Vol 53, No 5 (2019)
Research paper
Published online: 2019-10-17
Submitted: 2019-06-05
Accepted: 2019-08-01
Get Citation

Anti-interferon-beta antibodies in Polish multiple sclerosis patients: prevalence and clinical significance in a long-term prospective study

Anna Pietrzak, Alicja Kalinowska-Łyszczarz, Krystyna Osztynowicz, Alima Khamidulla, Wojciech Kozubski, Sławomir Michalak
DOI: 10.5603/PJNNS.a2019.0047
·
Pubmed: 31621888
·
Neurol Neurochir Pol 2019;53(5):348-357.

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Vol 53, No 5 (2019)
Research paper
Published online: 2019-10-17
Submitted: 2019-06-05
Accepted: 2019-08-01

Abstract

Aim of the study. To determine the prevalence of anti-interferon-β binding (BAb) and neutralising antibodies (NAb), and to investigate whether NAb measured by luciferase-based cell assay can predict treatment response in multiple sclerosis (MS) patients treated with interferon-β-1b (IFNβ-1b).

Clinical rationale for the study. A subgroup of IFNβ-treated MS patients develop NAb directed against the drug. The clinical significance remains controversial, which could be explained to some extent by technical difficulties in NAb detection and quantification. A simple, specific and reproducible test for NAb might help elucidate these uncertainties.

Materials and methods. Sera from 101 consecutive MS patients initiating treatment with IFNβ-1b were collected at baseline and during the first two years, and assessed for BAbNAb with a novel luciferase-based cell assay. Median clinical follow-up lasted 5.1 years.

Results. BAb were present in 97% and NAb in 88% of the study cohort. Unexpectedly, 92% of patients tested positive for Bab and 12.5% for NAb at baseline, before drug exposure. Patients with baseline NAb positivity were more likely to remain free of disease activity in the first three years of treatment. When baseline-positive cases were grouped together with those who remained NAb-negative, and the resulting group was compared to those who became positive after drug exposure, NAb positivity was associated with a higher risk of disease activity during the entire follow-up. Direct comparison of BAb/Nab-positive and BAb/Nab-negative patients only revealed an association of BAb positivity with more active disease after four years of treatment, while NAb failed to predict the outcome.

Conclusions and clinical implications. Antibodies developed after treatment initiation are associated with a worse outcome. Naturally- occurring antibodies appear to predict more benign disease. Their prevalence and specificity require further investigation.

Abstract

Aim of the study. To determine the prevalence of anti-interferon-β binding (BAb) and neutralising antibodies (NAb), and to investigate whether NAb measured by luciferase-based cell assay can predict treatment response in multiple sclerosis (MS) patients treated with interferon-β-1b (IFNβ-1b).

Clinical rationale for the study. A subgroup of IFNβ-treated MS patients develop NAb directed against the drug. The clinical significance remains controversial, which could be explained to some extent by technical difficulties in NAb detection and quantification. A simple, specific and reproducible test for NAb might help elucidate these uncertainties.

Materials and methods. Sera from 101 consecutive MS patients initiating treatment with IFNβ-1b were collected at baseline and during the first two years, and assessed for BAbNAb with a novel luciferase-based cell assay. Median clinical follow-up lasted 5.1 years.

Results. BAb were present in 97% and NAb in 88% of the study cohort. Unexpectedly, 92% of patients tested positive for Bab and 12.5% for NAb at baseline, before drug exposure. Patients with baseline NAb positivity were more likely to remain free of disease activity in the first three years of treatment. When baseline-positive cases were grouped together with those who remained NAb-negative, and the resulting group was compared to those who became positive after drug exposure, NAb positivity was associated with a higher risk of disease activity during the entire follow-up. Direct comparison of BAb/Nab-positive and BAb/Nab-negative patients only revealed an association of BAb positivity with more active disease after four years of treatment, while NAb failed to predict the outcome.

Conclusions and clinical implications. Antibodies developed after treatment initiation are associated with a worse outcome. Naturally- occurring antibodies appear to predict more benign disease. Their prevalence and specificity require further investigation.

Get Citation

Keywords

multiple sclerosis, interferon-beta, neutralising antibodies, treatment outcome

About this article
Title

Anti-interferon-beta antibodies in Polish multiple sclerosis patients: prevalence and clinical significance in a long-term prospective study

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 53, No 5 (2019)

Pages

348-357

Published online

2019-10-17

DOI

10.5603/PJNNS.a2019.0047

Pubmed

31621888

Bibliographic record

Neurol Neurochir Pol 2019;53(5):348-357.

Keywords

multiple sclerosis
interferon-beta
neutralising antibodies
treatment outcome

Authors

Anna Pietrzak
Alicja Kalinowska-Łyszczarz
Krystyna Osztynowicz
Alima Khamidulla
Wojciech Kozubski
Sławomir Michalak

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