Efficacy of natalizumab in multiple sclerosis patients with high disease activity: a Danish nationwide study.
BACKGROUND
Previous studies of natalizumab (Tysabri) in relapsing multiple sclerosis (MS) patients have included patients with moderate disease activity. We studied a patient population with high disease activity.


METHODS
We analyzed data from 234 consecutive, natalizumab-treated patients, followed for at least 3 months. Three groups of patients were eligible for natalizumab therapy: patients with two or more documented relapses or sustained increase of 2 EDSS points on disease modifying therapy (DMT) in the previous year; patients switching from mitoxantrone; and patients with very active MS as de novo therapy.


RESULTS
During a median observation time of 11.3 months (range 3.0-21.5) the annualized relapse rate decreased to 0.68 from a pre-treatment rate of 2.53 (73% reduction). We assessed the annualized relapse rate in three subgroups: (i) 0.83 in 14 (6.0%) de novo treated patients; (ii) 0.71 in 175 (74.8%) patients with >or=2 relapses or sustained increase in EDSS of >or=2 points on a first-line DMT; and (iii) 0.56 in 45 (19.2%) patients switching from mitoxantrone. Nine anaphylactoid reactions, two severe, were reported. Out of 215 patients 7 (3%) were persistently positive for antibodies to natalizumab.


CONCLUSIONS
Tysabri appears to be effective in MS patients with high disease activity, but the relapse rate was higher than in the pivotal study after the first treatment year. This is likely to reflect differences in disease activity before the initiation of natalizumab treatment.
The Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen.
A B
AB
Oturai
N
N
Koch-Henriksen
T
T
Petersen
P E H
PE
Jensen
F
F
Sellebjerg
P S
PS
Sorensen
D000293:Adolescent; D000328:Adult; D000707:Anaphylaxis / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003718:Denmark; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D018696:Neuroprotective Agents; D008942:Mitoxantrone