Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse
Abstract Background Relapse of disease is frequent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). It is unclear whether persistent ANCA when starting maintenance therapy increases the risk of relapse. We examined the association between ANCA status and relapse in two rando...
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-017-1321-1 |
| _version_ | 1811303580054847488 |
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| author | Matthew David Morgan Matthew Szeto Michael Walsh David Jayne Kerstin Westman Niels Rasmussen Thomas F. Hiemstra Oliver Flossmann Annelies Berden Peter Höglund Lorraine Harper on behalf of the European Vasculitis Society |
| author_facet | Matthew David Morgan Matthew Szeto Michael Walsh David Jayne Kerstin Westman Niels Rasmussen Thomas F. Hiemstra Oliver Flossmann Annelies Berden Peter Höglund Lorraine Harper on behalf of the European Vasculitis Society |
| author_sort | Matthew David Morgan |
| collection | DOAJ |
| description | Abstract Background Relapse of disease is frequent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). It is unclear whether persistent ANCA when starting maintenance therapy increases the risk of relapse. We examined the association between ANCA status and relapse in two randomised controlled trials. Methods ANCA-positive patients in two trials, CYCLOPS and IMPROVE, were switched from cyclophosphamide to maintenance therapy after achieving clinical remission. We classified patients as being either ANCA-positive or ANCA-negative at the time they started maintenance therapy. We compared the risk of relapse in ANCA-positive and ANCA-negative patients. Results Of 252 patients included, 102 (40%) experienced at least one relapse during the follow-up period. At the time of the switch from induction to maintenance therapy, 111 were ANCA-positive, of whom 55 (50%) relapsed, compared to 141 patients who were ANCA-negative, of whom 47 (33%) relapsed. In multivariable time-to-event analysis, a reduced risk of relapse was associated with having become ANCA-negative at the time of switching to maintenance therapy (hazard ratio 0.63, 95% confidence interval 0.42–0.95; p = 0.026). In addition, initial proteinase 3 (PR3)-ANCA, younger age, lower serum creatinine, pulsed cyclophosphamide for remission induction, and mycophenolate mofetil for remission maintenance were all associated with an increased risk of relapse. Conclusions Becoming ANCA-negative before the switch to maintenance is associated with a reduced risk of relapse. Trial registration CYCLOPS: ClinicalTrials.gov, NCT00430105 . Registered retrospectively on 31 January 2007. IMPROVE: ClinicalTrials.gov, NCT00307645 . Registered retrospectively on 27 March 2006. |
| first_indexed | 2024-04-13T07:49:19Z |
| format | Article |
| id | doaj.art-a0dce7e32c7247518e2fc40b195cf588 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-13T07:49:19Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-a0dce7e32c7247518e2fc40b195cf5882022-12-22T02:55:34ZengBMCArthritis Research & Therapy1478-63622017-06-011911710.1186/s13075-017-1321-1Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapseMatthew David Morgan0Matthew Szeto1Michael Walsh2David Jayne3Kerstin Westman4Niels Rasmussen5Thomas F. Hiemstra6Oliver Flossmann7Annelies Berden8Peter Höglund9Lorraine Harper10on behalf of the European Vasculitis SocietyRenal Immunobiology, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of BirminghamRenal Immunobiology, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of BirminghamDepartments of Medicine and Clinical Epidemiology and Biostatistics, McMaster UniversityDepartment of Medicine, Addenbrooke’s Hospital, University of CambridgeDepartment of Nephrology, Skane University Hospital Malmö, Lund UniversityDepartment of Autoimmune Serology, Statens SeruminstitutSchool of Clinical Medicine, University of Cambridge and Cambridge Clinical Trials Unit, Addenbrooke’s HospitalRenal Department, Royal Berkshire HospitalDepartment of Internal Medicine, Leiden University Medical CenterCompetence Centre for Clinical Research, Skane University HospitalRenal Immunobiology, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of BirminghamAbstract Background Relapse of disease is frequent in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). It is unclear whether persistent ANCA when starting maintenance therapy increases the risk of relapse. We examined the association between ANCA status and relapse in two randomised controlled trials. Methods ANCA-positive patients in two trials, CYCLOPS and IMPROVE, were switched from cyclophosphamide to maintenance therapy after achieving clinical remission. We classified patients as being either ANCA-positive or ANCA-negative at the time they started maintenance therapy. We compared the risk of relapse in ANCA-positive and ANCA-negative patients. Results Of 252 patients included, 102 (40%) experienced at least one relapse during the follow-up period. At the time of the switch from induction to maintenance therapy, 111 were ANCA-positive, of whom 55 (50%) relapsed, compared to 141 patients who were ANCA-negative, of whom 47 (33%) relapsed. In multivariable time-to-event analysis, a reduced risk of relapse was associated with having become ANCA-negative at the time of switching to maintenance therapy (hazard ratio 0.63, 95% confidence interval 0.42–0.95; p = 0.026). In addition, initial proteinase 3 (PR3)-ANCA, younger age, lower serum creatinine, pulsed cyclophosphamide for remission induction, and mycophenolate mofetil for remission maintenance were all associated with an increased risk of relapse. Conclusions Becoming ANCA-negative before the switch to maintenance is associated with a reduced risk of relapse. Trial registration CYCLOPS: ClinicalTrials.gov, NCT00430105 . Registered retrospectively on 31 January 2007. IMPROVE: ClinicalTrials.gov, NCT00307645 . Registered retrospectively on 27 March 2006.http://link.springer.com/article/10.1186/s13075-017-1321-1ANCAVasculitisRelapseTreatmentANCA-associated vasculitisClinical trial |
| spellingShingle | Matthew David Morgan Matthew Szeto Michael Walsh David Jayne Kerstin Westman Niels Rasmussen Thomas F. Hiemstra Oliver Flossmann Annelies Berden Peter Höglund Lorraine Harper on behalf of the European Vasculitis Society Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse Arthritis Research & Therapy ANCA Vasculitis Relapse Treatment ANCA-associated vasculitis Clinical trial |
| title | Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse |
| title_full | Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse |
| title_fullStr | Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse |
| title_full_unstemmed | Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse |
| title_short | Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse |
| title_sort | negative anti neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse |
| topic | ANCA Vasculitis Relapse Treatment ANCA-associated vasculitis Clinical trial |
| url | http://link.springer.com/article/10.1186/s13075-017-1321-1 |
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