To report real-world findings about efficacy and safety of cladribine (CLAD) in relapsing-remitting multiple sclerosis (RRMS), identifying predictors of response.

CLAD induces a transient lymphocyte depletion followed by immune reconstitution, with improved immune tolerance. Real-world data on CLAD performance and its predictors of response are limited.

Monocentric, observational, real-world study on pwMS who started CLAD from April 2018 to November 2021, with a minimum 6 month-follow-up.

Our population comprised 114 pwMS, 71.9% females, 50% naïves, mean age 33.0 years, median disease duration 3.0 years, median baseline EDSS 2.0, mean 1 and 2 year-baseline ARR 1.3 and 1.2. Median follow-up: 23.8 months.  4.4% and 30.7% patients presented relapses and MRI activity in the first 6 months. When considering data re-baselined towards month 6, 12 relapses were reported. 84% (CI 76-92) and 76% (CI 67-87) patients had no MRI activity at 12 and 24 months, respectively. At month 24, NEDA-3 status was reached by 69% of naïves, and 81% and 55% of switchers from low and high-efficacy treatments, respectively. Eleven patients switched to other treatments. Younger age (HR 0.94, CI: 0.89-0.99, p=0.011), baseline EDSS score > 3.0 (HR 4.29, CI: 1.83-10.05, p=0.0008) and gadolinium-enhancing lesion count > 4 (HR 2.24, CI: 0.95-5.26, p=0.065) were risk factors for loss of NEDA-3. 20.0% of pwMS referred side effects: skin rash, fever/infections, fatigue. Lymphopenia was more likely at months 3 and 15. No grade-4 lymphopenia cases were observed.

CLAD is more effective when placed early in the treatment algorithm: naïves or switchers from lower efficacy drugs seem to benefit more. Baseline age, disability and gadolinium-enhancing lesions are risk factors for loss of NEDA-3. CLAD was overall well tolerated. Real-world data on larger populations with longer follow-up are needed to confirm our findings.