ABSTRACT
Introduction: Natalizumab (NTZ) is a widely used second-line treatment for multiple sclerosis (MS), administered with a fourweeks infusion interval. Extending the interval between two infusions could reduce the economic costs of this therapy, the incidence of rare side effects such as progressive multifocal leukoencephalopathy and improve the patients' quality of life with less frequent day-hospitalizations. Aim(s): At the Fondation Rothschild Hospital in Paris, for sanitary reasons during COVID-19 lockdown, patients were systematically switched to a 6-weeks NTZ extended-interval dosing (EID) from April 2020 to the present day. In this monocentric retrospective study, we aimed at evaluating the clinical and radiological efficacy of NTZ EID compared to the 4 weeks standard-interval dosing (SID) in adult patients with active MS. Method(s): We screened the local pharmacy database for NTZ administration and included all adult patients diagnosed with MS and treated with NTZ for at least 6 months with a SID, before being treated with an EID for at least 12 months. Data about disease activity, treatments received, MRI and clinical data were retrospectively collected from the local French MS observatory (OFSEP) database. The primary outcomes were the incidence of MS attacks, new MRI lesions or the presence of gadoliniumenhancing lesions during NTZ SID or EID. Result(s): A total of 49 patients were included for final analysis. 21 (42.9%) were male, with a median MS duration from the first symptom to NTZ introduction of 60 [30, 110] months. Patients were treated for a median time of 34.6 [15.1, 72.4] months by a SID, followed by a median time of 18.6 [14.7, 20.6] months by an EID. The mean EDSS before EID was 2.0 [1.5, 3.0] and 1.5 [0.0, 2.8] during EID. During natalizumab SID, one patient (2%) presented a new MS attack, 5/45 patients (11%) had new MRI lesions, with gadolinium enhanced lesions in 1/45 (2%) patient. This did not differ significantly during natalizumab EID where no MS attack were observed (p = 1), new MRI lesions were present in 1/41 (2%) patient and no gadolinium-enhancing lesion was found. Patients were followed for a median time of 130 [78, 205] months in total. Conclusion(s): We did not observe more clinical attacks or MRI activity signs when extending the interval between NTZ infusions from 4 to 6 weeks. Data from randomized controlled trials are needed to allow better consideration of side-effects and safety.
ABSTRACT
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.