Smokers run increased risk of developing anti-natalizumab antibodies

Smokers run increased risk of developing anti-natalizumab antibodies

AK Hedström1
L Alfredsson1
M Lundkvist Ryner2
A Fogdell-Hahn2
Jan Hillert2
T Olsson3

1Institute of Environmental Medicine, Karolinska Institutet, Sweden
2Multiple Sclerosis Research Group, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, Sweden
3Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, Sweden
Anna Karin Hedström, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 14153, Sweden. Email: anna.hedstrom@ki.se

Background:

Smoking may contribute to the induction of neutralizing antibodies to interferon β-1a.

Objective:

In this study, we aimed to investigate the influence of smoking on the risk of developing antibodies to natalizumab, another biological drug in the treatment of multiple sclerosis.
Methods: This report is based on 1338 natalizumab-treated multiple sclerosis patients included in either of two Swedish case-control studies in which information on smoking habits was collected. Using logistic regression, patients with different smoking habits were compared regarding risk of developing anti-natalizumab antibodies, by calculating odds ratios with 95% confidence intervals.

Results:

 Compared with nonsmokers, the odds ratio of developing anti-natalizumab antibodies was 2.4 (95% CI 1.2–4.4) for patients who smoked at the time of screening, and a significant trend showed higher risk of developing antibodies with higher intensity of smoking. When smoking within two years prior to screening was considered, the odds ratio of developing anti-natalizumab antibodies was 2.7 (1.5–5.1).

Interpretations:

The finding strengthens our hypothesis of the lungs as immune-reactive organs on irritation in relation to autoimmune responses, and may also be of clinical relevance since antibodies against natalizumab abrogate the therapeutic effect of the treatment.