Leflunomide, an Immunosuppressant, Seen as Effective Maintenance Therapy for Lupus Nephritis in Clinical Trial

The immunosuppressant leflunomide appears to be as effective as azathioprine in maintaining remission and delaying disease relapse in people with lupus nephritis, a clinical trial in more than 200 patients in China showed.

The study’s results were recently presented at the American College of Rheumatology (ACR) 2018 Annual Meeting in Chicago, detailed in the poster, “Leflunomide Versus Azathioprine for Maintenance Therapy of Lupus Nephritis: A Prospective, Multicenter, Randomized, Open-Label Clinical Trial.”

Lupus nephritis, an inflammation of the kidneys, is the most frequent organ-specific complication associated with lupus.

To date, this condition is most often controlled though two distinct therapy phases: the first is one of intense treatment to force remission, and the second is a maintenance phase.

The most common maintenance therapies for lupus nephritis are the immunosuppressants mycophenolate mofetil and azathioprine. But in 2009, the China Food and Drug Administration approved leflunomide for the same indication. Like azathioprine, this immunosuppressant was initially approved as a treatment for rheumatoid arthritis.

However, the effectiveness of these treatments had never been compared in a clinical trial. To address this knowledge gap, researchers at centers across China conducted a randomized and controlled trial (NCT01172002) that compare the safety and efficacy of leflunomide to azathioprine as a maintenance treatment for lupus nephritis.

The study enrolled 215 adults with lupus nephritis who had responded to an initial intense treatment with cyclophosphamide plus steroids and were in remission, complete or partial, by the time they started receiving maintenance treatments.

Patients randomly were given prednisone in combination with either oral leflunomide (108 patients) or azathioprine (107 patients) as maintenance therapies for 24 months.

The trial’s principal outcome was the number of renal flares. Secondary outcomes included measures of inflammation and kidney damage, extra-renal flares, and adverse effects.

Among patients treated with leflunomide, 11.1% experienced renal flares, compared to 14.0% treated with azathioprine. In both cases, flares appeared after about 10 months of treatment.

Results for both therapies were similar in terms of the percentage of patients achieving full remission over the two years — from 60.2% to 87.7% for those given leflunomide, and from 71.9% to 88.7% in patients on azathioprine.

Extra-renal flares (outside the kidneys) were reported in  two patients on azathioprine and one on leflunomide. Safety was also similar, with adverse events recorded in 42.1% and 43.5% of patients on azathioprine and leflunomide, respectively.

The most common adverse events were low white blood cells, high levels of liver enzymes, and anemia. Both treatments showed similar incidence for each of these complications.

“[Leflunomide] is non-inferior to [azathioprine] for maintenance therapy of [lupus nephritis] regarding efficacy and safety profile,” the researchers concluded. “With maintenance therapy for 2 years, a trend of lower rate of relapse and higher [complete remission] rate was observed in the [leflunomide] group. [Leflunomide] may become a new candidate medicine for maintenance therapy of [lupus nephritis].”