A K Hedström1, L Alfredsson2, M Lundkvist Ryner3, A Fogdell-Hahn3, Jan Hillert3, T Olsson4. 1. Institute of Environmental Medicine, Karolinska Institutet, Sweden anna.hedstrom@ki.se. 2. Institute of Environmental Medicine, Karolinska Institutet, Sweden. 3. Multiple Sclerosis Research Group, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, Sweden. 4. Neuroimmunology Unit, Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet at Karolinska University Hospital, Sweden.
Abstract
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.
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 sclerosispatients 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.
Authors: Signe Hässler; Delphine Bachelet; Julianne Duhaze; Natacha Szely; Aude Gleizes; Salima Hacein-Bey Abina; Orhan Aktas; Michael Auer; Jerôme Avouac; Mary Birchler; Yoram Bouhnik; Olivier Brocq; Dorothea Buck-Martin; Guillaume Cadiot; Franck Carbonnel; Yehuda Chowers; Manuel Comabella; Tobias Derfuss; Niek De Vries; Naoimh Donnellan; Abiba Doukani; Michael Guger; Hans-Peter Hartung; Eva Kubala Havrdova; Bernhard Hemmer; Tom Huizinga; Kathleen Ingenhoven; Poul Erik Hyldgaard-Jensen; Elizabeth C Jury; Michael Khalil; Bernd Kieseier; Anna Laurén; Raija Lindberg; Amy Loercher; Enrico Maggi; Jessica Manson; Claudia Mauri; Badreddine Mohand Oumoussa; Xavier Montalban; Maria Nachury; Petra Nytrova; Christophe Richez; Malin Ryner; Finn Sellebjerg; Claudia Sievers; Dan Sikkema; Martin Soubrier; Sophie Tourdot; Caroline Trang; Alessandra Vultaggio; Clemens Warnke; Sebastian Spindeldreher; Pierre Dönnes; Timothy P Hickling; Agnès Hincelin Mery; Matthieu Allez; Florian Deisenhammer; Anna Fogdell-Hahn; Xavier Mariette; Marc Pallardy; Philippe Broët Journal: PLoS Med Date: 2020-10-30 Impact factor: 11.069