Lupus nephritis trial published, strength of conclusions challenged

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Rheumawire

Mar 10, 2004

Lupus nephritis trial published, strength of conclusions challenged

Bethesda, MD - The clinical trial in proliferative lupus nephritis

patients that concluded that, after induction with intravenous (IV)

cyclophosphamide, maintenance therapy with mycophenolate mofetil (MMF

[CellCept®, Roche Pharmaceuticals]) or azathioprine is more efficacious

and safer than long-term therapy with IV cyclophosphamide has been

published in the March 4, 2004 issue of the New England Journal of

Medicine [1]. But an accompanying editorial challenges the claims of

superiority expressed in the conclusion [2].

The trial involved 59 patients, was supported by Roche, and was

conducted by Dr Contreras and colleagues at the University of

Miami, FL. They initially presented the results last November at the

American Society of Nephrology 2003 annual meeting, as reported then by

rheumawire. In the paper, Contreras and colleagues reiterate their

conclusion that, after induction therapy with IV cyclophosphamide,

maintenance therapy (for 72 months) with either mycophenolate mofetil or

azathioprine was more efficacious and safer than long-term therapy with

IV cyclophosphamide. They also note that maintenance therapy with MMF

was associated with a significantly lower relapse rate than was

long-term therapy with IV cyclophosphamide.

However, in the accompanying editorial, Dr Balow and Dr Harlow

Austin (US National Institutes of Diabetes and Digestive and Kidney

Diseases), question the strength of the researchers' interpretation. " In

our opinion, it is important to recognize that the argument for the

superior efficacy of azathioprine and mycophenolate mofetil for lupus

nephritis emerged only when the authors combined the outcomes of patient

survival and renal survival, " they write. " Moreover, there was no

significant difference among the treatment groups in renal survivala

fact that modulates to some degree the authors' claim that azathioprine

and MMF are superior to cyclophosphamide. "

There are also other reasons to challenge the universal applicability of

the study results, say the editorialists. They point out that the risk

of death, renal failure, and relapse of nephritis were higher than

expected during maintenance therapy with cyclophosphamide, while the

rates of relapse during maintenance therapy with azathioprine and MMF

seem to be lower than would normally be expected. Also, the racial and

ethnic distribution of the trial participants (46% black, 49% Hispanic,

5% white) was not representative of the general population of SLE

patients in the US, they add, noting that previous studies have shown

cyclophosphamide to have a particularly abysmal record in preventing

renal failure among black patients with severe lupus nephritis.

" None of these potential caveats are meant to undermine the value of

this controlled trial, " Barlow and Austin comment. " In our opinion, the

most reliable take-home message of the study by Contretas et al is that

azathioprine and mycophenolate mofetil are good options for maintenance

therapy in patients with proliferative lupus nephritis. "

" Nonetheless, there is clearly a need for further studies, with longer

follow-up, conducted in a more broadly representative population of

patients with SLE, " they conclude.

Zosia Chustecka

Sources

1. Contreras G, Pardo V, Leclercq B, et al. Sequential therapies for

proliferative lupus nephritis. N Engl J Med 2004 Mar 4; 350(10):971-80.

2. Balow JE, Austin HA 3rd. Maintenance therapy for lupus

nephritis--something old, something new. N Engl J Med 2004 Mar 4;

350(10):1044-6.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org