Browsing by Author "Brecl Jakob, Gregor (56545621600)"

Background: Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS). Objectives: To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS). Methods: A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries. Results: We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment. Conclusion: Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals. © 2023 Elsevier B.V.

Background: Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS). Objectives: To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS). Methods: A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries. Results: We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment. Conclusion: Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals. © 2023 Elsevier B.V.

Background and purpose: The aim was to determine the extent of sudomotor dysfunction in people with neuromyelitis optica spectrum disorder (pwNMOSD) and to compare findings with a historical cohort of people with relapsing–remitting multiple sclerosis (pwRRMS). Methods: Forty-eight pwNMOSD were enrolled from four clinical centers. All participants completed the Composite Autonomic Symptom Score 31 to screen for symptoms of sudomotor dysfunction. Sudomotor function was assessed using the quantitative sudomotor axon reflex test. The results were compared with a historical cohort of 35 pwRRMS matched for age, sex and disease duration. Results: Symptoms of sudomotor dysfunction, defined by a score in the Composite Autonomic Symptom Score 31 secretomotor domain >0, were present in 26 (54%) of pwNMOSD. The quantitative sudomotor axon reflex test confirmed a sudomotor dysfunction in 25 (52.1%) of pwNMOSD; in 14 of them (29.2%) sudomotor dysfunction was moderate or severe. No difference was observed between pwNMOSD and pwRRMS in any of the studied parameters. However, symptomatic sudomotor dysfunction was more frequent in pwNMOSD (n = 8, 22.9%) compared to pwRRMS (n = 1, 3%; p = 0.028). In a multivariable logistic regression analysis, statistically significant predictors for symptomatic sudomotor failure were age and diagnosis of neuromyelitis optica spectrum disorder. Conclusions: Sudomotor dysfunction is common in pwNMOSD and more often symptomatic compared to pwRRMS. © 2022 European Academy of Neurology.

Background and purpose: The aim was to determine the extent of sudomotor dysfunction in people with neuromyelitis optica spectrum disorder (pwNMOSD) and to compare findings with a historical cohort of people with relapsing–remitting multiple sclerosis (pwRRMS). Methods: Forty-eight pwNMOSD were enrolled from four clinical centers. All participants completed the Composite Autonomic Symptom Score 31 to screen for symptoms of sudomotor dysfunction. Sudomotor function was assessed using the quantitative sudomotor axon reflex test. The results were compared with a historical cohort of 35 pwRRMS matched for age, sex and disease duration. Results: Symptoms of sudomotor dysfunction, defined by a score in the Composite Autonomic Symptom Score 31 secretomotor domain >0, were present in 26 (54%) of pwNMOSD. The quantitative sudomotor axon reflex test confirmed a sudomotor dysfunction in 25 (52.1%) of pwNMOSD; in 14 of them (29.2%) sudomotor dysfunction was moderate or severe. No difference was observed between pwNMOSD and pwRRMS in any of the studied parameters. However, symptomatic sudomotor dysfunction was more frequent in pwNMOSD (n = 8, 22.9%) compared to pwRRMS (n = 1, 3%; p = 0.028). In a multivariable logistic regression analysis, statistically significant predictors for symptomatic sudomotor failure were age and diagnosis of neuromyelitis optica spectrum disorder. Conclusions: Sudomotor dysfunction is common in pwNMOSD and more often symptomatic compared to pwRRMS. © 2022 European Academy of Neurology.

Introduction: We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. Methods: The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. Results: We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. Conclusion: Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19. © 2022 Elsevier B.V.

Introduction: We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. Methods: The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. Results: We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. Conclusion: Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19. © 2022 Elsevier B.V.

Based on the results of the pivotal CLARITY study, cladribine tablets were approved for use in the European Union in 2017 as a high-efficacy therapy for highly active relapsing-remitting multiple sclerosis (MS). Cladribine tablets are used as an induction therapy: half of the total dose is given in year 1 and the other half in year 2. In the CLARITY Extension trials, repeating the dose routinely in years 3 and 4, was not associated with significantly improved disease control. However, there is very limited evidence on how to manage people with MS (pwMS) beyond year 4, which is increasingly important because more and more patients are now ≥ 4 years after cladribine treatment. Overall, postapproval data show that treatment with two cladribine cycles effectively controls disease activity in the long term. However, there is general agreement that some pwMS with suboptimal response could benefit from retreatment. This study reviews the practical aspects of using cladribine tablets, summarizes the evidence from clinical trials and real-world studies on the safety and efficacy of cladribine, and proposes a treatment algorithm developed by expert consensus for pwMS previously treated with cladribine. In brief, we propose that additional courses of cladribine tablets should be considered in patients with minimal (no relapses, 1–2 new lesions) or moderate (1 relapse, 3–4 new lesions) disease activity, while significant disease activity (> 1 relapse, > 3 new lesions) or progression should warrant a switch to another high-efficacy treatment (HET). More evidence is needed to improve the treatment guidelines for pwMS who previously received cladribine. © 2022, The Author(s).

Based on the results of the pivotal CLARITY study, cladribine tablets were approved for use in the European Union in 2017 as a high-efficacy therapy for highly active relapsing-remitting multiple sclerosis (MS). Cladribine tablets are used as an induction therapy: half of the total dose is given in year 1 and the other half in year 2. In the CLARITY Extension trials, repeating the dose routinely in years 3 and 4, was not associated with significantly improved disease control. However, there is very limited evidence on how to manage people with MS (pwMS) beyond year 4, which is increasingly important because more and more patients are now ≥ 4 years after cladribine treatment. Overall, postapproval data show that treatment with two cladribine cycles effectively controls disease activity in the long term. However, there is general agreement that some pwMS with suboptimal response could benefit from retreatment. This study reviews the practical aspects of using cladribine tablets, summarizes the evidence from clinical trials and real-world studies on the safety and efficacy of cladribine, and proposes a treatment algorithm developed by expert consensus for pwMS previously treated with cladribine. In brief, we propose that additional courses of cladribine tablets should be considered in patients with minimal (no relapses, 1–2 new lesions) or moderate (1 relapse, 3–4 new lesions) disease activity, while significant disease activity (> 1 relapse, > 3 new lesions) or progression should warrant a switch to another high-efficacy treatment (HET). More evidence is needed to improve the treatment guidelines for pwMS who previously received cladribine. © 2022, The Author(s).