Clinical and biological predictors of Cladribine effectiveness in Multiple Sclerosis: A real-world, single Centre study considering a two-year interval from year-2 dosing

Objectives: Cladribine tablets (CLAD) for adult patients with highly active relapsing multiple sclerosis (RMS) have been available in Italy since 2018. We aimed to assess predictors of no-evidence-of-disease-activity-3 (NEDA-3) status after 24 months of the last dose of CLAD. Results: We included 88 patients (70.5% female, mean age at CLAD start 35.4 ± 11.4). Eighteen patients were treatment naïve, 48 switched to CLAD from a First line Disease Modifying Drug (DMD), and 22 from Second line DMDs. All patients were observed for a median follow-up time of 2.4 (1–4) years after the last dose of CLAD. Forty-nine patients (55.7%) showed NEDA at the last available follow-up. Naïve patients (p = 0.001), those with a lower number of previous DMDs (p < 0.001) and, even though not significantly, those switching from first line DMDs (p = 0.069) were more likely NEDA3 at the last available follow-up. In a subgroup of 30 patients (34%), Serum Light Neurofilaments (sNFL) levels showed a decrease from baseline to the 24 months of follow-up, statistically significant from baseline to the sixth month, and from the first to the second year detection. sNFL levels at 12th month showed a strong inverse correlation with the time to NEDA3 loss. Conclusions: Our experience provides information for the 2-years after the last dose of CLAD, confirming a higher effectiveness of CLAD when placed early in the treatment algorithm. Given the ongoing expansion of the therapeutic landscape in MS, sNfL could support individualized decision-making, used as blood-based biomarker for CLAD responses in clinical practice.