Treatment of lupus nephritis

Mycophenolate mofetil (MMF) appears to be at least as effective as IV cyclophosphamide in inducing remission in proliferative lupus nephritis.

A Cochrane review included 74 studies with a total of 5 175 subjects witj biopsy-proven proliferative lupus nephritis. Twenty-nine studies included adults and children (< 18 years), 29 studies included only adults, 2 only children, and 14 studies did not specify the age of the participants. Sixty-seven studies (n=4 791) investigated induction therapy, and 9 studies (n=767) considered maintenance therapy.

In induction therapy, mycophenolate mofetil (MMF) dosed at 2 g to 3 g daily tended to increase complete remission compared to IV cyclophosphamide, although the difference was not statistically significant. MMF was as effective as IV cyclophosphamide in preventing death or end-stage kidney disease, inducing partial renal remission, and achieving stable kidney function (RR 1.05, 95% CI 0.94 to 1.17), with reduced risk of alopecia, similar risks of major infection and ovarian failure, but with increased risk of diarrhea (Table ). MMF combined with tacrolimus increased complete disease remission (RR 2.38, 95% CI 1.07 to 5.30; 2 studies, n=402) compared with IV cyclophosphamide. The effects of biologics on most outcomes were uncertain compared to standard care.

Mycophenolate mofetil (MMF) plus corticosteroids versus intravenous cyclophosphamide (CYC) plus corticosteroid for induction therapy

Outcome	Participants (studies)	Illustrative comparative risks (95% CI)		Relative effect (95% CI)
		Assumed risk (CYC)	Corresponding risk (MMF)
Death Follow up: mean 24 weeks	826 (8)	40 per 1000	53 per 1000 (29 to 98)	RR 1.12 (0.61 to 2.06)
Complete renal remission Follow up: mean 24 weeks	828 (8)	222 per 1000	260 per 1000 (216 to 316)	RR 1.17 (0.97 to 1.42)
Partial renal remission Follow-up: mean 24 weeks	868 (9)	415 per 1000	423 per 1000 (369 to 490)	RR 1.02 (0.89 to 1.18)
ESKD Follow-up: mean 32 weeks	231 (3)	85 per 1000	61 per 1000 (23 to 157)	RR 0.71 (0.27 to 1.84)
Major infection Follow-up: mean 24 weeks	699 (6)	114 per 1000	116 per 1000 (76 to 175)	RR 1.02 (0.67 to 1.54)
Ovarian failure	539 (3)	41 per 1000	15 per 1000 (2 to 90)	RR 0.36 (0.06 to 2.18)
Alopecia Follow-up: mean 24 weeks	622 (3)	239 per 1000	69 per 1000 (45 to 110)	RR 0.29 (0.19 to 0.46)
Diarrhoea Follow-up: mean 24 weeks	609 (4)	100 per 1000	241 per 1000 (163 to 357)	RR 2.42 (1.64 to 3.58)

In maintenance therapy, the risk of renal relapse (RR 1.75, 95% CI 1.20 to 2.55; 4 studies, n=452) was significantly higher with azathioprine compared with MMF. Multiple other interventions were compared but outcome data were relatively sparse.

A systematic review including 10 studies with a total of 891 subjects was abstracted in DARE. A meta-analysis was performed to determine treatment efficacy and toxicity between mycophenolate mofetil (MMF) and CYC induction therapies, between MMF and AZA as maintenance therapies, and between low-dose intravenous (IV) CYC and high-dose IV CYC therapy in patients with lupus nephritis. Induction treatments (6 studies, n=662): There was no statistically significant difference between MMF and CYC induction regimes for complete remission (5 studies; statistical heterogeneity I2=54%), partial remission (4 studies), overall response rate (6 studies; statistical heterogeneity I2=49%), end-stage renal disease (2 studies), death (3 studies), herpes infection (4 studies), and any other infection (4 studies; statistical heterogeneity I2=79%). MMF was associated with a non-significant trend towards a lower risk of amenorrhoea (RR 0.17, 95% CI 0.02 to 1.34; 2 studies) and leukopenia (RR 0.41, 95% CI 0.15 to 1.14; 4 studies) than cyclophosphamide. Maintenance treatment (2 studies, n=91): There was no statistically significant difference between MMF and AZA maintenance regimes in response or end-stage renal disease (2 studies). MMF and AZA regimens were associated with significantly higher six-year event-free survival rates for death (p=0.05) and renal failure (p=0.009) than CYC regimes. The MMF group had a higher relapse-free survival than the CYC group (p=0.002) in one study (n=32). Low-dose versus high-dose CYC (2 studies, n=138): The cumulative doses of CYC differed between the two included trials. Low-dose CYC regimes were associated with a significantly reduced relapse rate (RR 0.47, 95% CI 0.26 to 0.83), a significantly reduced infection rate (RR 0.69, 95% CI 0.52 to 0.91; statistical heterogeneity I2=54%) and a reduced treatment failure rate of marginally significance (RR 0.45, 95% CI 0.20 to 1.01).

Comment: The quality of evidence is downgraded by imprecise results (few outcome events and wide confidence intervals).

Ədəbiyyat

1. Tunnicliffe DJ, Palmer SC, Henderson L et al. Immunosuppressive treatment for proliferative lupus nephritis. Cochrane Database Syst Rev 2018;(6):CD002922. Lee YH, Woo JH, Choi SJ, Ji JD, Song GG. Induction and maintenance therapy for lupus nephritis: a systematic review and meta-analysis. Lupus 2010 May;19(6):703-10.