DAGOBERTO CALLEGARO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/62 - Laboratório de Fisiopatologia Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Is there a role for off-label high-efficacy disease-modifying drugs in progressive multiple sclerosis? A network meta-analysis(2022) SILVA, Guilherme Diogo; CASTRILLO, Bruno Batitucci; APOSTOLOS-PEREIRA, Samira Luisa; CALLEGARO, DagobertoOcrelizumab and siponimod are the two on-label drugs used for progressive forms of multiple sclerosis (PMS). However, many patients with PMS do not have access to these high-efficacy disease-modifying drugs (DMDs). Off-label prescription of other high-efficacy DMDs (fingolimod, rituximab and natalizumab) may be a strategy to improve access to immunotherapy for these patients. We aim to compare on-label and off-label high-efficacy drugs for their effect on disability progression in PMS. In December 2021, we searched MEDLINE (PubMed), Embase, Cochrane Central and Scopus databases for randomized clinical trials involving patients with PMS. High-efficacy drugs were considered as intervention and placebos as comparison. The outcome contemplated was risk of Expanded Disability Severity Scale (EDSS) progression at 2 years. A network meta-analysis was performed to compare the relative risk of EDSS progression at 2 years compared with placebo in on-label and off-label drugs. We included five studies with 4526 patients. The median EDSS progression at 2 years in patients that received any immunotherapy was 30%, compared with 35% in placebo groups. Overall, the risk of bias of individual studies was low. Network analysis revealed overlapping confidence intervals in off-label drugs (CI95% 0.51-2.16) versus ocrelizumab (reference) and off-label drugs (CI 95% 0.53-1.96) versus siponimod (reference), suggesting similar efficacy. The same result was found even after excluding studies with the risk of publication bias. Off-label high efficacy immunotherapy in PMS has biological plausibility and presented similar effectiveness to on-label DMDs in this network meta-analysis. The use of fingolimod, rituximab or natalizumab may be a strategy that reduces costs and improves access to immunotherapy for patients with PMS.
- MOG-IgG-Associated Optic Neuritis, Encephalitis, and Myelitis: Lessons Learned From Neuromyelitis Optica Spectrum Disorder(2018) PASSOS, Giordani Rodrigues dos; OLIVEIRA, Luana Michelli; COSTA, Bruna Klein da; APOSTOLOS-PEREIRA, Samira Luisa; CALLEGARO, Dagoberto; FUJIHARA, Kazuo; SATO, Douglas KazutoshiAntibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been found in some cases diagnosed as seronegative neuromyelitis optica spectrum disorder (NMOSD). MOG-IgG allowed the identification of a subgroup with a clinical course distinct from that of NMOSD patients who are seropositive for aquaporin-4-IgG antibodies. MOG-IgG is associated with a wider clinical phenotype, not limited to NMOSD, with the majority of cases presenting with optic neuritis (ON), encephalitis with brain demyelinating lesions, and/or myelitis. Therefore, we propose the term MOG-IgG-associated Optic Neuritis, Encephalitis, and Myelitis (MONEM). Depending on the clinical characteristics, these patients may currently be diagnosed with NMOSD, acute disseminated encephalomyelitis, pediatric multiple sclerosis, transverse myelitis, or ON. With specific cell-based assays, MOG-IgG is emerging as a potential biomarker of inflammatory disorders of the central nervous system. We review the growing body of evidence on MONEM, focusing on its clinical aspects.
- Reducing infection risk in multiple sclerosis and neuromyelitis optica spectrum disorders: a Brazilian reference center's approach(2022) GOMES, Ana Beatriz Ayroza Galvao Ribeiro; FEO, Lucas Bueno; SILVA, Guilherme Diogo; DISSEROL, Caio Cesar Diniz; PAOLILO, Renata Barbosa; LARA, Amanda Nazareth; TONACIO, Adriana Coracini; MENDES, Maria Fernanda; PEREIRA, Samira Luisa Apostolos; CALLEGARO, DagobertoBackground Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the most common autoimmune diseases of the central nervous system (CNS). They present chronic relapsing courses that demand treatment with disease-modifying drugs (DMDs) to prevent inflammatory activity. Disease-modifying drugs lead to immunomodulation or immunosuppression through diverse mechanisms (e.g., shifting lymphocyte and cytokine profile, suppressing specific lymphocyte subpopulations). Thus, patients are more prone to infectious complications and associated worsening of disease. Objective To present feasible strategies for mitigating the infection risk of MS and NMOSD treated patients. Methods Targeted literature review concerning the management of infection risk with an emphasis on vaccination, therapy-specific measures, and particularities of the Brazilian endemic infectious diseases' scenario. Conclusion We propose a vaccination schedule, infectious screening routine, and prophylactic measures based on the current scientific evidence. Awareness of emergent tropical diseases is necessary due to evidence of demyelinating events and possible parainfectious cases of MS and NMOSD.
