Background and objectives: alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. Methods: lymphocyte subset counts were assessed longitudinally using linear mixed models. Subset counts at baseline and during follow-up were correlated with relapse rate, adverse events, or magnetic resonance (MRI) activity. Results: we recruited 150 patients followed for a median of 2.7 years (IQR: 1.9–3.7). Total lymphocytes, CD4, CD8, and CD20 significantly decreased in all patients over 2 years (p < 0.001). Previous treatment with fingolimod increased the risk of disease activity and adverse events (p = 0.029). We found a higher probability of disease reactivation in males and in patients with over three active lesions at baseline. Higher EDSS scores at baseline and longer disease duration predicted the switch to other treatments after alemtuzumab. Discussion and conclusions: Our real-world study supports data from clinical trials in which lymphocyte subsets were not useful for predicting disease activity or autoimmune disease during treatment. The early use of an induction therapy such as alemtuzumab in patients with a lower EDSS score and short history of disease could mitigate the risk of treatment failure.

Pivotal trials showed the effectiveness of the monoclonal antibody ocrelizumab in relapsing and progressive multiple sclerosis (MS). However, data on everyday practice in MS patients and markers of treatment effectiveness are scarce. We aimed to collect real-world data from ocrelizumab-treated MS patients, relapsing-remitting (RR) and progressive MS patients (PMS), including active secondary progressive MS (aSPMS) and primary progressive MS (PPMS) patients, and to explore potential prognostic factors of clinical outcome. Patients were enrolled at MS centres in the Campania region, Italy. We collected clinic-demographic features retrospectively one year before ocrelizumab start (T₋₁), at ocrelizumab start (T₀), and after one year from ocrelizumab start (T₁). We explored possible clinical markers of treatment effectiveness in those patients receiving ocrelizumab treatment for at least one year using multilevel-mixed models. We included a total of 383 MS patients (89 RRMS and 294 PMS; 205 females, mean age: 45.8 ± 11.2, disease duration: 12.7 ± 11.6 years). Patients had a mean follow-up of 12.4 ± 8.2 months, and 217 patients completed one-year ocrelizumab treatment. Overall, EDSS increased from T₋₁ to T₀ (coeff. = 0.30, 95% coefficient interval [CI] = 0.19–0.41, p < 0.001) without a further change between T₀ and T₁ (p = 0.61). RRMS patients did not show an EDSS change between T₋₁ and T₀ nor between T₀ and T₁. Conversely, PMS patients showed EDSS increase from T₋₁ to T₀ (coeff. = 0.34, 95% CI = 0.22–0.45, p < 0.001) without a further change between T₀ and T₁ (p = 0.21). PMS patients with a time from conversion shorter than 2 years showed increased EDSS from T₋₁ to T₀ (coeff. = 0.63, 95% CI = 0.18–1.08, p = 0.006) without a further change between T₀ and T₁ (p = 0.94), whereas PMS patients with a time from conversion longer than 2 years showed increased EDSS from T₀ to T₁ (coeff. = 0.30, 95% CI = 0.11–0.49, p = 0.002). Naïve patients showed an EDSS decrease between T₀ and T₁ (coeff. = −0.30, 95% CI = −0.50–−0.09, p = 0.004). In conclusion, our study highlighted that early ocrelizumab treatment is effective in modifying the disability accrual in MS patients.

Siponimod, a selective modulator of sphingosine 1-phosphate receptors 1 (S1P1) and 5 (S1P5), has recently been marketed for patients with Secondary Progressive Multiple Sclerosis (SPMS). Herein, we report three SPMS patients presenting disease reactivation in the first three months after switching from fingolimod to siponimod. Fingolimod binds to S1P1, S1P3, S1P4 and S1P5 receptors. S1P3 holds a central role in eliciting central proinflammatory responses, thus it has been hypothesized that upregulation of S1P3 may be the mechanism behind relapses after switching from fingolimod to siponimod. Further studies are needed to investigate the safety and efficacy of this treatment sequencing.

Background: Many factors are believed to be positively associated with the incidence of relapses in people with multiple sclerosis (MS), including infections. However, their role is still controversial. We aimed to investigate whether symptomatic infections in people with MS increase the risk of relapse in the short, medium, or long term. Materials and Methods: We enrolled consecutive patients with relapsing MS (RMS) from October to December 2018. From enrolment up to September 2020, an online questionnaire investigating the occurrence of infections was sent via WhatsApp^® monthly to the enrolled patients, while in-person visits were performed every six months. When patients complained of symptoms compatible with relapses, they attended an extra in-person visit. Results: We enrolled 155 patients with RMS, and 88.38% of patients were treated with disease-modifying therapies. In the dataset, 126,381 total patient days, 78 relapses, and 1202 infections were recorded over a period of about 2 years. No increased risk of relapse after clinically manifest infections was found in the short-, medium-, or long-term period. No correlation was found between all infections and the number of relapses (p = 0.212). The main analyses were repeated considering only those infections that had at least two of the following characteristics: duration of infection ≥ 4 days, body temperature > 37° Celsius, and the use of drugs (antibiotics and/or antivirals), and no significant associations were observed. Conclusions: No associations between infections and relapses were observed, likely suggesting that disease-modifying therapies may protect against the risk of relapse potentially triggered by infections.