Association of obesity with disease outcome in multiple sclerosis

Isabel Lutfullin¹, Maria Eveslage², Stefan Bittner³, Gisela Antony⁴, Martina Flaskamp⁵, Felix Luessi³, Anke Salmen^{6

7}, Barbara Gisevius⁶, Luisa Klotz¹, Catharina Korsukewitz¹, Achim Berthele⁵, Sergiu Groppa³, Florian Then Bergh⁸, Brigitte Wildemann⁹, Antonios Bayas¹⁰, Hayrettin Tumani¹¹, Sven G Meuth¹², Corinna Trebst¹³, Uwe K Zettl¹⁴, Friedemann Paul¹⁵, Christoph Heesen¹⁶, Tania Kuempfel¹⁷, Ralf Gold⁶, Bernhard Hemmer^{5

18}, Frauke Zipp³, Heinz Wiendl¹⁹, Jan D Lünemann²⁰; German Competence Network Multiple Sclerosis (KKNMS)

Affiliations

¹ Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
² Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
³ Department of Neurology, Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, JGU, Mainz, Germany.
⁴ Competence Network Parkinson's Disease, Central Information Office, Philipps-University Marburg, Marburg, Germany.
⁵ Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, München, Germany.
⁶ Department of Neurology, St Josef-Hospital, Ruhr-Universitat Bochum, Bochum, Germany.
⁷ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁸ Clinic and Polyclinic for Neurology, University Hospital Leipzig, University Leipzig, UL, Leipzig, Germany.
⁹ Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
¹⁰ Department of Neurology, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany.
¹¹ Department of Neurology, University of Ulm, Ulm, Germany.
¹² Department of Neurology, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹³ Department of Neurology, Hannover Medical School, Hannover, Germany.
¹⁴ Division of Neuroimmunology, Department of Neurology, University Medicine Rostock Center of Neurology, Rostock, Germany.
¹⁵ NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, CHA, Berlin, Germany.
¹⁶ Department of Neurology, University Medical Center Hamburg-Eppendorf, UKE, Hamburg, Germany.
¹⁷ Institute for Clinical Neuroimmunology, University Hospital und Centre for Biomedicine, Ludwig-Maximilians-University Munich, Munchen, Germany.
¹⁸ Department of Neurology, Technische Universitat Munchen and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹⁹ Department of Neurology with Institute of Translational Neurology, University Hospital Münster and University of Münster, Faculty of Medicine, Munster, Germany.
²⁰ Department of Neurology with Institute of Translational Neurology, University Hospital Münster and University of Münster, Faculty of Medicine, Munster, Germany jan.luenemann@ukmuenster.de.

PMID: 36319190
PMCID: PMC9763191
DOI: 10.1136/jnnp-2022-329685

Association of obesity with disease outcome in multiple sclerosis

Isabel Lutfullin et al. J Neurol Neurosurg Psychiatry. 2023 Jan.

. 2023 Jan;94(1):57-61.

doi: 10.1136/jnnp-2022-329685. Epub 2022 Nov 1.

Authors

Affiliations

¹ Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
² Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
³ Department of Neurology, Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, JGU, Mainz, Germany.
⁴ Competence Network Parkinson's Disease, Central Information Office, Philipps-University Marburg, Marburg, Germany.
⁵ Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, München, Germany.
⁶ Department of Neurology, St Josef-Hospital, Ruhr-Universitat Bochum, Bochum, Germany.
⁷ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁸ Clinic and Polyclinic for Neurology, University Hospital Leipzig, University Leipzig, UL, Leipzig, Germany.
⁹ Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
¹⁰ Department of Neurology, Faculty of Medicine, University of Augsburg, 86156, Augsburg, Germany.
¹¹ Department of Neurology, University of Ulm, Ulm, Germany.
¹² Department of Neurology, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹³ Department of Neurology, Hannover Medical School, Hannover, Germany.
¹⁴ Division of Neuroimmunology, Department of Neurology, University Medicine Rostock Center of Neurology, Rostock, Germany.
¹⁵ NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, CHA, Berlin, Germany.
¹⁶ Department of Neurology, University Medical Center Hamburg-Eppendorf, UKE, Hamburg, Germany.
¹⁷ Institute for Clinical Neuroimmunology, University Hospital und Centre for Biomedicine, Ludwig-Maximilians-University Munich, Munchen, Germany.
¹⁸ Department of Neurology, Technische Universitat Munchen and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
¹⁹ Department of Neurology with Institute of Translational Neurology, University Hospital Münster and University of Münster, Faculty of Medicine, Munster, Germany.
²⁰ Department of Neurology with Institute of Translational Neurology, University Hospital Münster and University of Münster, Faculty of Medicine, Munster, Germany jan.luenemann@ukmuenster.de.

