Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal

Abstract

Objectives: Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up.Methods: This was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021.Results: A total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1-3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening ( P = 0.843, Mann-Whitney U test) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects. Conclusion:Our study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.

Magnetic Resonance Imaging Evidence Supporting the Efficacy of Cladribine Tablets in the Treatment of Relapsing-Remitting Multiple Sclerosis

“…On the contrary, real-world observational data of MS cohorts are more representative of routine clinical practice and provide valuable insight into long-term effectiveness and safety [ 74 ]. Several observational real-world cohort studies have assessed the efficacy of cladribine tablets in patients with relapsing forms of MS (RMS) using clinical and MRI assessments [ 44 – 46 , 75 – 77 ].…”

Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France

“…In the CLARITY study, 14% of patients demonstrated MS disease activity after the first course of CladT, but 61% of these patients demonstrated no further MS disease activity in year 2, following the second course. Real-world evidence suggests that most patients who report MS disease activity during year 1 of treatment do not switch to an alternative DMT, a systematic review of real-world studies with CladT in 3628 people with MS [ 20 ] showed that only 2.4% of patients discontinued or switched away from CladT in the 1st year of treatment (Table 1 ) [ 14 , 65 – 76 ]. The phenomenon of MS disease reactivation after withdrawing an S1P inhibitor or natalizumab is a different phenomenon to residual MS disease activity during the time needed for the efficacy of CladT to build.…”

“…of patients No. of discontinuations or switches [N (%)] [ 65 ] Canada 111 0 [ 66 ] Italy 60 1 (1.7) [ 67 ] Spain 85 5 (5.9) [ 68 ] Spain 88 2 (2.3) [ 69 ] Czechia 436 12 (2.8) [ 70 ] USA 616 6 (1.0) [ 71 ] Germany 270 3 (1.1) [ 72 ] Sweden 140 5 (3.5) [ 73 ] United Arab Emirates 88 1 (1.1) [ 14 ] Finland 179 4 (3) [ 74 ] International 610 1 (0.2) [ 75 ] International a 782 31 (4.0) [ 76 ] …”

“…Compiled from data presented in reference [ 20 ]. References [ 14 ] and [ 76 ] were updated to reflect articles included in reference [ 20 ] as an abstract but subsequently followed by publication of a full paper…”