Assessing the Effectiveness of Immunomodulatory Treatment in MS

BOSTON—MRI activity and neutralizing antibody status within the first six months of interferon beta treatment are statistically significant predictors of treatment response in patients with multiple sclerosis (MS), according to Luca Durelli, MD, and colleagues. A combination of the two indicators had an even higher predictive value for clinical disease activity during an 18-month follow-up, the researchers found.

“The high specificity (86%) of the combined MRI and neutralizing antibody tests confirms that the vast majority of patients without MRI activity and neutralizing antibodies during the first months of interferon beta treatment have a high probability of a good clinical response to the drug,” stated Dr. Durelli at the 59th Annual Meeting of the American Academy of Neurology. “The good sensitivity (71%) of the combined tests indicates that most patients with both MRI activity and neutralizing antibodies during the first months of treatment have a high probability of a poor clinical response over subsequent follow-up.” Dr. Durelli is Director of the Division of Neurology at the University of Turin in Italy.

MEASURING THE EFFECTS OF TREATMENT

The researchers evaluated patients with relapsing-remitting MS who were treated with 250 µg interferon beta subcutaneously every other day for six months, after which they were then followed up for an additional 18 months. Each patient’s physician had the discretion to change the treatment during the follow-up period. Neurologic assessments were performed every three months or in cases of suspected relapse; MRI scans were conducted at baseline and at months 3 through 6. The primary outcome measure was suboptimal treatment response, which the investigators defined as clinical disease activity consisting of relapse or confirmed disability progression of at least 1 point on the Expanded Disability Status Scale after the first six months of treatment.

A total of 147 relapsing-remitting MS patients began interferon beta treatment; by the end of the two-year follow-up 132 patients had been treated with interferon beta for the duration of the study, 120 of whom had been previously receiving interferon beta. Neutralizing antibody status was evaluated in 88 of those 120 patients (73%). A suboptimal clinical response was observed in 63 of 147 patients (43%).

RELIABLE INDICATORS

Analysis revealed that activity on MRI during the first six months of interferon beta treatment was a good predictor of clinical disease activity during the subsequent follow-up, yielding an 80% specificity and a 52% sensitivity, according to Dr. Durelli. An active MRI scan at month 6 was also a good predictor, producing a specificity of 84% and a sensitivity of 35%, he said.

A positive neutralizing antibody status during the first six months of interferon beta treatment was observed in 34 of 88 (39%) patients. “It was a good predictor of subsequent relapse or disease progression during the following 18 months of treatment, with a lower (66%) specificity but a higher (71%) sensitivity,” noted Dr. Durelli. “The combination of MRI activity and neutralizing antibody positivity during the first six months of interferon beta treatment was the best predictor of subsequent clinical activity, with both high (86%) specificity and high (71%) sensitivity.”

Dr. Durelli added that having both MRI activity at month 6 of interferon beta treatment and a neutralizing antibody–positive status retained a high specificity (91%), with a lower sensitivity (50%) for predicting the occurrence of a suboptimal clinical treatment response.

“Patients [with MS] are at high risk of persistent clinical activity despite long-term interferon beta treatment and may, therefore, benefit from early adjustment of their treatment regimen,” advised Dr. Durelli. “Receiver operating characteristic curve analysis confirmed that the combination of the two tests—an MRI scan and neutralizing antibody—was the best predictor of further clinical activity.”      

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