Cladribine is a novel disease-modifying therapy (DMT) that has recently been licensed for the treatment of highly active relapsing-remitting multiple sclerosis (rrMS) in Scotland. Lymphocytopaenia (LLC) was reported as the main side-effect of this treatment, in clinical trials.
1. Determining the real-world incidence of adverse effects of cladribine
2. Assessing the temporo-spatial likelihood of adverse effects
3. Commenting on current practice for monitoring and managing adverse incidents.
A retrospective cohort analysis of 120 patients prescribed cladribine, over four health boards in Scotland, assessed the incidence of adverse effects at 1 and 2 year intervals, by examination of patient notes, documented self-reported patient comments and follow-up blood monitoring results.
It is affirmed that LLC is the main adverse effect of cladribine, occurring in around 68% of patients following receipt of the first treatment cycle and 75% following receipt of the second. Mild to moderate LLC (Grades 0-2) was present in 84% of LLC patients within treatment year 1, but only 58% of LLC patients after year 2. The average lag to peak LLC is noted to be two to four months after first treatment (n patients = 75%) and similarly after the second (n = 66%), indicating the optimal time frame for routine follow-up screening.
Other adverse effects were noted in 25 patients (21%), most commonly fatigue (incidence = 0.07), hair loss (incidence = 0.05) and nausea (incidence = 0.03). Allergic-type reactions were also observed in 2% of patients, but these were mild and treatable, without interruption to therapy. All patients in this cohort had adequate V. zoster pre-screening and prophylaxis. Treatment continuation was disrupted in 31% of patients due to COVID-19.
Adequate infection prophylaxis and counselling are noted to be key aspects of preassessment. Treatment is interrupted where no adequate protection can be provided. It is essential to ensure adequate lymphocyte populations, via routine screening and follow-up monitoring, before treatment initiation or progression. Shielding of cladribine patients from COVID-19 or similar may be indicated for up to 6 months after treatment, covering the nadir of LLC.