Objective: To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort. Methods: We included newly diagnosed patients (2010–2016) followed in 20 MS centers and collected demographic and clinical data. We evaluated baseline factors related to the presence of comorbidities and the association between comorbidities and the clinical course of MS and the time to the first treatment switch. Results: The study cohort included 2,076 patients. Data on comorbidities were available for 1,877/2,076 patients (90.4%). A total of 449/1,877 (23.9%) patients had at least 1 comorbidity at MS diagnosis. Age at diagnosis (odds ratio 1.05, 95% confidence interval [CI] 1.04–1.06; p < 0.001) was the only baseline factor independently related to the presence of comorbidities. Comorbidities were not significantly associated with the choice of the first disease-modifying treatment, but were significantly associated with higher risk to switch from the first treatment due to intolerance (hazard ratio 1.42, CI 1.07–1.87; p = 0.014). Association of comorbidities with risk of switching for intolerance was significantly heterogeneous among treatments (interferon β, glatiramer acetate, natalizumab, or fingolimod; interaction test, p = 0.04). Conclusions: Comorbidities at diagnosis should be taken into account at the first treatment choice because they are associated with lower persistence on treatment.

Objective: Despite cognitive tests have been validated in multiple sclerosis (MS), a neuropsychological evaluation is not implemented in the Expanded Disability Status Scale (EDSS) scoring. Methods: We used the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and orientation tests (OTs) to measure the cerebral functional system (CFS) score and to evaluate its impact on the EDSS. We compared EDSS calculated as usual (Native-EDSS) and after the use of the BICAMS and OT (NPS-EDSS). Results: We tested 604 MS patients with BICAMS, OTs, and EDSS. In all, 384 patients (63.6%) had at least one altered test at the BICAMS. Older age, lower education, higher Native-EDSS, and male gender were independently associated with at least one impaired BICAMS test. Native-EDSS was different from NPS-EDSS (−0.112; p < 0.001) in 99 patients (16%). When considering patients with a Native-EDSS ⩽ 4.0, the proportion of miscalculated EDSS was 25%. Conclusion: The use of brief neuropsychological tests leads to a more accurate CFS assessment in two-thirds of MS patients, and a more accurate EDSS calculation in 25% of patients with a score ⩽4.0. This may help clinicians to better recognize cognitive impairment in everyday clinical practice, especially in the case of isolated cognitive worsening.

With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences. To identify prognostic factors for early switch after first therapy choice. Newly diagnosed relapsing–remitting MS patients from 24 Italian centers were included. We evaluated the association of baseline demographics, clinical, and magnetic resonance imaging (MRI) data to the switch probability for lack of efficacy or intolerance/safety with a multivariate Cox analysis and estimated switch rates by competing risks models. We enrolled 3025 patients. The overall switch frequency was 48% after 3 years. Switch risk for lack of efficacy was lower with fingolimod (hazard ratio (HR) = 0.50; p = 0.009), natalizumab (HR = 0.13; p < 0.001), dimethyl-fumarate (HR = 0.60; p = 0.037), teriflunomide (HR = 0.21; p = 0.031) as compared to interferons. Younger age (HR = 0.96; p < 0.001), diagnosis delay (HR = 1.23; p = 0.021), higher baseline Expanded Disability Status Scale (HR = 1.17; p = 0.001), and spinal cord lesions (HR = 1.46; p = 0.001) were independently associated with higher inefficacy switch rates. We found lower switch for intolerance/safety with glatiramer acetate (HR = 0.61; p = 0.001), fingolimod (HR = 0.35; p = 0.002), and dimethyl-fumarate (HR = 0.57; p = 0.022) as compared to interferons, while it increased with natalizumab (HR = 1.43; p = 0.022). Comorbidities were associated with intolerance switch (HR = 1.28; p = 0.047). Several factors are associated with higher switch risk in patients starting a first-line therapy and could be integrated in the decision-making process of first treatment choice.

Background: Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines. Objective: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs). Methods: Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT. Results: 19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74–4.58, p < 0.001) and fingolimod (0.58% vs 1.62%, RR = 2.65, 95% CI = 1.75–4.00, p < 0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% versus 19.4% in the pre-vaccination era (RR = 0.86, p = 0.74) and it was 3.9% in all the other DMT groups versus 11.9% in the pre-vaccination period (RR = 0.33, p = 0.02). Conclusions: The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab.