Aggressive MS Needs Early Aggressive Treatment
Multiple sclerosis is a disease which affects people in many different ways. For some, it can be relatively mild, while for others it can be very aggressive and cause high levels of disability in a short period of time. The more aggressive presentation of MS has been called “malignant MS” or “highly active MS” or simply “aggressive MS.” This type of MS would be different from advanced MS, in that disability accumulates very quickly, up to Expanded Disability Status Scale (EDSS) score 6.0, within the first few years after diagnosis. Patients with aggressive onset MS, or AOMS, may have smaller windows of opportunity for receiving the most effective treatment to slow down the disease.
Studying aggressive onset MS (AOMS)
To date, there are no established criteria or biomarkers by which neurologists can easily identify cases of aggressive MS. To learn more about this type of MS, researchers in New York reviewed the published literature to carefully select a set of criteria with early clinical features and MRI findings that doctors can use to identify these cases. They published their findings in August 2016 in the Journal of Neuropsychiatric Disease and Treatment. The criteria included: 1) two or more relapses in the year after disease onset and two or more gadolinium-enhancing lesions on brain MRI scans; or 2) one relapse if it results in sustained disability (at least EDSS 3.0) along with two or more gadolinium-enhancing lesions.
Why is early treatment so important?
Researchers have recognized a small therapeutic window of opportunity, particularly in the first year of symptoms during which disease control has the greatest impact on long-term outcomes. Most of our currently available disease-modifying therapies are anti-inflammatory and more effective when used during the early inflammatory phase of the disease. Controlling the disease during this phase is important to protect the brain and delay the onset and decrease the severity of the neurodegenerative phase of the disease when brain atrophy and nerve death occurs.
The goals of MS disease-modifying therapy have long been to slow down the disease, reduce the number and severity of relapses, reduce lesion load, and delay disability. A more current proposed goal of therapy is called “no evidence of disease activity.” No evidence of disease activity, or NEDA, is achieved in a person with MS if the following criteria are met: 1) no change in baseline neurological exam, 2) no relapses, and 3) no new or enlarging T2 lesions or gadolinium-enhancing lesions on the MRI scan. Basically, someone who meets the criteria for NEDA is in a stable disease state that is not progressing.
How should AOMS be treated?
When the researchers in New York applied their chosen criteria to a database of 783 MS patients in a retrospective study, they found that 58 (7.4 percent) had AOMS. Of the 58 patients, 43 were included in the final analysis. The majority of the patients were female (70 percent), Caucasian (65 percent), and had experienced two relapses during the year prior to treatment (84 percent). Median age was 33 years (range 22-59 years) and mean duration of follow-up was 54 months.
Early aggressive therapy was more effective in achieving NEDA in patients with AOMS. Thirty-five of the 43 patients (81 percent) were initially prescribed traditional first-line therapies (beta interferon or glatiramer acetate), while eight were prescribed more aggressive therapy (natalizumab or alemtuzumab) at disease onset. Only two of the 35 patients (5.7 percent) prescribed self-injectable therapy maintained NEDA status during the study follow-up period compared to 7 of 8 (87.5 percent) who started on more aggressive therapy.
Among the 35 patients initially started on first-line therapy, 22 were switched to more aggressive therapies (natalizumab, rituximab, cyclophosphamide, alemtuzumab) due to continued disease activity. Fifteen were switched because of clinical disease activity, such as relapses, and seven because of radiologic progression alone, such as new or worsening lesions. The average time that elapsed before the patient was switched from first-line therapy to a more aggressive therapy was 9.5 months (although the range was wide: two to 43 months). Researchers note that not all patients were switched at the first sign of breakthrough disease activity.
Achieving NEDA with aggressive treatment
Of the 43 patients with AOMS in the study, 30 received aggressive treatment, either at disease onset or after they were switched due to disease activity. Of those 30, 28 showed NEDA with an average duration of follow-up of 32.4 months (range 12 to 85 months). The annual relapse rate (ARR) for patients on first-line treatment was 0.45 (average relapses per year/per patient) compared to 0.025 ARR for those on aggressive treatment.
In other words, the aggressive treatment was much more effective in preventing relapses.
Patients who started directly on aggressive treatment were 3.5 times more likely to have improved disability scores compared to patients who started with a first-line therapy. Factors that reduced the odds of having improved disability scores included Caucasian ethnicity (69 percent reduction) and increase in age (10 percent reduction). Gender had no effect on disability improvement.
The results of early aggressive immunosuppressive therapy in patients with AOMS in this study demonstrate the importance of identifying these patients quickly so that more effective treatment can be initiated before they accumulate excessive amounts of irreversible disability.
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