Centre hospitalier universitaire de Rennes, Hôpital Pontchaillou, Service de neurologie, CIC1414 INSERM

Author Of 1 Presentation

COVID-19 Late Breaking Abstracts

SS02.04 - First results of the COVID-19 in MS Global Data Sharing Initiative suggest anti-CD20 DMTs are associated with worse COVID-19 outcomes

Abstract

Background

As the COVID-19 pandemic amplifies, efforts to minimise the risk on vulnerable people are essential. People with multiple sclerosis (MS) may be a vulnerable group due to the high proportion taking long-term immunosuppressive disease-modifying therapies (DMTs). Studies from Italy and France suggest older age, higher disability and progressive MS are associated with severe COVID-19, yet there remains uncertainty around the influence of DMTs.

Objectives

Given the many approved MS DMTs and the relatively low frequency of COVID-19 in MS patients per country, international data sharing is desirable to examine the impact of DMTs on COVID-19 severity. Here, we present the first results of the COVID-19 in MS global data sharing initiative of the MS International Federation and MS Data Alliance and many other data partners to inform MS clinical management during the COVID-19 pandemic.

Methods

Clinician-reported data from 21 countries were aggregated into a dataset of 1540 patients. Characteristics of admission to hospital, admission to intensive care unit (ICU), need for artificial ventilation, and death, were assessed in patients with confirmed or suspected COVID-19 infection using log-binomial regression. Adjusted prevalence ratios (aPR) were calculated adjusting for age, sex, MS type, and Expanded Disability Status Scale (EDSS).

Results

Of 1540 patients, 476 (30.9%) with suspected and 776 (50.4%) with confirmed COVID-19 were included in the analysis. Older age, progressive MS and higher EDSS were associated with higher frequencies of severe outcomes. Anti-CD20 DMTs, ocrelizumab and rituximab, were positively associated with hospital admission (aPRs=1.19 & 1.58), ICU admission (aPRs=3.53 & 4.12), and the need for artificial ventilation (aPRs=3.17 & 7.27) compared to dimethyl fumarate. Higher frequencies of all three outcomes were associated with combined anti-CD20 DMT use compared to all other DMTs (hospitalisation aPR=1.49; ICU aPR=2.55; ventilation aPR=3.05) and compared to natalizumab (hospitalisation aPR=1.99; ICU aPR=2.39; ventilation aPR=2.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases and upon exclusion of each contributing data source in turn. No associations were observed between DMTs and death.

Conclusions

This study used the largest federated international cohort of people with MS and COVID19 currently available. We demonstrate a consistent association of anti-CD20 DMTs with hospitalisation, ICU admission and use of artificial ventilation suggesting their use among MS patients at risk for COVID-19 exposure may be a risk factor for more severe COVID-19 disease. To address study limitations, further research incorporating comorbidities, smoking and body mass index is required. Alternative study designs are needed to address questions on COVID-19 susceptibility among people with MS.

Collapse

Author Of 2 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0132 - Prediction of 15-year MS outcomes in BENEFIT trial patients using serum neurofilament light chain concentrations (ID 1726)

Speakers
Presentation Number
P0132
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Serum neurofilament light chain (sNfL) levels are a promising biomarker for quantifying neuro-axonal injury in multiple sclerosis (MS). Recent studies showed sNfL levels relate to disease activity and treatment response.

Objectives

To analyze the predictive capacity of baseline (BL) sNfL levels for disease outcomes in the 15-year BENEFIT study long-term follow-up

Methods

Monofactorial regression analyses were conducted on outcomes at Year 15, including sNfL age-adjusted percentiles (80th, 90th, 95th, 97.5th and 99th; Disanto et al., 2017).

Further BL covariates included sex; age; lowest EDSS up to Month 6; mono/multifocal onset; presence of optic nerve, brainstem, or spinal cord lesions; Paced Auditory Serial Addition Test 3 (PASAT-3), Timed 25 Foot Walk (T25W), and 9 Hole PEG test (9HPT) scores; number/volume of hypointense T1, gadolinium-enhancing T1, and T2 lesions; cerebral volume; and initial treatment assignment. On-study covariates at Years 1, 2, and 5 were annualized relapse rate; EDSS change; PASAT-3, T25W, and 9HPT scores; annualized rate of new lesions; lesion number/volume; brain volume change; and relative duration of treatment. Covariates with p≤0.1 (at ≥2 time points for on-study covariates) were entered into multifactorial models.

