Background: There is concern amongst the MS community regarding increased risk of COVID-19 infection in patients on Disease Modifying Therapies (DMTs) Guidance from the Association of British Neurologists (ABN) recommends to continue most oral DMTs during the pandemic Objectives: To identify number of patients on oral DMTs in a single centre who reported COVID-19 symptoms To identify how this compares to national infection rate, whether there was a link to lymphocyte counts prior to infection and how many patients stopped or interrupted treatment Methods: Patients on oral DMTs (dimethyl fumarate (DMF), teriflunomide (TF) & fingolimod (FING)) were identified through a local database The pharmacy team called these patients to advise on DMT monitoringduring the pandemic Patients were also asked if they had experienced any symptoms of COVID-19 infection, had been tested, or had stopped treatment Recent lymphocyte counts were obtained Results: 501 patients on oral DMTs were identified (14 on TF, 169 on FING, 318 on DMF) 50% of these were contacted (DMF=174, FING=71, TF=10) The average age of those on treatment was 45, average EDSS 2 2, and average time on DMT 3 7 years Of those asked 90% (229) reported that they had not exprienced COVID-19 symptoms 10% (26) reported that they had experienced COVID- 19 symptoms (3 on TF, 8 on FING, 15 on DMF) According to a recent study by the UK Office of National statistics, of those individuals providing blood samples in the UK, 7% tested positive for antibodies to COVID-19 Of those who reported symptoms the last recorded lymphocyte counts were all within accepted ranges, with a mean of 1 2 (TF 2 0, DMF 1 5, FING 0 4) One patient taking DMF died due to COVID-19 Further data will be presented on the average lymphocyte counts in those who did not report symptoms, number of patients who went on to be tested for COVID-19 and the number who stopped or interrupted treatment Conclusions: Results present real world data on COVID-19 infection in patients on oral DMTs for MS and how these relate to lymphocyte count and infections rates in general population

It is well recognised that the majority of the impact of multiple sclerosis (MS), both personal and societal, arises in the progressive phase where disability accumulates inexorably. As such, progressive MS (PMS) has been the target of pharmacological therapies for many years. However, there are no current licensed treatments for PMS. This stands in marked contrast to relapsing remitting MS (RRMS) where trials have resulted in numerous licensed therapies. PMS has proven to be a more difficult challenge compared to RRMS and this review focuses on secondary progressive MS (SPMS), where relapses occur before the onset of gradual, irreversible disability, and not primary progressive MS where disability accumulation occurs without prior relapses. Although there are similarities between the two forms, in both cases pinpointing when PMS starts is difficult in a condition in which disability can vary from day to day. There is also an overlap between the pathology of relapsing and progressive MS and this has contributed to the lack of well-defined outcomes, both surrogates and clinically relevant outcomes in PMS. In this review, we used the search term 'randomised controlled clinical drug trials in secondary progressive MS' in publications since 1988 together with recently completed trials where results were available. We found 34 trials involving 21 different molecules, of which 38% were successful in reaching their primary outcome. In general, the trials were well designed (e.g. double blind) with sample sizes ranging from 35 to 1949 subjects. The majority were parallel group, but there were also multi-arm and multidose trials as well as the more recent use of adaptive designs. The disability outcome most commonly used was the Expanded Disability Status Scale (EDSS) in all phases, but also magnetic resonance imaging (MRI)-measured brain atrophy has been utilised as a surrogate endpoint in phase II studies. The majority of the treatments tested in SPMS over the years were initially successful in RRMS. This has a number of implications in terms of targeting SPMS, but principally implies that the optimal strategy to target SPMS is to utilise the prodrome of relapses to initiate a therapy that will aim to both prevent progression and slow its accumulation. This approach is in agreement with the early targeting of MS but requires treatments that are both effective and safe if it is to be used before disability is a major problem. Recent successes will hopefully result in the first licensed therapy for PMS and enable us to test this approach.