Kinetics and incidence of anti-natalizumab antibodies in multiple sclerosis patients on treatment for 18 months

Abstract

Natalizumab is a monoclonal antibody shown to be highly effective in the treatment of relapsing-remitting multiple sclerosis (RRMS). Patients treated with natalizumab can develop antibodies directed against this agent that may affect the efficacy and safety of the drug. In this observational study, the kinetics of the appearance and the incidence of anti-natalizumab antibodies were followed prospectively for 18 months in a cohort of 64 consecutive patients treated with natalizumab for relapsing MS. Blood samples were drawn immediately before starting natalizumab therapy and each month afterwards. The presence of antibodies against natalizumab was assessed by enzyme-linked immunosorbent assay (ELISA) in all patients. Anti-natalizumab antibodies were detected in nine (14.1%) natalizumab-treated patients, three (4.68%) of whom were transiently positive while six (9.37%) were persistently positive (these patients discontinued natalizumab). All positive titres were observed during the first 4 months of treatment. One patient with a hypersensitivity reaction also had persistent antibodies. We conclude that antibodies against natalizumab develop early, within the first 6 months of therapy with natalizumab. Although no antibodies were detected after 4 months of therapy in this particular study, this does not rule out their development later on in exceptional cases.

Characterization of anti-natalizumab antibodies in multiple sclerosis patients

“…After exclusion of patients with uncertain reactivity to natalizumab a total of 57 patients were considered positive for anti-natalizumab antibodies, giving an overall seroprevalence of 4.1% (57 out of 1379 patients). As previously observed, we found that antibody responses to natalizumab develop early after treatment onset [139,166]. In 96% of the positive patients, anti-natalizumab antibodies were detected in the first collected sample, after median treatment duration of three months (range 1-12 months).…”

“…Using the same enzyme-linked immunosorbent assay (ELISA) procedure as was used in the first clinical studies, later observational studies have found that anti-natalizumab antibodies develop in 4.5-14% of treated patients, of whom 1.6-9% have been persistently positive and 1-5% have been transiently positive [87,139,140]. Other studies have also found that anti-natalizumab antibodies develop early, with most patients becoming positive during the first six months of treatment [87,139].…”

CD49d expression as a promising biomarker to monitor natalizumab efficacy

“…The lack of relationship between antibody status and adverse drug reaction was confirmed in recent post-marketing observational studies [12,13]. Indeed, some patients developed transient or persistent Nabs in the first months of treatment without any infusion reactions and then remained clinically undetectable.…”

“…In addition, a post-marketing observational study in patients receiving natalizumab reported a similar incidence rate (37%) of persistent NAbs positive patients without any infusion or allergic reactions [12]. More recently, upon 64 MS patients evaluated over 18 months [13], a slightly higher frequency of persistently Nabs positive patients was found in the first months of treatment, with no relationship between antibody status and adverse drug reactions.…”

Best practice in the use of natalizumab in multiple sclerosis

“…Positive antibody status is associated with allergic or hypersensitivity reactions, especially during the second infusion. If resources permit, it would be recommendable to monitor antinatalizumab antibodies in all patients after the first 6 months of treatment, because they have been shown to appear early during the treatment [Oliver et al 2011;Fernández et al 2011b]. Monitoring should, however, be mandatory in patients with allergic or hypersensitivity reactions and those with clinical relapse or new MRI findings indicative of disease activity.…”