MRI activity and neutralising antibody as predictors of response to interferon β treatment in multiple sclerosis
- L Durelli1,
- P Barbero1,
- M Bergui2,
- E Versino1,3,
- M A Bassano4,
- E Verdun1,
- C Rivoiro1,
- C Ferrero1,
- E Picco1,
- P Ripellino1,
- G Giuliani5,
- E Montanari6,
- M Clerico1
- 1Dipartimento di Scienze Cliniche e Biologiche, Universita’ di Torino, Divisione di Neurologia, Ospedale Universitario S Luigi Gonzaga, Orbassano, Torino, Italy
- 2Dipartimento di Neuroscienze, Universita’ di Torino, Neuroradiologia, Ospedale Universitario S Giovanni Battista, Torino, Italy
- 3Dipartimento di Salute Pubblica, Universita’ di Torino, Torino, Italy
- 4Dimensione Ricerca, Contract Research Organization, Roma, Italy
- 5Unita’ di Neurologia, Dipartimento di Medicina, Ospedale S Lucia, Macerata, Italy
- 6Divisione di Neurologia, Ospedale Civile, Fidenza, Italy
- Professor L Durelli, Divisione di Neurologia, Ospedale San Luigi Gonzaga, Regione Gonzole, 10, I-10043 Orbassano, Torino, Italy; luca.durelli{at}unito.it
- Received 25 July 2007
- Revised 24 September 2007
- Accepted 17 October 2007
- Published Online First 6 November 2007
Abstract
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 T1 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: 147 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%), 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 β 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.
Footnotes
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Funding: The study was supported by Bayer Schering Pharma AG (formerly Schering AG), Berlin, Germany.
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Competing interests: LD has received honoraria for speaking and for consultancy from Industria Farmaceutica Serono, Italy, Bayer Schering Pharma AG, Germany, and Dompe’ Biotec, Italy. MC has received honoraria for speaking from Bayer Schering Pharma AG, Germany. In neither case did these honoraria exceed $10 000/year.
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Ethics approval: Ethics approval was obtained.