PMID: 36319190
PMCID: PMC9763191
DOI: 10.1136/jnnp-2022-329685

Abstract

Background: Obesity reportedly increases the risk for developing multiple sclerosis (MS), but little is known about its association with disability accumulation.

Methods: This nationwide longitudinal cohort study included 1066 individuals with newly diagnosed MS from the German National MS cohort. Expanded Disability Status Scale (EDSS) scores, relapse rates, MRI findings and choice of immunotherapy were compared at baseline and at years 2, 4 and 6 between obese (body mass index, BMI ≥30 kg/m²) and non-obese (BMI <30 kg/m²) patients and correlated with individual BMI values.

Results: Presence of obesity at disease onset was associated with higher disability at baseline and at 2, 4 and 6 years of follow-up (p<0.001). Median time to reach EDSS 3 was 0.99 years for patients with BMI ≥30 kg/m² and 1.46 years for non-obese patients. Risk to reach EDSS 3 over 6 years was significantly increased in patients with BMI ≥30 kg/m² compared with patients with BMI <30 kg/m² after adjustment for sex, age, smoking (HR 1.87; 95% CI 1.3 to 2.6; log-rank test p<0.001) and independent of disease-modifying therapies. Obesity was not significantly associated with higher relapse rates, increased number of contrast-enhancing MRI lesions or higher MRI T2 lesion burden over 6 years of follow-up.

Conclusions: Obesity in newly diagnosed patients with MS is associated with higher disease severity and poorer outcome. Obesity management could improve clinical outcome of MS.

Keywords: immunology; multiple sclerosis.

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Conflict of interest statement

