It works in combination with other drugs
WASHINGTON, DC—Infliximab is effective for systemic lupus erythematosus (SLE) nephritis when used in combination with azathioprine or methotrexate, according to data presented here at the AmericanCollege of Rheumatology annual meeting.
“For short-term therapy, we were pleased with the overall outcome,” said the lead investigator Martin Aringer, MD, associate professor of medicine at the Medical University of Vienna in Austria. “We saw a large decrease in proteinuria, and, if it works, this com-bination seems to result in a decrease in proteinuria for at least a year,” Dr. Aringer said. “When we looked at the side effects, we mainly found infections. Some of the patients had an increase in urinary tract infections that may be due to the TNF antibodies, which probably end up in the urine.”
Dr. Aringer cautioned, however, that deep vein thrombosis developed in one patient; this was the only major non-infectious event among the treated patients. Long-term therapy may reveal additional risks.
Dr. Aringer’s group conducted an open-label follow-up study of 11 SLE patients—10 women and one man—ranging in age from 25 to 57 years. All patients received infliximab (Remicade) in combination with azathioprine or methotrexate. The investigators measured the therapeutic responses and potential side effects, and closely monitored proteinuria levels, serum creatinine, and swollen and tender joints.
Nine of the patients suffered from lupus glomerulonephritis (GN) and four had lupus arthritis (two patients had both). Eight patients were treated with four infusions, one patient received six infusions, one received eight injections and one received a total of 16.
Among the nine patients with GN, five suffered from World Health Organization (WHO) class IV ne-phritis, three from class V, and one from class III. In seven of these patients (78%), infliximab resulted in a rapid and significant reduction (more than 50%) in proteinuria; in six of the seven patients, this reduction was sustained for more than 12 months. Uncomplicated UTIs developed in four of the 11 patients.
Lupus arthritis went into remission in all four patients with the condition, but this effect did not con-tinue when therapy was stopped, Dr. Aringer reported. One patient who was continued on infliximab had continued improvement. After 16 infusions over 18 months, however, the patient experienced an increase in anti-dsDNA autoantibodies and developed cerebral lymphoma. Another patient who was pretreated with cyclophosphamide and rituximab died from Legionella pneumonia acquired in the Middle East two months after her last infliximab infusion.
By blocking TNF, infliximab largely removes an essential proinflammatory mediator, which is also involved in increasing vessel permeability. TNF also has effects on the immune system, and its blockade can lead to autoantibody formation. The long-term effects seen in this study, however, are not yet sufficiently explained.
“What we can say now is that short-term therapy with this agent appears promising for patients with lupus nephritis,” Dr. Aringer told Renal & Urology News. “We did see some serious side effects, but it is important to note that these are severely sick patients, and so you have to expect some side effects.”