Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy.
OBJECTIVE
Natalizumab is a humanized recombinant monoclonal antibody against very late activation antigen-4 approved for the treatment of patients with multiple sclerosis (MS). A phase II study failed to demonstrate a difference between natalizumab treatment groups and the placebo group with regard to gadolinium enhancing lesions on MRI 3 months after discontinuation of therapy. The objective of this study was to assess clinical MS disease activity, surrogate disease markers on MRI, immunologic parameters in peripheral blood and CSF, as well as safety in patients with MS after discontinuation of natalizumab therapy.


METHODS
This study is a longitudinal and serial cross-sectional assessment, in which 23 patients who were treated with natalizumab in the context of two phase III clinical trials were originally enrolled. A subgroup of patients was followed over 14 months. The annual relapse rate, neurologic disease progression assessed by the Expanded Disability Status Scale, disease surrogate markers on MRI, cellular and humoral immune markers in peripheral blood and CSF, and adverse events of the drug were monitored.


RESULTS
With regard to clinical disease activity, neuroimaging, and immune responses, the majority of patients in our cohort were stable. Decreased lymphocyte cell numbers and altered cell ratios returned to normal 14 months after cessation of natalizumab. No infectious complications were observed.


CONCLUSIONS
This is the first long-term follow-up of patients who discontinued natalizumab. We did not observe a clinical, radiographic, or immunologic rebound phenomenon after discontinuation of natalizumab therapy.
Stüve
O
O
Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX 75216, USA. olaf.stuve@utsouthwestern.edu
Cravens
P D
PD
Frohman
E M
EM
Phillips
J T
JT
Remington
G M
GM
von Geldern
G
G
Cepok
S
S
Singh
M P
MP
Tervaert
J W Cohen
JW
De Baets
M
M
MacManus
D
D
Miller
D H
DH
Radü
E W
EW
Cameron
E M
EM
Monson
N L
NL
Zhang
S
S
Kim
R
R
Hemmer
B
B
Racke
M K
MK
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000069442:Natalizumab; D017063:Outcome Assessment, Health Care / Q000379:methods; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D007166:Immunosuppressive Agents; D000069442:Natalizumab