A Double Blind, Randomized, Placebo Controlled, Multi-Center Trial of Anti-TNF alfa Chimeric Monoclonal Antibody (Infliximab, Remicade) and Azathioprine in Patients Suffering from Systemic Lupus Erythematosus (SLE) with WHO Class V Glomerulonephritis.

Systemic Lupus Erythematosus (SLE) is a prototypical autoimmune disease in
which a variety of autoantibodies, and the consecutive formation of immune
complexes ultimately inflict injury on a variety of organ systems. The
classical severe lupus organ manifestation is immune-complex
glomerulonephritis. Standard treatment for WHO class V glomerulonephritis has
yet to be defined. Some patients respond favourably to ACE inhibitors with or
without glucocorticoids, but for those not responding sufficiently, the overall
risk of renal failure, cardiovascular complications and death is considerable.
In the limited experience with infliximab therapy in SLE patients, infliximab
in combination with azathioprine was safe and led to rapid improvement in
proteinuria in all patients treated so far, including patients with class V
glomerulonephritis.

Primary: To prove that infliximab in combination with azathioprine is superior
to azathioprine alone in rapidly inducing a meaningful renal improvement,
defined as a reduction in preoteinuria of at least 50%, in patients with
membranous SLE glomerulonephritis not adequately responding to ACE inhibitors
and glucocorticoids.

Secundary: Lab studies on renal markers, disease activity measurements, safety
evalutation of infliximab for this population, general quality of life and
fatigue.

This is a double-blind, randomized, placebo-controlled trial in which treatment
of the combination of infliximab and azathioprine will eb compared to
azathioprine alone in patients with SLE and WHO class V glomerulonephritis.

Subjects will be randomly assigned to one of the 2 groups. Subjects in both
groups will receive azathioprine on a daily basis, administered orally. The
dose build up should be done in 50 mg steps every two weeks, up to a total
daily dose of 2 mg/kg. Subjects in the experimental group will receive , next
to azathioprine, Infliximab infusions at weeks 0, 2, 6 and 10. The total dose
(5 mg/kg) will be administered over a period of 2 hours. Subjects in the
control group will receive a placebo-infusion (saline solution 0.9%) at these
times.

After informed consent has been obtained, subjects that meet all eligibility
criteria will be screened and randomized. 3 Days prior to the first infusion of
the blinded infliximab/placebo infusion, treatment with azathioprine will be
started.
There will be 12 visits to the site in total en the following procedures will
be peformed at various visits throughout the study: Medical and medication
history, physical exam, vital signs, blood pressure, heart rate, ECG, TBC skin
test, chest x-ray, pregnancy test, Hepatitis B and C tests, ESR, haematology
and serum chemistry, serum samples, urine analysis, recording concomitant
medication, receive study medication. Adverse events will be recorded
throughout the study.
The most frequently reported adverse events are infections and infusion
reactions and these are the most important reason for discontinuing of the
treatment.