Table 1.
Characters of 19 observational studies
| No. | Study | Patient characters | n e | Dose | Other immunosuppressant agents | t m | Remission rate | SLEDAI change | BILAG change | Achieving BCD | Relapse rate | Relapse date | Adverse effect |
| 1 | Leandro et al., 2002 | Patient with active SLE and resistant to standard immunosuppressive therapy | 6 | 500 mg 2 infusions 1 week apart | 750 mg cyclophosphamide 2 infusions, prednisolone 30/60 mg for 5 d, continue hydroxychloroquine, and prednisolone | 12 | Not mentioned | 5 (83%) | 6 (100%) | Not registered | Not registered | Acute respiratory infection (3), acute gastroenteritis (3), shingles (1), folliculitis (1), oral candidiasis (1) | |
| 2 | Leandro et al., 2005 | Active SLE failed to conventional immunosuppressive therapy | 24 | 6 patients 2 infusions of 500 mg, 18 patients 2 infusions of 1000 mg, all 2 weeks apart | Infusion with cyclophosphamide/prednisolone, continue prednisolone, and hydroxychloroquine | 6 | Not mentioned | 19 (80%) | 23 (95.8%) | 7 (29.2%) | Not registered | Thrombocytopenia (1), infusion reaction (1) | |
| 3 | Vigna-Perez et al., 2006 | Active SLE and renal involvement refractory to conventional therapy | 22 | 0.5 to 1.0 g on Days 1 and 15 | Continue previous immunosuppressant including GC, CYC, MMF, AZA | 3 | PR: 7 (32%); CR: 5 (23%) | 20 (90%) | 20 (90%) | Not registered | Not registered | 1 patient died for invasive histoplasmosis | |
| 4 | Gunnarsson et al., 2007 | Active SLE and renal involvement refractory to conventional therapy | 7 | 375 mg/m2 of body surface area on Days 2, 9, 16, 23 | Infusion with methylprednisolone 250 mg and CYC 0.5 g/m2, continue with prednisolone 0.5–1.0 kg/d | 6 | PR: 1 (14%); CR: 3 (43%) | 7 (100%) | 7 (100%) | Not registered | Not registered | Photosensitive eruption (1), herpes zoster (limited) (1), neutrogena fever (1), urinary tract infection (1) | |
| 5 | Tokunaga, 2007 | Active SLE, with CNS | 10 | 375 mg/m2 2 infusions for 6, 500 mg 4 infusions for 1, 1 week apart; 1000 mg 4 infusions for 2, 2 weeks apart; 375 mg/m2 single for 1 | Infusion and continue with (15–40 mg of prednisolone, 1–3 mg betamethasone | 24 | Not mentioned | 9 (90%) | 10 (100%) | 6 (60%) | 4–23 months | Pneumonia (2), herpes zoster (1), chickenpox (1), intractable infection of decubitus ulceration (1) | |
| 6 | Sutter et al., 2008 | Active SLE failed to previous immunosuppressive therapy | 12 | 375 mg/m2 intravenously 4 infusions, 1 week apart | Pretreated with 50 mg diphenhydramine, 650 mg of acetaminophen, and 100 mg of intravenous methylprednisolone | 12 | Not mentioned | 10 (83.3%) | 11 (91.7%) | Not registered | Not registered | Not mentioned | |
| 7 | Tamimoto et al., 2008 | Active SLE failed to previous immunosuppressive therapy | 8 | 100 mg/m2 for 3, 250 mg/m2 for 2, 375 mg/m2 for 3, on Days 1, 8, 15 and 22 | Prednisolone 12.5–50.0 mg, CSA 75–175 mg | 12 | PR: 3 (38%); CR: 2 (25%) | 7 (87.5%) | 7 (87.5%) | 4 (50%) | 3–9 months | Nasopharyngitis (1), bacterial bronchitis (1), bacterial pneumonia (1), cutaneous candidiasis (1) | |
| 8 | Melander et al., 2009 | Lupus nephritis refractory to previous therapy (12) and relapse (8) | 20 | 375 mg/m2 of body surface area 4 infusions, 1 week apart | 3 patients receive CYC infusion with rituximab, 13 companied with high dose GC | 22 | PR: 7 (35%); CR: 5 (25%) | Not mentioned | Not mentioned | 12 (70.6%) | 1 | 9 months | RTX injection (2), infection (5), cutaneous herpes zoster (2) |
| 9 | Lateef et al., 2010 | Severe,refractory SLE patients | 10 | 375 mg/m2 infusions, 1 week apart | Infusion with CYC 500 mg | 12 | PR: 4 (57%); CR: 3 (43%) | 10 (100%) | 10 (100%) | 9 | 6–12 months | No obvious adverse effect observed | |
| 10 | Vital et al., 2011 | Active SLE refractory to previous therapy | 39 | 1000 mg rituximab on Days 1 and 14 | Infusion with methylprednisolone 100 mg and continue prednisolone 30–60 mg and background immunosuppressants | 12 | PR: 12 (31%); CR: 20 (51%) | 27 (69.2%) | 18 (46.2%) | 14, 14 | 12 months, 33 months | 1 patient died at 92 weeks non opportunisitic infections (4) | |
| 11 | Turner-Stokes et al., 2011 | Patients received at least two cycles of BCD with rituximab refractory to treatment with other immunosuppressive agents | 18 | 1000 mg rituximab given in two infusions 2 weeks apart | Infusion with 750 mg CYC and 100–250 mg methylprednisolone, continue with oral prednisolone, but the dose gradually tapered | 12 | PR: 7 (41%); CR: 4 (24%) | 15 (83%) | 15 (83%) | 8 (45%) | 12 months | Severe allergic reactions (2), 1 patient died for varicella pneumonia, another died for septicaemia | |
