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Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis

Author

Ann Rheum Dis. 2020 Jun 24;annrheumdis-2019-216863.doi: 10.1136/annrheumdis-2019-216863. Online ahead of print.

Rona M Smith 1 2, Rachel Bronwen Jones 2, Ulrich Specks 3, Simon Bond 4, Marianna Nodale 4, Reem Aljayyousi 5, Jacqueline Andrews 6, Annette Bruchfeld 7, Brian Camilleri 8, Simon Carette 9, Chee Kay Cheung 10, Vimal Derebail 11, Tim Doulton 12, Lindsy Forbess 13, Shouichi Fujimoto 14, Shunsuke Furuta 15, Ora Gewurz-Singer 16, Lorraine Harper 17, Toshiko Ito-Ihara 18, Nader Khalidi 19, Rainer Klocke 20, Curry Koening 21, Yoshinori Komagata 22, Carol Langford 23, Peter Lanyon 24, Raashid Ahmed Luqmani 25, Hirofumi Makino 26, Carole McAlear 27, Paul Monach 28, Larry W Moreland 29, Kim Mynard 2, Patrick Nachman 11, Christian Pagnoux 30, Fiona Pearce 31, Chen Au Peh 32, Charles Pusey 33, Dwarakanathan Ranganathan 34, Rennie L Rhee 35, Robert Spiera 36, Antoine G Sreih 37, Vladimir Tesar 38, Giles Walters 39, Michael H Weisman 13, Caroline Wroe 40, Peter Merkel 41, David Jayne 42 2, RITAZAREM coinvestigators; RITAZAREM co-investigators

 

Collaborators

Y Arimura, M Clarkson, J de Zoysa, T Endo, Y Hamano, H Kono, S Lawman, E Muso, K Sada, R Smith, K Suzuki, T Tsukamoto, S Uchida, A Vaglio, R Watts

Author Information

1 University of Cambridge, Cambridge, UK ronasmith@doctors.net.uk.

2 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

3 Mayo Clinic, Rochester, Minnesota, USA.

4 Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

5 University Hospitals of Leicester NHS Trust, Leicester, Leicester, UK.

6 NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals Trust, Leeds, UK.

7 Department of Renal Medicine, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.

8 Ipswich Hospital NHS Trust, Ipswich, UK.

9 University of Toronto, Toronto, Ontario, Canada.

10 University of Leicester, Leicester, UK.

11 University of North Carolina, Chapel Hill, North Carolina, USA.

12 East Kent Hospitals University NHS Foundation Trust, Canterbury, Kent, UK.

13 Cedars-Sinai Medical Center, Los Angeles, California, USA.

14 University of Miyazaki, Miyazaki, Japan.

15 Chiba University, Chiba, Japan.

16 University of Michigan, Ann Arbor, Michigan, USA.

17 University of Birmingham, Birmingham, UK.

18 Kyoto University, Kyoto, Japan.

19 McMaster University, Hamilton, Ontario, Canada.

20 Dudley Group NHS Foundation Trust, Dudley, West Midlands, UK.

21 University of Utah Vasculitis Center, Salt Lake City, Utah, USA.

22 Kyorin University School of Medicine, Tokyo, Japan.

23 Cleveland Clinic Foundation, Cleveland, Ohio, USA.

24 Rheumatology, Nottingham University Hospital, Nottingham, UK.

25 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science (NDORMs), University of Oxford, Oxford, UK.

26 Okayama Universty Hospital, Okayama, Japan.

27 Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

28 Division of Rheumatology, VA Boston Healthcare System, West Roxbury, Massachusetts, USA.

29 University of Pittsburg, Pittsburg, Pennsylvania, USA.

30 Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

31 Nottingham University Hospitals NHS Trust, Nottingham, Nottingham, UK.

32 Royal Adelaide Hospital, Adelaide, South Australia, Australia.

33 Imperial College London, London, UK.

34 Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.

35 Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

36 HSS, New York, New York, USA.

37 University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

38 Department of Nephrology, Charles University, Prague, Czech Republic.

39 Canberra Hospital, Canberra, Australian Capital Territory, Australia.

40 South Tees Hospitals NHS Foundation Trust, Middlesbrough, Middlesbrough, UK.

41 University of Pennsylvania, Philadelphia, Pennsylvania, USA.

42 University of Cambridge, Cambridge, UK.

Abstract

Objectives: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial.

Methods: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse.

Results: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19-89), prior disease duration 5.0 years (range 0.4-34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections.

Conclusions: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.