ABSTRACT
Background: 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. Objectives: 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. Methods: 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. 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. Conclusions: 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.
ABSTRACT
Introduction: COVID-19 may be particularly detrimental for people with MS (pwMS). Disease modifying therapies (DMT) alters immune function with an unknown effect on response to COVID-19. More disabled pwMS may be at increased risk of death from COVID-19. We have attempted to link data from the Scottish Multiple Sclerosis Register (SMSR) with COVID-19 test result data to develop a mechanism to inform neurologists across Scotland of pwMS who catch COVID-19. Methods: The SMSR is an incidence register which aims to record all new diagnoses of multiple sclerosis in Scotland since 2010. This anonymised dataset is held within Public Health Scotland. COVID-19 test results are recorded by Health Protection Scotland. These datasets will be linked and a weekly report will be generated. Positive cases will be investigated by regional neurologists. Additional cases in pwMS diagnosed pre-2010 will be collected if reported by specialist teams. Results: The SMSR holds data on more than 4256 pwMS. As of 22/3/20 1616 people in Scotland are known to have died with a COVID-19 infection with 9038 positive cases from a total of 43,309 tests. As of today we know of 6 pwMS with positive tests in Scotland. More data will be presented. Conclusion: Data linkage using existing national datasets may give a better picture of the spread of COVID-19 amongst people with MS in Scotland. This may help inform future 'shielding' strategies to protect those most at risk of death from the COVID-19 and also may help us understand the interaction of DMT with COVID-19.