A number of studies have indicated that adolescent obesity is a risk factor for the development of MS, most notably in patients with the HLA-DRB1*15 genotype (Hedstrom et al. Mult Scler 2015; epublished September 11, 2015; Hedstrom et al. Neurology 2014;82:865-872). The relationship between obesity and clinical course once MS has been diagnosed is less clear. A recent study found that obesity (body-mass index >30 kg/m2) did not appear to be associated with increased severity (relapse rate), or disability (EDSS score), nor was obesity linked to the presence of oligoclonal bands (Coban et al. Obes Res Clin Pract 2015;9:533-535).
A study of older MS patients (mean age 55.8 years) with significant disability (mean EDSS 5.5) found that obese and non-obese subjects were comparable with respect to EDSS score and number of steroid courses received (Pinhas-Hamiel et al. Eur J Neurol 2015;22:1275-1279).
However, BMI can have significant effects on the metabolism of disease-modifying therapies used in MS and on treatment-associated adverse effects. An analysis of interferon-beta-treated patients found that BMI influenced treatment response (Kyistad et al. J Neuroimmunol 2015;288:92-97). The proportion of IFN-treated patients who had no evidence of disease activity (NEDA) was 26% in those with normal BMI compared to 13% for those with BMI >25. Underweight women (BMI < 18.5) have been reported to have an increased risk of lymphopenia (nadir ≤ 0.2×109 lymphocytes/L) during treatment with fingolimod (Warnke et al. Neurology 2014;83:2153-2157), and may require closer monitoring.
A number of studies have reported that patients with lower BMI have an elevated risk of progressive multifocal leukoencephalopathy (PML) during treatment with natalizumab (Foley et al. AAN 2013; abstract S30.002). This was attributed to high drug levels per kilogram body weight and elevated natalizumab saturation of VLA-4. A subsequent analysis found that natalizumab dosing varied widely – from 1.89 to 6.67 mg/kg – when BMI was considered, corresponding to a mean VLA-4 receptor occupancy of 80-91% (Foley et al. AAN 2016; abstract P3.020). In comparing patients with versus without PML, 72% of PML patients were dosed above the median of the non-PML cohort.
A recent suggestion has been to extend the dosing interval of natalizumab to q5-8 weeks. A retrospective study of data from nine MS centres reported that reducing the dosing of natalizumab to every 8 weeks did not result in less effectiveness with respect to annual relapse rate or number of new lesions (Zhovis Ryerson et al. J Neurol Neurosurg Psychiatry 2016; epublished February 25, 2016). There were four PML cases with monthly dosing compared to 0 with extended dosing, although additional data are needed to determine if extended dosing will lower PML risk.
Comment
Dr. François Grand’Maison: There is no doubt that BMI should be taken into consideration in the treatment of MS. Catherine Larochelle from the CHUM in Montréal wrote the following in our report of IFNβ-treated patients who developed thrombotic thrombocytopenic purpura (TTP): “Interestingly, the body mass index of our three patients was low and all three were of short stature. Although speculative, this could suggest a form of dose-related toxicity of IFNβ in women of lower (than average) body mass index and body surface area. This observation raises questions about the concept of a single dose approach for the treatment of MS, as it is the case for most medications used in MS” (Larochelle et al. Mult Scler 2014;20:1783-1787).