Implications of neutralising antibodies on therapeutic efficacy.
All biopharmaceutical preparations are potentially immunogenic and need to be evaluated for the risk of development of neutralising antibodies (NAbs). In the case of interferon-beta preparations for the treatment of multiple sclerosis, persistently high-titres of NAbs are detectable in up to one-third of patients depending on the preparation used. In contrast, treatment with glatiramer acetate is not associated with the development of such antibodies, since its mechanism of action does not involve binding and activation of a specific receptor. The development of NAbs to interferon-beta abrogates biological activity in the short term, although the loss of clinical benefit usually only becomes manifest a year or more after antibodies are first detected. This loss of clinical benefit is apparent as a recrudescence of disease activity visible on magnetic resonance imaging, an increase in the frequency of relapses and a progression of neurological disability. Loss of biological activity can be detected very early after the appearance of NAbs using the MxA test, which can be used as a prognostic biological marker for probable future treatment failure. Current European guidelines recommend that all patients treated with an interferon-beta should be monitored systematically for the appearance of NAbs and that patients who develop persistent NAbs should discontinue their interferon-beta treatment. An option for the patients who have experienced less than two relapses in the previous year is to switch to treatment with glatiramer acetate. Such a strategy offers the best guarantee of providing good control of disease activity and optimal allocation of healthcare resources.
Bertolotto
Antonio
A
San Luigi Hospital, Orbassano, Turin, Italy. antonio.bertolotto@gmail.com
D000906:Antibodies / Q000097:blood / Q000276:immunology*; D004351:Drug Resistance / Q000276:immunology; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000627:therapeutic use; D016899:Interferon-beta / Q000276:immunology* / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D055502:Secondary Prevention; D016896:Treatment Outcome
D000906:Antibodies; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D016899:Interferon-beta