Randomized clinical trials in ANCA-associated vasculitis: a systematic analysis of the WHO - International Clinical Trials Registry Platform

Iudici, Michele; Puéchal, Xavier; Brigante, Alejandro; Atal, Ignacio; Gabay, Cem

doi:10.1186/s13023-020-01408-6

Cited by 2 publications

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“…Differences in key AAV outcomes may not be apparent in clinical trials owing to their own limitations, including the fact that more than 1 disease had often been included to overcome their rarity, and, hence, they were not powered to detect significant differences about a given intervention’s efficacy within a single disease entity. 20 Our clinical data from a larger subset of patient with GPA indicated a specific advantage of rituximab over cyclophosphamide induction therapy for patients classified as having GPA, most of whom had PR3-ANCA–positive disease.…”

Section: Discussionmentioning

confidence: 68%

“…Furthermore, a post hoc analysis of trial data from 131 patients with PR3-AAV (127 of whom were classified as having GPA) showed that patients with PR3-AAV were more than twice as likely to achieve complete remission at 6 months when treated with rituximab rather than with cyclophosphamide (65% vs 48%, respectively; P = .04). Differences in key AAV outcomes may not be apparent in clinical trials owing to their own limitations, including the fact that more than 1 disease had often been included to overcome their rarity, and, hence, they were not powered to detect significant differences about a given intervention’s efficacy within a single disease entity . Our clinical data from a larger subset of patient with GPA indicated a specific advantage of rituximab over cyclophosphamide induction therapy for patients classified as having GPA, most of whom had PR3-ANCA–positive disease.…”

Section: Discussionmentioning

confidence: 94%

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Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis

et al. 2022

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ImportanceResults of randomized clinical trials have demonstrated rituximab’s noninferiority to cyclophosphamide as induction therapy for antineutrophil cytoplasm antibody (ANCA)–associated vasculitides (AAV), with neither treatment having a specific advantage for granulomatosis with polyangiitis (GPA). However, post hoc analysis results have suggested that rituximab might be more effective than cyclophosphamide in inducing remission in patients with proteinase 3–positive AAV.ObjectiveTo compare the effectiveness of rituximab and cyclophosphamide in inducing GPA remission in a large population of unselected patients.Design, Setting, and ParticipantsThis comparative effectiveness study used multicenter target trial emulation observational data from 32 French hospitals in the French Vasculitis Study Group Registry. Groups were determined according to treatments received, without any intervention from the investigators. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Participants included patients with newly diagnosed or relapsing GPA who satisfied American College of Rheumatology classification criteria and/or Chapel Hill Consensus Conference nomenclature. Data were analyzed from October 1, 2021, to May 31, 2022.ExposuresAt least 1 infusion of rituximab or cyclophosphamide for induction therapy between April 1, 2008, and April 1, 2018.Main Outcomes and MeasuresThe primary outcome was remission rate at month 6 (±2 months), with remission defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and prednisone dose of 10 mg/d or less. The BVAS is a validated tool for small-vessel vasculitis and used to assess the level of disease activity, with a numerical weight attached to each involved organ system. The BVAS has a range of 0 to 63 points; a score of 0 indicates no disease activity. Subgroup analyses included the primary outcome for patients with a new diagnosis, for most recently treated patients, and for patients with myeloperoxidase-ANCA positivity.ResultsAmong 194 patients with GPA included in the analysis (mean [SD] age, 54 [15] years; 110 men [56.7%]), 165 (85.1%) had a new diagnosis, and 147 of 182 with data available (80.8%) had proteinase 3–ANCA positivity. Sixty-one patients received rituximab and 133 received cyclophosphamide for induction therapy. In the weighted analysis, the primary outcome was reached for 73.1% of patients receiving rituximab vs 40.1% receiving cyclophosphamide (relative risk [RR], 1.82 [95% CI, 1.22-2.73]; risk difference, 33.0% [95% CI, 12.2%-53.8%]; E value for RR, 3.05). Similar results were observed in the subgroup of patients with newly diagnosed GPA and those with a more recent treatment. In the subset of 27 patients with myeloperoxidase-ANCA–positive GPA, 8 of 10 rituximab recipients and 8 of 17 cyclophosphamide recipients met the primary end point (unweighted RR, 1.73 [95% CI, 0.96-3.11]).Conclusions and RelevanceIn this comparativeness effectiveness study using clinical data, rituximab induction therapy for GPA was more frequently associated with remission than cyclophosphamide. These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 94%

Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis

et al. 2022

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Localized versus systemic granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry

et al. 2021

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Objective To describe the main features at diagnosis and evolution over time of patients with localised granulomatosis with polyangiitis (L-GPA) compared to those of systemic GPA (S-GPA). Methods EULAR definitions of L-GPA, i.e., upper and/or lower respiratory tract involvement, and S-GPA were applied to patients from the French Vasculitis Study Group Registry. L-GPA and S-GPA patients’ characteristics at diagnosis and long-term outcomes were analyzed and compared. Results Among the 795 Registry patients, 79 (10%) had L-GPA. Their main clinical manifestations were rhinitis, lung nodules, sinusitis and otitis. L-GPA versus S-GPA patients at diagnosis, respectively, were younger, more frequently had saddle nose deformity or subglottic stenosis and were less often PR3-ANCA–positive. L-GPA versus S-GPA induction therapy less frequently included cyclophosphamide but more often a combination of methotrexate and glucocorticoids; 64% of methotrexate-treated patients experienced disease progression within 18 months post-diagnosis. L- and S-GPA patients’ estimated relapse-free–survival probabilities, relapse rates and refractory disease rates at each time point were comparable, but L-GPA patients had more frequent ENT and lung relapses, and higher overall survival rates (P <0.02). Over a median follow-up of 3.5 years, 18 (22.8%) L-GPA progressed to S-GPA, either as a relapse after a period in remission or more frequently in the context of refractory disease. L-GPA patients experienced more ENT-related damage. Conclusions The relapse risks of L-GPA and S-GPA were similar, but relapse patterns differed and L-GPA overall survival rate was higher. About one-quarter of L-GPA patients developed S-GPA over time, but without end-stage organ involvement.

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Randomized clinical trials in ANCA-associated vasculitis: a systematic analysis of the WHO - International Clinical Trials Registry Platform

Cited by 2 publications

References 28 publications

Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis

Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis

Localized versus systemic granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry

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