the same
characteristics. Dexamethasone is typically less expensive than methylprednisolone,
and when given in a brief course, may offer similar benefits. While no
studies have been performed to compare the two drugs, dexamethasone may
provide a less-expensive option.
The Optic Neuritis Treatment Trial has given doctors some new insights
into prescribing steroids to those with MS. Individuals with optic neuritis
were selected because it is often a presenting symptom for people who
have yet to be diagnosed with MS, and related outcome measures (such
as visual field, visual sharpness, and the ability to see color and contrast)
are very sensitive.
A group of 457 patients experiencing optic neuritis were randomly selected
to receive one of three treatments:
Those in the first group had a significantly faster rate of recovery than those in the second two groups – whose rates of recovery were the same. Researchers were surprised to see that during the six-month to two-year follow-up analysis, those who were in the second group (and treated with the low-dose oral prednisone) had an increased risk of experiencing a reoccurrence of optic neuritis in either eye.
Those in the first group (who were treated with high-dose IV methylprenisolone), were 50 percent less likely to experience a new attack leading to the diagnosis of MS within the two-year follow-up period. This result was especially true for those with the most lesions at the beginning of the trial (and who had the greatest chance of having a relapse).
After three years, the treatment groups did not differ in terms of relapse rate. The result suggests that the group treated with high-dose IV methylprenisolone may have experienced a delay in the onset of MS, but ultimately, the treatment was unable to stop the development of the disease.
While most treating physicians have prescribed steroids for their patients who are experiencing a significant relapse, physicians do not all agree on the ideal treatment regimen. Research has yet to confirm the best type of steroid, the optimal route of administration (such as IM, IV, or oral), the most effective dosage, and the value of an oral steroid taper.
In the past, researchers thought that intrathecal injections of methylprednisolone directly into the cerebrospinal fluid would be beneficial by allowing the drug to reach MS lesions directly and at higher concentrations. After 20 years of use, results are questionable. For this reason, along with the risks involved, intrathecal injection of this drug is rarely used today.
Long-term use of steroids is not generally recommended. They can cause many side effects when given over a long period of time and appear to have no affect on the progression of MS.
Although MRI scans illustrate a rapid response to steroids – with a reduction in gadolinium-enhancing lesions – the results are brief. Within as little as a week's time following treatment, new enhancing lesions can begin to reappear. In addition, with each corticosteroid treatment an individual receives, the drug's effectiveness is reduced.
Plasmapheresis
(plasma exchange or "PE") is used for individuals who are
experiencing a severe exacerbation, and are not responding to high-dose
IV steroid treatment. With this procedure, blood is taken from the
patient and cleansed of toxic elements. The cleansed blood is then
returned to the patient. The long-term effectiveness of PE has not
been proven.
Side effects are mild – typically a transient drop in blood pressure for some, which may cause fainting during the process.
A reduction in red blood cells and platelets may also occur.
PE is not effective for those with progressive forms of MS, but it may be helpful in treating very severe relapses. PE can also be very expensive.
Nonsteroidal
anti-inflammatory drugs (NSAIDs) include fenoprofen (Nalfon®), ibuprofen (Advil®, Motrin®), indomethacin (Indocin®), ketoprofen (Orudis®), naproxen (Naprosyn®), phenylbutazone (Butazolidin®), sulindac (Clinoril®), and tolmetin (Tolectin®).
Most of these synthetic drugs slow or stop the formation of prostaglandins.
Produced by macrophages, certain prostaglandins promote inflammation
and immune functions, while others suppress these same functions. These
drugs are not used to treat exacerbations, but they may be helpful
in treating the flu-like side effects of interferons. Indomethacin,
however, may worsen MS in some individuals.
Aspirin and sodium salicylate are two moderately anti-inflammatory agents that affect the prostaglandin pathways. Peptic ulceration and gastrointestinal bleeding are two side effects common to these agents which appear to have no effect on MS. Aspirin may be beneficial for pain relief, but acetaminophen has fewer side effects and certain advantages over aspirin. Neither are used to treat MS.
Sulfasalazine is a drug similar to aspirin yet also contains an antibacterial
component. Immunomodulating, anti-inflammatory, and analgesic, this drug
has been prescribed for more than 50 years — typically to treat inflammatory
diseases of the bowel. Following trials, results indicate that sulfasalazine
provides no therapeutic
benefit in the treatment of MS.
The drugs and other therapies used in an attempt to slow or stop the progression of MS are based upon research into possible causes and suspected cellular changes within a person with MS. For instance, evidence strongly suggests that MS is an autoimmune disease. With this in mind, agents affecting the immune system are often used. These include drugs which cause immunosuppression (the weakening of most or certain aspects of the immune system) and immune modulators (agents which alter the immune system).
