Prospective observational study to evaluate treatment satisfaction and effectiveness in patients with relapsing multiple sclerosis starting cladribine tablets (CLADREAL) in Italy.

Disease-modifying therapies (DMTs) for multiple sclerosis (MS) reduce relapse frequency, magnetic resonance imaging (MRI) activity, and slow disability progression. Numerous DMTs are approved for relapsing forms of MS although real-world data on patient-reported outcomes (PROs) and quality of life (QoL) are needed to inform treatment choice. Immune reconstitution therapy with cladribine tablets is a highly effective treatment for relapsing MS (RMS). We present the protocol for an observational study to prospectively assess the effectiveness of cladribine tablets on clinical and MRI parameters as well as on PROs, including treatment satisfaction, QoL, sleep quality, self-perceived health, fatigue, and physical function. Enrolled patients at study sites in Italy will be adults with RMS (including relapsing-remitting and active secondary progressive MS) who are either treatment naïve or have received at least one first-line disease modifying DMT or no more than one second-line DMT. The primary objective will be change in global treatment satisfaction measured with the Treatment Satisfaction Questionnaire for Medication Version 1.4 approximately 24 months after initiating cladribine tablets in patients switching from previous DMTs. Secondary objectives will include global treatment satisfaction at earlier timepoints, will comprise treatment naïve patients, and will quantify treatment effectiveness and tolerability. We will also assess relapses, disability progression, MRI activity, and other PROs at approximately 12 and 24 months. The findings will provide insight from daily clinical practice into the patient's experience to complement data from controlled trials and inform treatment choice. EU PAS Registration Number EUPAS49334 filed 17/10/2022.

Magnetic Resonance Imaging Evidence Supporting the Efficacy of Cladribine Tablets in the Treatment of Relapsing-Remitting Multiple Sclerosis.

Numerous therapies are currently available to modify the disease course of multiple sclerosis (MS). Magnetic resonance imaging (MRI) plays a pivotal role in assessing treatment response by providing insights into disease activity and clinical progression. Integrating MRI findings with clinical and laboratory data enables a comprehensive assessment of the disease course. Among available MS treatments, cladribine is emerging as a promising option due to its role as a selective immune reconstitution therapy, with a notable impact on B cells and a lesser effect on T cells. This work emphasizes the assessment of MRI's contribution to MS treatment, particularly focusing on the influence of cladribine tablets on imaging outcomes, encompassing data from pivotal and real-world studies. The evidence highlights that cladribine, compared with placebo, not only exhibits a reduction in inflammatory imaging markers, such as T1-Gd+, T2 and combined unique active (CUA) lesions, but also mitigates the effect on brain volume loss, particularly within grey matter. Importantly, cladribine reveals early action by reducing CUA lesions within the first months of treatment, regardless of a patient's initial conditions. The selective mechanism of action, and sustained efficacy beyond year 2, combined with its early onset of action, collectively position cladribine tablets as a pivotal component in the therapeutic paradigm for MS. Overall, MRI, along with clinical measures, has played a substantial role in showcasing the effectiveness of cladribine in addressing both the inflammatory and neurodegenerative aspects of MS.

Cladribine Tablets Mode of Action, Learning from the Pandemic: A Narrative Review.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system, characterized by chronic, inflammatory, demyelinating, and neurodegenerative processes. MS management relies on disease-modifying drugs that suppress/modulate the immune system. Cladribine tablets (CladT) have been approved by different health authorities for patients with various forms of relapsing MS. The drug has been demonstrated to deplete CD4+ and CD8+ T-cells, with a higher effect described in the former, and to decrease total CD19+, CD20+, and naive B-cell counts. COVID-19 is expected to become endemic, suggesting its potential infection risk for immuno-compromised patients, including MS patients treated with disease-modifying drugs. We report here the available data on disease-modifying drug-treated-MS patients and COVID-19 infection and vaccination, with a focus on CladT. MS patients treated with CladT are not at higher risk of developing severe COVID-19. While anti-SARS-CoV-2 vaccination is recommended in all MS patients with guidelines addressing vaccination timing according to the different disease-modifying drugs, no vaccination timing restrictions seem to be necessary for cladribine, based on its mechanism of action and available evidence. Published data suggest that CladT treatment does not impact the production of anti-SARS-CoV-2 antibodies after COVID-19 vaccination, possibly due to its relative sparing effect on naïve B-cells and the rapid B-cell reconstitution following treatment. Slightly lower specific T-cell responses are likely not impacting the risk of breakthrough COVID-19. It could be stated that cladribine's transient effect on innate immune cells likely contributes to maintaining an adequate first line of defense against the SARS-CoV-2 virus.

ProspeCtive study to evaluate efficacy, safety and tOlerability of dietary supplemeNT of Curcumin (BCM95) in subjects with Active relapsing MultIple Sclerosis treated with subcutaNeous Interferon beta 1a 44 mcg TIW (CONTAIN): A randomized, controlled trial.

BACKGROUND: multiple sclerosis (MS) is a complex disease sustained by several pathogenic mechanisms. As such, combination therapy strategies, targeting a range of disease mechanisms, might represent the ideal therapeutic approach. Here we investigated the efficacy of curcumin, a naturally occurring poly-phenolic phytochemical with potent anti-inflammatory and antioxidant properties, in subjects under treatment with IFN ß-1a, to test the effects of this combination therapy on clinical and MRI parameters of inflammation and neurodegeneration in relapsing MS (RMS). METHODS: eighty active RMS were prospectively enrolled, randomized (1:1) to either the IFN-curcumin or the IFN-placebo group and followed up longitudinally with clinical and MRI assessments for 24 months. Primary endpoint was the efficacy of curcumin versus placebo as add-on therapy on new/enlarging T2 lesions in RMS subjects under treatment with subcutaneous IFN ß-1a 44 mcg TIW. Efficacy on clinical parameters (relapses and disability progression), other MRI parameters of inflammation (T1 Gd-enhancing lesions, combined unique active-CUA lesions) and neurodegeneration (T1-hypointense lesions, grey matter loss and white matter microstructural damage) as well as safety and tolerability of curcumin were explored as secondary endpoints. RESULTS: ten subjects dropped out from the study by month 12 (6 in the IFN-curcumin group and 4 in the IFN-placebo group), and 27 by month 24 (11 in the IFN-curcumin group and 16 in the IFN-placebo group). Although no between-group difference was present in terms of proportion of subjects free from new/enlarging T2 lesions, a lower proportion of patients with CUA lesions was noted at month 12 in the IFN-curcumin group in comparison with the IFN-placebo group (7.5% vs 17.5%, χ² test p= 0.0167). This result was not confirmed at month 24. The statistical analysis failed to reveal any difference between the two treatment groups - IFN-curcumin and IFN-placebo - in terms of relapses, disability progression, other MRI metrics of inflammation and MRI changes suggestive of ongoing neurodegeneration. No difference in the rate and nature of adverse events was observed between the two treatment groups. CONCLUSION: Although the study drop-out rate was too high to allow definite conclusions, our findings suggest that curcumin might add to IFN ß-1a efficacy on radiological signs of inflammation in MS, while it did not seem to exert any neuroprotective effect as assessed by clinical and MRI parameters. (NCT01514370).