Salford Royal NHS Foundation Trust
Manchester Centre for Clinical Neurosciences

Author Of 2 Presentations

Clinical Trials Late Breaking Abstracts

LB01.02 - Phase 2 clinical trial evidence that a retinoid-X receptor agonist promotes remyelination in people with relapsing-remitting multiple sclerosis

Abstract

Background

Retinoid acid X receptor [RXR] gamma agonists promote oligodendrocyte progenitor cell differentiation and remyelination following experimental demyelination.

Objectives

To assess the safety and efficacy of bexarotene, a non-specific RXR agonist licensed for cutaneous T-cell lymphoma, as a remyelinating therapy in people with relapsing remitting multiple sclerosis.

Methods

In a double-blind, placebo-controlled, phase 2a trial (Cambridge Centre for Myelin Repair: CCMR-One), participants aged 18-50 years with relapsing remitting multiple sclerosis, stable on dimethyl fumarate for at least 6 months, were randomised to bexarotene 300mg/m2 or placebo for 6 months. The primary efficacy outcome was change in mean lesional magnetisation transfer ratio (MTR) for lesions whose baseline MTR was below the median lesional MTR for that patient. The secondary efficacy outcome was change in full-field visual evoked potential (VEP) latency in eyes with electrophysiological evidence of optic neuropathy (baseline latency >118ms). We analysed by intention to treat.

Results

52 patients were randomised 1:1 to receive six months of bexarotene or placebo. Two placebo patients withdrew before receiving study drug and one bexarotene patient withdrew consent during the trial. All bexarotene patients experienced adverse effects, notably central hypothyroidism (26 [100%]) and hypertriglyceridaemia (24 [92%, mean maximum of 6.79 mmol/L ,SD 4.4]; as well as rash (13 [50%]) and neutropenia (10 [38%]). Two discontinued placebo because of adverse events and five discontinued bexarotene because of rash [2], neutropenia, triglyceridaemia and mood disturbance. The primary efficacy outcome was negative (mean submedian lesion MTR change was 0.25pu in the bexarotene group versus 0.09pu in the placebo group, p=0.54), but in an exploratory, lesion-level analysis, though treatment difference in submedian lesions was too small to achieve significance, it was statistically significantly greater than in supermedian lesions (p=0·007). This suggests that bexarotene has a biological effect on MTR and that this effect is dependent on baseline lesional MTR. This interpretation is supported by the finding that bexarotene treatment reduced full field visual evoked potential latency compared to placebo in the 52 eyes with delayed VEPS at baseline, by 4·66 ms/eye (95% CI -8·38 -0·93; p=0·014) and in all eyes, by a per-protocol analysis, by 4.02ms/eye (P=0.015).

Conclusions

Despite a negative primary efficacy outcome, evidence from both magnetisation transfer ratio imaging and visual evoked potentials suggest that a retinoic X receptor agonist, bexarotene, promotes remyelination in people with multiple sclerosis. We have also a heterogeneous response of MS lesions to a drug promoting remyelination. Although bexarotene’s safety profile precludes its widespread use, these data support efforts to develop a selective RXR-gamma agonist.

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COVID-19 Late Breaking Abstracts

SS02.01 - COVID-19 in people with MS: A large community-based study of the UK MS Register

Speakers
Presentation Number
SS02.01
Presentation Topic
COVID-19
Lecture Time
10:45 - 10:57

Abstract

Background

The Coronavirus Disease 2019 (COVID-19) pandemic has introduced uncertainties into the multiple sclerosis (MS) community and the focus so far has been the severity of infection among people with MS (pwMS) who have COVID-19. This approach has left questions about the risk of contracting disease in pwMS unanswered which has implications as society gradually returns to normal.

Objectives

To evaluate the trend of COVID-19 incidence in pwMS, their behaviour in response to the outbreak, and the effect of their demographic and clinical characteristics on the likelihood of contracting COVID-19.

Methods

The United Kingdom MS Register (UKMSR) has been collecting demographic and MS related data since 2011 from pwMS all over the UK. On 17 March 2020, existing participants of the UKMSR were asked to join the COVID-19 study. The study was also advertised through social media. In this on-going study, pwMS answer a COVID-19 related survey at participation and a different follow-up survey every two weeks depending on whether they report COVID-19.

