Natalizumab proved to be very effective in patients with active relapsing-remitting multiple sclerosis but harbors the risk of progressive multifocal leukoencephalopathy (PML). It is recommended to consider switching natalizumab treatment after two years with JCV antibody-index above 1.5.

Accordingly, a safe and an equally effective therapeutic alternative is warranted in this patient group. A new high efficacy therapy for RMS is cladribine tablets, a short course oral therapy. It has been approved in Europe since 2017 and in the USA since April 2019.

67 patients with prior natalizumab-treatment and initiated on oral cladribine were reviewed, coming from: 30 patients were participants of the ongoing non-interventional studies in Germany (CLADQoL and CLEVER) and 37 patients treated in two neurological centers in Barsinghausen, Germany and Salford, UK. The rationale for treatment modification was either JCV-index positivity or an ongoing disease activity. Patients were closely monitored and the data were collected regarding MS relapses, disease progression, or possible adverse events.

Patients were initiated on to cladribine tablet treatment between 01/2018 and 07/2019 with a follow-up observation period from 3 weeks to 18 months. Five of the 67 patients presented with mild clinical relapses. Treatment was well tolerated and there were no severe opportunistic infections. Besides expectable lymphopenia, only mild to moderate adverse events were reported: mild urinary tract infections (n=5), headache (n=3), fatigue (n=2), skin rash (n= 3), or unspecific gastrointestinal symptoms (n= 3) occurred in 23 patients.

According to this review of 67 patients, treatment with cladribine tablets was safe when given to patients that were previously treated with natalizumab and at high risk for PML. So far, no serious adverse events other than transient lymphopenia have been observed, especially no cases of PML.