- Vitamin D3 as an add-on treatment for multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials(2024) MAHLER, Joao Vitor; SOLTI, Marina; APOSTOLS-PEREIRA, Samira Luisa; ADONI, Tarso; SILVA, Guilherme Diogo; CALLEGARO, DagobertoBackground: Vitamin D deficiency has been linked to a higher risk of multiple sclerosis (MS) and disease progression. However, the efficacy of vitamin D3 as an adjuvant therapy for MS remains a controversial topic. Objective: To perform a systematic review and meta-analysis of randomized controlled trials to assess the impact of adjunct high-dose vitamin D3 on clinical and radiological outcomes. Methods: PubMed, Embase, and Cochrane Library were searched for trials published until December 18th, 2022. Authors independently selected randomized controlled trials involving patients with MS, with an intervention group receiving high dose (>= 1000 IU/day) cholecalciferol and reporting clinical or radiological outcomes. Authors independently extracted data and assessed the risk of bias using a standardized, pilot-tested form. The meta-analysis was conducted using RStudio for EDSS at the last follow-up, ARR, and new T2 lesion count. Results: We included 9 studies with 867 participants. No significant reduction of EDSS (MD = 0.02, CI 95 % [-0.37; 0.41], p = 0.91), ARR (MD -0.03, CI 95 % [-0.08; 0.02], p = 0.26), or new T2 lesions (MD -0.59, CI 95 % [-1.24;0.07], p = 0.08) was observed at 6-24 months. We found no evidence of publication bias. Conclusion: The findings of this meta-analysis strengthen current evidence that vitamin D3 supplementation has no significant impact on clinical outcomes in patients with MS. However, the non-significant reduction of new T2 lesions could precede long-term clinical benefits and should be validated in additional studies.
- Cost, efficacy, and safety comparison between early intensive and escalating strategies for multiple sclerosis: A systematic review and meta-analysis(2023) PIPEK, Leonardo Zumerkorn; MAHLER, Joao Vitor; NASCIMENTO, Rafaela Farias Vidigal; APOSTOLOS-PEREIRA, Samira Luisa; SILVA, Guilherme Diogo; CALLEGARO, DagobertoBackground: The optimal treatment strategy of multiple sclerosis (MS) is a matter of debate. The classical approach is the escalating (ESC) strategy, which consists of starting with low-to moderate-efficacy disease-modifying drugs (DMDs) and upscale to high-efficacy DMDs when noting some evidence of active disease. Another approach, the early intensive (EIT) strategy, is starting with high-efficiency DMDs as first-line therapy. Our goal was to compare effectiveness, safety, and cost of ESC and EIT strategies.Methods: We searched MEDLINE, EMBASE and SCOPUS until September 2022, for studies comparing EIT and ESC strategies in adult participants with relapsing-remitting MS and a minimum follow-up of 5 years. We examined the Expanded Disability Severity Scale (EDSS), the proportion of severe adverse events, and cost in a 5-year period. Random-effects meta-analysis summarized the efficacy and safety and an EDSS-based Markov model estimated the cost.Results: Seven studies with 3,467 participants showed a 30% reduction in EDSS worsening in 5 years (RR 0.7; [0.59-0.83]; p < 0.001) in the EIT group vs in the ESC group. Two studies with 1,118 participants suggested a similar safety profile for these strategies (RR 1.92; [0.38-9.72]; p = 0.4324). EIT with natalizumab in extended interval dosing, rituximab, alemtuzumab, and cladribine demonstrated cost-effectiveness in our model.Discussion: EIT presents higher efficacy in preventing disability progression, a similar safety profile, and can be cost-effective within a 5-year timeline.
- Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents(2023) PAOLILO, Renata Barbosa; PAZ, Jose Albino da; APOSTOLOS-PEREIRA, Samira Luisa; RIMKUS, Carolina de Medeiros; CALLEGARO, Dagoberto; SATO, Douglas KazutoshiNeuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, similar to 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.
- Management of central nervous system demyelinating diseases during the coronavirus disease 2019 pandemic: a practical approach(2020) APOSTOLOS-PEREIRA, Samira Luisa; SILVA, Guilherme Diogo; DISSEROL, Caio Cesar Diniz; FEO, Lucas Bueno; MATOS, Aline de Moura Brasil; SCHOEPS, Vinicius Andreoli; GOMES, Ana Beatriz Ayroza Galvao Ribeiro; BOAVENTURA, Mateus; MENDES, Maria Fernanda; CALLEGARO, DagobertoBackground: The novelcoronavirus disease 2019(COVID-19) pandemic poses a potential threattopatients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, noconsensus has been reached on how to manage MS and NMOSD patients during the pandemic. Objective: To discuss strategies to manage those patients. Methods: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. Conclusions: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.