Neutralizing and binding anti‐interferon‐β (IFN‐β) antibodies. A comparison between IFN‐β‐1a and IFN‐β‐1b treatment in multiple sclerosis

Abstract

Interferon-beta (IFN-beta) is currently the most commonly used treatment of relapsing-remitting multiple sclerosis (MS). At the time of this study, two preparations of IFN-beta were available, IFN-beta-1a (Avonextrade mark) and IFN-beta-1b (Betaferon(R)), which both can elicit an immune response with the development of anti-IFN-beta antibodies. Direct comparisons between these two preparations regarding antibody frequencies have, however, been difficult to perform, because two different analysis methods measuring partly different biological effects of IFN-beta have been employed. In the present study, binding and neutralizing anti-IFN-beta-1a and -1b antibodies were detected in parallel by an independent, well-acknowledged, interferon research laboratory using an immunoassay and a cytopathic virus inhibition assay. Five per cent of patients treated with IFN-beta-1a intramuscularly (n = 20) had neutralizing antibodies (NABs) compared with 44% of patients treated with IFN-beta-1b subcutaneously (n = 48). A high degree of cross-reactivity between neutralizing anti-IFN-beta-1a and -1b antibodies was observed. No effect of NABs on clinical outcome could be detected in this limited material. Binding anti-IFN-beta antibodies were observed in 20% of IFN-beta-1a treated patients compared with 81% of patients treated with IFN-beta-1b. Only one of 17 patients examined (6%) had detectable titres of binding anti-IFN-beta-1b antibodies in the cerebrospinal fluid (CSF). These data are the first using identical methodology to show that IFN-beta-1a gives rise to fewer NABs than IFN-beta-1b at recommended treatment schedules.

The Impact of Methylprednisolone Pulses during Relapses of Multiple Sclerosis on the Kinetics of Anti-Interferon-Beta Antibodies

“…This is not surprising since Nabs(+) patients are more prone to relapse than Nabs(-) and we included, by design, only patients being treated for a relapse. In our study, the high rates of Babs positivity as well as the frequent coexistence of Nabs and Babs positivity are in accordance with the literature [16] . The simultaneous presence of high levels of Nabs and Babs is correlated with higher disease activity and progression [7] .…”

“…In treated MS patients, Nabs develop up to 45% and Babs up to 88% [1,[16][17][18][19] . Three out of 4 of our patients were Nabs(+) and 20% of them in high titers.…”

Immunogenicity of interferon-? in multiple sclerosis patients: Influence of preparation, dosage, dose frequency, and route of administration

“…8 -10 Reduced bioavailability of IFN␤ has also been demonstrated in MS patients with neutralizing antibodies, 11,12 and antibody-positive patients have presented with relapse rates and MRI results similar to those of patients receiving placebo. [13][14][15][16] The reported frequencies of neutralizing anti-IFN␤ antibodies in MS have varied from 7 to 42%, although binding antibodies have been found in up to 78% of IFN␤-treated patients. 14,16,17 These numbers not only depend on the IFN␤ preparations, dosage, dose frequency, and route of administration but also on the antibody detection methods, emphasizing the need for standardized IFN antibody measurements.…”

“…[13][14][15][16] The reported frequencies of neutralizing anti-IFN␤ antibodies in MS have varied from 7 to 42%, although binding antibodies have been found in up to 78% of IFN␤-treated patients. 14,16,17 These numbers not only depend on the IFN␤ preparations, dosage, dose frequency, and route of administration but also on the antibody detection methods, emphasizing the need for standardized IFN antibody measurements. Unfortunately, attempts to achieve this have failed, and together with difficulties in assessing the impact of these antibodies in individual MS patients, this has led to controversies with regard to the clinical importance of IFN␤-induced antibodies.…”

Adverse side-effects of biological agents: Hypersensitivity reactions

“…Takođe, pojava visokog titra anti-IFN-β antitela tokom terapije pacijenata sa MS, odnosno anti-IFN-α antitela tokom terapije pacijenata obolelih od leukemije i hroničnog hepatitisa, bila je u korelaciji sa gubitkom kliničke efikasnosti ovih bioloških lekova (32)(33)(34)(35). Štaviše, neutrališuća anti-IFN-1b antitela, koja nastaju tokom terapije pacijenata sa MS, ispoljavaju visok stepen ukrštene reaktivnosti i sa IFN-1a, što onemogućava zamenu jednog leka drugim i dovodi do pogoršanja bolesti (33).…”