Background

Risk factors associated with the severity of COVID-19 in patients with multiple sclerosis (MS) begin to be identified from several cohort studies. Disease modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities.

Objectives

The objective was to describe the clinical characteristics and outcomes in patients with COVID-19 and to identify the factors associated with COVID-19 severity.

Methods

This multicenter, retrospective, observational cohort study (COVISEP registry, NCT04355611) included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020 and July 14, 2020. The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1: not hospitalized, no limitations on activities, to 7: death; cutoff at 3: hospitalized, not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Score (EDSS), comorbidities, COVID-19 characteristics and outcome. Univariate and multivariate logistic regression models were used to estimate the influence of collected variables on COVID-19 outcome.

Results

A total of 405 patients (mean age: 44.7 years, female/male: 293/112, mean disease duration: 13.4 years) were analyzed. Seventy-eight patients (19.3%) had a COVID-19 severity score ≥ 3, and 12 patients (3.0%) died from COVID-19. Median EDSS was 2.0 (range: 0-9.5), 326 patients (80.5%) were on DMT. There was a higher proportion of patients with COVID-19 severity score ≥ 3 among patients with no DMT relative to patients on DMTs (39.2% versus 14.4%, p<0.001). Multivariate logistic regression models determined that age (OR for 10 years: 1.8, 95% CI: 1.4-2.4), EDSS (OR for EDSS ≥ 6: 4.5, 95% CI: 2.0-10.0) were independent risk factors for COVID-19 severity score ≥ 3 (hospitalization or higher severity) while immunomodulatory treatment (interferon or glatiramer acetate) was associated with lower risk of COVID-19 severity score ≥ 3 (OR: 0.2, 95% CI: 0.05-0.8). EDSS was associated with the highest variability of COVID-19 severe outcome (R²= 0.18), followed by age (R²= 0.06) and immunomodulatory treatment (R²= 0.02).

Conclusions

EDSS and age were independent risk factors of severe COVID-19, while exposure to immunomodulatory DMTs (interferon and glatiramer acetate) were independently associated with lower COVID-19 severity. We did not find an association between other DMTs exposure (including immunosuppressive therapies) and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of MS patients during the COVID-19 pandemic.

Background

Therapeutic options are growing for active RRMS patients, however, few prospective studies are available to compare the efficacy of those treatments. Best Escalation Strategy in MS (BEST MS) started in France in 2013 when natalizumab (NTZ) and fingolimod (FTY) were the two most employed second-line therapies in active RRMS.

Objectives

To compare the efficacy between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting multiple sclerosis (RRMS).

Methods

BEST-MS is a French prospective multicentric study.

Patients with active RRMS (defined as at least 1 relapse in the last 12 months on a well-conducted 1^st line treatment with at least 9 T2 hyperintensities on MRI, OR at least 2 relapses in the last 12 months with evidence of active disease on MRI for naïve patients) were enrolled to be treated either with NTZ or FTY. Treatments choice was at the discretion of the physician.

Relapses, EDSS and brain MRI were collected at baseline and at 12 months.

The main outcome measure was the proportion of patients reaching No Evidence of Disease Activity (NEDA) at 12 months, defined as the absence of relapses, absence of new T2 lesions, absence of new gadolinium enhancing lesions and a stable EDSS score.

Results

230 patients were included (age: 38.2 yrs, F/M: 3.1, FTY: 117, NTZ: 113). There was no statistical difference between groups regarding baseline characteristics.

Treatment drop out rate was higher in FTY group (22% vs 12%, p<0.0001) and most of thoses cases were related to a lack of efficacy.

At M12, 43% of patients treated with NTZ reached NEDA versus 27% in the FTY group (p=0.04)

NTZ indicated a better efficacy regarding new T2 lesions (0.7 vs 1.4, p=0.01) and gadolinium enhancing lesions (0.03 vs 0.5, p<0.0001).

Relapse rate (ARR) was lower in NTZ group (0.2 vs 0.27, p = 0.04), even if most relapses occurred during the first 4 months of treatment in both groups.

Conclusions

NTZ showed higher efficacy than FTY on MRI in active RRMS patients. ARR was also lower in favor of NTZ, but most relapses occurred early. However, the rate of drop out was higher for patients treated with FTY.

Background

At any time in multiple sclerosis (MS) management, a disease-modifying therapy (DMT) stop, restart or change can occur. In PRO-MSACTIVE (NCT03589105), an open-label, single-arm, phase IV study designed to evaluate the efficacy, safety and impact of ocrelizumab on patient reported outcomes in patients with active relapsing MS (RMS), every patient’s treatment history was gathered.

Objectives

To describe the therapeutic management of French patients with active RMS (relapsing-remitting [RRMS] and secondary progressive [SPMS]), as reported at baseline, prior to the first ocrelizumab infusion (IV OCR).

Methods

PRO-MSACTIVE is being conducted in France (46 active centers) in patients with active RMS, ≥18 years old, naïve or pretreated with DMT. Washout periods between the last DMT taken by the patient and baseline IV OCR were pre-specified. For each patient, all previous DMTs were collected during the screening period, ≤4 weeks prior to baseline.

Results

Treatment history was documented for the 422 enrolled patients: 376 RRMS and 46 SPMS. Most (74.9%) had at least one previous DMT prior to the first IV OCR: 73.9% for RRMS and 82.6% for SPMS patients. The longest therapeutic sequence includes 8 DMTs prior to the first IV OCR. The most frequent previous DMTs were β interferons and assimilated products (IFN-AP) (51.4% all patients, 49.2% RRMS, 69.6% SPMS); selective oral immunosuppressants (30.8% all patients, 30.6% RRMS, 32.6% SPMS; mainly fingolimod); and teriflunomide (24.2% all patients, 24.5% RRMS, 21.7% SPMS). IFN-AP ranked first among the older DMTs (46.5% all patients, 45.0% RRMS, 58.7% SPMS). Mean time (standard deviation, SD) from the oldest DMT to the first IV OCR was 6.55 yrs (5.44) for RRMS patients, and 14.20 yrs (8.46) for SPMS patients. The most recent DMTs prior to IV OCR were fingolimod (22.8% all patients, 23.7% RRMS, 15.2% SPMS); dimethyl fumarate (14.7% all patients, 15.7% RRMS, 6.5% SPMS); teriflunomide (14.5% all patients, 14.6% RRMS, 13.0% SPMS); IFN-AP (14.0% all patients, 14.1% RRMS, 13.0% SPMS); and natalizumab (4.3% all patients, 4.5% RRMS, 2.2% SPMS). Mean time (SD) from the most recent DMT to the first IV OCR was 2.65 yrs (2.12) for RRMS patients and 3.01 yrs (2.85) for SPMS patients.

Conclusions

Treatment history with DMTs prior to the first IV OCR is well characterized in the PRO-MSACTIVE study. These data permit a better understanding of the therapeutic strategies in RMS patients in current medical practice.