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SAN DIEGO -- The injectable drug ustekinumab (Stelara) showed promising efficacy and no special safety signals in patients with systemic lupus erythematosus (SLE), according to phase II study results reported here.

The primary endpoint and nearly all secondary endpoints were met in the 102-patient trial, Ronald van Vollenhoven, MD, of Amsterdam Rheumatology and Immunology Center ARC in The Netherlands, reported at a late-breaking abstract session at the American College of Rheumatology's annual meeting.

"We believe this phase II clinical trial shows ustekinumab has the potential to be a new treatment in SLE with a novel mechanism of action," he said.

The drug -- currently approved for psoriasis, psoriatic arthritis, and Crohn's disease -- targets interleukins 12 and 23 by binding to the p40 subunit that both proteins share. Van Vollenhoven explained that both appear to have a role in SLE: IL-12 through its part in TH1 cell development and cytotoxic T cell activation, and IL-23 for driving pathogenic TH17 cell expansion, which is believed to be a key player in tissue inflammation. Studies in animal models of SLE supported the potential for ustekinumab as a therapy.

In the current trial, patients with active SLE were recruited, on the basis of SLE Disease Activity Index (SLEDAI) scores of at least 6, the presence of SLE biomarkers such as autoantibodies against double-stranded DNA, and BILAG A/B flares. The primary endpoint was achievement at week 24 of so-called SRI-4, a composite of a 4-point or greater decrease in SLEDAI score, no worsening in physician global assessment, no new BILAG A flares, and no more than one new BILAG B event.

Patients were randomized in a 3:2 ratio to ustekinumab or placebo, given by intravenous infusion for the first dose and then as subcutaneous injections every 8 weeks through week 24, after which all patients received ustekinumab injections at weeks 32 and 40. Evaluations continued until week 56.

Mean disease duration for participants was about 10 years. SLEDAI score at baseline averaged 11. Mean steroid dose was approximately 10 mg/day; two-thirds of patients were receiving an anti-malarial agent and smaller numbers were taking immunosuppressives such as azathioprine or methotrexate.

The primary endpoint of SRI-4 was met at week 24 by 60% of patients assigned to ustekinumab compared to 31% of the placebo group (P=0.0046), van Vollenhoven said, in a modified intent-to-treat analysis that regarded dropouts and patients with missing data as non-responders.

Secondary endpoints included changes from baseline in SLEDAI and physician global assessment scores, active joint counts, BILAG Combined Lupus Assessment (BICLA), prevalence of mucocutaneous disease, time to BILAG flare, and levels of C3 and anti-dsDNA. For most of these, the ustekinumab group showed significantly greater favorable responses. And only BICLA response did not show at least a numerical advantage for the active drug versus placebo.

Safety data were mostly in ustekinumab's favor and consistent with that seen in other conditions. (Van Vollenhoven noted that cumulative exposure to the drug in clinical practice is approaching 800,000 patient-years.) Rates of overall adverse events were nearly the same between groups. More patients receiving ustekinumab developed gastrointestinal events (13.3% versus 9.5%) and those classified as general (8.3% versus 4.8%), but the placebo group had more treatment-emergent adverse events leading to discontinuation (9.5% versus 5%).

Ustekinumab's manufacturer, Janssen, said it plans to begin phase III testing next year.