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Pneumocystis jiroveci prophylaxis in non-HIV patients treated with rituximab
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Introdução: A profilaxia contra a pneumonia por Pneumocystis jiroveci (PJ) é altamente eficaz em doentes com VIH e os seus benefícios parecem manter-se nos não VIH. O objetivo deste estudo foi avaliar a eficácia e efeitos adversos da profilaxia contra o PJ, em doentes não VIH tratados com rituximab.
Métodos: Realizámos uma revisão sistemática utilizando o modelo “Preferred Reporting Items for Systematic Review and Meta-Analyses” (PRISMA).
Resultados: Incluímos 8 estudos retrospetivos, com uma população total de 6048 doentes. O principal fármaco utilizado para a profilaxia foi o cotrimoxazol (TMP-SMX). Ocorreram 17 infeções por PJ no grupo profilático e 147 no controlo (0.3% vs. 2.4%; OR, 0.35; 95% CI, 0.19-0.64). O NNT para prevenir uma pneumonia por PJ foi de 36 doentes (CER, 3.6%). A taxa de mortalidade por PJ foi 25%. Todos os efeitos adversos medicamentosos reverteram com a descontinuação da profilaxia.
Discussão: A diminuição da incidência de PJ favorece o uso de profilaxia. O efeito da profilaxia com o rituximab em monoterapia não foi possível de avaliar visto que em todos os estudos foi utilizada imunossupressão combinada. O fator de risco mais importante para o PJ foi o uso de doses cumulativas elevadas de corticoesteróides. O tempo médio para o desenvolvimento da pneumonia por PJ variou entre 69-86 dias. Um estudo verificou um atraso no desenvolvimento da pneumonia com a profilaxia comparando com o controlo. As taxas de admissão em cuidados intensivos e de ventilação mecânica, variaram entre 20-50% e 18-91%, respetivamente, ocorrendo sobretudo no grupo controlo. A profilaxia parece reduzir a gravidade da pneumonia. A elevada taxa de mortalidade global e a resolução dos efeitos adversos com a suspensão terapêutica também apoiam o uso da profilaxia.
Conclusão: A profilaxia com TMP-SMX aparenta ser benéfica quando ao rituximab se associam outras terapêuticas. Contudo, em contexto de monoterapia, a evidência não é tão robusta. Desconhece-se também a duração considerada ótima da profilaxia.
Introduction: Pneumocystis jiroveci pneumonia (PJP) prophylaxis is highly effective in HIV patients and seems to have a similar effect in non HIV patients. The objective of this study was to examine the efficacy and adverse effects of PJP prophylaxis among rituximab treated non HIV patients. Methods: We performed a Systematic Review based on a Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) model. Results: 8 retrospective studies were included with a combined cohort of 6048 patients. The most common prophylaxis drug used was Trimethoprim/sulfamethoxazole (TMP SMX). There were 17 PJP infections in the prophylaxis arm against 147 in the control arm (incidence 0.3% vs. 2.4%; OR, 0.35; 95% CI, 0.19 0.64). The NNT to prevent 1 PJP episode was 36 patients (CER, 3.6%). The mortality rate due to PJP was 25%. All ADRs (adverse drug reaction) resolved with TMP SMX discontinuation. Discussion: The difference in the PJP incidence between prophylaxis and control supports the prophylaxis use. The PJP risk in rituximab monotherapy was difficult to access since all studies had combined immunosuppressors. The most important identified PJP risk factor was high cumulative corticosteroid doses. Median time for PJP development varied from 69 to 86 days. One study showed an increase in this period between control and prophylaxis patients. Such difference might be attributed to prophylaxis effect. The intensive care unit (ICU) admission and mechanical ventilation rates varied from 20 50 % and 18 91 %, respectively, and were both majorly based on control patients. This seems to indicate a preventive effect of prophylaxis against PJP severity. The high global PJP mortality rate and the fact that ADRs resolve with TMP SMX cessation also support PJP prophylaxis. Conclusion: Prophylaxis with TMP SMX seems justifiable in combined therapies with rituximab. But in monotherapy the results are not so robust. The optimal duration of prophylaxis is also unclear.
Introduction: Pneumocystis jiroveci pneumonia (PJP) prophylaxis is highly effective in HIV patients and seems to have a similar effect in non HIV patients. The objective of this study was to examine the efficacy and adverse effects of PJP prophylaxis among rituximab treated non HIV patients. Methods: We performed a Systematic Review based on a Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) model. Results: 8 retrospective studies were included with a combined cohort of 6048 patients. The most common prophylaxis drug used was Trimethoprim/sulfamethoxazole (TMP SMX). There were 17 PJP infections in the prophylaxis arm against 147 in the control arm (incidence 0.3% vs. 2.4%; OR, 0.35; 95% CI, 0.19 0.64). The NNT to prevent 1 PJP episode was 36 patients (CER, 3.6%). The mortality rate due to PJP was 25%. All ADRs (adverse drug reaction) resolved with TMP SMX discontinuation. Discussion: The difference in the PJP incidence between prophylaxis and control supports the prophylaxis use. The PJP risk in rituximab monotherapy was difficult to access since all studies had combined immunosuppressors. The most important identified PJP risk factor was high cumulative corticosteroid doses. Median time for PJP development varied from 69 to 86 days. One study showed an increase in this period between control and prophylaxis patients. Such difference might be attributed to prophylaxis effect. The intensive care unit (ICU) admission and mechanical ventilation rates varied from 20 50 % and 18 91 %, respectively, and were both majorly based on control patients. This seems to indicate a preventive effect of prophylaxis against PJP severity. The high global PJP mortality rate and the fact that ADRs resolve with TMP SMX cessation also support PJP prophylaxis. Conclusion: Prophylaxis with TMP SMX seems justifiable in combined therapies with rituximab. But in monotherapy the results are not so robust. The optimal duration of prophylaxis is also unclear.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2024
Palavras-chave
Pneumocistose Profilaxia Rituximab