Tacrolimos tópico para dermatite atópica moderada a grave: revisão sistemática da literatura
Arquivos
Data
2015-08-31
Autores
Martins, Jade Cury 
Orientadores
Silva, Edina Mariko Koga da
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Avaliar eficácia e segurança do tacrolimo tópico para dermatite atópica comparado aos tratamentos ativos disponíveis. Métodos: Revisão sistemática realizada segundo a metodologia do Cochrane Handbook of Systematic Reviews of Interventions. Foi realizada busca eletrônica nas seguintes bases de dados: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, EMBASE, LILACS e GREAT. Foi realizada busca separada para efeitos adversos em estudos não randomizados. Incluíram-se ensaios clínicos randomizados de participantes com dermatite atópica moderada a grave (adultos e crianças) que usaram tacrolimo tópico em qualquer dose, duração e tempo de seguimento comparado a outros tratamentos ativos. Desfechos primários incluíram avaliação de resposta pelo médico, pelo paciente e efeitos adversos. Desfecho secundário foi a avaliação de melhora por ferramentas validadas. Resultados: Foram incluídos 20 estudos com 5885 participantes. Comparando-se a melhora na resposta global avaliada pelo médico, tacrolimo 0,1% foi melhor que corticosteroides tópicos de baixa potência (RR 3,09, IC95% 2,14-4,45, 1estudo, n=371); que corticosteroides de baixa potência na cabeça e pescoço e moderada potência no tronco e extremidades (RR 1,32, IC95% 1,17-1,49, 1estudo, n=972) e que o pimecrolimo 1% (RR 1,80, IC95% 1,35-2,42, 3estudos, n=543). Comparado à formulação de 0,03%, os tratados com 0,1% tiveram 18% menos risco de não apresentarem melhora na resposta avaliada pelo médico (RR 0,82, IC95% 0,72-0,92, 6estudos, n=1640). Na comparação com corticosteroides de moderada-a-alta potência, não foi encontrada diferença em três dos desfechos (1 estudo, n=377) e benefício marginal favorecendo tacrolimo 0,1% foi visto na autoavaliação da resposta pelo participante (RR 1,21, IC95% 1,13-1,29, 1estudo, n=972). Tacrolimo 0,03% foi superior aos corticosteroides de baixa potência na avaliação médica da resposta (RR 2,58, IC95% 1,96-3,38, 2estudos, n=790) e na autoavaliação pelo participante (RR1,64, IC95% 1,41-1,90, 1estudo, n=416). Um estudo mostrou benefício do tacrolimo 0,03% comparado ao pimecrolimo na avaliação médica (RR 1,42, IC95% 1,02-1,98, 1estudo, n=139), mas com resultados ambíguos num dos desfechos secundários. Comparando-se tacrolimo 0,03% com corticosteroides de moderada a alta potência, não foi vista diferença na maioria dos desfechos, porém, em dois estudos, uma diferença pequena favorecendo os corticosteroides foi notada. Queimação e prurido foram mais frequentes nos usuários de inibidores da calcineurina (8estudos, n=3603). Não houve diferença na ocorrência de infecções. Na comparação do tacrolimo com pimecrolimo, os efeitos adversos locais foram pouco mais frequentes no primeiro grupo, com maior duração dos sintomas (2estudos, 178 participantes). Eventos adversos graves foram raros e ocorreram em todos os grupos. Nenhum caso de linfoma foi encontrado nos ensaios clínicos, tampouco nos estudos nãocomparativos. Absorção sistêmica foi rara, em níveis baixos, exceto em doenças com defeito de barreira grave como na Síndrome de Netherton. Não se encontrou evidência de que tacrolimo tópico possa causar atrofia cutânea. Conclusões: Tacrolimo 0,1% foi superior ao 0,03%. Em suas duas formulações, foi superior aos corticosteroides de baixa potência e pimecrolimo, com resultados ambíguos na comparação aos corticosteroides de moderada-a-alta potência. Pareceu seguro e não há evidência de possíveis riscos de malignidade ou atrofia cutânea. A força da evidência é limitada pela falta de dados, devendo-se interpretar os resultados com cautela.
