MRI activity and neutralising antibody as predictors of response to interferon beta treatment in multiple sclerosis.
OBJECTIVE
To prospectively validate MRI activity and neutralising anti-interferon antibody (NAb) during the first 6 months of interferon beta 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 >or=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 beta 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.
Durelli
L
L
Dipartimento di Scienze Cliniche e Biologiche, Universita' di Torino, Ospedale San Luigi Gonzaga, Regione Gonzole, 10, I-10043 Orbassano, Torino, Italy. luca.durelli@unito.it
Barbero
P
P
Bergui
M
M
Versino
E
E
Bassano
M A
MA
Verdun
E
E
Rivoiro
C
C
Ferrero
C
C
Picco
E
E
Ripellino
P
P
Giuliani
G
G
Montanari
E
E
Clerico
M
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000906:Antibodies / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D009460:Neurologic Examination / Q000187:drug effects*; D009500:Neutralization Tests; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000906:Antibodies; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta