乌鸦传媒

CHICAGO -- The monoclonal antibody ustekinumab (Stelara) showed sustained clinical benefits for systemic lupus erythematosus (SLE) through 1 year and may offer a new therapeutic option, according to a researcher here.

At week 24, the SLE Responder Index-4 (SRI4) response rate was achieved by 61.7% of patients randomized to receive ustekinumab compared with 33.3% of those given placebo, a difference of 29% (P=0.0057), reported Ronald van Vollenhoven, MD, of the Amsterdam Rheumatology and Immunology Center in the Netherlands, at the American College of Rheumatology annual meeting.

Ustekinumab inhibits the interleukin (IL)-12/23 pathways, both of which have been implicated in the incompletely understood pathogenesis of SLE. This monoclonal antibody has been approved for use in psoriasis, psoriatic arthritis, and Crohn's disease.

The last agent to be approved for use in SLE was belimumab (Benlysta) in 2011, and that was the first drug to be approved in half a century. "Drug development has been very bittersweet in lupus," said Susan Manzi, MD, who is co-director of the Lupus Center of Excellence, Allegheny Health Network, in Pittsburgh. "But ustekinumab looks like a promising treatment," she told 乌鸦传媒.

To investigate whether ustekinumab could be useful in lupus, van Vollenhoven and colleagues undertook a phase II trial of 102 patients with active, seropositive disease.

The treatment involved the intravenous administration of a loading dose of ustekinumab (6 mg/kg) followed by 90 mg subcutaneously every 8 weeks or placebo through week 24, after which all patients received ustekinumab.

Participants were mostly women whose average age was 42. They had disease duration of almost 10 years, and active disease as shown by the mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) being above 10. Background medications included glucocorticoids in most patients and antimalarials in two-thirds. Some patients also used immunosuppressives such as mycophenolate and azathioprine.

The current analysis focused on the 52-week results, addressing the question of whether the clinical responses seen at week 24 could be maintained when all patients had been switched to ustekinumab.

For the SRI4, which had been achieved by 61.7% of patients at week 24, the response was almost the same, at 63.3%, at 1 year. Similar results were seen for other endpoints, such as improvement on the SLEDAI, which had been been seen in 65% of patients at week 24 and was observed in 66.7% at 1 year.

The number of patients who experienced a 30% or more improvement over baseline on the physician global assessment was 67.9% at week 24 and rose slightly to 75% at 1 year, while the percentages with an improvement of 50% or more in the number of joints with pain and inflammation remained at 86.5% at both time points. A more pronounced improvement was seen on the Cutaneous Lupus Erythematosus Disease Area and Severity Index, with improvements of 50% or more being seen in 53.1% at week 24 and in 68.6% at 1 year.

More than 60% of patients had sustained responses at 1 year, "and that's good news," Manzi commented. "What you don't want to see is that they get better but then lose the response at 1 year," she said in an interview.

With regard to safety, one or more serious adverse events were reported in 9.5% of the placebo group and in 8.3% of the ustekinumab group at week 24, and serious infections were seen in 0% and 3.3%, respectively. At 1 year, serious adverse events had been reported in 16.7% of those receiving ustekinumab throughout the trial and in 15.1% of those initially receiving placebo. Serious infections were seen in 10% and 7.5% of those two groups, respectively.

"The safety was consistent with the known safety profile of ustekinumab," van Vollenhoven observed.

A phase III trial has begun enrolling patients. "We are very hopeful that the phase III results will be just as successful," Manzi said.