We assessed the predictive capacity of BL sNfL levels for the following outcomes: EDSS ≥4, clinically silent disease, T2 lesion volume, and cerebral volume.

Results

Patients with sNfL values at screening (N=258) above the 90th (n=176), 95th (n=157), 97.5th (n=149), and 99th (n=129) percentiles (adjusted for other relevant covariates) had a significantly higher risk of EDSS≥4 at Year 15 for BL model (odds ratio 2.45 [95% CI: 1.05,5.68] p=0.0376; 2.60 [1.18,5.75] p=0.0181; 2.61 [1.20,5.66] p=0.0154; 2.47 [1.19,5.13] p=0.0150, for the 90th, 95th, 97.5th and 99th percentiles, respectively), and for on-study models at Year 1 (3.86 [1.16,12.78] p=0.0272; 3.38 [1.13,10.14] p=0.0296; 2.92 [1.02,8.35] p=0.0461; 2.98 [1.11,8.00] p=0.0305, respectively) and Year 2 (5.36 [1.26,22.85] p=0.0231; 4.88 [1.34,17.77] p=0.0163; 3.86 [1.18,12.66] p=0.0259; 3.34 [1.17,9.48] p=0.0237, respectively). Covariates that remained statistically significant with EDSS≥4 as the endpoint in most percentile models were lowest EDSS value up to Month 6 for BL and Year 1, and change in brain volume at Year 1, 2, and 5.

Conclusions

Findings in this unique long-term BENEFIT study suggest that higher sNfL values in early MS disease stages are independent predictors of long-term disability.

Collapse
Observational Studies Poster Presentation

P0876 - High and low efficacy therapy in secondary progressive multiple sclerosis after accounting for therapeutic lag. (ID 760)

Abstract

Background

In secondary progressive multiple sclerosis (SPMS), reduction in the rates of disability accrual after starting disease modifying therapy (DMT) has largely been limited to patients with ongoing inflammatory activity. A delayed treatment effect, termed therapeutic lag, may obscure therapeutic benefits in SPMS.

Objectives

To compare the effect of high and low efficacy DMT on disability outcomes in patients with recently active and inactive SPMS after accounting for therapeutic lag.

Methods

Using data from MSBase, a multinational MS registry, and OFSEP, the French MS registry, we identified patients with SPMS as per a previously validated objective definition. We identified patients treated with high- (natalizumab, alemtuzumab, mitoxantrone, ocrelizumab, rituximab, cladribine, fingolimod) or low-efficacy (interferons, glatiramer acetate, teriflunomide) DMT after SPMS onset. Based on our previous work, an individualised estimate of duration of therapeutic lag was calculated for each patient. Only events that occurred after the estimated therapeutic lag period were included in the analysis. Propensity score matching was used to select groups with comparable baseline characteristics. Disability and relapse outcomes were compared in paired, pairwise-censored analyses adjusted for visit density.

Results

Of 7359 patients with SPMS, 1000 patients fulfilled the criteria for study inclusion (510 active SPMS, 490 inactive SPMS). For the relapse outcomes, patients with active SPMS treated with high-efficacy DMTs experienced lower probabilities of relapses than low-efficacy DMTs (hazard ratio [HR] 0.7 [95%CI 0.5-0.9], p=0.006). Patients with inactive SPMS had similar probabilities of relapses in the high and low efficacy DMT groups (0.8 [0.6-1.2], p=0.39). No difference in the risk of 6-month sustained disability accumulation, or proportion of patients reaching EDSS>=7, was observed between groups when accounting for therapeutic lag.

Conclusions

The risk of disability accumulation in SPMS seems to be comparable in patients treated with high- and low- efficacy DMT. High efficacy DMT is superior to low efficacy therapy in reducing relapse activity in patients with active SPMS, but not those with inactive SPMS. Pre-treatment inflammatory activity, clinical or radiological, is a treatable target in SPMS which may benefit from higher-efficacy anti-inflammatory therapies.

Collapse