Sclerosis, Volume 3, Issue 4 (December 2025) – 3 articles

Background: There is varied practice with Disease-Modifying Treatment (DMT) for Multiple Sclerosis worldwide. We evaluated early DMT initiation within a real-world population for long-term outcomes. Method: The Scottish Multiple Sclerosis Register (SMSR) identified participants diagnosed with Relapsing Remitting Multiple Sclerosis (RRMS) in 2010/2011. We compared two groups of propensity-matched participants at diagnosis, who went on to receive either early treatment (<12 months from diagnosis) or late/never treated. Participants underwent detailed clinicoradiological evaluation and patient-reported outcome measures 11–13 years post-diagnosis. The primary outcome was mean Expanded Disability Status Scale (EDSS). Results: The SMSR identified 298 participants. A total of 141 had complete retrospective clinical data and 81 agreed to participate, with 32 successfully matched (16 pairs). Median time on DMT was 10.8 years (range 0.4–12.5) for those treated early and 4.0 (0–11.5) years for the late/never-treated group. A total of 7/16 (44%) never received a DMT of those not treated early. All early-treated participants commenced first-line DMT (5/16 subsequently escalated to second-line DMTs). Of those treated later (9/16), 7/9 participants (78%) commenced first-line and 2/9 s-line DMT. There were no serious adverse events identified with any DMT. There was no significant difference in the primary outcome, with mean EDSS 3.93 in the late/never-treated group vs. 4.53 in the early-treated group at 11–13 years post-diagnosis (p = 0.57). There was no significant difference in median change in EDSS from the time of diagnosis to prospective assessment between early and late/never-treated groups. Patient Reported Outcome Measurement Information System (PROMIS) scores for cognition favoured no early treatment (p = 0.02), whilst satisfaction with treatment choice favoured early treatment (p = 0.03). Conclusions: Our cohort did not show clear benefit with early DMT in RRMS, contrasting with other larger studies, with no significant differences between early and late/never-treated patients on clinicoradiological outcomes. Possible explanations include confounding by variables not included in matching and group allocation based on diagnosis date rather than first clinical symptom. Most participants were treated with injectable DMTs, not in keeping with current practice. A prospective, long-term follow-up deep phenotyping study would help characterise benefits of early DMT use, but this is clearly challenging in practice. Full article

Objectives: The purpose of this study was to analyze the effect of daily intake of cladribine tablets on the course of multiple sclerosis (MS) while monitoring for 1–4 years during and after the course in several neurological clinics from different regions of the Russian Federation. Materials and Methods: Information was collected on 235 patients from 12 neurological clinics and regional centers for MS, who were observed for an average of 3.4 years after starting treatment with cladribine. Results: An independent analysis of cases of prescription of cladribine in tablets showed that the reason for prescription of cladribine was highly active MS (HAMS) in 159 patients (67.7%), rapidly progressive MS (RPMS) in 20 patients (8.5%), active remitting MS in 50 patients (21.3%) and secondary progressive MS (SPMS) with exacerbations in 6 (2.5%). Among them, only 12 patients (5.1%) had not previously received DMTs, i.e., in these cases, the drug was prescribed as the first DMT. In total, 22 patients had previously received natalizumab, 5—ocrelizumab, and in 1 case—fingolimod. The remaining 207 patients were crossed over from the first-line DMTs. In all cases, there was a decrease in the frequency of exacerbations during and after the completion of the course of cladribine. Exacerbations between the first and second courses of cladribine were noted in 36 patients (15.3% of all treated), almost half of the cases—those who previously received natalizumab (17 exacerbations, or 47.2% of all exacerbations between the 1st and 2nd courses of cladribine), and in 3 cases—from ocrelizumab (in 60% of all patients crossed over from ocrelizumab). During 4 years of follow-up after a full course of cladribine, exacerbations were in 14 patients (6% of all patients included in the analysis), of which in 6 cases—after crossover from natalizumab. Discussion and Conclusions: The data obtained are generally consistent with the results of meta-analyses and reviews published recently, but high probability of exacerbations in patients who were crossed over from second-line drugs such as natalizumab and ocrelizumab were seen. The crossover from natalizumab is carried out more often due to the increased risk of developing progressive multifocal encephalopathy (PML). It is likely that the restoration of MS activity after the withdrawal of natalizumab is quite frequent, cladribine tablets were not able to fully prevent this. Such a crossover does not seem to be optimal, unlike the crossover from first-line DMTs. If such a crossover is still planned, it could be performed within 4 weeks after stopping natalizumab. Full article

Chalcones, a class of flavonoid compounds, are recognized for their unique biological properties, and especially for their antithrombotic, anti-inflammatory, and antioxidant health-promoting properties against inflammation-related disorders. Chalcones are phytochemicals naturally found in plants, fruits, and vegetables, such as tomatoes, apples, and licorice. Their characteristic chemical structure, which includes two aromatic rings and an α,β-unsaturated carbonyl group, makes them particularly versatile for pharmaceutical use. At the same time, chalcones exhibit strong antioxidant activity by neutralizing free radicals and enhancing endogenous antioxidant defense systems, such as glutathione. Structural modifications have improved their biological activity, leading to important applications in the treatment of atherosclerosis and cardiovascular diseases, cancer, neurodegenerative diseases, and inflammatory disorders. In addition, they have been successfully used in agriculture as natural pesticides and in the food industry as antioxidant additives. This review demonstrates the interdisciplinary importance of chalcones, highlighting the need for further research into their molecular mechanisms of action. A deeper understanding of their properties may open new avenues for the development of innovative drugs and environmentally friendly applications. In this way, chalcones can be a decisive factor in improving human health and environmental sustainability. Full article