Lower lymphocyte counts and older age are associated with reduced multiple sclerosis disease activity during dimethyl
Riccardo Garbo1, Simone Lorenzut2, Ilaria Del Negro1
1Clinical Neurology Unit, Udine University Hospital, Piazzale Santa Maria della Misericordia 15, 33100, Udine, Italy.
Background:
delayed-release dimethyl fumarate (DMF) is a disease modifying therapy for relapsing-remitting multiple sclerosis (MS) with antioxidant and anti-inflammatory properties. The drug causes lymphocyte count reduction, which can lead to lymphopenia development during treatment. This is an important safety issue, due to infectious risk, mainly progressive multifocal leukoencephalopathy (PML). If the lymphocyte count influences the response to treatment is still a matter of debate, as there are contrasting contrasting data in the literature. Considering this, we aimed to identify DMF induced lymphopenia risk factors and to evaluate lymphopenia impact on MS disease activity in a real world setting.
Methods:
a retrospective study on 135 MS patients receiving DMF with a mean treatment duration of 32.3±15.9 months was performed. Baseline and follow-up demographic, clinical, magnetic resonance imaging (MRI) and laboratory data were collected.
Results:
44 patients (32.6%) developed lymphopenia, with 11 (8.1%) grade 1, 23 (17.0%) grade 2 and 10 (7.4 %) grade 3. Older age and lower basal absolute lymphocyte count were found to be associated with lymphopenia development on a binary regression model (p<0.001 and p=0.009). When compared with non lymphopenic+lymphopenia grade 1 patients, those experiencing lymphopenia grade 2+3 had longer disease activity free survival (p<0.001), fewer clinical relapses (p=0.005) and lower MRI disease activity (p≤0.001). On Cox regression model, older age and lymphopenia grade 2+3 were found to be protective factors against disease activity (HR=0.966; 95% C.I.=0.942-0.992; p=0.009 for age; HR=0.137; 95% C.I.=0.043-0.439; p=0.001 for lymphopenia grade 2+3) and MRI disease activity (HR=0.968; 95% C.I.=0.941-0.997; p=0.030 for age; HR=0.142; 95% C.I.=0.034-0.591; p=0.007 for lymphopenia grade 2+3). Only lymphopenia grade 2+3 was found to be a predictor of clinical relapses (HR=0.970; 95% C.I.=0.936-1.005; p=0.095 for age; HR=0.115; 95% C.I.=0.016-0.854; p=0.034 for lymphopenia grade 2+3), with a protective effect.
Conclusion:
older age and lower basal lymphocyte count were found to be associated with lymphopenia development. Lymphopenia grade 2+3 and older age could be protective against clinical and radiologic disease activity during DMF treatment.
