Fatigue in natalizumab-treated Multiple Sclerosis patients: How much is wearing-off to blame?

Introduction: Fatigue is a widely reported symptom of Multiple Sclerosis and it is the main Wearing-off Symptom (WoS) in Natalizumab (NTZ) treated patients. Whether fatigue presenting as a WoS exclusively depends on NTZ or is influenced by other factors, such as Mood Disturbances, has not been thoroughly investigated. Objectives: The primary aim of the study is to investigate the possible correlation of fatigue with depression and to compare fatigue as a chronic symptom to fatigue as a WoS. Materials and methods: 87 MS-patients treated with NTZ (both on standard and extended-dose intervals) were asked on the day of infusion to specify whether fatigue was present and if so whether it was habitual or occurred only as a WoS. The population was divided into three main categories: Chronic Fatigue, End Dose Fatigue, No Fatigue. All patients underwent a clinical evaluation comprising EDSS, FSMC, BDI-II, MSQoL-29, STAI-Y, and SDMT. Results: 73 (84 %) patients complained of fatigue. Among them, 30 (34.5 %) complained of End Dose Fatigue and 43 (49.4 %) Chronic Fatigue. BDI-II was higher in those complaining of Chronic Fatigue compared to those complaining of End Dose Fatigue only (16.6 vs. 9.3, p < 0.01), while we found no difference in Mood Disturbances frequency and BDI-II between the No Fatigue and End Dose Fatigue group. Conclusions: These results suggest that depression and Mood Disturbances do not play a role in the End Dose Fatigue phenomenon and that fatigue as a WoS is probably different and strictly related to the NTZ mechanism of action.