MRI activity and neutralising antibody as predictors of response to interferon 1~ treatment in multiple sclerosis

Durelli, L.; Barbero, P.; Bergui, M.; Versino, E.; Bassano, M. A.; Verdun, E.; Rivoiro, C.; Ferrero, C.; Picco, E.; Ripellino, P.; Giuliani, G.; Montanan, E.; Clenico, M.
June 2008
Journal of Neurology, Neurosurgery & Psychiatry;Jun2008, Vol. 79 Issue 6, p646
Academic Journal
Objective: To prospectively validate MRI activity and neutralising anti-interferon antibody (NAb) during the first 6 months of interferon β treatment as response indicators in multiple sclerosis (MS). Methods: Patients with relapsing-remitting MS were followed during the first 2 years of treatment. Neurological assessments were performed every 3 months or when a relapse was suspected. MRI scans performed at baseline and at 3, 4, 5 and 6 months after the start of treatment were assessed centrally for disease activity: new T2 or gadolinium enhancing Ti lesions. NAb were assessed using the MxA protein assay; positivity was defined as two consecutive titres ⩾20 NU/ml. We evaluated the predictivity of an active scan, NAb positivity, or both, during the first 6 months of treatment, on the occurrence of clinical disease activity in the following 18 months. Results: i 47 patients were assessed at 16 centres. Predictivity parameters (with confidence intervals) were as follows: active scan, sensitivity (SN( 52% (34-69%), specificity (SP( 80% (65-91%(, negative predictive value (NPV( 73% (58-77%), positive predictive value (PPV( 62% (42-79%), p = 0.002; NAb positivity, SN 71% (45-88%), SP 66% (55-76%), NPV 92% (82-97%), PPV 29% (16- 45%L p = 0.01; active scan and NAb positivity, SN 71% (38-91%), SP 86% (73-94%), NPV 94% (86-98%), PPV 50% (29-70%), p = 0.0003. Conclusions: MRI activity and NAb occurrence during the first 6 months of interferon )3 treatment were reliable predictors of long term clinical response, particularly when combined. Patients with negative predictors showed a less than 10% risk of developing clinical activity. Patients with positive predictors showed a 50% risk of further clinical activity. These patients need to be followed carefully with further MRI and NAb tests.


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