| 12 | Roccatello et al., 2011 | Severe SLE refractory to previous immunosuppressive agents | 8 | 375 mg/m2 on Days 2, 8, 15 and 22, 2 more dose in Days 30, 60 | Infusion with methyl prednisolone 1.5 mg/kg, continue with oral prednisone, 50 mg for 2 weeks rapidly tapered until 5 mg in 2 months | 36 | Not mentioned | 8 (100%) | 8 (100%) | 8 (100%) | 2 | 41 months | Show significant mild-to-moderate infusion reactions nor clinically relevant infection sequelas |
| 13 | Arce-Salinas et al., 2012 | Refractory lupus nephritis | 8 | 375 mg/m2 4 infusions 1 week apart | Infusion with steroids (1.5 mg/kg), tapered after 6 weeks, continue with no modification of steroids, AZA, or MM doses | 24 | PR: 2 (25%); CR: 2 (250%) | 4 (50%) | Not mentioned | 3 | 12 months | Minor acute adverse reactions (blood pressure variations, chills, and some mild rash), no major reactions or infections follow-up period | |
| 14 | Catapano et al., 2010 | Refractory or relapsing SLE | 31 | 15: a dose of 375 mg/m2 4 infusions; 1 week apart; 16: 1 000 mg with a 2-week interval 2 infusions | Infusion with cyclophosphamide (500 mg) and IV methyl prednisolone (500–1 000 mg) | 30 | PR: 10 (32.2%); CR: 17 (54.8%) | 27/31 (87%) | 30 (97%) | 18/27 (67%) | 11 months | Sever adverse effect (pericarditis, serum sickness reaction, throat swelling, et al.), patient have 11 severe infection | |
| 15 | Pepper et al., 2009 | Patients with class III/IV/V lupus nephritis | 18 | 2 doses of rituximab, 1 g, given at Days 1 and 15 | Infusion with 500 mg methyl prednisolone IV maintenance with MMF 1 g/d | 12 | PR: 6 (333.3%); CR: 6 (33.3%) | Not registered | Not registered | 10 (55.5%) | 2 (11.1%) | 4.5 months | Infection-related admissions (3), cannula site cellulites (1) |
| 16 | Pinto et al., 2011 | Colombian patients with severe and refractory SLE | 42 | 1 g of RTX every 2 weeks 2 infusions | Infusion with paracetamol 1 g, diphenhy 50 mg, methyl prednisolone 200 mg, continue with prednisolone 1 mg/(kg∙d) | 24 | 80% PR+CR | 25 (60%) | Not mentioned | 9 (21.4%) | 0–44 months | Urinary infection (13),bacteremia (3), delayed infusion reaction (2), respiratory infection (1) | |
| 17 | Terrier et al., 2010 | 136 active SLE patient from 44 centers, refractory to previous treat-ments | 136 | 82: 1 g (2 infusions); 48:375 mg/m2 (4 infusions) | 125 associate prednisone wit dosage of 29.9 mg/d, 72 patients (53%) receive HCQ and 52% associate other concomitant immunosuppressive agents | 18 | In LN, PR: 6 (29%), CR: 14 (45%) | 80 (71%) | Not mentioned | 31/76 (41%) | 16.6 months | Sever infection (12 (9%)), serum sick-ness (5), acute infusion reactions 12 (9%) | |
| 18 | Ramos-Casals et al., 2010 | 196 SAD patients refractory to standard therapy | 107* | 375 mg/m2 of rituximab weekly for 4 weeks (85%), 1000 mg 2 infusions, 2 weeks apart (15%) | All patients continue with corticosteroid 60% patients continue with previous immunosuppressive agents | 27 | CR: 45%; PR: 32% | Not mentioned | Not mentioned | Not mentioned | 20/81 (25%) | 0–26 months | Infections in 12 patients, including respiratory infection, urinary tract infection, cutaneous infection |
| 19 | Tony et al., 2011 | 370 patients from 42 centers with a diagnosis of an autoimmune, condition other than RA or NHL | 85# | Mean dose of rituximab was 2 440 mg each patient over a median period of 194 d | 7 SLE patients receive CYC with infusion of rituximb, 67 patients continue immunosuppressive agents | 12 | CR: 30%; PR: 20% | Not mentioned | Not mentioned | Not mentioned | Not mentioned | Not mentioned | 13.2% patients experience infection, serious infections was 5.3 per 100 patient-years in the total 370 patients |
SLEDAI: systemic lupus erythematosus disease activity index; BILAG: British isles lupus assessment group index; BCD: B-cell depletion; PR: partial remission; CR: complete remission; SLE: systemic lupus erythematosus; LN: lupus nephritis; SAD: systemic autoimmune diseases, GC: glucocorticoid; CYC: cyclophosphamide; MMF: mycophenolate mofetil; AZA: azathioprine; HCQ: hydroxychloroquine. n e:number enrolled; t m:median follow month
*
including 107 SLE patients
#
23.0% (85 patients) were SLE