Table 2.
Randomized controlled trials of induction therapy for lupus nephritis
| Author | N | Study duration | Histological classes of lupus nephritis | Steroid regimen | Comparators | Primary end points | Adverse events |
|---|---|---|---|---|---|---|---|
| Houssiau29 | 84 | 10 yrs | WHO III, IV, Vc, Vd | Prednisolone (0.5 mg/kg/d) for 4 wks, then taper to 5–7.5 mg/d for at least 30 mths | IV CYC (0.5 g/m2 to a max of 1.5 g) monthly for 8 doses vs 6 biweekly low dose pulses of 500 mg, followed by AZA in both | Rates of mortality, sustained doubling of serum creatinine and end stage renal disease similar between the two groups | Cardiovascular events similar; but cancers were numerically more common in the low dose CYC group |
| Appel31 | 370 | 24 wks | ISN/RPS III, IV, V | Prednisolone 60 mg/day then taper | IV CYC (0.5–1.0 g/m2) monthly for 6 doses vs MMF (3 g/d) | Clinical response similar at 6 months; MMF higher response rate than CYC in non- Caucasians non-Asians | Nausea, vomiting and alopecia more common in CYC group; diarrhea more common with MMF; numerically more deaths in MMF group |
| Grootscholten32 | 87 | 5.7 yrs | WHO III, IV, Vc, Vd | Prednisone 1 mg/kg/day, tapered to 10 mg/d after 6 mths vs IV MP for 9 doses + prednisone 20 mg/d and taper | IV CYC (750 mg/m2) monthly for 6 then 3 monthly for another 7 doses followed by AZA vs AZA (2 mg/kg/d) following pulse MP | Complete and partial response rate similar at 2 years; at 5 years, significantly more relapses in AZA group with a higher incidence of doubling of serum creatinine | More herpes zoster in the AZA group than CYC; major infection rate similar; more ovarian toxicities in the CYC-treated patients |
| Bao33 | 40 | 9 mths | Mixed IV + V | Pulse MP (0.5 g/day x 3d) + prednisolone (0.6–0.8 mg/kg/day) then taper | IV CYC (0.5–1 g/m2/monthly for 9 months) vs MMF (1 g/d) + Tac (4 mg/d) | Complete response rate significantly higher in MMF + Tac than CYC group at 6 and 9 mths | Gastrointestinal upset, leucopenia, alopecia, menstrual irregularities and upper respiratory tract infection more common in CYC group |
| Chen34 | 81 | 6 mths | ISN/RPS III, IV, V | Prednisolone (1 mg/kg/d) then taper | IV CYC (0.5–1 g/m2/monthly for 6 months) vs Tac (0.05 mg/kg/d) titrating to a level of 5–10 ng/mL | Clinical response at 6 months similar between the two groups | Infection rate similar; more leucopenia and gastrointestinal upset with CYC |
| Mok35 | 130 | 6 mths | ISN/RPS III, IV, V | Prednisolone (0.6 mg/kg/d) then taper | MMF (2–3 g/d) vs Tac (0.1–0.06 mg/kg/d) | Clinical response similar at 6 months | Herpes zoster more common with MMF; alopecia, tremor and reversible increase in serum creatinine more common with Tac |
| Rovin36 | 144 | 52 wks | ISN/RPS III, IV | High-dose prednisone | MMF (2–3 g/d) in both; rituximab x 2 courses (1 g × 2 each course) vs placebo | Clinical efficacy similar at 52 wks | Infection rate and major infection rate similar between the two groups |
Abbreviations: N, number; yrs, years; mths, months; wks, weeks; CYC, cyclophosphamide; MMF, mycophenolate mofetil; AZA, azathioprine; Tac, tacrolimus.