Cancer Risk and Multiple Sclerosis: Evidence From a Large Italian Cohort

Introduction: The complexity of understanding cancer risk in MS is increased by inconsistencies in study design, and the lack of age-, sex-, and ethnicity-specific risk estimates. Aims of our study were to estimate the incidence of cancers in the MS population of Catania (Italy) and to evaluate the impact of disease-modifying treatments (DMTs) in cancer risk.Materials and Methods: We screened 2,730 PwMS according to the MS criteria of Mc Donald 2010 referring to MS center of Catania in the period between 2003 and 2013. We matched database of MS patients with the Integrated Cancer of Catania-Messina-Siracusae-Enna. We calculated age and sex specific standardized incidence ratios (SIR) and the relative risk (RR) of developing cancer in MS patients treated with at least two different DMTs compared to who received one or no treatment.Results: Out of 2,730, 1,180 MS patients (67.1% females; mean age 41.2 ± 12.9) were enrolled. We found 36 cancers. Global SIR was 1.18 (CI95% 0.78–1.58), with a significantly higher risk in men with a range age of 20 to 50 years [2.84; (CI95% 1.59–4.09)] and in women over 50 years [1.82 (CI95% 1.08–2.55)]. RR of developing cancer was 1.99 (CI95% 1.14–3.45) in MS patients switching one DMT and 3.38 (CI95% 1.83–6.22) in who switched at least twice.Discussion: Our results demonstrated that cancer risk was not increased in our MS population; but age and sex different distribution may partly drive cancer risk. Higher cancer risk in MS patients switching more than two DMTs should take into account in treatment decision making

Long-term effectiveness of natalizumab in secondary progressive multiple sclerosis: A propensity-matched study

treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. we aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). this multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st june 2012 and the 15th may 2018 ​at 33 Italian MS centers contributing to the Italian MS registry NTZ or IFNb-1b. confirmed expanded disability status scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. after applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. the proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). the proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67-5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22-3.35; p ​= ​0.01, respectively). patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04-4.87; p ​= ​0.001). treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment

Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have a significant impact on patients’ disability. Inflammatory demyelinating lesions, especially occurring in the posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia (INO), among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease. Quantitative measurement and modeling of eye movement disorders, such as INO, may lead to a better understanding of common symptoms encountered in MS, such as Uhthoff’s phenomenon and fatigue. In turn, the pathophysiology of a range of eye movement abnormalities, such as APN, has been clarified based on correlation of experimental model with lesion localization by neuroimaging in MS. Eye movement disorders have the potential of being utilized as structural and functional biomarkers of early cognitive deficit, and possibly help in assessing disease status and progression, and to serve as platform and functional outcome to test novel therapeutic agents for MS. Knowledge of neuropharmacology applied to eye movement dysfunction has guided testing and use of a number of pharmacological agents to treat some eye movement disorders found in MS, such as APN and other forms of central nystagmus

Pharmacokinetic drug evaluation of daclizumab for the treatment of relapsing-remitting multiple sclerosis

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Despite the availability of several disease-modifying therapies for relapsing MS, there is a need for highly efficacious targeted therapy with a favorable benefitârisk profile and a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Areas covered: Daclizumab blocks the activation and expansion of autoreactive T cells that plays a role in the immune pathogenesis of MS. As its modulatory effects on the immune system, daclizumabâs potential for use in MS was tested extensively showing a high efficacy in reducing relapse rate, disability progression and the number and volume of gadolinium-enhancing lesions on brain magnetic resonance imaging. Moreover, phase II and III trials showed a favorable pharmacokinetic (PK) profile with slow clearance, linear pharmacokinetics at doses above 100 mg and high subcutaneous bioavailability, not influenced by age, sex or other clinical parameters. Expert opinion: Among the new emerging drugs for MS, daclizumab also, thanks to a favorable PK profile, may represent an interesting and promising therapeutic option in the wide MS therapies armamentarium

An update on the safety of treating relapsing-remitting multiple sclerosis

Introduction: In the last 20 years the armamentarium for multiple sclerosis (MS) treatment has been enriched from an increasingly wider variety of new drugs in order to reach a better control of the disease with a better patient compliance. Areas covered: With this great variety of therapeutic options, physicians may face new and major challenges. The huge amount of data from pilot studies and real-life settings showed that the first-line therapies have a better safety profile. On the other hand, the risks associated with newer drugs, with more selective mechanism of action and targeting specific pathways of MS pathophysiology, are not yet fully established. In particular, real-life use of these advanced drugs has raised important safety issues as long-term effects and potential risks are not yet known and remain to be carefully evaluated. Expert opinion: No time like the present, the physician faces new and major challenges in order to choose the best available therapy for MS. With the increasing number of drugs for treating MS and the lack of safety data, observational studies and post-marketing surveillance activities are crucial in order to improve the knowledge about the safety profile of these drugs and the therapeutic management in clinical practice settings

Cancer Risk and Multiple Sclerosis: Evidence From a Large Italian Cohort

The complexity of understanding cancer risk in MS is increased by inconsistencies in study design, and the lack of age-, sex-, and ethnicity-specific risk estimates. Aims of our study were to estimate the incidence of cancers in the MS population of Catania (Italy) and to evaluate the impact of disease-modifying treatments (DMTs) in cancer risk

Effectiveness of Ocrelizumab in Primary Progressive Multiple Sclerosis: a multicenter, retrospective, real-world study (OPPORTUNITY)

Ocrelizumab is a recombinant humanized monoclonal antibody selectively targeting CD20-expressing B cells. The effect of ocrelizumab on primary progressive multiple sclerosis (PPMS) has been evaluated during phase 3 trials that enrolled patients under 55 years with a maximum Expanded Disability Status Scale (EDSS) of 6.5. However, little is known on older disabled patients with longer disease duration. We aimed to assess the clinical effectiveness of ocrelizumab in PPMS patients out of the ORATORIO eligibility criteria. This multicenter retrospective study collected data about the effectiveness of ocrelizumab in PPMS patients who received treatment between May 2017 and June 2022 in the Italian MS centers contributing to the Italian MS Registry who adhered to the Compassionate Use Program. The confirmed EDSS worsening (CEW) (defined as either a ≥ 1-point or ≥ 2-point increase in EDSS score from baseline that was confirmed at T12 and T24) was calculated. At the date of data extraction, out of 887 PPMS patients who had received ocrelizumab, 589 (mean age 49.7 ± 10.7 years, 242 (41.1%) females) were enrolled. The mean follow-up period was 41.3 ± 12.3 months. A total of 149 (25.3%) received ocrelizumab according to the ORATORIO criteria (ORATORIO group) and 440 (74.7%) outside the ORATORIO criteria (non-ORATORIO group). No differences in terms of cumulative probabilities of 12 and 24 months of CEW of ≤ 1 point were found between ORATORIO and non-ORATORIO groups. Cox regression analyses showed that age older than 65 years (HR 2.51, 25% CI 1.07-3.65; p = 0.01) was associated with higher risk of CEW at 24 months. Patients not responding to ORATORIO criteria for reimbursability may benefit from ocrelizumab treatment, as disease activity, disease duration, and EDSS seem to not impact the disability outcome. Our results may suggest to extend the possible use of this powerful agent in selected patients under the age of 65 years