Research Papers: Immunology:

The “4 plus 2” rituximab protocol makes maintenance treatment unneeded in patients with refractory ANCA-associated vasculitis: A 10 years observation study

Dario Roccatello _, Savino Sciascia, Daniela Rossi, Mirella Alpa, Carla Naretto, Massimo Radin, Roberta Fenoglio, Simone Baldovino and Elisa Menegatti

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Oncotarget. 2017; 8:52072-52077. https://doi.org/10.18632/oncotarget.18120

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Dario Roccatello1,2,*, Savino Sciascia1,2,*, Daniela Rossi1, Mirella Alpa1, Carla Naretto1, Massimo Radin1, Roberta Fenoglio2, Simone Baldovino1,2 and Elisa Menegatti1

1 Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

2 Nephrology and Dialysis Unit, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy

* These authors have equally contributed to this manuscript

Correspondence to:

Dario Roccatello, email:

Keywords: rituximab, systemic vasculitis, ANCA-associated vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, Immunology and Microbiology Section, Immune response, Immunity

Received: March 10, 2017 Accepted: April 19, 2017 Published: May 23, 2017


Background: ANCA 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.

Methods: 11 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.

Results: After 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.

Conclusion: In 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.

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