Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis
IntroductionRituximab and azathioprine are used to induce or maintain remission in patients with ANCA-associated vasculitis (AAV). We evaluated the incidence of serious infections and infection-related deaths in patients with AAV treated with rituximab and azathioprine, during the maintenance of rem...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1110548/full |
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| author | Athanasios Vassilopoulos Athanasios Vassilopoulos Stephanos Vassilopoulos Stephanos Vassilopoulos Markos Kalligeros Markos Kalligeros Fadi Shehadeh Fadi Shehadeh Fadi Shehadeh Eleftherios Mylonakis Eleftherios Mylonakis |
| author_facet | Athanasios Vassilopoulos Athanasios Vassilopoulos Stephanos Vassilopoulos Stephanos Vassilopoulos Markos Kalligeros Markos Kalligeros Fadi Shehadeh Fadi Shehadeh Fadi Shehadeh Eleftherios Mylonakis Eleftherios Mylonakis |
| author_sort | Athanasios Vassilopoulos |
| collection | DOAJ |
| description | IntroductionRituximab and azathioprine are used to induce or maintain remission in patients with ANCA-associated vasculitis (AAV). We evaluated the incidence of serious infections and infection-related deaths in patients with AAV treated with rituximab and azathioprine, during the maintenance of remission period.MethodsWe searched PubMed and EMBASE for randomized clinical trials (RCTs) and observational studies evaluating immunosuppressive agents in patients with AAV. We defined serious or severe infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study was registered on PROSPERO (CRD42022366269).ResultsFrom 1,265 abstracts, we identified 21 studies (7 RCTs and 14 observational), with relevant data. We included data from 1,284 and 2,938 individuals for assessment in our primary and secondary outcomes, respectively. The overall cumulative incidence of serious infections was 15.99% (CI 95%: 6.95–27.53%) during the total follow-up period (induction and maintenance) and 7.62% (CI 95%: 4.43–11.43%) during the maintenance period. Additionally, we found a 0.49% overall case fatality rate (CI 95%: 0.02–1.37%) and a 0.09% infection-related mortality rate (CI 95%: 0.00–0.51%) during maintenance treatment. Notably, we found a 14.61% (CI 95%: 10.19–19.61%) cumulative incidence of serious infections among patients who received rituximab and a 5.93% (CI 95%: 1.19–13.26%) cumulative incidence of serious infections among patients who received azathioprine during maintenance. Moreover, the cumulative incidence of serious infections during the total follow-up period (induction and maintenance) was 20.81% (CI 95%:4.56–43.70%) for the combination of cyclophosphamide and azathioprine and 14.12% (CI 95%: 5.20–26.00%) for rituximab.DiscussionThe cumulative incidence of serious infections during total follow-up and maintenance was within expected limits, while fatal infections during maintenance treatment were uncommon. Additionally, treatment with rituximab for both induction and maintenance did not exceed the anticipated by previous studies incidence of serious infections. Clinical practice and long-term follow up data are needed to corroborate these findings.Systematic review registrationIdentifier: PROSPERO (CRD42022366269). |
| first_indexed | 2024-04-10T06:31:52Z |
| format | Article |
| id | doaj.art-6321247b221f43a292ed69b69f6ed8e5 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-10T06:31:52Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-6321247b221f43a292ed69b69f6ed8e52023-03-01T05:49:31ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-03-011010.3389/fmed.2023.11105481110548Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysisAthanasios Vassilopoulos0Athanasios Vassilopoulos1Stephanos Vassilopoulos2Stephanos Vassilopoulos3Markos Kalligeros4Markos Kalligeros5Fadi Shehadeh6Fadi Shehadeh7Fadi Shehadeh8Eleftherios Mylonakis9Eleftherios Mylonakis10Infectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesSchool of Electrical and Computer Engineering, National Technical University of Athens, Athens, GreeceInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesIntroductionRituximab and azathioprine are used to induce or maintain remission in patients with ANCA-associated vasculitis (AAV). We evaluated the incidence of serious infections and infection-related deaths in patients with AAV treated with rituximab and azathioprine, during the maintenance of remission period.MethodsWe searched PubMed and EMBASE for randomized clinical trials (RCTs) and observational studies evaluating immunosuppressive agents in patients with AAV. We defined serious or severe infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study was registered on PROSPERO (CRD42022366269).ResultsFrom 1,265 abstracts, we identified 21 studies (7 RCTs and 14 observational), with relevant data. We included data from 1,284 and 2,938 individuals for assessment in our primary and secondary outcomes, respectively. The overall cumulative incidence of serious infections was 15.99% (CI 95%: 6.95–27.53%) during the total follow-up period (induction and maintenance) and 7.62% (CI 95%: 4.43–11.43%) during the maintenance period. Additionally, we found a 0.49% overall case fatality rate (CI 95%: 0.02–1.37%) and a 0.09% infection-related mortality rate (CI 95%: 0.00–0.51%) during maintenance treatment. Notably, we found a 14.61% (CI 95%: 10.19–19.61%) cumulative incidence of serious infections among patients who received rituximab and a 5.93% (CI 95%: 1.19–13.26%) cumulative incidence of serious infections among patients who received azathioprine during maintenance. Moreover, the cumulative incidence of serious infections during the total follow-up period (induction and maintenance) was 20.81% (CI 95%:4.56–43.70%) for the combination of cyclophosphamide and azathioprine and 14.12% (CI 95%: 5.20–26.00%) for rituximab.DiscussionThe cumulative incidence of serious infections during total follow-up and maintenance was within expected limits, while fatal infections during maintenance treatment were uncommon. Additionally, treatment with rituximab for both induction and maintenance did not exceed the anticipated by previous studies incidence of serious infections. Clinical practice and long-term follow up data are needed to corroborate these findings.Systematic review registrationIdentifier: PROSPERO (CRD42022366269).https://www.frontiersin.org/articles/10.3389/fmed.2023.1110548/fullANCA-associated vasculitisazathioprinecyclophosphamidemaintenancemethotrexatemycophenolate mofetil |
| spellingShingle | Athanasios Vassilopoulos Athanasios Vassilopoulos Stephanos Vassilopoulos Stephanos Vassilopoulos Markos Kalligeros Markos Kalligeros Fadi Shehadeh Fadi Shehadeh Fadi Shehadeh Eleftherios Mylonakis Eleftherios Mylonakis Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis Frontiers in Medicine ANCA-associated vasculitis azathioprine cyclophosphamide maintenance methotrexate mycophenolate mofetil |
| title | Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis |
| title_full | Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis |
| title_fullStr | Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis |
| title_full_unstemmed | Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis |
| title_short | Incidence of serious infections in patients with ANCA-associated vasculitis receiving immunosuppressive therapy: A systematic review and meta-analysis |
| title_sort | incidence of serious infections in patients with anca associated vasculitis receiving immunosuppressive therapy a systematic review and meta analysis |
| topic | ANCA-associated vasculitis azathioprine cyclophosphamide maintenance methotrexate mycophenolate mofetil |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1110548/full |
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