Results

We estimate the nationwide overall incidence of COVID-19 in pwMS as 10% (n=522) among 5237 participants until 24 June 2020. The weekly incidence peaked during the 2nd week after lockdown started on 23 March 2020 (13.2%) and remained high until it dropped to 3.5% in the 10th week. The mean (standard deviation) age of the study population was 52.4 (11.9), 76.1% (n=3985) were female, and 95.7% (n=5012) were of white ethnicity. PwMS with a higher web-based Expanded Disability Status Scale (EDSS) score are more likely to self-isolate (odds ratio [OR] 1.389, 95%CI [confidence interval] 1.333−1.447). PwMS who are taking disease modifying therapies (DMTs) and those with progressive MS tend to self-isolate more (OR 1.259, 95%CI 1.059−1.497 and OR 1.245, 95% CI 1.013−1.531, respectively). Older age, progressive MS, and white ethnicity were associated with a lower likelihood of having COVID-19 (OR 0.969, 95%CI 0.957−0.982 and OR 0.595, 95% 0.422−0.838 and OR 0.495, 95%CI 0.347−0.705, respectively). Gender, EDSS, MS Impact Scale version 29 scores and DMTs did not alter the likelihood of contracting COVID-19.

Conclusions

To our knowledge, this is the largest community-based study of COVID-19 in pwMS worldwide. The trend of COVID-19 in pwMS is comparable to that of the UK general population. During a period with strict physical distancing measures, pwMS are not at an increased risk of contracting COVID-19.

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Author Of 3 Presentations

Patient-Reported Outcomes and Quality of Life Poster Presentation

LB1176 - Anxiety affects the general well-being of people with MS during the COVID-19 pandemic more than the infection itself (ID 1893)

Speakers
Presentation Number
LB1176
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Anxiety and depression are more common in people with multiple sclerosis (pwMS) compared to people without MS. The unpredictable nature of the COVID-19 pandemic has caused widespread distress, but it is unknown if it would affect pwMS disproportionately.

Objectives

To evaluate the impact of the COVID-19 pandemic on the mood and well-being of pwMS in the UK and compare it to that of controls.

Methods

The UK MS Register has been collecting Hospital Anxiety and Depression Scale (HADS) data of pwMS since 2011. In the mood and well-being UKMSR COVID-19 study, we asked pwMS (n=5240) and controls (n=376) to answer questions on General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) for depression and Revised Impact of Event Scale (IES-R) for post-traumatic stress disorder (PTSD) in addition to changes in their lifestyle and well-being during the COVID-19 outbreak.

Results

The HADS score of pwMS (n=2225) during the COVID-19 outbreak had not changed compared to the year before (mean difference 0.004, 95%CI -0.11−0.12, p=0.952 for anxiety and mean difference 0.05, 95%CI -0.05−0.15, p=0.283 for depression). The rate of anxiety (GAD-7>5) in male pwMS (37.2%) was more than controls (24.3%) (p=0.032) but was similar in female pwMS and controls. More male pwMS had moderate to severe depression (PHQ-9>9) compared to controls (28.5.4% vs 12.2%, p=0.003), but again, the rate was similar in females. More pwMS who had COVID-19, experienced anxiety or PTSD (IES-R>32) compared to those without the infection (54% vs 44%, p=0.018; 30.5% vs 22.5%, p=0.024, respectively). The rate of depression was similar in pwMS with or without symptoms of the disease. Anxiety, compared to the actual infection, was more strongly associated with subjective worsening of general health (57.1% vs 37.3%, with anxiety or COVID-19 respectively, p=0.008) or MS symptoms (61% vs 31.3%, p<0.001).

A high proportion of both pwMS and controls did not experience any change in the quality of their relationships. However, more pwMS reported worsening of their relationships compared to controls (21.4% vs 16.7%, p<0.001). The change in loneliness was similar between the two groups with 4 in 10 pwMS and controls feeling lonelier during the outbreak.

Conclusions

Anxiety during the COVID-19 pandemic is having a more profound effect on the general well-being of most patients compared to the infection itself.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0345 - Interim Analysis of Pregnancy Outcomes Following Exposure to Dimethyl Fumarate in a Prospective International Registry (ID 412)

Speakers
Presentation Number
P0345
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Recent US estimates suggest that the prevalence of multiple sclerosis (MS) is nearly 3 times higher in women, many of childbearing age. Oral delayed-release dimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in trials and post-marketing surveillance. DMF should be used in pregnant women with MS only if the potential benefit justifies the potential risk to the fetus.

