Systematic review of the role of rituximab in treatment of antineutrophil cytoplasmic autoantibody-associated vasculitis, hepatitis C virus-related cryoglobulinemic vasculitis, Henoch–Schönlein purpura, ankylosing spondylitis, and Raynaud’s phenomenon

Figures & data

Table 1 Summary of publications describing use of RTX in vasculitides

Study	Design	Patients (n)	RTX treatment regimen
ANCA-associated vasculitis
Brodowska-Kania et al^Citation41	CR	1	I: RTX 1 g ×2, 2 weeks apart
Awad et al^Citation35	CR	1	I: RTX 1 g ×2, 2 weeks apart M: RTX 500 mg ×2 weekly
Wendt et al^Citation27	CS	16	I: RTX 375 mg/m^2/week ×4 (n=5), 1 g ×2, 2 weeks apart (n=6), 500 mg ×2, 2 weeks apart (n=5)
Lovric et al^Citation29	CS	15	I: 375 mg/m^2/week ×4
Rhee et al^Citation31	Ret	39	M: 1 g 4-monthly for 2 years
Roubaud-Baudron et al^Citation32	Ret	28	M: 375 mg/m^2 6-monthly (n=13), 1 g biannually (n=4), 1 g every 12 months (n=3), other regimens (n=8); average infusions: 4 (2–10)
Smith et al^Citation34	Ret	73	I: 375mg/m^2/week ×4 or 1 g ×2 M: RTX only in response to relapses (n=28), RTX regularly 1 g 6-monthly for 2 years postinduction (n=45), or RTX regularly 1 g 6-monthly for 2 years initiated at relapse; cumulative dose in patients treated regularly: 6 (2–11) g
Cartin-Ceba et al^Citation30	Ret	53	I: 375 mg/m^2/week ×4 M: 375 mg/m^2/week ×4 or 1 g every 2 weeks ×2
Besada et al^Citation40	Ret	35	I: 1 g ×2 M: RTX 2 g annually
Calich et al^Citation37	Ret	66	I: 375mg/m^2/week ×4 or 1 g ×2 M: 500 mg every 6 months ×1.5 years
Pendergraft et al^Citation39	Ret	172	M: 1 g every 3–4 months
Charles et al^Citation38	Ret	80	I: 375 mg/m^2/week ×4 or 1 g ×2, 2 weeks apart M: 375 mg/m^2every 6 months (26%), 500 mg every 6 months (14%), 1 g every 6 months (11%)
Moog et al^Citation36	Ret	17	I: RTX 375 mg/m^2 ×1 M: RTX 375 mg/m^2 ×1 every 6–9 months (if rising antibody titers or B-cell return)
Alberici et al^Citation80	Ret	69	I: 375 mg/m^2/week ×4 or 1 g ×2, 2 weeks apart M: 1 g every 6 months for 24 months
Nagafuchi et al^Citation26	POL	7	I: RTX 375 mg/m^2/week ×4 weeks
Stone et al,^Citation11 Specks et al^Citation10 (RAVE)	RCT	197	I: RTX 375 mg/m^2/week ×4 or CYC 2 mg/kg/per day orally
Jones et al^Citation19,Citation23 (RITUXVAS)	RCT	44	I: randomized 3:1 to GC plus either RTX (375 mg/m^2/week ×4) with two intravenous CYC pulses (n=33, rituximab group), or intravenous CYC for 3–6 months followed by AZA (n=11, control group)
Guillevin et al^Citation33 (MAINRITSAN)	RCT	118	I: CYC + GC M: RTX 500 mg days 0 and 14 and months 6, 12, and 18 or AZA (daily orally) until month 22
de Menthon et al^Citation28	RCT	17	I: 375 mg/m^2/week ×4 v infliximab M: 375 mg/m^2/week at months 4, 8, and 12
Specific tissue involvement in AAV
Necrotising scleritis
Recillas-Gispert et al^Citation21	Ret	8 (12 eyes)	I: RTX 1 g ×2, 2 weeks apart
Pulmonary nodules
Henderson et al^Citation20	CS	5	RTX 1 g ×2, 2 weeks apart
Eosinophilic granulomatosis with polyangiitis
Umezawa et al^Citation42	CR	1	I: 375 mg/m^2/week ×4
Thiel et al^Citation43	Ret	9	I: RTX 1 g ×2, 2 weeks apart
Mohammad et al^Citation44	Ret	41	I: 375 mg/m^2/week ×4 or 1 g ×2, 2 weeks apart M: 375 mg/m^2/week ×4 (3), 1 g ×2, 2 weeks apart (2), 1 g ×1 (16), 600 mg ×1 (1)
Henoch–Schönlein purpura
Pillebout et al^Citation48	CR	1	RTX 1 g ×2, 2 weeks apart
Donnithorne et al^Citation47	CS	3	RTX 1 g ×2, 2 weeks apart (n=1), 375 mg/m^2/week ×4 (n=2, repeated for relapse in one patient)
HCV-related vasculitis
Lamprecht et al^Citation57	CR	1	RTX 500 mg every 3 weeks ×6
Petrarca et al^Citation56	CS	19	RTX 375 mg/m^2/week ×4
Visentini et al^Citation55	CS	6	RTX 250 mg/m^2 ×2
Saadoun et al^Citation50	PC	16	RTX 375 mg/m^2 on days 1, 8, 15, and 22 over a period of 1 month + PEG-IFNα + ribavirin
Terrier et al^Citation52	PC	32	RTX 375 mg/m^2 on days 1, 8, 15, and 22 or 1,000 mg on days 1 and 15 + PEG-IFNα + ribavirin (n=20) vs RTX 375 mg/m^2 on days 1, 8, 15, and 22 or 1,000 mg on days 1 and 15 (n=12)
Saadoun et al^Citation49	PC	95	RTX 375 mg/m^2 on days 1, 8, 15, and 22 over 1 month + PEG-IFNα + ribavirin (n=40) versus PEG-IFNα + ribavirin (n=55)
Visentini et al^Citation54	PC	27	RTX 250 mg/m^2 ×2
Dammacco et al^Citation53	PR	41	RTX (375 mg/m^2) once a week for 1 month followed by two 5-monthly infusions + PEG-IFNα + ribavirin (n=22) versus PEG-IFNα + ribavirin (n=19)
De Vita et al^Citation51	PR	57	RTX 1 g on days 0 and 14 vs conventional therapy (GC, n=17; PE, n=5; CYC, n=4; AZA, n=3); note four of 57 not associated with HCV
Sneller et al^Citation9	RCT	24	RTX 375 mg/m^2 on days 1, 8, 15, and 22 vs conventional therapy