Competing interests: SB has received honoraria from Biogen Idec, Bristol Meyer Squibbs, Merck Serono, Novartis, Sanofi-Genzyme, Roche and Teva. His research is funded by the Deutsche Forschungsgemeinschaft (DFG) and Hertie Foundation. FL has served on the advisory board of Roche and received travel funding from Teva. AS has received speaker honoraria and/or travel compensation for activities with Bristol Myers Squibb, CSL Behring, Novartis and Roche, and research support by the Swiss MS Society and Baasch Medicus Foundation, not related to this manuscript. LK has received compensation for serving on Scientific Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Genzyme, Horizon, Janssen, Merck Serono, Novartis and Roche. She has received speaker honoraria and travel support from Bayer, Biogen, Bristol-Myers Squibb, Genzyme, Grifols, Merck Serono, Novartis, Roche, Santhera and Teva. She has received research support from the German Research Foundation, the IZKF Münster, IMF Münster, Biogen, Immunic AG, Novartis and Merck Serono. CK has received speaker fees, travel support and/or served on advisory boards by Biogen, Merck, Roche and Sanofi. BW has received grants from the German Ministry of Education and Research, Deutsche Forschungsgemeinschaft, Dietmar Hopp Foundation and Klaus Tschira Foundation, grants and personal fees from Merck, and personal fees from Alexion, Bayer, Biogen, Teva; none related to this work. AB has received personal compensation from Merck Serono, Biogen, Novartis, Teva, Roche, Sanofi/Genzyme, Celgene/BMS and Janssen; he has received grants for congress travel and participation from Biogen, Teva, Novartis, Sanofi/Genzyme, Merck Serono and Celgene. None related to this report. HT has received consulting and/or speaker honoraria from Alexion, Bayer, Biogen, Celgene, GSK, Jannssen, Merck, Novartis, Roche, Sanofi Genzyme and Teva. SM has received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS and Teva. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and by Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche and Teva. CT has received honoraria for consultation and expert testimony from Alexion Pharma Germany, Chugai Pharma Germany and Roche Pharma. None of this interfered with the current report. UKZ has received speaking fees, travel support and financial support for research activities from Alexion, Almirall, Bayer, Biogen, Bristol-Myers-Squibb, Janssen, Merck-Serono, Novartis, Octapharm, Roche, Sanofi-Genzyme and Teva as well as EU, BMBF, BMWi. CH has received speaker honoraria from Merck and Roche. He has received grant support from Merck, Novartis and Roche. TK has received speaker honoraria and/or personal fees for advisory boards from Bayer Healthcare, Merck, Novartis Pharma, Sanofi-Aventis/Genzyme, Roche Pharma, Alexion and Biogen as well as grant support from Novartis and Chugai Pharma in the past. None of this interfered with the current report. RG has received speaker and board honoraria from Baxter, Bayer Schering, Biogen Idec, Bristol Meyer Squibb, CSL Behring, Eisai, Genzyme, Janssen, Merck Serono, Novartis, Stendhal, Talecris and Teva. His department has received grant support from Bayer Schering, BiogenIdec, Genzyme, Merck Serono, Novartis and Teva. All of RG’s declarations are unrelated to the content of this manuscript. BH has served on scientific advisory boards for Novartis; he has served as DMSC member for AllergyCare, Polpharma, Sandoz and TG therapeutics; he or his institution has received speaker honoraria from Desitin; his institution has received research grants from Regeneron for multiple sclerosis research. He holds part of two patents: one for the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis and one for genetic determinants of neutralising antibodies to interferon. FZ has recently received research grants and/or consultation funds from Biogen, Ministry of Education and Research (BMBF), Bristol-Meyers-Squibb, Celgene, German Research Foundation (DFG), Janssen, Max-Planck-Society (MPG), Merck Serono, Novartis, Progressive MS Alliance (PMSA), Roche, Sanofi Genzyme and Sandoz. HW has received honoraria for acting as a member of Scientific Advisory Boards for Janssen, Merck and Novartis as well as speaker honoraria and travel support from Alexion, Amicus Therapeuticus, Biogen, Biologix, Bristol Myers Squibb, Cognomed, F. Hoffmann-La Roche Ltd, Gemeinnützige Hertie-Stiftung, Medison, Merck, Novartis, Roche Pharma AG, Genzyme, Teva and WebMD Global. HW is acting as a paid consultant for Biogen, Bristol Myers Squibb, EMD Serono, Idorsia, Immunic, Novartis, Roche, Sanofi, the Swiss Multiple Sclerosis Society and UCB. His research is funded by the German Ministry for Education and Research (BMBF), Deutsche Forschungsgesellschaft (DFG), Deutsche Myasthenie Gesellschaft e.V., Alexion, Amicus Therapeutics, Argenx, Biogen, CSL Behring, F. Hoffmann - La Roche, Genzyme, Merck KgaA, Novartis Pharma, Roche Pharma and UCB Biopharma. JDL has received speaker fees, research support, travel support, and/or served on advisory boards by Abbvie, Alexion, Argenx, Biogen, Merck, Novartis, Roche, Sanofi and Takeda. JDL has received speaker fees, research support, travel support, and/or served on advisory boards by Abbvie, Alexion, Argenx, Biogen, Merck, Novartis, Roche, Sanofi and Takeda.

Figures

**Figure 1**
Clinical disability as assessed by EDSS in MS patients with BMI ≥30 kg/m² compared with <30 kg/m² at disease onset. EDSS at baseline was significantly higher in the cohort (median (IQR): 2 (1–2) (vs 1.5 (1–2) =0.118; p<0.001), determined by Mann-Whitney U test) EDSS after 2 years deteriorated and showed a stronger correlation and at year 2 (r=0.13; p<0.001) year 4 (r=0.155; p<0.001), year 6 (r=0.186; p<0.001). BMI, body mass index; EDSS, Expanded Disability Status Scale.

**Figure 2**
Comparison of the cumulative hazard of reaching EDSS of 3 in obese versus non-obese patients with MS. HR=1.87 (95% CI 1.324 to 2.627, p<0.001), adjusted for sex, age and smoking. BMI, body mass index; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis.

See this image and copyright information in PMC

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Association of obesity with disease outcome in multiple sclerosis

Affiliations

Association of obesity with disease outcome in multiple sclerosis

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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