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1.
Neurol Neuroimmunol Neuroinflamm ; 6(4): e581, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31355317

RESUMO

Objective: To assess whether canakinumab, a monoclonal antibody against IL-1ß approved for autoinflammatory diseases, is effective as target-specific therapy in patients with sporadic inclusion body myositis (sIBM). Methods: Because in sIBM IL-1ß colocalizes with amyloid precursor protein and upregulates amyloid aggregates enhancing degeneration, targeting IL-1ß with canakinumab may arrest disease progression. On this basis, 5 ambulatory patients with sIBM participated in an institutional review board--approved open-labeled study with 150 mg canakinumab [4 bimonthly, then monthly subcutaneous injections] for a mean period of 15.8 months. Patients were assessed bimonthly with a manual dynamometer in 12 proximal and distal muscles and with grip force (GF) in both hands. Total muscle strength (TMS) was expressed in kilograms. Efficacy was defined as >15% increased strength after 12 months. Results: Patient 1 stopped at month 5 because of 23% loss in TMS and 32.35% in GF; patient 2 showed 37.1% increase in TMS and 13% in GF by month 9; patient 3 exhibited 26.7% reduction in TMS and 10% in GF at month 33; patient 4 showed 6.5% reduction in TMS and 1.6% in GF after 15 months, denoting relative stability; and patient 5 showed 30.4% loss in TMS and 20.8% in GF after 18 months. In patients 2 and 4, in whom 3-year longitudinal data were available, no effect on disease progression was noted. Conclusions: In this long-term, open-label study, canakinumab showed small, but not clinically appreciable, stabilizing benefits in 2 of 5 patients with sIBM over 1 year, was ineffective in 2 others, and might have worsened one. No patient improved. Classification of evidence: This study provides Class IV evidence that canakinumab was ineffective for patients with sIBM.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Interleucina-1beta/antagonistas & inibidores , Miosite de Corpos de Inclusão/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Força da Mão , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Resultado do Tratamento
2.
J Neurol Sci ; 347(1-2): 143-7, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25304055

RESUMO

OBJECTIVES: Fibromyalgia (FM) is one of the most common chronic pain syndromes. Various pathogenetic mechanisms have been implicated but none is proven. Our scope was to determine if Intraepidermal Nerve Fiber Density (IENFD) is reduced in the skin of FM patients, as observed in patients with painful small fiber sensory neuropathy (SFSN). DESIGN, SETTING AND PARTICIPANTS: We prospectively studied 46 FM patients (5 men and 41 women), aged 29 to 76 (mean: 52.5) years, diagnosed according to the ACR 2010 criteria, and 34 controls (18 women and 16 men) aged 19 to 84 (mean: 31.7) years. IENFD was measured using published guidelines and immune markers were sought immunocytochemically. In 30 FM patients, pain intensity was assessed with the Neuropathic Pain Symptom Inventory (NPSI), a scale validated for neuropathic pain. RESULTS: 15 of 46 (32.6%) FM patients had reduced IENFD [range: 0.6-12.5 fibers/mm (mean: 4.83 SD: 2.5)], compared to healthy controls [2.8-11.5 fibers/mm (mean: 7.35, SD: 1.85)] (p<0.0001). No significant correlation was noticed between NPSI scores and IENFD. No difference in the Langerhans cells, the major Antigen Presenting Cells (APCs) in the epidermis, or in IL-6 staining, was noted between FM and controls. IENFD was equally reduced in a subset of FM patients who also had another autoimmune disease. CONCLUSION: This is one of the largest series of FM patients demonstrating a significant reduction of IENFD in their skin biopsies. The findings indicate that in a subset of FM patients, the pain syndrome is, at least partially, of neuropathic origin. Skin biopsy may prove a useful tool and a potential biomarker in future studies of FM patients.


Assuntos
Fibromialgia/diagnóstico , Fibromialgia/patologia , Fibras Nervosas/patologia , Neuralgia/patologia , Pele/inervação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Epiderme/inervação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/diagnóstico , Estudos Prospectivos , Adulto Jovem
3.
J Neurol Sci ; 334(1-2): 123-5, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23998706

RESUMO

In sIBM, an inflammatory process mediated by cytotoxic T cells and cytokines in conjunction with a degenerative process, deposits of beta amyloid and misfolded proteins appear to be the main culprits in disease pathogenesis. IL-1ß may play a key role because it is upregulated in sIBM myofibers, co-localizes with Amyloid Precursor Protein (APP) and promotes the production of APP and amyloid deposits. We performed a small, pilot study to examine whether anakinra, an IL1 receptor antagonist could benefit sIBM patients. Four patients with biopsy-proven sIBM received anakinra for a mean period of 7.7 months. No improvement in muscle strength or stabilization was noted in any of the patients based on grip strength and MRC measurements. The treatment failure may be due to insufficiency of anakinra to suppress the intramuscular IL1, the short study period, or the irrelevance of IL1 in the disease process.


Assuntos
Antirreumáticos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Miosite de Corpos de Inclusão/tratamento farmacológico , Adulto , Idoso , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Projetos Piloto
4.
PLoS One ; 8(2): e55843, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23424638

RESUMO

BACKGROUND: The incidence and prevalence of CNS involvement in SLE remains unclear owing to conflicting results in the published studies. The aim of the study was to evaluate the incidence and prevalence of major definite CNS events in SLE patients. METHODS: 370 SLE patients with no previous history of CNS involvement were prospectively evaluated in a tertiary hospital referral center for 3 years. Major CNS manifestations were codified according to ACR definitions, including chorea, aseptic meningitis, psychosis, seizures, myelopathy, demyelinating syndrome, acute confusional state and strokes. Minor CNS events were excluded. ECLAM and SLEDAI-SELENA Modification scores were used to evaluate disease activity and SLICC/ACR Damage Index was used to assess accumulated damage. RESULTS: 16/370 (4.3%) patients presented with a total of 23 major CNS events. These included seizures (35%), strokes (26%), myelopathy (22%), optic neuritis (8.7%), aseptic meningitis (4.3%) and acute psychosis (4.3%). Incidence was 7.8/100 person years. Among hospitalizations for SLE, 13% were due to CNS manifestations. Epileptic seizures were associated with high disease activity, while myelopathy correlated with lower disease activity and NMO-IgG antibodies (P≤0.05). Stroke incidence correlated with APS coexistence (P = 0.06). Overall, CNS involvement correlated with high ECLAM and SLEDAI scores (P<0.001). CONCLUSIONS: Clinically severe CNS involvement is rare in SLE patients, accounting for 7.8/100 person years. CNS involvement correlates with high disease activity and coexistence of specific features that define the respective CNS syndromes.


Assuntos
Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Lúpus Eritematoso Sistêmico/epidemiologia , Adulto , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Prevalência , Estudos Prospectivos
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