Most treatments in these categories affect the lymphocytes – either by destroying, redirecting, or removing those causing damage. Several anticancer drugs and therapies have been investigated for MS disease progression.
Autoimmune diseases fall under the category of "allergy" since this type of malfunction is a reaction to a substance – only this time the reaction is to the individual's own myelin. To treat an allergy, desensitization therapies (those that promote a tolerance) may be used.
Oral
tolerization is based on the fact that the body naturally builds a tolerance
to things that are ingested, and an immune response to such substances
is rare. Actual cow (bovine) myelin taken orally was in clinical trials
for MS (Myloral®), but failed toshow an effect. Based on this theory, an oral form of glatiramer acetate (Copaxone®)
was tried but did not prove effective.
Viruses are also suspects in the development and worsening of MS. For this reason, antiviral drugs have been investigated for many years in the treatment of MS. These include the interferon (IFN) drugs (drugs which "interfere" with viruses) and agents which prevent and treat viruses such as influenza type A and herpes viral infections.
The advantage of such drugs is twofold. First, should a slow-acting
virus be involved in the acquisition of MS, an antiviral drug may have
an effect on the cause of the disease. Second, these drugs might theoretically
prevent the cause of some attacks.
For example, many relapses are preceded by an viral upper respiratory
infection.
Some physicians will prescribe a combination of drugs or therapies to be used at one time. One possible advantage to this type of approach may be a reduction of side effects, since patients may be receiving a smaller dose of each agent. Another advantage is the potential for treating more than one aspect of MS at one time — and as mentioned, MS could well be the result of a combination of factors.
On the downside, no data is available on combination therapies, and such treatment could have negative results. Trials are presently being conducted to assess the potential of various combination treatments.
In the early-1990s, individuals with MS had no proven long-term disease treatment options. Treatments at that time were limited to steroids for relapses, and cytotoxic drugs (strong immunosuppressive drugs often used for cancer) to minimize relapses and disease progression. While these agents are still used to treat MS, five drug treatments for MS have since become available within a nine-year span. These drugs are well-tolerated and approved by the FDA to reduce disease activity.
The first three long-term MS treatments to be approved were dubbed the "A-B-C" drugs because of their brand names: Avonex®, Betaseron®, and Copaxone®. These are interferon beta-1a, interferon beta-1b, and glatiramer acetate, respectively. All were approved for treating RRMS.
The fourth drug to be approved was mitoxantrone (Novantrone®), and this was the first drug indicated for both worsening RRMS and SPMS. News then arrived of a fifth FDA-approved drug for RRMS: interferon beta-1a (Rebif®). This is the same drug as Avonex®, but is given subcutaneously (under the skin) in more frequent and higher doses.
This is a promising time for individuals who have been diagnosed with MS. In less than a decade, treatment options have gone from zero to five – and more therapeutic agents are on their way. Approximately 80 drugs and therapies are being investigated worldwide for the treatment of MS, the most in the history of MS research. And these include everything from antiviral medications, to vaccines, to procedures and agents that repair myelin.
Each of the approved treatments is well tolerated and side effects are mild. Novantrone® is the only drug that has a set limit of doses, which is necessary to avoid cardiotoxicity. The other drugs appear safe as long as the person taking the drug is not experiencing any adverse effects and blood tests continue to be normal. While no damage to the reproductive systems has been observed, none of these drugs may be taken if a patient is pregnant or considering pregnancy during her treatment period.
More experts are now recommending treatment as early as possible with one
of these agents, possibly delaying time to the second relapse. Early treatment
is also thought to possibly limit axonal injury, which may be irreversible,
and later lead to progressive disease.
Two independent trials were recently conducted with Avonex® (known as
the "CHAPS" study) and with Rebif® (known as the "ETOMS" study)
to determine if early treatment could delay the second disease event leading
to a confirmed MS diagnosis. Individuals whose symptoms indicated they
were at high risk of developing CDMS (clinically definite multiple sclerosis),
took part in these two trials.
In the Avonex® study, treated and placebo groups received IV methylprednisolone followed by oral prednisone. The treatment group then received the regular weekly dose of Avonex®. At 18 months, investigators found that compared to the placebo group, the rate of conversion to CDMS was decreased by 44 percent, and the MRI showed reductions in the number of new lesions, the number of enhancing lesions, and the percentage of change in T2 lesion volume.
Similar results were observed with the Rebif® study, although the dose used was one-sixth of the normal dose. At two years, a 24-percent reduction in the rate of conversion was realized, along with reductions in T2 active lesions and T2 disease burden.
