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

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.

• Authors: Anna Pietrzak, Alicja Kalinowska-Łyszczarz, Krystyna Osztynowicz, Alima Khamidulla, Wojciech Kozubski, Sławomir Michalak
• Journal: Neurologia i neurochirurgia polska (Neurol Neurochir Pol) Vol. 53 Issue 5 Pg. 348-357 ( 2019) ISSN: 0028-3843 [Print] Poland
• PMID: 31621888 (Publication Type: Journal Article)

Chemical References

• Interferon-beta

Topics

• Humans
• Interferon-beta
• Multiple Sclerosis
• Poland
• Prevalence
• Prospective Studies