Background

In the present pandemic, gathering information regarding Multiple Sclerosis (MS) patients with COVID-19 is needed.

Objectives

To investigate the incidence of COVID-19 in a Barcelona cohort of MS patients, to describe the characteristics of MS patients with COVID-19, and to identify risk factors for susceptibility and severity.

Methods

Retrospective cohort study of adult MS patients included from February to May 2020. COVID-19 and non-affected cases were identified through a COVID-19 mail survey and clinical visits. Demographic, clinical, MS characteristics, and laboratory data (lymphocyte and CD19+ count, immunoglobulins, and vitamin D) were obtained. Serological SARS-CoV-2 testing was performed in all suspected cases. We examined the relationship between the previously mentioned variables with COVID-19 susceptibility and severity.

Results

Out of the 2903 surveys sent, a total of 875 were answered. 117 (13.37%) patients were excluded for not meeting inclusion criteria. 48 out of 758 were suspected COVID-19 and the remaining were classified as non-COVID-19. The estimated incidence was 6.3%. 45 additional suspected COVID-19 cases were detected in clinical visits. In the multivariate analysis, COVID-19 susceptibility was associated with being younger (OR 0.54, IC95% 0.34-0.87,p<0.01), having had contact with a confirmed case (OR 193.20, IC95% 55.34-674.43,p<0.01), living in Barcelona (OR 2.35, IC95% 1.08-5.09, p=0.03) and a longer MS disease duration (OR 1.43, IC95% 1.10-1.85,p<0.01). In patients treated with an anti-CD20 therapy, COVID-19 susceptibility increased with treatment duration (OR 3.36, IC95% 1.42-7.96, p<0.01). 19 (20.43%) of the 93 COVID-19 cases were hospitalized, 9(9.68%) presented a severe course and 2(2.15%) of them died. In the univariate analysis, older patients with comorbidities, a progressive and longer MS duration, and without disease-modifying therapies, presented a more severe disease although these results were not observed in the multivariate analysis. Out of the 79 (84.9%) with serological test, 45.6% had generated antibodies and 17.6% in patients receiving anti-CD20. No relation of lymphopenia, vitamin D, or immunoglobulins levels with COVID-19 susceptibility or severity was found.

Conclusions

MS patients present similar incidence, risk factors, and outcomes for COVID-19 than the general population. Patients treated with an anti-CD20 therapy for a longer period of time might be in a higher risk of COVID-19 and of generating lower antibody response.

Background

In the constantly evolving field of MS, personalized medicine is still one of the most important unmet need that requires further attention

Objectives

We aimed to develop a dynamic risk calculator to predict the long-term prognosis of MS in the context of a large MS Centre in Catalonia

Methods

This is an observational study based on data prospectively acquired from a deeply phenotyped CIS cohort from Barcelona. We first built a natural history baseline risk score (BRS) for predicting moderate disability, integrating baseline prognostic factors: Sex, age at CIS, CIS topography, number of T2 lesions, contrast-enhancing lesions (CEL) and oligoclonal bands. This BRS was designed as follows: For untreated patients, we built a Weibull model to estimate the median time to confirmed EDSS 3.0 and with these estimates we identified risk groups based on the median of the cut-offs of 2000 survival trees. Then we obtained the BRS of the full cohort. In patients with more than ten years of follow-up, we performed an inverse probability weighting to balance patients during their follow up for the propensity of being treated or lost to follow-up. The weights were estimated via a proportional hazards (PH) Cox model considering both baseline information (CIS year, BRS) and time-dependent (diagnosis status, new T2 lesions, CEL and cumulative number of relapses). Finally, a weighted PH Cox model was built to estimate the time to confirmed EDSS 3.0 considering the BRS and time-dependent events (new T2 lesions, cumulative number of relapses and first or second-line treatment use). Sensitivity analyses using other disability outcomes and different follow-ups were conducted.