Clearly the use of interferon beta-1a (Avonex® and Rebif®) has the ability to delay the time to the next disease episode, when an individual with possible or probable MS would be diagnosed with CDMS. Investigators do not know if delaying time between the first and second MS events will affect the long-term outcome of MS, nor do these results support the idea that such treatment could prevent the development of CDMS.
Some medical professionals delay treatment because they may want to see if the disease is taking a benign early course. They may feel that evidence does not support the long-term efficacy of the treatment, or they may be concerned with the development of neutralizing antibodies, which might prevent this treatment option later on in the disease course.
Neutralizing antibodies (NAbs) may occur with the interferons. Those produced with the interferons (Avonex®, Betaseron®, and Rebif®) may potentially neutralize the drug's effectiveness. The antibodies associated with Copaxone® do not appear to neutralize the drug's performance. Fewer antibodies are developed with Avonex® and Rebif® than Betaseron®.
The actual impact of NAbs is not known. Most doctors would not switch treatments based on NAbs. In most cases, if an individual is doing well but has NAbs, the treating physician would not change this person's treatment. Conversely, if an individual is not responding optimally to treatment but hasn't developed NAbs, many doctors would consider changing the treatment.
Interferons: Avonex®, Betaseron®, and Rebif® work to decrease inflammatory or damaging cells and increase those that suppress inflammation. Avonex® and Rebif® are derived from mammalian cells (specifically Chinese Hamster ovaries), and their amino acid sequence is identical to that of naturally occurring interferon beta. Betaseron® comes from bacterial cells and its amino acid sequence is nearly identical to naturally occurring interferon-beta.
The study of interferons is an intriguing component of antiviral treatment research. Interferons are produced by cells in the body as a response to certain substances, including viruses. Interferons are appropriately named as they are secreted by cells exposed to viruses and "interfere with" viral Different lymphocytes produce different interferons.
For instance, natural killer lymphocytes (NK cells) create interferon-alpha; fibroblast cells create interferon-beta; and Th-2 lymphocytes create interferon-gamma when "turned on" by an antigen or virus. Interferons are able to protect nearby cells from viral infection as well as affect immune regulation.
Natural interferons are difficult to produce in large numbers and most interferons used in treatments today are produced by recombinant DNA techniques. This process allows researchers to synthetically produce interferons in cell cultures programmed with interferon genes. Recombinant interferons have greater "purity" than those produced by "natural" methods.
Trials with interferon-alpha had slightly positive results, and studies with this agent are ongoing. Interferon-gamma trials showed a rapid worsening of MS. It promotes HLA antigen expression on cell surfaces, a factor enabling sensitized T-lymphocytes and macrophages to target and destroy these cells. Interferon-gamma along with interferon-gamma producing drugs (such as tilorone and staphage lysate) should not be used in the treatment of MS.
Interferon betas have been shown to affect the immune system through several actions. Examples include:
Copaxone®:
Copaxone® is a synthetic chain of four amino acids that structurally
resembles the myelin basic protein (MBP) molecule. Formerly known as "copolymer
1 or COP 1," this drug is believed to block the immune system from
attacking myelin. Copaxone® also
switches the immune response from Th-1 cells (pro-inflammatory) to Th-2 cells
(anti-inflammatory) which could reduce myelin damage.
Copaxone® is the first approved treatment for MS management which does
not involve steroids or interferons. The antibodies produced by Copaxone® do
not appear to affect the drug's performance, and unlike interferon treatments,
Copaxone® does
not cause certain side effects such as flu symptoms, fatigue, or depression.
Novantrone®: Novantrone® is an antineoplastic agent, which means that it inhibits or prevents the development of any uncontrolled new or abnormal growth (such as a neoplasm or tumor). This drug has been identified as an immunosuppressant and specific immunomodulator. Its actions include suppressing B-cell as well as T-cell immunity.
Novantrone® is the first treatment approved in the US specifically for SPMS (along with RRMS). This drug is indicated for reducing neurologic disability and/or frequency of clinical relapses in those with SPMS, or worsening RRMS.
Avonex®, Betaseron®, and Copaxone® have each been extensively marketed to individuals with MS and medical professionals. All three cost approximately the same (about $10,000 per year) and all three appear to be the most effective for those with early RRMS.
Novantrone® costs less but requires periodic heart and blood tests. At the time of this writing, Rebif® had just entered the US marketplace. The cost is expected to be $14,000 annually, and with the approval of Rebif®, marketing efforts by all companies will likely be escalated.
Several large, double-blind, placebo-controlled, randomized clinical trials have been conducted to study each of these drugs separately for their effects on MS. Although differences exist in study design and specific findings, trials generally showed these common results:
To follow are the results of some of the individual trials conducted on the approved drugs for MS.