Purpose: To evaluate the effectiveness and safety of statins for aortic valve stenosis. Methods: Systematic review of Objectives: To assess the efficacy and safety of topical tacrolimus for moderate and severe atopic dermatitis compared with other active treatments.Methods: Systematic review performed according to methodology of Cochrane Handbook of Systematic Reviews of Interventions. An electronic search was performed in: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, EMBASE, LILACS and GREAT. A separate search for adverse effects of topical tacrolimus was undertaken in MEDLINE and EMBASE. All randomised controlled trials of participants with moderate to severe atopic dermatitis (children and adults) using topical tacrolimus at any dose, course duration, and follow-up time compared with other active treatments were included. The three prespecified primary outcomes were physician's and participant's assessment of improvement, and adverse effects. The secondary outcomes included assessment of improvement of the disease by validated tools.Results: We included 20 studies, with 5885 participants. On the physician´s assessment of global response tacrolimus 0.1% was better than low-potency topical corticosteroids (TCS) (RR3.09, 95%CI 2.14-4.45, 1study, n=371); marginally better than low-potency TCS on face and neck areas and moderate-potency TCS on trunk and extremities (RR1.32, 95%CI 1.17- 1.49, 1study, n=972) and better than pimecrolimus 1% (RR1.80, 95%CI 1.35-2.42, 3studies, n=543). Compared with the lower concentration of 0.03%, the tacrolimus 0.1% formulation reduced the risk of not having an improvement by 18% as evaluated by the physician's assessment (RR0.82, 95%CI 0.72-0.92, 6studies, n=1640). Tacrolimus 0.1% compared with moderate-to-potent TCS showed no difference on three outcomes (1study, 377participants) and a marginal benefit favouring tacrolimus 0.1% was found by the participant's assessment (RR1.21, 95%CI 1.13-1.29, 1study, n=974). Tacrolimus 0.03% was superior to mild TCS for the physician's assessment (RR2.58, 95%CI 1.96-3.38, 2studies, n=790) and the participant's self-assessment (RR1.64, 95%CI 1.41-1.90, 1study, n=416). One trial showed moderate benefit of tacrolimus 0.03% compared with pimecrolimus 1% on the physician's assessment (RR1.42, 95%CI 1.02-1.98, 1study, n=139), but the effects were equivocal when evaluating a zsecondary outcome. In the comparison of tacrolimus 0.03% with moderate-to-potent corticosteroids, no difference was found in most of the outcomes measured, but in two studies, a marginal benefit favouring the corticosteroid group was found.Burning and pruritus were more frequent in those using calcineurin inhibitors (8studies, n=3603), but no difference was found for skin infections. The comparison between pimecrolimus and tacrolimus, the local adverse effects were slightly more frequent on the tacrolimus group with longer duration of the symptoms (2studies, n=178).Serious adverse events were rare and occurred in all groups. No cases of lymphoma were noted in the included studies and also in the noncomparative studies. Systemic absorption was rarely detectable, only in low levels, and this decreased with time. Exception is made for diseases with severe barrier defects, such as Netherton's syndrome. We found no evidence that topical tacrolimus could cause skin atrophy. Conclusions: Tacrolimus 0.1% was better than 0.03%. On both formulations, tacrolimus was better than low-potency corticosteroids and pimecrolimus, with equivocal results when compared to moderate-to-potent corticosteroids. It seemed to be safe and no evidence was found to support the possible risk of malignancies or skin atrophy with their use. The reliability and strength of the evidence was limited by the lack of data; thus, findings of this review should be interpreted with caution.
Purpose: To evaluate the effectiveness and safety of statins for aortic valve stenosis. Methods: Systematic review of Objectives: To assess the efficacy and safety of topical tacrolimus for moderate and severe atopic dermatitis compared with other active treatments.Methods: Systematic review performed according to methodology of Cochrane Handbook of Systematic Reviews of Interventions. An electronic search was performed in: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, EMBASE, LILACS and GREAT. A separate search for adverse effects of topical tacrolimus was undertaken in MEDLINE and EMBASE. All randomised controlled trials of participants with moderate to severe atopic dermatitis (children and adults) using topical tacrolimus at any dose, course duration, and follow-up time compared with other active treatments were included. The three prespecified primary outcomes were physician's and participant's assessment of improvement, and adverse effects. The secondary outcomes included assessment of improvement of the disease by validated tools.Results: We included 20 studies, with 5885 participants. On the physician´s assessment of global response tacrolimus 0.1% was better than low-potency topical corticosteroids (TCS) (RR3.09, 95%CI 2.14-4.45, 1study, n=371); marginally better than low-potency TCS on face and neck areas and moderate-potency TCS on trunk and extremities (RR1.32, 95%CI 1.17- 1.49, 1study, n=972) and better than pimecrolimus 1% (RR1.80, 95%CI 1.35-2.42, 3studies, n=543). Compared with the lower concentration of 0.03%, the tacrolimus 0.1% formulation reduced the risk of not having an improvement by 18% as evaluated by the physician's assessment (RR0.82, 95%CI 0.72-0.92, 6studies, n=1640). Tacrolimus 0.1% compared with moderate-to-potent TCS showed no difference on three outcomes (1study, 377participants) and a marginal benefit favouring tacrolimus 0.1% was found by the participant's assessment (RR1.21, 95%CI 1.13-1.29, 1study, n=974). Tacrolimus 0.03% was superior to mild TCS for the physician's assessment (RR2.58, 95%CI 1.96-3.38, 2studies, n=790) and the participant's self-assessment (RR1.64, 95%CI 1.41-1.90, 1study, n=416). One trial showed moderate benefit of tacrolimus 0.03% compared with pimecrolimus 1% on the physician's assessment (RR1.42, 95%CI 1.02-1.98, 1study, n=139), but the effects were equivocal when evaluating a zsecondary outcome. In the comparison of tacrolimus 0.03% with moderate-to-potent corticosteroids, no difference was found in most of the outcomes measured, but in two studies, a marginal benefit favouring the corticosteroid group was found.Burning and pruritus were more frequent in those using calcineurin inhibitors (8studies, n=3603), but no difference was found for skin infections. The comparison between pimecrolimus and tacrolimus, the local adverse effects were slightly more frequent on the tacrolimus group with longer duration of the symptoms (2studies, n=178).Serious adverse events were rare and occurred in all groups. No cases of lymphoma were noted in the included studies and also in the noncomparative studies. Systemic absorption was rarely detectable, only in low levels, and this decreased with time. Exception is made for diseases with severe barrier defects, such as Netherton's syndrome. We found no evidence that topical tacrolimus could cause skin atrophy. Conclusions: Tacrolimus 0.1% was better than 0.03%. On both formulations, tacrolimus was better than low-potency corticosteroids and pimecrolimus, with equivocal results when compared to moderate-to-potent corticosteroids. It seemed to be safe and no evidence was found to support the possible risk of malignancies or skin atrophy with their use. The reliability and strength of the evidence was limited by the lack of data; thus, findings of this review should be interpreted with caution.
Descrição
Citação
MARTINS, Jade Cury. Tacrolimos tópico para dermatite atópica moderada a grave: revisão sistemática da literatura. 2015. 202 f. Tese (Doutorado em Saúde Baseada em Evidências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.