Results

Of 956 patients, 577 (60.4%) were untreated before confirmed EDSS 3.0. Two BRS were obtained: low and high-BRS. Of 400 patients followed for more than ten years, 226 (56.5%) were low-BRS and 174 (43.5%) were high-BRS. High-BRS showed a HR=2.16 95%CI (1.16,4.02). Each new T2 lesion presented HR=1.04 95%CI (1.00,1.08) and each new relapse HR=1.46 95%CI (1.23,1.74). Being on second-line treatment showed a protective effect (HR=0.23 95%CI (0.06,0.94)) but no association was found for first-line treatments (HR=1.32 95%CI (0.67,2.60). Sensitivity analyses confirmed the association between BRS, new T2 lesions and the accumulation of relapses with the prognosis. However, treatment results were inconclusive.

Conclusions

Presenting a high-BRS doubles the risk of reaching moderate disability. Each new lesion and new relapse increses the risk by 4% and 46%, respectively; and second-line treatments seem to be protective. If validated, this risk calculator could be a crucial step to personalized medicine.

Background

The highly effective therapies for multiple sclerosis (MS) could potentially interfere in the immune response against novel antigens, but evidence is lacking.

Objectives

To evaluate the immunogenicity to the hepatitis B virus vaccine (HBV-v) in MS patients who are candidate to highly effective therapies.

Methods

This is an observational retrospective cohort study. MS patients were eligible if they had a complete HBV-v primo-vaccination course (40 mcg or adjuvated 20 mcg HBV-v at months 0, 1, 2 and 6-12) and a post-vaccination serology at least 1 month after the last dose, to assess the response to the vaccine. Seroprotection status (VHB surface antigen antibody titers of at least 10 UI/L) and geometric mean antibody titers were evaluated taking into account the time of vaccination in relation to the specific MS disease-modifying therapies (DMT). We considered the DMT received at baseline (onset of vaccination) as well as, the possible treatment change over the course of vaccination.

Results

153 patients were included, with mean age 48 (SD 8.6) years, of which 68% were female. Mean disease duration was 13.8 (SD 9.4) years. Median EDSS was 4 (IQR 3). 78 patients (51%) were under DMT at the onset of vaccination and 115 (75.2%) patients changed their DMT during the course of vaccination. The global seroprotection rate was 66.7% (IC 95% 58.6-74.1). The highest seroprotection rate was observed in non-treated patients (N=17; 94.1% 95%CI 71.3-99.0) and in those treated with injectables, dimethyl fumarate, teriflunomide or natalizumab (N=31; 96.8% 95%CI 83.3%-99.9%). Starting anti-CD20 therapy during the course of vaccination reduced the seroprotection rate regardless of the preceding therapeutic situation: 1) non-treated patients (N=40; 52.5% 95%CI 36.1%-68.5%), 2) treated with injectables, dimethylfumarate, teriflunomide or natalizumab (N=33; 48.5% 95%CI 30.8%-66.5%) and 3) treated with fingolimod (N=11; 18.2% 95%CI 23%-51.8%). Onset of AntiCD20 also resulted in a significant decrease in the antibody titers (p<0.001) compared to those without AntiCD20. There was a dose-gradient effect in the achieved seroprotection with the number of vaccine doses administered before the onset of the anti-CD20 therapy (16.7%, 30%, 66.7% and 92.9% with one, two, three and four doses, respectively).

Conclusions

MS patients on anti-CD20 therapy mount deficient immune responses to VHB vaccination and therefore, vaccination should be completed in advance of treatment onset.

Background

Comorbidities and adverse health behaviors are associated with worse outcomes in multiple sclerosis (MS) and increased use of healthcare resources. Some comorbid conditions are more frequent in MS compared to the general population. The frequency and impact of comorbidities in our region is unknown.

Objectives

Describe the frequency of common comorbidities, adverse health behaviors, and healthcare resource usage in MS patients compared to the general population in Catalonia.

Methods

This is a population-based case-control study of the primary healthcare information system that covers 80% of the population of Catalonia. Cases were identified using the CIE-10 MS code (G35), and age/sex- matched controls (ratio 1:5) were randomly chosen, if they had at least one visit since 2006 and did not have active CIE-10 coding for any demyelinating disease. We obtained information on demographics (age, sex, socioeconomic status), comorbidities (by count and type), adverse health behaviors (smoking, alcohol), annual visits (primary care and specialists), sick leave days and medication dispensing.

Bivariate analysis and adjusted logistic regressions were done and odds ratios (OR) with 95% confidence interval (CI) were calculated.

