Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis.
BACKGROUND
It is unknown whether immunosuppression of patients who have developed interferon-beta (IFN-beta) neutralizing antibodies (NAbs) hastens disappearance of NAbs in the blood.


OBJECTIVE
We wanted to test whether immunosuppression with cyclic methylprednisolone (MP) in combination with azathioprine (AZA) for 6 months accelerates recovery of IFN-beta bioactivity in patients with multiple sclerosis (MS) with abolished in-vivo myxovirus resistance protein A (MxA) mRNA response to IFN-beta.


METHODS
We included 13 patients with MS with NAbs and a low IFN-beta bioavailability detected by the MxA-mRNA response in a descriptive, non-randomized trial. Another 14 NAb-positive patients with a low MxA-mRNA response served as controls. The primary outcome was the fraction of patients who regained an MxA-mRNA response to IFN-beta. NAbs were measured by means of a clinically validated cytopathic effect assay and a new reporter gene assay. The in-vivo MxA-mRNA response was measured by real-time polymerase chain reaction.


RESULTS
A total of 11 patients in the treatment group completed the trial. In all, two of these 11 patients regained an in-vivo MxA-mRNA response as compared to one of 14 patients in the control group.


CONCLUSIONS
Treatment with AZA and cyclic MP for 6 months has little or no effect on IFN-beta bioactivity in NAb-positive patients with MS.
Ravnborg
M
M
The Danish Multiple Sclerosis Research Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. mads.ravnborg@ouh.regionsyddanmark.dk
Bendtzen
K
K
Christensen
O
O
Jensen
P E H
PE
Hesse
D
D
Tovey
M G
MG
Sørensen
P S
PS
D000906:Antibodies / Q000097:blood; D001379:Azathioprine / Q000008:administration & dosage*; D004351:Drug Resistance / Q000276:immunology; D004359:Drug Therapy, Combination; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use; D008775:Methylprednisolone / Q000008:administration & dosage*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger / Q000378:metabolism; D017211:Treatment Failure
D000906:Antibodies; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D016899:Interferon-beta; D019204:GTP-Binding Proteins; D001379:Azathioprine; D008775:Methylprednisolone