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Highlights • People with advanced (“progressive”) MS (pwPMS) currently have only one licensed disease modifying treatment (DMT) option (ocrelizumab), and this option is highly restricted to a specific MS subpopulation living in high cost economies. • The cerebro-spinal fluid (CSF) neurofilament light chain (NfL) level is a sensitive index of ongoing neuro-axonal damage. • pwPMS who had significantly elevated NfL levels alongside MRI detectable disease activity, were treated using off-label injectable cladribine. • Cladribine was well tolerated without any side effects and led to reduction of disease activity as indicated by a substantial drop in CSF NfL concentration alongside reduction in active MRI lesions, whilst total lymphocyte counts remained within the normal reference range. Abstract Background Evidence suggests people with non-relapsing deteriorating (“progressive”) multiple sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However, only one such treatment (ocrelizumab) has been licensed and is highly restricted to pwPMS suffering from the primary progressive phenotype. The difficulties assessing treatment outcome in pwPMS is one important reason for the lack of respective DMT. The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels have been used as outcome indices and to guide treatment choices. Methods We report on two pwPMS, who were treated with subcutaneous cladribine undergoing CSF NfL testing, alongside MRI and clinical follow-up, before and after treatment. Results Cladribine treatment was well tolerated without any side effects. CSF NfL after treatment revealed significant reduction (by 73% and 80%, respectively) corroborating the MRI detectable drop in disease activity. Disability mildly progressed in one, and remained stable in the other pwPMS. Conclusions pwPMS with detectable disease activity (MRI, elevated NfL) should be considered for DMT. NfL appears to be a sensitive index of treatment effect in pwPMS, and may be a useful outcome in clinical trials targeting this patient group. Over and above its licensed indication (relapsing MS), cladribine may be an effective treatment option for pwPMS. [ABSTRACT FROM AUTHOR]

Current guidelines recommend vaccination against SARS-CoV2 for people with multiple sclerosis (pwMS). The long-term review of the safety and effectiveness of COVID-19 vaccines in pwMS is limited. Service re-evaluation. PwMS using the MS service at Barts Health National Health Service Trust were sent questionnaires via email to report symptoms following first and second COVID-19 vaccinations (n = 570). A retrospective review of electronic health records was conducted for clinical and safety data post-vaccination(s); cut-off was end of September 2021. Separate logistic regressions were carried out for symptoms experienced at each vaccination. Two sets of regressions were fitted with covariates: (i) Disease-modifying therapy type and (ii) patient characteristics for symptoms experienced. 193/570 pwMS responded. 184 pwMS had both vaccinations. 144 received the AZD1222 and 49 the BNT162b2 vaccine. 87% and 75% of pwMS experienced any symptoms at first and second vaccinations, respectively. The majority of symptoms resolved within a short timeframe. No severe adverse effects were reported. Two pwMS subsequently died; one due to COVID-19 and one due to aspiration pneumonia. Males were at a reduced risk of reporting symptoms at first vaccination. There was evidence that pwMS in certain treatment groups were at reduced risk of reporting symptoms at second vaccination only. Findings are consistent with our preliminary data. Symptoms post-vaccination were similar to the non-MS population and were mostly temporary. It is important to inform the MS community of vaccine safety data. [ABSTRACT FROM AUTHOR]

Some people with multiple sclerosis (pwMS) are at increased risk of severe Coronavirus disease 19 (COVID-19) and should be rapidly vaccinated. However, vaccine supplies are limited, and there are concerns about side-effects, particularly with the ChAdOx1nCoV-19 (AstraZeneca) vaccine. To report our first experience of pwMS receiving the AstraZeneca vaccine. Service evaluation. pwMS using the MS service at Barts Health NHS Trust were sent questionnaires to report symptoms following vaccination. Thirty-three responses were returned, 29/33 pwMS received a first dose of AstraZeneca vaccine, the remaining four received a first dose of BioNTech/Pfizer vaccine. All but two patients (94%) reported any symptoms including a sore arm (70%), flu-like symptoms (64%), fever (21%), fatigue (27%), and headache (21%). In more than 2/3 patients, symptoms lasted up to 48 hours, and with the exception of two pwMS reporting symptom duration of 10 and 12 days, respectively, symptoms in the remainder resolved within seven days. No severe adverse effects occurred. pwMS report transient symptoms following AstraZeneca vaccination, characteristics of which were similar to those reported in the non-MS population. Symptoms may be more pronounced in pwMS due to the temperature-dependent delay in impulse propagation (Uhthoff's phenomenon) due to demyelination. [ABSTRACT FROM AUTHOR]

• Severe allergic skin reactions (SARS) to cladribine have not been reported in multiple sclerosis. • We report three cases of MS, in which SARS occurred using injectable cladribine. • SARS might also occur with cladribine tablets (Mavenclad) licensed for MS. • Each case of SARS responded well to standard treatment. To report three cases of severe skin reactions in patients treated with cladribine for multiple sclerosis. Case study. Patients developed severe rash 3–192 days after receiving cladribine. All were effectively treated with steroids and antihistamines. Additional doses of cladribine were administered after pretreatment with steroids and anti-histamines. One patient developed mild recurrence following re-exposure, which resolved within three days, whilst another patient tolerated re-exposure without further adverse reaction. Severe skin reactions, well described in patients receiving cladribine for treatment of haematological conditions, may occur in patients treated with this compound for multiple sclerosis. Neurologists need to be aware of this rare, but significant adverse reaction. Re-exposure may be safe with standard pre-treatment against allergic reactions. [ABSTRACT FROM AUTHOR]