A two-year trial with 301 RRMS participants with mild to moderate neurologic disability ended early when the drop-out rate was less than expected. Those who completed the two years experienced one-third fewer exacerbations, as well as a reduction in gadolinium-enhancing lesions and new or enlarging lesions on MRI. No differences were observed with total lesion load. Also, a significant percentage of people in the treated group did not progress to new levels of disability as measured by the EDSS.
Avonex® significantly delays the time to the second MS episode and diagnosis of CDMS (clinically definite MS). Additionally, the full benefit of Avonex® may be delayed for a year or more after beginning treatment.
At double the regular dose, according to a preliminary report, Avonex® was shown to be beneficial for treating individuals with SPMS over a two-year period.
In a US multi-center trial, 372 RRMS participants with mild to moderate disability were given a high dose of Betaseron®, low dose, or placebo. The higher dose group experienced a reduction in relapse rate by about one-third. Time to first relapse was increased, as well as the number of those who did not have a relapse. Also, the treated groups had a significant reduction in disease activity as measured by MRI. Progression of disease was not statistically different with Betaseron®.
In this study, Betaseron® was found to specifically reduce the number of relapses by 31 percent, and reduce the number of severe attacks by 51 percent. As a result, these patients had 20 percent fewer days on steroid treatment, and the need to stay in a hospital was reduced by 48 percent. MRI studies showed that 93 percent of these patients experienced a significant reduction in the amount of total or new enhancing lesions.
A group of participants from this original study have continued to be monitored. After 12 years, these patients have remained stable (according to MRI studies), with few side effects and minimal NAbs.
A large study in Europe has shown that interferon beta -1b is effective in slowing the progression of disability in people with SPMS. The European study consisted of 718 patients with SPMS, ranging from moderate to severe stages of disability.
The study was conducted by the company that markets interferon beta-1b in Europe (known there as "Betaferon®"). Following two years of this three-year trial, the results were so impressive that the independent advisory board recommended all patients in the placebo group be switched to the active drug. Progression of disease, annual relapse rate, and MRI measures were used in determining the success of this treatment.
In the US, the marketers of Betaseron conducted a trial with more than 800 individuals with SPMS in North America. While this trial did not show a reduction in rate of progression, it did have significant reductions in clinical attack rate, MRI attack rate, and volume of lesions on T2 MRI.
Why the results of the two SPMS trials differed is not known, however, this latter study had individuals with significantly fewer relapses than those in Europe. This suggests that interferon beta-1b might be more effective for people who are still experiencing relapses and are in an earlier phase of SPMS.
A major trial of Rebif® was conducted with 560 individuals who were diagnosed with RRMS and exhibited mild to moderate disability. They were given a low dose, high dose, or placebo three times a week for two years.
The results showed a significant decrease in the number and severity of relapses, as well as a delay in time to the second relapse, and a delay in the time to confirmed progression as measured by EDSS. The percentage of those in the treated groups who remained relapse-free was increased. MRI disease activity was also significantly reduced along with total T2 lesion load.
Similar to Avonex®, Rebif® also delays the time to the second MS episode and diagnosis of CDMS (clinically definite MS), according to the results of the "ETOMS" study. In a large SPMS study, disease progression was not significantly affected, however, positive results were similar to the Betaseron® SPMS study in North America.
A two-year US trial with 251 individuals with RRMS who had mild to moderate disability resulted in 29 percent fewer relapses per year. This study may have also shown a favorable effect on EDSS progression, although this is not confirmed. MRI studies were not included in this trial.
A nine-month study was conducted to determine Copaxone®’s affect on disease activity as measured by MRI. Results included a reduction in enhancing lesions, clinical attack rate, and T2-weighted burden of disease. EDSS change
A subgroup of the 251 individuals from the original two-year trial chose to continue in a follow-up study. At the six-year mark, the 152 participants have experienced a stabilization of EDSS score and a substantial reduction in clinical attack rate. This study is one of the longest continuous follow-up of any MS treatment, but with 40 percent of the original participants dropping out, the robustness of the findings is reduced.
A
multisite study in France and London found a combination of Novantrone® and
methylprednisolone (steroid) was effective for people with MS who have
very active disease in improving both clinical and MRI indications
of disease activity over a period of six months. Those taking the two
drugs experienced a month-by-month decrease almost to zero in the number
of new enhancing lesions as well as the total number of enhancing lesions.
Additionally, twice as many participants in the Novantrone®- steroid group remained free of exacerbations compared to the steroid-alone group. The steroid-alone group also experienced more than four times as many relapses as the combination-drug group. Those taking the two drugs exhibited a mean average EDSS improvement of more than one point.
In a two-year European multi-center phase III study of 194 individuals with SPMS, participants received two doses of either IV Novantrone® or placebo, every three months. Results showed a significant reduction in relapse rate and progression of disability for those in the treatment group.