Abstract
BackgroundANCA associated vasculitides (AAV) often present with a chronic relapsing course. Relapse leads to increased immunosuppressive exposure and consequent toxicity. While two randomized controlled trials have shown rituximab (RTX) to be the most effective induction treatment in patients with relapsing disease, the optimal treatment duration and RTX dose remain debated. Whether to administer a maintenance dose to every patient, at a fixed time interval or on the basis of B cell count and ANCA titre or only when disease manifestations do occur is still debated as well.Methods11 patients (5 with granulomatosis with polyangiitis, 4 with microscopic polyangiitis-MPA-, and 2 with eosinophilic granulomatosis with polyangiitis -EGPA-) intolerant or refractory to conventional therapies including cyclophosphamide were enrolled. All patients received the so called “improved 4+2” RTX scheme as a rescue therapy. Following RTX administration, immunosuppressive drugs were rapidly tapered and no immunosuppressive maintenance therapy had been given.ResultsAfter a mean follow-up of 85 months since the “4+2” RTX protocol: four out of 11 patients (37%, 1 EGPA and 3 MPA, all MPO-positive) remained in remission after one cycle of “4+2” RTX infusion protocol with no relapse for a median 66 months [60–108]). Seven relapsing patients were re-treated once with RTX (again as monotherapy with the same protocol) after a median of 54 months (24-96). Following re-treatment, they again showed complete remission over a median of 32 months (12-96) of observation.ConclusionIn one of the longest-term observation (85 months) studies, sustained clinical remission without immunosuppressive maintenance therapy (and a negligible dose of prednisone since the 5thmonth) was obtained by the “4 + 2” RTX infusion protocol in patients with ANCA-associated vasculitis intolerant or refractory to conventional therapy.
Highlights
Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) are small-vessel vasculitides associated with antineutrophil cytoplasm antibodies (ANCA) [1]
Classification has been historically performed according to the clinical phenotype together www.impactjournals.com/oncotarget with ANCA positivity or histological confirmation [2], a recent genome-wide association (GWAS) study demonstrated that, from a genetic perspective, ANCA-associated vasculitis (AAV) are best defined by ANCA specificity rather than clinical features [3]
We have previously shown a favorable outcome of 11 patients with refractory associated vasculitides (AAV) treated with a “4+2” RTX protocol [12]
Summary
Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) are small-vessel vasculitides associated with antineutrophil cytoplasm antibodies (ANCA) [1]. AAV are characterized, in the proteinase 3 (PR3)-associated group [4], by a chronic relapsing course leading to repeat exposure to immunosuppression with increased adverse events and organ damage [5]. Rituximab (RTX), an anti-CD20 monoclonal antibody, is an effective induction treatment of AAV in both newly diagnosed and relapsing patients [6,7,8]. While two randomized controlled trials have shown rituximab (RTX) to be the most effective induction treatment in patients with relapsing disease, the optimal treatment duration and RTX dose remain debated. Whether to administer a maintenance dose to every patient, at a fixed time interval or on the basis of B cell count and ANCA titre or only when disease manifestations do occur is still debated as well
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