Objectives

To provide pregnancy outcomes and DMF exposure data as of 08 April 2020 in women with MS treated with DMF in an ongoing prospective international registry (NCT01911767, TecGistry).

Methods

Women exposed to DMF from the first day of their last menstrual period before conception or during pregnancy were evaluated. Data were obtained at enrolment, 6−7 months of gestation, 4 weeks after estimated due date, and 4, 12 and 52 weeks after birth. As reported previously, outcomes included live births, pregnancy loss, ectopic/molar pregnancies, birth defects and anomalies, and infant or maternal death after delivery. Gestational weight was classified by percentile (<10th, 10th−90th, >90th) based on standardized growth charts.

Results

As of 08 April 2020, 345 patients were enrolled, with a median age of 32 years. Median gestational week at first exposure to DMF was 1 (range: 0, 13) and at enrollment was 9 (0, 39.3). Median (range) duration of fetal DMF exposure duration was 5 (0, 40) weeks. Among discontinuations, one was due to a serious AE. Of the known outcomes, 277 were live births (122 with 52 weeks of follow-up), 19 fetal losses including 1 molar and 1 ectopic pregnancy resulting in spontaneous abortions. One neonatal death and no maternal deaths were reported. Of 274 infants of known gestational age, 249 (91%) were full term, and 25 (9%) premature (<37 weeks). Gestational weight data were available for 232 infants, of whom 26 (11%) were small, 190 (82%) appropriate, and 16 (7%) large. Overall, 8 infants had adjudicator-confirmed birth defects, including ventricular septal defect, congenital hydronephrosis, ureteral duplication, pyloric stenosis, transposition of the great vessels, unilateral developmental dysplasia of the hip, and 1 premature infant with multiple birth defects.

Conclusions

The pregnancy outcome frequencies observed in this updated analysis were consistent with previous reports and did not exceed those seen in the MS and general populations. No additional safety signals were identified.

Supported by: Biogen

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Epidemiology Poster Presentation

P0501 - The impact of socioeconomic status on the access to disease modifying therapy in people with multiple sclerosis. (ID 1507)

Speakers
Presentation Number
P0501
Presentation Topic
Epidemiology

Abstract

Background

Disease modifying therapies (DMTs) are unaffordable to many people with multiple sclerosis (MS) in privately funded health care systems. Evidence, to date, to support whether socioeconomic inequality in accessing DMTs for MS exists in publicly funded healthcare systems is equivocal.

Objectives

To examine whether access to DMTs for MS depends on the socioeconomic status (SES) using a geographically diverse population through the UK MS Register

Methods

The UK MS register, which was launched in 2011, aims to capture real world data about living with MS in the UK and collaborates with many hospitals across the country. We included all patients of working age with disease duration less than 6 years who were living in England and were diagnosed with relapsing remitting MS after the age of 29, between 2010 and 2017. SES was measured by their levels of education, financial resources and English index of multiple deprivation (IMD). IMD were divided into quintiles for the analysis. Any patients who did not provide information about their SES were excluded.

Results

A total of 1060 patients registered in the UK MS registry with mean age of 44 (standard error (SE), 0.25) years and mean disease duration of 2.34 (SE, 0.05) years were eligible. 819/1060 (77%) patients were female and 388/1060 (37%) patients received DMTs. We observed that people with MS who had postgraduate education had significantly better access to DMTs compared to secondary school attendees even when the analysis was adjusted for age, disease duration and financial resources. Access to DMTs did not depend upon whether the patients were employed, homemakers, receiving disability benefits, unemployed or retired. However, patients who worked in skilled and trade professions were less likely to receive DMTs compared to those who worked as managers, directors and senior officials with an odds ratio (OR) of 0.46 (95% confidence interval (CI), 0.22-0.96) even when the analysis was adjusted for education levels, age and disease duration. People who were less deprived were more likely to be treated with DMTs; OR for receiving DMT in the 5th IMD quintile (least deprived) was 1.96 (95% CI, 1.23-3.11) compared to 1st IMD quintile (most deprived), when adjusted for age and disease duration. The R2 value of these models showed that 3-5% of variation in accessing DMTs were dependent on these SES indices indicating that the influence of SES was small in our publicly funded national health service.

Conclusions

We found that the likelihood of receiving DMTs depend on the level of education, occupation and IMD suggesting that SES may influence the access to DMTs, in an English population.

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