Abbreviations: AAV, ANCA-associated vasculitis; ANCA, antineutrophil cytoplasmic autoantibody; AZA, azathioprine; CR, case report; CS, case series; CYC, cyclophosphamide; GC, glucocorticoid; HCV, hepatitis C virus; I, induction; M, maintenance; POL, prospective open-label; PC, prospective cohort; PEG, polyethylene glycol; PR, prospective randomized; RCT, randomized controlled trial; Ret, retrospective cohort study; RTX, rituximab.

Figure 1 Search strategy and articles excluded and selected.

Abbreviations: ANCA, antineutrophil cytoplasmic autoantibody; DMARD, disease-modifying antirheumatic drug; HCV, hepatitis C virus; NSAID, nonsteroidal anti-inflammatory drug.

Table 2 Summary of publications describing use of RTX in nonvasculitic musculoskeletal disease

Study	Design	Patients (n)	RTX treatment regimen
Ankylosing spondylitis
Rodríguez-Escalera and Fernández-Nebro^Citation61	CR	1	I: RTX 1 g ×2, 2 weeks apart + lamivudine for hepatitis B infection
Huang et al^Citation62	CR	1	I: RTX 500 mg ×2, 2 weeks apart (anti-TNF blocker-naïve)
Omair et al^Citation63	CR	1	I: RTX 1 g ×2, 2 weeks apart, repeated 8 months later
Kobak et al^Citation60	CR	1	I: RTX 1 g ×2, 2 weeks apart, repeated 6 months later
Aldhaheri et al^Citation64	CR	1	I: 375 mg/m^2/week ×2, 2 weeks apart M: 375 mg/m^2/week ×2 at 6 months and 12 months from induction
Nocturne et al^Citation58	CS	8	I: RTX 1 g ×2, 2 weeks apart (only one patient was anti-TNF blocker-naïve)
Song et al^Citation59	POL	20	I: RTX 1 g ×2, 2 weeks apart (TNF blocker-naïve vs TNF blocker-treated)
Raynaud’s phenomenon
Rech et al^Citation67	CR	1	RTX 375 mg/m^2 after each plasma exchange ×9
Dunkley et al^Citation66	CR	1	RTX 1g ×2, 2 weeks apart
Haroon et al^Citation65	CR	1	RTX 1g + iloprost + methylprednisolone + CYC; 2 weeks later, full schedule repeated; two further courses of RTX 1 g + iloprost + methylprednisolone
Shabrawishi et al^Citation68	CR	1	RTX 1g ×2, 2 weeks apart. Second treatment for relapse RTX 375 mg/m^2/week ×4

Abbreviations: CR, case report; CS, case series; CYC, cyclophosphamide; I, induction; M, maintenance; POL, prospective open-label; RTX, rituximab.

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