Table 2.
Summary of the Main RCTs of B-cell Depleting Agents in SLE
| Author (Year) | n (Female %) Ethnicity | Study Design Location | Drug and Placebo (Number of Patients) Premedication | Inclusion Criteria SOC | Exclusion Criteria | Main Outcomes Evaluated | Adverse Events (P-Value) |
|---|---|---|---|---|---|---|---|
| Navarro et al (2011) | 867 (95%) | RCT 52w | Belimumab 1 mg/kg (n = 289) Belimumab 10 mg/kg (n = 290) Placebo (n = 288) |
Aged ≥18 years SELENA-SLEDAI ≥6 Standard of care therapy (cortic <40 mg/d) SLE criteria (mandatory ANA/DNA+) | Severe LN/CNS involve Pregnancy Previous B-cell-targeted therapies Previous CYC (<6 months) Previous IVIG or cortic >60 mg/d (<3 months) |
Primary outcome (SRI improvement 52w): 51% and 58% vs. 44% plac (0.0129 and 0.0006) | Serious adverse event ≥1 (16% and 14% vs 13%, P > .05) Infections (68% and 67% vs 64%, P >.05) Serious infection ≥1 (8% and 4% vs 6%, P >.05) Death (1% and 1% vs 1%, P >.05) Withdrawals (17% and 17% vs 21%) |
| IA 32% W 26% AA 3% A 37% H 48% |
90 centers 13 countries (Latin America, Asia-Pacific, eastern Europe) |
No premedication | Use of prednisone ≥7.5 mg/d 69% Immunosuppressive drugs 42% MMF 6% Aza 26% MTX 9% Antimalarials 67% |
Secondary outcomes:
|
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| Furie et al (2010) | 819 (95%) | RCT 76w | Belimumab 1 mg/kg (n = 271) Belimumab 10 mg/kg (n = 273) Placebo (n = 275) |
Aged ≥18 years SELENA-SLEDAI ≥6 Standard of care therapy (cortic <40 mg/d) SLE criteria (mandatory ANA/DNA+) |
Severe LN/CNS involv Pregnancy Previous B-cell targeted therapies Previous CYC (<6 months) Previous IVIG or cortic >60 mg/d (<3 months) |
Primary outcome (SRI improvement 52w): 41% and 43% vs 34% plac (0.09 and 0.017) | Serious adverse event (23% and 22% vs 20%, P >.05) Infections (74% and 74% vs 69%, P >.05) Serious infection (7% and 7% vs 6%, P >.05) Malignancies (1.5% and 1% vs 0.5%) Death (1% and 0.5% vs 0%, P >.05) Withdrawals (27% and 30% vs 32%) |
| NA | 90 centers 19 countries (North America, Europe, Central America) |
No premedication | NA | Secondary outcome: (SRI improvement 76w): 38% and 39% vs 32% plac (0.11 and 0.13) | |||
| Merrill et al (2010) | 257 (91%) | RCT 52w | Rituximab 1 g × 2 (n = 169) Placebo (n = 88) |
Aged 16–75 SLE criteria (mandatory ANA) Active SLE (BILAG A ≥1 or B ≥2) |
Severe CNS Organ-threatening lupus Previous CYC/CyA (<12w) Pregnancy Previous B-cell-targeted therapies Cancer, HBV, HCV, severe cytopenias, raised ATF |
Primary outcome (major, partial or no clinical response using BILAG):
|
Serious adverse event (36% vs 38%, P >.05) Infections (82% vs 83%, P >.05) Serious infection (9.5% vs 17%) Death (4% vs 1%, P >.05) Withdrawals (29% vs 27%) |
| A/PI 4% W 56% AA 25% H 12% Other 1.5% |
55 centers (North America) | Premedication with 100 mg MP | Immunosuppressive drugs 100% MMF 38.5% Aza 33.5% MTX 28% Mean prednisone dose at baseline 46 mg/d Added oral prednisone according to the BILAG score at entry (0.5, 0.75 or 1 mg/kg) |
Secondary outcomes:
|
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| Furie et al (2010) | 144 (90%) | RCT 52w | Rituximab 1 g × 2 (n = 72) Placebo (n = 72) |
SLE criteria Active ISN/RPS class III/IV LN Proteinuria Aged 16–75 y |
Severe CNS Previous MMF >2 gr (<12w) Pregnancy Previous B-cell-targeted therapies Cancer, HBV, HCV, severe cytopenias |
Primary outcome (complete, partial, no renal response)
|
Serious infection (4% vs 1%) Deaths (3% vs 0%) Neutropenia (6% vs 1%) Infusion-related (34% vs 41%) Serious infusion-related (1% vs 3%) |
| NA | NA | Steroids MMF |
Secondary outcome:
|
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| Wallace et al (2010) | 227 93% | RCT 12w | Epratuzumab 100 mg EOW (n = 39) Epratuzumab 400 mg EOW (n = 39) Epratuzumab 600 mg weekly (n = 37) Epratuzumab 1200 mg EOW (n = 37) Epratuzumab 1800 mg EOW (n = 38) Placebo (n = 38) |
SLE criteria (ANA+ at visit 1) ≥BILAG 2004 A or ≥2 Bs | Active CNS Active renal disease Creatinine >2.5 Antiphospholipid syndrome Anticoagulants, antiplatelet agents Acute/chronic infection |
Primary outcome (CRI)
|
NA |
| NA | US, Europe, South America, Asia | NA | NA | ||||
| Mysler et al (2010) | 381 87% | RCT 48w | Ocrelizumab 400 mg fortnightly (n = 74) Ocrelizumab 1000 mg fortnightly (n = 73) Placebo (n = 74) |
SLE criteria Age >16 Active ISN/RPS class III/IV LN (80% class IV) |
Active CNS Severe renal disease Pregnancy, lactation Acute, chronic infections (HIV, HBV, HCV) Severe chronic pulmonary disease History of cancer Previous B-cell-targeted therapies |
Primary (overall renal response)
|
Serious AE (36% and 24% vs 29%) Infections (62% and 56% vs 52%) IRRs (11% and 12% vs 5%) Serious infections (25% and 17% vs 14%) Deaths (2% and 4% vs 2%) Opportunistic infections (7 vs 1 patient) |
| NA | NA | MMF or CYC (Eurolupus regimen) |
A = Asian; AA = African-American; ATF = liver aminotransferases; AUCMB = area under the curve minus baseline; Aza = azathioprine; CNS = central nervous system; CRI = Combined Responder Index; CyA = cyclosporin A; CYC = cyclophosphamide; H = Hispanics; HBV = hepatitis B virus; HCV = hepatitis C virus; IA = Indian; ISN/RPS = International Society of Nephrology/Renal Pathology Society; IVIG = intravenous immunoglobulins; LN = lupus nephritis; MMF = mycophenolate; MP = methylprednisolone; MTX = methotrexate; NA = not available; PGA = physical global assessment; PI = Pacific Islander; RCT = randomized controlled trials; SF-36 = 36-item short-form health survey; SLE = systemic lupus erythematosus; SOC = standard of care; SRI = Systemic Lupus Erythematosus Responder Index; w = week; W = white; BILAG = British Isles Lupus Assessment Group disease activity index; SELENA = Safety of Estrogen in Lupus Erythematosus National Assessment; SLEDAI = Systemic Lupus Erythematosus Disease Activity Index; EOW = every other week.