Results

5548 MS cases and 27710 controls were included. 70% were female and mean age was 48.3 years. A total of 3334 (60.1%) of cases vs. 15756 (56.8%) of controls had at least one comorbidity (p<0.001). A higher frequency of comorbidities was found in MS in the 20-39 (OR: 1.377; 95%CI: 1.229-1.542) and 40-59 (OR: 1.231; 95%CI: 1.135-1.336) age ranges, whereas it was lower in 60-79 (OR: 0.648; 95%CI: 0.551-0.763) and >80 years (OR: 0.268; 95%CI: 0.115-0.625) age ranges. Socioeconomic deprivation was associated with a higher presence of comorbidities in MS cases (OR: 1.456; 95%CI: 1.161-1.824). Stroke (OR: 1.513; 95%CI: 1.173-1.952) and epilepsy (OR 2.566; 95%CI: 2.034-3.237), as well as any psychiatric disorder (OR 1.425; 95%CI: 1.377-1.519), bipolar disorder (OR: 1.882 95%CI: 1.335-2.654), or major depression (OR: 1.791: 95%CI 1.660-1.932) were more frequent in MS. Cardiovascular diseases were more frequent in males, whereas psychiatric diseases were more frequent in females. MS cases had higher annual sick leave days (11 vs. 6.7; p<0.001) and nurse (3 vs. 1.7; p<0.001), primary care (5 vs. 3.8; p<0.001) and specialist visits (11.9 vs. 0.5; p<0.001), as well as yearly medication dispensing. MS patients were more prone to smoking but not to alcohol consumption, especially among males.

Conclusions

MS patients have higher risk of psychiatric comorbidities, stroke and epilepsy, as well as adverse health behaviors and higher healthcare resource usage than the general population. The profile of comorbidities differs between women and men. Comorbidities are more frequent in the mos deprived socioeconomic strata.

Background

The highly effective therapies for multiple sclerosis (MS) could potentially interfere in the immune response against novel antigens, but evidence is lacking.

Objectives

To evaluate the immunogenicity to the hepatitis B virus vaccine (HBV-v) in MS patients who are candidate to highly effective therapies.

Methods

This is an observational retrospective cohort study. MS patients were eligible if they had a complete HBV-v primo-vaccination course (40 mcg or adjuvated 20 mcg HBV-v at months 0, 1, 2 and 6-12) and a post-vaccination serology at least 1 month after the last dose, to assess the response to the vaccine. Seroprotection status (VHB surface antigen antibody titers of at least 10 UI/L) and geometric mean antibody titers were evaluated taking into account the time of vaccination in relation to the specific MS disease-modifying therapies (DMT). We considered the DMT received at baseline (onset of vaccination) as well as, the possible treatment change over the course of vaccination.

Results

153 patients were included, with mean age 48 (SD 8.6) years, of which 68% were female. Mean disease duration was 13.8 (SD 9.4) years. Median EDSS was 4 (IQR 3). 78 patients (51%) were under DMT at the onset of vaccination and 115 (75.2%) patients changed their DMT during the course of vaccination. The global seroprotection rate was 66.7% (IC 95% 58.6-74.1). The highest seroprotection rate was observed in non-treated patients (N=17; 94.1% 95%CI 71.3-99.0) and in those treated with injectables, dimethyl fumarate, teriflunomide or natalizumab (N=31; 96.8% 95%CI 83.3%-99.9%). Starting anti-CD20 therapy during the course of vaccination reduced the seroprotection rate regardless of the preceding therapeutic situation: 1) non-treated patients (N=40; 52.5% 95%CI 36.1%-68.5%), 2) treated with injectables, dimethylfumarate, teriflunomide or natalizumab (N=33; 48.5% 95%CI 30.8%-66.5%) and 3) treated with fingolimod (N=11; 18.2% 95%CI 23%-51.8%). Onset of AntiCD20 also resulted in a significant decrease in the antibody titers (p<0.001) compared to those without AntiCD20. There was a dose-gradient effect in the achieved seroprotection with the number of vaccine doses administered before the onset of the anti-CD20 therapy (16.7%, 30%, 66.7% and 92.9% with one, two, three and four doses, respectively).

Conclusions

MS patients on anti-CD20 therapy mount deficient immune responses to VHB vaccination and therefore, vaccination should be completed in advance of treatment onset.