Biological activity of interferon betas in patients with multiple sclerosis is affected by treatment regimen and neutralising antibodies.
BACKGROUND
MxA gene expression is one of the most appropriate markers of biological activity of exogenous interferon (IFN) beta.


METHODS
We quantified MxA mRNA for five consecutive days in 62 patients treated with IFN beta (16, Avonex; 10, Betaferon; 24, Rebif 22; 12, Rebif 44), by quantitative-competitive polymerase chain reaction. Every three months, IFN beta induced neutralising antibodies (NAbs) were evaluated in sera using a cytopathic effect assay.


RESULTS
Two categories of patients were identified: one group (49/62) had a sharp post-injection increase in MxA expression (defined as "IFN beta biological responder"), whereas the other group (13/62) had no MxA induction after IFN beta administrations (defined as "IFN beta biological non-responder"). In 11/13 biological non-responders, the persistent presence of NAbs correlated with abolished biological activity, independently of treatment regimen. The two remaining IFN beta biological non-responders were NAb-. Among the 49 IFN beta biological responders, biological activity was comparable between the four preparations on day 2 and 3 (+12 and +36 hours post-injection), but it was greater in Betaferon and both Rebif preparations on day 1, 4, and 5. In biological responders treated three times a week, only 82% (59/72) of injections were considered effective, compared with 100% (13/13) of Avonex injections.


CONCLUSIONS
Our results suggest that an optimal IFN beta regimen is not yet available: Avonex, given once a week, shows lower cumulative biological activity. On the other hand, both Betaferon and Rebif, given three times a week, show 18% biologically ineffective injections and higher risk of developing NAbs, which abolish biological activity.
Centro di Riferimento Regionale per la Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy. sclerosi.multipla@sanluigi.piemonte.it
A
A
Bertolotto
A
A
Sala
S
S
Malucchi
F
F
Marnetto
M
M
Caldano
A
A
Di Sapio
M
M
Capobianco
F
F
Gilli
D000917:Antibody Formation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies
D007155:Immunologic Factors; D012333:RNA, Messenger; D016899:Interferon-beta