End of dose interval symptoms in patients treated with natalizumab : a role for serum cytokines?

Background: Many natalizumab treated patients experience end of dose interval (EDI) symptoms towards the end of the administration cycle. Natalizumab has previously shown to influence cytokine profiles in relapsing remitting MS patients. We hypothesize that EDI symptoms might be explained by variability in serum cytokine levels during natalizumab treatment.Methods: 42 relapsing remitting MS patients were included. Participants were evaluated before natalizumab administration (day 0) and 7 days afterwards (day 7). At both time points fatigue, depressed mood and cognition were evaluated using the fatigue severity scale (FSS), the visual analogue scale for fatigue (VAS-F), the symbol digit modality test (SDMT) and the inventory for depressive symptomatology (IDS-SR). Serum samples were tested for concentrations of IL-6, IFN-gamma and TNF-alpha at both timepoints. On day 7 an additional EDI questionnaire was completed. Data were analyzed with SPSS by means of non-parametric tests.Results: EDI symptoms were reported by 59.5%. Although fatigue was most frequently reported, fatigue scales did not significantly change from day 0 to 7 in (fatigued) EDI patients. Mood and cognition significantly ameliorated in both EDI and non-EDI patients. Cytokines remained stable at day 0 vs 7 except for a significant increase in IFN-gamma. On day 0, IFN-gamma concentration was positively correlated with a depressed mood in the whole cohort, and with mood and fatigue in the EDI group. Depressed mood positively whilst cognition negatively correlated with IFN-gamma concentration on day 0 in the EDI subgroup reporting fatigue. No significant correlations between IL-6 nor TNF-alpha and symptom scores could be found.Conclusion: In our study EDI symptoms could not be objectified since EDI and non-EDI groups did not differ in terms of change in mood, cognition and fatigue between day 0 and 7 suggesting that symptom recrudescence could be a subjective experience. Although our results need to be interpreted cautiously, we found no clear correlation between studied serum cytokines concentrations and the occurrence of EDI symptoms.Background: Many natalizumab treated patients experience end of dose interval (EDI) symptoms towards the end of the administration cycle. Natalizumab has previously shown to influence cytokine profiles in relapsing remitting MS patients. We hypothesize that EDI symptoms might be explained by variability in serum cytokine levels during natalizumab treatment.Methods: 42 relapsing remitting MS patients were included. Participants were evaluated before natalizumab administration (day 0) and 7 days afterwards (day 7). At both time points fatigue, depressed mood and cognition were evaluated using the fatigue severity scale (FSS), the visual analogue scale for fatigue (VAS-F), the symbol digit modality test (SDMT) and the inventory for depressive symptomatology (IDS-SR). Serum samples were tested for concentrations of IL-6, IFN-gamma and TNF-alpha at both timepoints. On day 7 an additional EDI questionnaire was completed. Data were analyzed with SPSS by means of non-parametric tests.Results: EDI symptoms were reported by 59.5%. Although fatigue was most frequently reported, fatigue scales did not significantly change from day 0 to 7 in (fatigued) EDI patients. Mood and cognition significantly ameliorated in both EDI and non-EDI patients. Cytokines remained stable at day 0 vs 7 except for a significant increase in IFN-gamma. On day 0, IFN-gamma concentration was positively correlated with a depressed mood in the whole cohort, and with mood and fatigue in the EDI group. Depressed mood positively whilst cognition negatively correlated with IFN-gamma concentration on day 0 in the EDI subgroup reporting fatigue. No significant correlations between IL-6 nor TNF-alpha and symptom scores could be found.Conclusion: In our study EDI symptoms could not be objectified since EDI and non-EDI groups did not differ in terms of change in mood, cognition and fatigue between day 0 and 7 suggesting that symptom recrudescence could be a subjective experience. Although our results need to be interpreted cautiously, we found no clear correlation between studied serum cytokines concentrations and the occurrence of EDI symptoms.A