Place in therapy of rituximab in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis

Figures & data

Table 1 Landmark studies where rituximab was used in induction or maintenance therapy for ANCA-associated vasculitis

Citation	Study design	Number of patients	AAV type	Intervention	Outcome
Specks et al^Citation16	Case report	1	Relapsing GPA	Induction: RTX 375 mg/m^2 weekly ×4 + high dose steroids	Achieved remission, relapsed, repeated course, and achieved remission again
Keogh et al^Citation17	Retrospective case series	11	Refractory AAV: 10 GPA 1 MPA	Induction: RTX 375 mg/m^2 weekly ×4 + high dose steroids	10 remission events within 6 months
Keogh et al^Citation19	Prospective open label pilot trial	10	Refractory or relapsing GPA	Induction: RTX 375 mg/m^2 weekly ×4 + high dose steroids	BVAS/WG=0 by 3 months in all patients
Jones et al^Citation18	Retrospective cohort study	65	Refractory AAV: 46 GPA 10 MPA 5 EGPA 4 unclassified	Induction: RTX 375 mg/m^2 weekly ×4 + high dose steroids	75% complete remission; 23% partial remission, 1% no response
Stone et al^Citation14 (RAVE Trial)	Randomized control trial	197	151 GPA 48 MPA 1 unclassified	RTX group: Induction with RTX 375 mg/m^2 weekly ×4 + high dose steroids and no maintenance CYC group: Induction with CYC 2 mg/kg/d PO + AZA maintenance Both groups received high dose steroids	64% in RTX group vs 53% in CYC group achieved BVAS/WG=0 and successful completion of prednisone taper by 6 months
Jones et al^Citation15 (RITUXVAS trial)	Randomized control trial	44	22 GPA 16 MPA 6 RLV	RTX group: Induction with RTX 375 mg/m^2 weekly ×4 + CYC 15 mg/kg IV with first and third RTX infusion + no maintenance Control group: CYC 15 mg/kg infusions q 2–3 weeks + AZA maintenance	76% in RTX vs 82% in control had sustained remission at 12 months
Rhee et al^Citation24	Retrospective cohort study	39	Not classified by AAV: 24 anti-PR3 15 anti-MPO	Maintenance RTX 1 g q 4–6 months for ≥ 1 year in those with complete or partial remission after RTX loading	Median BVAS/WG=0 in 20 patients with 2-year follow-up
Smith et al^Citation23	Retrospective cohort study	73	Refractory/relapsing AAV: 61 GPA 12 MPA	Group A: Induction with RTX 375 mg/m^2 weekly ×4 OR 1 g biweekly ×2 Group B: Induction with RTX 1 g biweekly ×2 + maintenance RTX 1 g q 6 months Group C: Relapsed Group A patients, induction with RTX 1 g biweekly ×2 + maintenance RTX 1 g q 6 months	Complete or partial remission in 93% in Group A vs 96% in Group B vs 95% in Group C Relapse in 73% in Group A vs 12% in Group B vs 11% in Group C
Roubaud-Baudron et al^Citation26	Retrospective cohort study	28	24 GPA 4 MPA	Maintenance with 375 mg/m^2 q 6 months or1 g q 6 months or 1 g q 12 months or other for median of 4 RTX infusions	Two patients developed pulmonary relapse, six had complete remission, nine had partial remission by last follow-up (median follow-up 38 months)
Cartin-Ceba et al^Citation25	Retrospective cohort study	53	Chronic relapsing or refractory GPA	At least two courses of RTX for induction after relapse or to maintain remission	85 courses done to treat relapses lead to remission
Specks et al^Citation21 (RAVE follow-up)	Randomized control trial	197	151 GPA 48 MPA 1 unclassified	Same as RAVE Trial	39% in RTX vs 33% in CYC maintained complete remission at 18 months
Rhee et al^Citation24	Retrospective cohort study	172	Not classified by AAV: 74 Anti-PR3 98 Anti-MPO	Maintenance RTX often with 1 g q 4 months up to 7 years	Complete remission in all patients, median remission follow-up 2.1 years; 20% developed relapse
Guillevin et al^Citation30 (MAINRITSAN trial)	Randomized control trial	115	87 GPA 23 MPA 5 RLV	RTX group: RTX 500 mg at day 0 and 14 and month 6, 12, and 18 AZA group: AZA 2 mg/kg/d ×12 months, then 1.5 mg/kg/d ×6 months, then 1 mg/kg/d ×4 months	5% in RTX group vs 29% in AZA group with major relapse by 28 months
Jones et al^Citation22 (RITUXVAS follow-up)	Randomized control trial	44	22 GPA 16 MPA 6 RLV	Same as RITUXVAS trial	42% in RTX vs 36% in control achieved composite of death/ESRD/relapse by 24 months

Abbreviations: ANCA, antineutrophil cytoplasmic antibody; AAV, ANCA-associated vasculitis; GPA, granulomatosis with polyangiitis; RTX, rituximab; MPA, microscopic polyangiitis; BVAS/WG, Birmingham Vasculitis Score/Wegener’s granulomatosis; EGPA, eosinophilic granulomatosis with polyangiitis; d, days; CYC, cyclophosphamide; PR3, proteinase 3; MPO, myeloperoxidase; RLV, renal limited vasculitis; AZA, azathioprine; ESRD, end stage renal disease; PO, per oral; q, every.

Figure 1 Treatment algorithm for AAV.

Abbreviations: AAV, antineutrophil cytoplasmic antibodies-associated vasculitis; MPA, microscopic polyangiitis; GPA, granulomatosis with polyangiitis ; PR3, proteinase-3; MPO, myeloperoxidase; CYC, cyclophosphamide; RTX, rituximab; AZA, azathioprine; PLEX, plasma exchange; RCT, randomized controlled trial, Cr, serum creatinine; MMF, mycophenolate mofetil.

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