Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study

Abstract

Introduction Cladribine administration has been approved for the treatment of relapsing–remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging. Methods We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia. The relationship between baseline features and the selected outcomes was tested via multivariate logistic models. Results Of the 243 subjects included in the study (66.5% female, age 34.2 ± 10 years, disease duration 6.6 ± 9.6 years), 64% showed NEDA-3 at median follow-up (22 months). Patients with higher number of previous treatments had lower probability to retain NEDA-3 [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41–0.98, p = 0.04] and were more prone to experience clinical relapses (OR 1.6, 95% CI 1–2.6, p = 0.04). The presence of active lesions at baseline was associated with follow-up magnetic resonance imaging (MRI) activity (OR 1.92, 95% CI 1.04–3.55, p = 0.04). Patients with higher rate of relapses in the year prior to cladribine start were at higher risk of developing sustained disability worsening (OR 2.95% CI 1–4.2, p = 0.04). Lymphopenia grade III/IV over the follow-up was associated with baseline lymphocyte count (OR 0.998, 95% CI 0.997–0.999, p = 0.01). Conclusion In this large cohort, we confirm previous data about cladribine effectiveness on disease activity and disability worsening and provide information on response predictors that might inform therapeutic choices.

Expert opinion on the long-term use of cladribine tablets for multiple sclerosis: Systematic literature review of real-world evidence

“…Treatment-naive patients were more likely to achieve no evidence of DA (NEDA)-3 with CladT than those switching from other DMTs (Zanetta et al, 2021) and retention of NEDA-3 status correlated with a lower number of prior therapies (Petracca et al, 2022) in real-world analyses of Italian patients. Zhong et al (2021) described 333 patients from the MSBase registry who switched to CladT from a prior DMT (DMF, teriflunomide, fingolimod or natalizumab), with a mean washout of 43.1 days.…”

Multiple sclerosis patients treated with cladribine tablets: expert opinion on practical management after year 4

“…5 Finally, data on cladribine tablets from the realworld MS setting confirm efficacy and safety comparable to findings in phase 3 clinical trials and extensions. [34][35][36][37] Real-world data from an Israeli cohort of patients with highly active relapsing/remitting MS (⩾ 1 relapse in the previous year, and ⩾ 1 T1 gadolinium-enhancing lesion or ⩾ 9 T2 lesions while on treatment with another DMT; or ⩾ 2 relapses in the previous year regardless of treatment status) provided evidence that 2 years of cladribine (cumulative dose 3.5 mg/kg) is effective for preventing relapse activity and neurological worsening in year 3 (59.0%; 36/61) and year 4 (74.3%; 26/35). 38 All these findings raise the question of whether additional treatment should be administered after year 4, based on the patient-profile, to provide better disease control.…”

Expert Opinion on Long-Term Use of Cladribine Tablets for Multiple Sclerosis: Systematic Literature Review of Real-World Evidence

“…Treatment-naive patients were more likely to achieve no evidence of DA (NEDA)-3 with CladT than those switching from other DMTs (Zanetta et al, 2021) and retention of NEDA-3 status correlated with a lower number of prior therapies (Petracca et al, 2022) in real-world analyses of Italian patients. Zhong et al (2021) described 333 patients from the MSBase registry who switched to CladT from a prior DMT (DMF, teriflunomide, fingolimod or natalizumab), with a mean washout of 43.1 days.…”