Experience with the use of cladribine tablets in real-life clinical practice: independent analysis of data from 12 Russian clinical centres

Abstract

Multiple sclerosis (MS) is an autoimmune-inflammatory and neurodegenerative disease of the central nervous system. The article analyses the ability of cladribine, which due to its selective lymphotoxic effect on activated cells and central effect on immunomodulation in brain tissue underwent successful clinical trials in 2010, when it was (temporarily) approved in Russia.Objective: to analyse the effect of cladribine tablets in daily practice on the course of MS over 3–4 year observational period after immune reconstitution therapy (IRT) in several neurological clinics from different regions of Russia.Material and methods. We collected data on 235 patients from 12 neurological clinics and regional MS centres who were followed for an average of 3.4 years after starting cladribine treatment.Results. An independent analysis of cases in which cladribine tablets were prescribed showed that the reason for prescribing cladribine was highly active MS (HARS) in 159 (67.7%) patients, rapidly progressive MS (RPMS) in 20 (8.5%), active relapsing-remitting MS – in 50 (21.3%) and secondary progressive MS with exacerbations – in 6 (2.5%). Only 12 (5.1%) of these patients had not previously received disease-modifying therapies (DMTs), i.e. in these cases the drug was the first DMT prescribed. Among patients who had received a second-line DMTs before switching to cladribine, 22 had previously received natalizumab, 5 had received ocrelizumab and only 1 had received fingolimod. Remaining patients (n=195) were switched from first-line DMTs. In all cases, a decrease in the frequency of exacerbations was observed during and after completion of the IRT course. Exacerbations between the first and second course of cladribine were observed in 36 patients (15.3% of all treated patients), including in almost half of the cases those who were switched from natalizumab (17 exacerbations or 47.2% of all exacerbations, that developed between the first and second course of therapy) and in three cases – from ocrelizumab (8.3 % of exacerbations that developed between the first and second course of therapy, or 60 % of all those switched from ocrelizumab to cladribine). After completion of full cladribine treatment during the four-year observation period, exacerbations occurred in 14 patients (6% of all patients included in the analysis), six of which occurred after switching from natalizumab.Conclusion. The results are generally consistent with the results of recently published meta-analyses and reviews, but the high likelihood of exacerbations in patients switched from second-line therapies such as natalizumab and ocrelizumab is noteworthy. Both drugs are prescribed for aggressive types of MS with exacerbations (highly active and rapidly progressive) who had a high frequency of exacerbations and an increase in Expanded Disability Status Scale (EDSS) scores prior to being prescribed these drugs. The switch from natalizumab is usually due to an increased risk of developing progressive multifocal encephalopathy with a high titre of antibodies against the JC-virus and the duration of natal izumab use of more than 2 years. It is likely that the resumption of MS activity after discontinuation of natalizumab is quite pronounced, and replacement with treatment with cladribine in tablet form is not able to completely prevent this. In this respect, such a switch does not appear to be optimal, in contrast to cases where first-line drugs are switched to cladribine.

Keywords

• real-world clinical practice
• multiple sclerosis disease-modifying treatment
• observational study
• cladribine