RESUMO
Despite the success and ongoing promise of monoclonal antibody-targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint-targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunoterapia/efeitos adversos , Neoplasias/terapia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Oncologia/métodos , Oncologia/tendências , Neoplasias/epidemiologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologiaRESUMO
Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently widened our therapeutic options. By directly stimulating bone formation, anabolic agents reduce fracture incidence by improving bone qualities besides increasing bone mass. In this article, we review the role of anabolic treatment for osteoporosis. The only anabolic agent currently approved in the United States for osteoporosis, teriparatide [recombinant human parathyroid hormone(1-34)], has clearly emerged as a major approach to selected patients with osteoporosis. Teriparatide increases bone density and bone turnover, improves microarchitecture, and changes bone size. The incidence of vertebral and nonvertebral fractures is reduced. Teriparatide is approved for both postmenopausal women and men with osteoporosis who are at high risk for fracture. Other potential anabolic therapies for osteoporosis, including other forms of parathyroid hormone, strontium ranelate, growth hormone, and insulin-like growth factor-1, are also reviewed in this article.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Teriparatida/uso terapêutico , Conservadores da Densidade Óssea/farmacologia , Ensaios Clínicos como Assunto , Feminino , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Hormônio do Crescimento/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/uso terapêutico , Masculino , Compostos Organometálicos/uso terapêutico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Hormônio Paratireóideo/uso terapêutico , Fatores de Risco , Teriparatida/farmacologia , Tiofenos/uso terapêuticoRESUMO
Antiresorptive agents for osteoporosis are a cornerstone of therapy, but anabolic drugs have recently widened our therapeutic options. By directly stimulating bone formation, anabolic agents reduce fracture incidence by improving bone qualities besides increasing bone mass. In this article, we review the role of anabolic treatment for osteoporosis. The only anabolic agent currently approved in the United States for osteoporosis, teriparatide [recombinant human parathyroid hormone(1-34)], has clearly emerged as a major approach to selected patients with osteoporosis. Teriparatide increases bone density and bone turnover, improves microarchitecture, and changes bone size. The incidence of vertebral and nonvertebral fractures is reduced. Teriparatide is approved for both postmenopausal women and men with osteoporosis who are at high risk for fracture. Other potential anabolic therapies for osteoporosis, including other forms of parathyroid hormone, strontium ranelate, growth hormone, and insulin-like growth factor-1, are also reviewed in this article.
Os agentes anti-reabsortivos são as drogas mais usadas no tratamento da osteoporose, porém os anabólicos recentemente ampliaram nossas opções terapêuticas. Por estimular diretamente a formação, os agentes anabólicos reduzem a incidência de fraturas por melhorar a qualidade óssea, além do aumento da massa óssea. Neste artigo, nós revisaremos o papel do tratamento anabólico para a osteoporose. O único agente anabólico, atualmente aprovado nos Estados Unidos, é o teriparatida (hormônio paratiroidiano recombinante humano), o qual tem sido considerado como a principal abordagem em pacientes selecionados. O teriparatida aumenta a densidade mineral óssea e o turnover ósseo, melhorando a microarquitetura, e altera o tamanho do osso. A incidência de fraturas vertebrais e não vertebrais é reduzida. O teriparatida é aprovado tanto para mulheres na pós-menopausa quanto para homens com osteoporose que apresentem alto risco para fraturas. Outras terapias anabólicas potenciais para a osteoporose incluem outras formas de hormônio da paratiróide, ranelato de estrôncio, hormônio de crescimento e IGF1 (insulin-like growth factor-1), e serão revisados neste artigo.