Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis
IntroductionThe present study aimed to evaluate leprosy cure and relapse rates as primary outcomes related to two additional strategies for leprosy treatment: clofazimine for paucibacillary (PB) leprosy patients and clarithromycin for patients with rifampicin-resistant leprosy.MethodsWe conducted tw...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1139304/full |
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| author | Thais Montezuma Sebastian Vernal Elaine Nascimento Andrade Jurema Guerrieri Brandão Jurema Guerrieri Brandão Gustavo Laine Araújo de Oliveira Ciro Martins Gomes Ciro Martins Gomes |
| author_facet | Thais Montezuma Sebastian Vernal Elaine Nascimento Andrade Jurema Guerrieri Brandão Jurema Guerrieri Brandão Gustavo Laine Araújo de Oliveira Ciro Martins Gomes Ciro Martins Gomes |
| author_sort | Thais Montezuma |
| collection | DOAJ |
| description | IntroductionThe present study aimed to evaluate leprosy cure and relapse rates as primary outcomes related to two additional strategies for leprosy treatment: clofazimine for paucibacillary (PB) leprosy patients and clarithromycin for patients with rifampicin-resistant leprosy.MethodsWe conducted two systematic reviews (protocols CRD42022308272 and CRD42022308260). We searched the PubMed, EMBASE, Web of Science, Scopus, LILACS, Virtual Health Library and Cochrane Library databases, registers of clinical trial databases and gray literature. We included clinical trials evaluating the addition of clofazimine to PB leprosy treatment and the use of clarithromycin for treating patients with rifampicin-resistant leprosy. Risk of bias (RoB) in randomized clinical trials was assessed by the RoB 2 tool and that in non-randomized clinical trials was assessed by the ROBINS-I tool; and the certainty of the evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. A meta-analysis of dichotomous outcomes was performed.ResultsFor clofazimine, four studies were included. Cure and relapse rates were not different with the addition of clofazimine to PB leprosy treatment and demonstrated very low certainty of evidence. For clarithromycin, six studies were included. Considerable heterogeneity resulted from the difference between comparators, and studies showed no difference in the assessed outcomes with the addition of clarithromycin to rifampicin-resistant leprosy treatment. Mild adverse events were reported for both drugs but did not significantly impact treatment.DiscussionThe effectiveness of both drugs still needs to be determined. Adding clofazimine to PB leprosy treatment may reduce the repercussions of an incorrect operational classification with no apparent relevant side effects.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308272; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308260, identifier: CRD42022308272; CRD42022308260. |
| first_indexed | 2024-04-09T13:29:16Z |
| format | Article |
| id | doaj.art-1835440874fe4c729921db4c6325e99f |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-09T13:29:16Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-1835440874fe4c729921db4c6325e99f2023-05-10T04:37:16ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-05-011010.3389/fmed.2023.11393041139304Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysisThais Montezuma0Sebastian Vernal1Elaine Nascimento Andrade2Jurema Guerrieri Brandão3Jurema Guerrieri Brandão4Gustavo Laine Araújo de Oliveira5Ciro Martins Gomes6Ciro Martins Gomes7Health Technology Assessment Unit, Hospital Alemão Oswaldo Cruz, São Paulo, BrazilLIM-49, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo, BrazilCoordenação-Geral de Vigilância das Doenças em Eliminação, Ministério da Saúde do Brasil, Brasília, BrazilCoordenação-Geral de Vigilância das Doenças em Eliminação, Ministério da Saúde do Brasil, Brasília, BrazilPrograma de Pós-Graduação em Ciências Médicas, Universidade de Brasília, Brasília, BrazilCoordenação-Geral de Vigilância das Doenças em Eliminação, Ministério da Saúde do Brasil, Brasília, BrazilPrograma de Pós-Graduação em Ciências Médicas, Universidade de Brasília, Brasília, BrazilPrograma de Pós-Graduação em Patologia Molecular, Universidade de Brasília, Brasília, BrazilIntroductionThe present study aimed to evaluate leprosy cure and relapse rates as primary outcomes related to two additional strategies for leprosy treatment: clofazimine for paucibacillary (PB) leprosy patients and clarithromycin for patients with rifampicin-resistant leprosy.MethodsWe conducted two systematic reviews (protocols CRD42022308272 and CRD42022308260). We searched the PubMed, EMBASE, Web of Science, Scopus, LILACS, Virtual Health Library and Cochrane Library databases, registers of clinical trial databases and gray literature. We included clinical trials evaluating the addition of clofazimine to PB leprosy treatment and the use of clarithromycin for treating patients with rifampicin-resistant leprosy. Risk of bias (RoB) in randomized clinical trials was assessed by the RoB 2 tool and that in non-randomized clinical trials was assessed by the ROBINS-I tool; and the certainty of the evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. A meta-analysis of dichotomous outcomes was performed.ResultsFor clofazimine, four studies were included. Cure and relapse rates were not different with the addition of clofazimine to PB leprosy treatment and demonstrated very low certainty of evidence. For clarithromycin, six studies were included. Considerable heterogeneity resulted from the difference between comparators, and studies showed no difference in the assessed outcomes with the addition of clarithromycin to rifampicin-resistant leprosy treatment. Mild adverse events were reported for both drugs but did not significantly impact treatment.DiscussionThe effectiveness of both drugs still needs to be determined. Adding clofazimine to PB leprosy treatment may reduce the repercussions of an incorrect operational classification with no apparent relevant side effects.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308272; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308260, identifier: CRD42022308272; CRD42022308260.https://www.frontiersin.org/articles/10.3389/fmed.2023.1139304/fullleprosymeta-analysisdrug resistancemicrobialGRADE approachsystematic review |
| spellingShingle | Thais Montezuma Sebastian Vernal Elaine Nascimento Andrade Jurema Guerrieri Brandão Jurema Guerrieri Brandão Gustavo Laine Araújo de Oliveira Ciro Martins Gomes Ciro Martins Gomes Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis Frontiers in Medicine leprosy meta-analysis drug resistance microbial GRADE approach systematic review |
| title | Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis |
| title_full | Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis |
| title_fullStr | Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis |
| title_full_unstemmed | Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis |
| title_short | Effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin-resistant leprosy: a systematic review and meta-analysis |
| title_sort | effectiveness and safety of multidrug therapy containing clofazimine for paucibacillary leprosy and clarithromycin for rifampicin resistant leprosy a systematic review and meta analysis |
| topic | leprosy meta-analysis drug resistance microbial GRADE approach systematic review |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1139304/full |
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