Risk Factors Associated with Relapse in Japanese Patients with Microscopic Polyangiitis

Wada, Takashi; Hara, Akinori; Arimura, Yoshihiro; Sada, Ken‐ei; Makino, Hírofumi

doi:10.3899/jrheum.110705

Cited by 27 publications

(15 citation statements)

References 21 publications

(39 reference statements)

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“…However, it is highly controversial whether fast tapering of GC is associated with increasing risk of relapse in AAV patients. While some studies supported this notion [ 26 , 27 ], it has recently been demonstrated that GC therapy beyond 6 months is associated with a greater risk of infections, but not with a decreased risk of relapse [ 24 ]. The incidence of SIs in the present study was notably higher than those in previous observational studies from European countries [ 24 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Different responses to treatment across classified diseases and severities in Japanese patients with microscopic polyangiitis and granulomatosis with polyangiitis: a nationwide prospective inception cohort study

et al. 2015

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IntroductionThis study aims to elucidate the prognosis and the effectiveness of current treatments for Japanese patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).MethodsPatients with newly diagnosed MPA and GPA were enrolled in a nationwide, prospective, inception cohort study from 22 tertiary Japanese institutions, and treatment patterns and responses were evaluated for 24 months. Primary outcome measures were rates of remission (Birmingham Vasculitis Activity Score, 0) and remission with low-dose glucocorticoids (GC) (prednisolone ≤ 10 mg) (GC remission).ResultsOf 156 enrolled patients, 78 MPA patients and 33 GPA patients were included. Concomitant cyclophosphamide (CY) was used in 24 MPA (31 %) and 20 GPA (60 %) patients during the initial 3 weeks of treatment. After 6 months, remission was achieved in 66 MPA (85 %) and 29 GPA (87 %) patients, while GC remission was obtained in only 31 MPA (40 %) and 13 GPA (39 %) patients. During the 24-month period, 14 MPA patients and 2 GPA patients died; end stage renal disease (ESRD) was noted in 13 MPA patients but no GPA patients. Patients with severe disease, according to the European Vasculitis Study Group (EUVAS) classification, showed poorer ESRD-free and overall survival rates than those with generalized disease (p < 0.0001). There were no differences in relapse-free survival rates between GPA and MPA, among EUVAS-defined disease severity categories, and between anti-neutrophil cytoplasmic antibody subspecialties.ConclusionsThe majority of Japanese patients with MPA and GPA received treatment with high-dose GC and limited CY use, and showed high remission and relapse-free survival rates but low GC remission rates in clinical practice.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry UMIN000001648. Registered 28 February 2009.

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Section: Discussionmentioning

confidence: 99%

Different responses to treatment across classified diseases and severities in Japanese patients with microscopic polyangiitis and granulomatosis with polyangiitis: a nationwide prospective inception cohort study

et al. 2015

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“…One recent underpowered retrospective study compared the relapse rate of patients who were cANCA-positive or cANCA-negative at the time of remission and found no significant difference in relapse risk [24]. The significance of persistent MPO-ANCA at the time of switch to maintenance therapy was investigated in 62 Japanese patients with MPA and was not found to be associated with an increased risk of relapse, although several studies have reported an increased risk of relapse associated with an increase in MPO-ANCA titre once in remission [9, 25]. Rituximab is now increasingly being used for both remission induction and maintenance in AAV.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies suggested that the persistence of PR3-ANCA, but not MPO-ANCA, at the time of discontinuing cyclophosphamide and switching to maintenance therapy is associated with an increased risk of relapse [7, 9]. We used long-term follow-up data from two of the previous European Vasculitis Study Group (EUVAS) clinical trials, CYCLOPS and IMPROVE, to identify whether persistent ANCA positivity at the time of discontinuing cyclophosphamide and switching to maintenance therapy is associated with an increased risk of relapse in patients with moderate-to-severe ANCA-associated vasculitis (AAV) treated with cyclophosphamide as initial remission induction therapy [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse

et al. 2017

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BackgroundRelapse 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.MethodsANCA-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.ResultsOf 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.ConclusionsBecoming ANCA-negative before the switch to maintenance is associated with a reduced risk of relapse.Trial registrationCYCLOPS: ClinicalTrials.gov, NCT00430105. Registered retrospectively on 31 January 2007. IMPROVE: ClinicalTrials.gov, NCT00307645. Registered retrospectively on 27 March 2006.

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“…Since 2008, we have conducted a retrospective cohort study elucidating risk factors associated with relapse in microscopic polyangiitis (MPA) patients [ 1 ] and a nationwide epidemiologic study of eosinophilic granulomatosis with polyangiitis. The clinical studies described below are in progress currently.…”

Section: The Research Committee On Intractable Vasculitides the Minimentioning

confidence: 99%

“…Based on our retrospective study elucidating the risk factors for relapse in patients with myeloperoxidase (MPO)-ANCA positive MPA [ 1 ], we are conducting an observational cohort study of remission maintenance therapy in Japanese AAV patients (Co-RemIT-JAV) (UMIN000006373). The study objective is to clarify the safety and efficacy of remission maintenance therapy in Japanese AAV patients.…”

Section: Co-remit-javmentioning

confidence: 99%

Clinical studies of the Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of Japan

Makino

Sada

2013

Clin Exp Nephrol

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In Japan, the Research Committee on Intractable Vasculitides, supported by the Ministry of Health, Labour and Welfare, has been promoting basic and clinical research on vasculitis since 1972. The present Research Committee on Intractable Vasculitides comprises 4 subcommittees under the direction of a Principal Investigator: Basic and Pathological Research Subcommittee, Clinical Research Subcommittee of Small and Medium-sized Vessel Vasculitis, Clinical Research Subcommittee of Large-sized Vessel Vasculitis, and International Cooperation Research Subcommittee. Since 2008, 9 nationwide clinical studies for vasculitis have been conducted and 8 clinical and basic studies are in progress.

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Risk Factors Associated with Relapse in Japanese Patients with Microscopic Polyangiitis

Abstract: In Japan, relapse of MPO-ANCA-positive MPA may be associated with the reduction rate of oral prednisolone administration during maintenance therapy.

Cited by 27 publications

References 21 publications

Different responses to treatment across classified diseases and severities in Japanese patients with microscopic polyangiitis and granulomatosis with polyangiitis: a nationwide prospective inception cohort study

Different responses to treatment across classified diseases and severities in Japanese patients with microscopic polyangiitis and granulomatosis with polyangiitis: a nationwide prospective inception cohort study

Negative anti-neutrophil cytoplasm antibody at switch to maintenance therapy is associated with a reduced risk of relapse

Clinical studies of the Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of Japan

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