Efficacy and Safety Profile of Cladribine Tablets in an Italian Real-Life Cohort of Relapsing-Remitting Multiple Sclerosis Patients: A Monocentric Longitudinal Observational Study (P8-3.015)

Abstract

<h3>Objective:</h3> To report real-world findings about efficacy and safety of cladribine (CLAD) in relapsing-remitting multiple sclerosis (RRMS), identifying predictors of response. <h3>Background:</h3> 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. <h3>Design/Methods:</h3> Monocentric, observational, real-world study on pwMS who started CLAD from April 2018 to November 2021, with a minimum 6 month-follow-up. <h3>Results:</h3> 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, <i>p=0.011</i>), baseline EDSS score ≥ 3.0 (HR 4.29, CI: 1.83–10.05, <i>p=0.0008</i>) and gadolinium-enhancing lesion count ≥ 4 (HR 2.24, CI: 0.95–5.26, <i>p=0.065</i>) 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. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Chiara Zanetta has nothing to disclose. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Alessandro Meani has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck . Laura Ferrè, 3233 has received intellectual property interests from a discovery or technology relating to health care. Dr. Moiola has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).