Blog entry by Arif Khwaja

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by Arif Khwaja - Thursday, 19 January 2012, 4:02 PM
Anyone in the world

The results of the LUNAR study have finally been published in Arthritis and Rheumatism nearly 3 years after being first presented. The study was an RCT of 144 patients looking at the impact of Rituximab (4 doses of 1gm) as add on therapy to steroids and MMF in patients with Class III and IV lupus nephritis. Patients received two doses of methylprednisolone and the steroid taper was from 60mg to around 10 mg at 4 months. The primary endpoint was a composite of CR+PR. At 12 months there was NO significantdifference in renal complete remission (CR) or partial remission (PR). Those in CR/PR were 56.9% in the Rituximab group and 45.8% in the placebo group. CR and PR were rigorously defined by creatinine, proteinuria and haematiuria. Interestingly there was a significant reduction in the C3, C4 and DsDNA (all secondary endpoints) in the Rituximab group and at 72 weeks proteinuria was lower in the Rituximab group. Also in a pre-specified sub-group analysis of race, the primary endpoint was achieved in 70% of black patients receiving Rituximab versus 45% of black patients who received MMF an dsteroids only – this difference wasn’t statistically significant.

This really well designed study seems to suggest there is no role for Rituximab in lupus nephritis in contrast to earlier observational data. Does this mean we should never use Rituximab in lupus nephritis? Well my thoughts are as follows:

  1. Clearly for most patients with lupus nephritis treated with MMF and steroids, Rituximab will have no added benefit
  2. We don’t know if there is a role of Rituximab in patients with difficult disease refractory to cyclophosphamide/MMF – as these kinds of patients weren’t in the study. Like most recent studies in LN kidney function was well preserved.
  3. The study wasn’t really designed to address the role of Rituximab as a steroid minimising/sparing agent as advocated by Imperial College and others. To do this would require a much more aggressive steroid taper than that in the study.
  4. Finally but importantly as always the choice of endpoint is important in determining whether a study is positive or negative as we have seen in the lipid lowering studies. The study was powered to detect a 25% improvement in renal response rate but this power calculation was heavily skewed towards detecting complete remission rather than partial remission. Thus the authors state that with this sample size the power was less than 70% to detect a 25% improvement in renal response rate where the remissions were predominantly partial rather than complete. Thus whilst the partial remission rate was 31% in the Rituximab group compared to 15% in the placebo group the study was underpowered to detect this difference. Therefore Rituximab maybe having a clinically meaningful effect that this study wasn’t powered to detect.
  5. Class V LN was excluded and its worth noting that for idiopathic data there is increasing evidence of efficacy of Rituximab


Based on this paper my own practice will continue to be to use MMF and Prednisolone as first line therapy with Cyclophosphamide reserved for those with severe disease. I tend to use Rituximab in i) those who have not responded to MMF/cyclophosphamide ii) those who are unable to take cyclophosphamide ( due to previous exposure or fertility issues) and iii) those who are unable to come off steroids and/or have problems with steroid toxicity.



2. Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids.Pepper R, Griffith M, Kirwan C, Levy J, Taube D, Pusey C, Lightstone L, Cairns T. Nephrol Dial Transplant. 2009 Dec;24(12):3717-23. Epub 2009 Jul 17.

  1. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: The lupus nephritis assessment with rituximab (LUNAR) study. Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G; for the LUNAR Investigator Group. Arthritis Rheum. 2012 Jan 9. doi: 10.1002/art.34359.


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