Table 2

Summary of the randomised-controlled trials of rituximab therapy in systemic lupus erythematosus

Study

Rituximab regimen

Concomitant therapy

Endpoints

Results


LUNAR

Randomised 1:1 to receive either rituximab or placebo on days 1, 15, 168, and 182

MMF and corticosteroids

Primary: (i) % patients with complete or partial renal responses at week 52. Secondary: (ii) patients with BL UPCR >3 to UPCR <1; (iii) % change from BL in anti-dsDNA; and (iv) mean change from BL in C3 (mg/dl)

(i) and (ii) no significant difference; (iii) placebo (50%) and rituximab (69%) (P <0.01); and (iv) placebo (25.9%) and rituximab (37.5%) (P <0.03). % patients requiring a new immunosuppressive agent placebo (11.1%) and rituximab (1.4%)

EXPLORER

Randomised 1:2 to receive placebo or rituximab, methyl prednisolone 100 mg and acetaminophen and diphenhydramine or placebo on days 1, 15, 168, and 182

Usual dose prednisolone and either azathioprine 100 to 250 mg/day, MMF 1 to 4 g/day or MTX 7.5 to 27.5 mg/week, and additional prednisolone (0.5 mg/kg, 0.75 mg/kg, or 1.0 mg/kg), tapered beginning on day 16 to a dosage of 10 mg/day over 10 weeks and 5 mg/day by week 52

Primary: effect of placebo or rituximab in achieving and maintaining a major, partial or no response at week 52 in each of the eight BILAG index organ system scores. Secondary: described earlier

Primary EP: major clinical response 15.9% vs. 12.4% and PCR 12.5% vs. 17.2% for placebo and rituximab, respectively. In the African American/Hispanic group: major clinical response 9.4% vs. 13.8% and PCR 6.3% vs. 20.0% for placebo and rituximab, respectively

Li and colleagues [68]

Randomised to receive either rituximab or a combination of rituximab and cyclophosphamide 750 mg on day 1 and day 15, followed by intravenous methylprednisolone 250 mg and oral prednisolone 30 mg from day 2 to day 5, then 0.5 mg/kg for 4 weeks and then reducing the dose by 5 mg every 2 weeks to 5 mg/day

Other medications were stopped except for hydroxychloroquine, oral prednisolone and statins. All patients also received angiotensin-converting enzymes inhibitors

Primary: in each of the groups, % patients with complete response at week 48. Secondary: % patients with partial response; and duration of complete CD19+ B-lymphocyte depletion, histological assessment, adverse effects or death at week 48

Primary EP: no significant difference between the two groups. Overall, at week 48, 21% had a complete response, 58% achieved partial response, 11% remained the same and 11% worsened. Secondary EP: 42% patients achieved a complete response; 95% achieved effective depletion; no significant difference in the proportion of patients achieving a complete depletion at weeks 4, 8, 24 and 48 between the two groups except at week 2; a significant improvement in mean serum albumin levels (28.1 to 39.4), changes in the concentration of serum C3 (0.55 to 0.85), dsDNA antibody (693 to 8) and immunoglobulins. At week 48, the urinary protein excretion improved and there was an improvement in the ESR (62.1 to 30) and SLEDAI (9.2 to 2.5)


BL, baseline; EP, endpoint; ESR, erythrocyte sedimentation rate; MMF, mycophenolate mofetil; MTX, methotrexate; PCR, partial clinical response; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; UPCR, urine protein creatinine ratio.

Reddy et al. Arthritis Research & Therapy 2013 15(Suppl 1):S2   doi:10.1186/ar3910