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Evidence summaries

Treatment of Lupus Nephritis

Mycophenolate mofetil (MMF) appears to be at least as effective as IV cyclophosphamide in inducing remission in proliferative lupus nephritis. Level of evidence: "B"

A Cochrane review [Abstract] 1 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 T1).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

OutcomeParticipants (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 100053 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 1000260 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 1000423 per 1000
(369 to 490)
RR 1.02
(0.89 to 1.18)
ESKD
Follow-up: mean 32 weeks
231 (3)85 per 100061 per 1000
(23 to 157)
RR 0.71
(0.27 to 1.84)
Major infection Follow-up: mean 24 weeks699 (6)114 per 1000116 per 1000
(76 to 175)
RR 1.02
(0.67 to 1.54)
Ovarian failure539 (3)41 per 100015 per 1000 (2 to 90)RR 0.36(0.06 to 2.18)
Alopecia
Follow-up: mean 24 weeks
622 (3)239 per 100069 per 1000
(45 to 110)
RR 0.29
(0.19 to 0.46)
Diarrhoea
Follow-up: mean 24 weeks
609 (4)100 per 1000241 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.

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

    References

    • Tunnicliffe DJ, Palmer SC, Henderson L et al. Immunosuppressive treatment for proliferative lupus nephritis. Cochrane Database Syst Rev 2018;(6):CD002922. [PubMed]

Primary/Secondary Keywords