MS Speaks

Best First-Line Treatment for Aggressive MS May Be Equally Aggressive Immunotherapies

 Ines Martins, PhD

Patients with aggressive onset multiple sclerosis, characterized by a rapidly progressing disease course and accumulation of disability, may benefit from early aggressive therapies instead of the escalation approach commonly given multiple sclerosis (MS) patients, according to researchers at Weill-Cornell Medical College.

Their article, titled “A study of patients with aggressive multiple sclerosis at disease onset,” was published in the journal Neuropsychiatric Disease and Treatment.

The clinical course of MS is highly variable, ranging from a relatively mild disease that takes years to progress,... to an extremely virulent and disabling disease known either as malignant MS, highly active MS, or aggressive onset MS (AOMS).

Since current disease-modifying drugs for MS are anti-inflammatory, it is important to identify the therapeutic window of opportunity that would best control the disease in its inflammatory phase, when treatment has the greatest chance of delaying onset and severity. But the current lack of uniform criteria or guidelines to define AOMS patients at disease onset hampers the development of rigorous studies addressing best treatment options for these patients.

Weill researchers selected a set of criteria that could be easily applied in clinical practice to diagnose AOMS within one year of diagnosis. They are: two or more relapses in the year after onset, and two or more gadolinium-enhancing lesions seen in brain magnetic resonance imaging (MRI); or one relapse that results in sustained baseline EDSS (Expanded Disability Status Scale) score of 3, plus two or more gadolinium-enhancing lesions.

The researchers used their criteria to identify AOMS among the 783 patients in the Weill-Cornell Medical College MS database, determining that 58 (7.4%) had aggressive disease. Among these patients, 43 were included in the study, with a mean followup of 54 months.

Results revealed that of the 35 patients (81%) who were treated with traditional first-line therapies, only two showed no evidence of disease activity. Twenty-two were refractory to treatment and switched to a more aggressive therapy, including Tysabri (natalizumab), Rituxan (rituximab), Lemtrada (alemtuzumab), and Cytoxan (cyclophosphamide).

The remaining eight patients (19%) were started on aggressive therapy at disease onset, and seven (87.5%) did not exhibit disease activity at their last follow-up.

These results suggest that AOMS patients may not benefit from a conventional escalation therapy approach, the researchers said, and should be treated with an early aggressive treatment or with an induction followed by maintenance therapy to better control their disease progression.