Background

New York became one of the first epicenters of the COVID-19 pandemic in the United States and many neurologists were faced with the unprecedented challenge of providing medical advice to patients with multiple sclerosis (MS) without the support of evidence-based scientific data. Large collaborative studies are needed to determine whether MS itself, or associated disease-modifying therapies (DMT), increase the risk of acquiring COVID-19 or worsen its course.

Objectives

We aim to characterize the patterns of COVID-19 infection in patients with MS and to identify risk factors for severe infection.

Methods

Demographics, MS and COVID-19 clinical features were collected on patients currently followed at 5 large MS Centers in New York City and the tri state area (MSSM, Columbia, Northwell, NYU, and Neurological Associates Of Long Island). Patients with MS or related disorders, who self-identified as diagnosed with COVID-19 by a healthcare provider (based on characteristic symptoms, radiographic findings and/or positive COVID-19 PCR/serology when available) were included. The severity of COVID-19 infection was measured by a 4-point ordinal scale (home care, hospitalization, ICU, death). Univariate and multivariate logistic regression models were used to assess associations of demographic variables with hospitalization.

Results

Our cohort included 349 patients with median age of 45 (range 13-76), 70.8% female, 25.3% African-American, 23.7% Hispanic. Mean disease duration was 11.5y [SD 9.1]. The prevalence of DMT use was 87.2%, and 80.2% were ambulatory without assistance. Forty-eight (14.2%) patients were hospitalized, and 13 (3.9%) patients died. Multivariate logistic regression models showed associations between EDSS ≥6 (OR 3.9 [95% CI, 1.7-8.8]), obesity (OR 2.4 [95% CI, 1.1-4.9]) and age (OR per 10 year increase: 1.5 [95% CI, 1.1-2.2]) with hospitalization for COVID-19. There were no significant associations between race, ethnicity, comorbidities (cardiac, pulmonary or diabetes), smoking status, or specific DMT and severe COVID-19 infection requiring hospitalization.

Conclusions

Age, obesity, and higher EDSS independently predicted severe COVID -19 infection necessitating hospitalization. This is in agreement with COVID -19 outcome predictors in the general population and other MS cohorts. Older patients with limited mobility should be counseled to maintain increased vigilance during the ongoing pandemic.

Background

Natalizumab extended interval dosing (EID) is associated with lower risk of progressive multifocal leukoencephalopathy than every-4-week standard interval dosing (SID). Independent real-world (RW) studies suggest that natalizumab effectiveness is maintained in patients who switch from SID to EID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a learning health system comprised of a collaborative network of healthcare institutions that provides access to RW clinical and MRI data collected using standardized acquisition protocols.

Objectives

Compare the effectiveness of natalizumab EID and SID using quantitative MRI metrics from highly standardized RW images in MS PATHS.

Methods

An MRI segment was defined as 2 MRI acquisitions and associated interval duration. MS PATHS patients with ≥1 MRI segment, ≥2 infusion cycles (infusion interval >21 days and ≤84 days), and complete covariate information were eligible. MRI segments with average infusion cycle (AIC) ≤35 days and >35 days were defined as SID and EID, respectively. For each MRI segment, new T2 lesions and changes in T2 lesion volume (T2LV) and brain parenchymal fraction (BPF) were compared for SID and EID using inverse probability weighting (IPW) with logistic regression and robust linear regression.

Results

IPW analysis included 327 SID patients (596 MRI segments) and 67 EID patients (85 MRI segments). The mean AIC for SID was 29.5 (standard deviation [SD] 1.8) days and 40.8 (4.9) days for EID. Mean MRI segment duration for SID and EID was 9.7 (SD 5.5) and 9.6 (5.3) months, respectively. Proportions of patients with no new T2 lesions were similar for the SID and EID groups (75.6% vs 75.3%; adjusted odds ratio for 0 vs ≥1 lesion=0.967 [95% CI 0.500, 1.871]; P=0.921). SID and EID patients did not differ significantly in adjusted T2LV change (−0.070 [95% CI −0.129, 0.111] mL vs 0.022 [−0.132, 0.180] mL; P=0.233) or BPF change (−0.1222% [95% CI −0.1524%, −0.0921%] vs −0.1442% [−0.2234%, −0.0649%]; P=0.617).

Conclusions

MRI activity was low in SID and EID MS PATHS patients, and there were no significant differences in MRI outcomes between the 2 groups. These results confirm and extend previous RW studies of natalizumab EID effectiveness. Study limitations include modest EID sample size and potential channeling bias. The ongoing phase 3b randomized trial NOVA (clinicaltrials.gov NCT03689972) will further evaluate the effectiveness of natalizumab EID versus SID.

MS PATHS is supported by Biogen.

Background

Natalizumab extended interval dosing (EID) is associated with lower risk of progressive multifocal leukoencephalopathy than every-4-week standard interval dosing (SID). Independent real-world (RW) studies suggest that natalizumab effectiveness is maintained in patients who switch from SID to EID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a learning health system comprised of a collaborative network of healthcare institutions that provides access to RW clinical and MRI data collected using standardized acquisition protocols.

Objectives

Compare the effectiveness of natalizumab EID and SID using quantitative MRI metrics from highly standardized RW images in MS PATHS.

Methods

An MRI segment was defined as 2 MRI acquisitions and associated interval duration. MS PATHS patients with ≥1 MRI segment, ≥2 infusion cycles (infusion interval >21 days and ≤84 days), and complete covariate information were eligible. MRI segments with average infusion cycle (AIC) ≤35 days and >35 days were defined as SID and EID, respectively. For each MRI segment, new T2 lesions and changes in T2 lesion volume (T2LV) and brain parenchymal fraction (BPF) were compared for SID and EID using inverse probability weighting (IPW) with logistic regression and robust linear regression.

Results

IPW analysis included 327 SID patients (596 MRI segments) and 67 EID patients (85 MRI segments). The mean AIC for SID was 29.5 (standard deviation [SD] 1.8) days and 40.8 (4.9) days for EID. Mean MRI segment duration for SID and EID was 9.7 (SD 5.5) and 9.6 (5.3) months, respectively. Proportions of patients with no new T2 lesions were similar for the SID and EID groups (75.6% vs 75.3%; adjusted odds ratio for 0 vs ≥1 lesion=0.967 [95% CI 0.500, 1.871]; P=0.921). SID and EID patients did not differ significantly in adjusted T2LV change (−0.070 [95% CI −0.129, 0.111] mL vs 0.022 [−0.132, 0.180] mL; P=0.233) or BPF change (−0.1222% [95% CI −0.1524%, −0.0921%] vs −0.1442% [−0.2234%, −0.0649%]; P=0.617).

Conclusions

MRI activity was low in SID and EID MS PATHS patients, and there were no significant differences in MRI outcomes between the 2 groups. These results confirm and extend previous RW studies of natalizumab EID effectiveness. Study limitations include modest EID sample size and potential channeling bias. The ongoing phase 3b randomized trial NOVA (clinicaltrials.gov NCT03689972) will further evaluate the effectiveness of natalizumab EID versus SID.

MS PATHS is supported by Biogen.