Ask the Doctor
Q: What
long-term approved or experimental treatments are available for individuals
with secondary-progressive and primary-progressive types of MS? Are any drugs
under investigation showing potential for these types of MS?
A: These questions need to be answered in two parts, according to the type
of MS.
Part one: Potential treatments for secondary-progressive MS (SPMS):
Relapsing-remitting MS (RRMS) often leads to SPMS after several years. Since
SPMS is more difficult to treat successfully, we usually recommend that people
start therapy as soon as possible after an MS diagnosis is established.
Regarding treatment options for SPMS, European researchers created excitement when they reported that Betaseron® was so successful in reducing disability in SPMS, their clinical trial was stopped early to allow placebo-treated patients to take Betaseron as soon as possible. While quick approval for its use in SPMS in Europe was forthcoming, a consequent SPMS study in North America with Betaseron reported success on relapse rate and MRI parameters – but not disability. These divergent results (related to disability) may be attributed to when the participants began treatment. The European participants had earlier, more active SPMS, which may have enhanced their opportunity for positive results.
Similar results were seen with Rebif®, where SPMS patients who were still experiencing relapses had better results than those without relapses who were treated later in the course of their disease. Avonex® studies have shown mixed results in SPMS. While standard measurements of disability (EDSS) were not helped, new standards (MSFCS) showed some positive effects. Copaxone® has not been studied in a large SPMS clinical trial.
More recently, mitoxantrone (Novantrone®), an anti-cancer therapy, was FDA approved for “worsening MS” after researchers demonstrated effectiveness in treating SPMS. This treatment can only be given for two to three years because of potential heart toxicity. Fortunately, many MS experts have been able to safely add Novantrone to Avonex, Betaseron, Copaxone, and Rebif (ABCR drugs) so a combined benefit may be recognized.
Other anti-cancer drugs (Campath®, Cytoxin® and cladribine) are also potential SPMS treatments. Once again, these drugs appear to be the most effective in early MS versus late SPMS. While superior in reducing inflammation and attacks, Campath, Cytoxin, and cladribine may not significantly slow the progression of disability in SPMS. As another option, some doctors add or substitute oral anti-cancer drugs such as methotrexate or azathioprine (Imuran®) in patients with SPMS who do not respond adequately to the ABCR drugs. Controlled studies involving such therapies have been inconclusive. Pulse steroids every month is another approach which has yet to be proven definitively in clinical trials. Individuals with SPMS often go through several therapy combinations.
In conclusion, the initial excitement of finding THE definitive treatment for SPMS with interferons has waned. Individuals who are still experiencing relapses in addition to progressive MS, however, have benefited from interferons. Novantrone has shown positive results but is limited to two to three years of therapy because of potential toxicity. Potent anti-cancer drugs appear to reduce inflammation but not progression in late SPMS. Although definitive clinical trials are lacking, other oral anti-cancer drugs have been reported to help some individuals with SPMS.
Part two: Potential treatments for primary-progressive MS (PPMS):
Finding a treatment for PPMS has been less encouraging than treatments for
SPMS. Primary-progressive MS differs from SPMS in that people with PPMS tend
to be older and have progression from disease onset without actual relapses.
PPMS mainly affects the spinal cord and is associated with less inflammation
than SPMS, leading some to suggest that PPMS is a completely different disease
than other forms of MS. Taking this into consideration, PPMS may not respond
as well to the anti-inflammatory ABCR drug therapies, and may explain why
Copaxone failed to show benefit for individuals with PPMS in a very recent
trial. On the other hand, and on a brighter note, researchers from Spain
just reported positive preliminary results with Betaseron in PPMS. More comprehensive
trials are needed before any definitive conclusions can be made.
Novantrone is approved for “worsening MS;” however, data with regards to PPMS is limited. Novantrone is currently undergoing more definitive clinical trials with PPMS and we await these results. As stated with SPMS, Novantrone is a relatively short-term treatment (two to three years). Some doctors treat PPMS patients with oral methotrexate or Imuran®, but no definitive clinical trials have been reported. Those taking these medications have mixed perceptions as to the benefits they are deriving.
In conclusion, trials are ongoing for the treatment of PPMS. While no definitive therapy has been proven effective for long-term treatment, some of the drugs mentioned have shown positive results. We look forward to the findings of present and future studies aimed at helping individuals affected by this form of MS.
Q: Do you believe that MS activity may slow or stop when a person reaches the age of 60?
A: Most MS experts agree that some people with MS seem to become stable later in life (“burned-out MS”). Unfortunately, a majority of these individuals already have significant disability from years of relapses and progression of their disease. The reason for a slowing in disease progression may be related to a decrease in the rate of myelin degeneration, possibly because much of the potential damage has already taken place. If MS activity in older adults may be “turned off,” this could lead to new research and treatments that would ultimately help all individuals with MS “turn off” disease activity.
Q: Since researchers are looking at the anti-inflammatory and possibly immunomodulating properties of statins in the treatment of MS, should I add a cholesterol-lowering drug to my daily regimen?
A: We are very fortunate to have a great deal of new and exciting research being conducted at this time for the treatment of MS. One area of new research looks at the possibility that cholesterol-lowering drugs called statins may help individuals with MS.
While this is an exciting theory, much of this work has only been done on animals. We do not have enough research data to prove the effectiveness of statins, and they are not free of risks. In fact, one statin was withdrawn from the market because of liver toxicity. Fortunately, the current statins being considered seem to be fairly safe, although adverse effects have been reported for all statins.
To further study statins, a total of 30 people with MS from three MS centers (Yale, Colorado, and South Carolina) were recently given simvastatin (Zocor®) for six months at the highest FDA recommended dose (80 mg daily). No serious toxicity was noted for this short period of time. While the participants had no demonstrated clinical benefit, MRI scans showed improvement with less inflammation reported. However, no placebo-treated patients were studied for comparison. The fact that individuals with MS often improve spontaneously or when they are started on a placebo is well known. The scientific explanation is called “regression to the mean.” Therefore, without a placebo group, we cannot determine if the positive MRI response was directly related to Zocor.
While optimism is high for statins, more comprehensive MS patient trials are needed before a place for statins in the treatment of MS can be established. Until positive results are available from clinical trials with MS patients, I would not recommend taking a statin-type of medication for any reason other than lowering one’s cholesterol. If someone does need it for this latter reason, then this individual may take it (according to his or her physician’s directions) without any worry of potential problems with MS as a result of the medication.