Phase 3 data for the PSUMMIT I and PSUMMIT II clinical trials show that ustekinumab (Stelara) is safe and effective in patients with psoriatic arthritis (PsA), and that the improvement persists over 1 year of treatment.
Ustekinumab is the first new biologic agent in phase 3 clinical trials for the treatment of PsA. The drug is an interleukin (IL)-12 and IL-23 inhibitor, a mechanism that is thought to be specific to PsA and not to other autoimmune arthritic diseases. Ustekinumab is approved by the US Food and Drug Administration for the treatment of psoriasis, and is investigational for PsA. Approximately 20% of patients with psoriasis will develop PsA.
The only drugs currently approved by the FDA for the treatment of PsA are tumor necrosis factor (TNF) inhibitors. “TNF inhibitors are not universally effective, and there is a need for new treatments. The PSUMMIT II data are promising,” said lead investigator Arthur F. Kavanaugh, MD, Professor of Clinical Medicine and Director of the Center for Innovative Therapy at the University of California, San Diego.
Week 24 Data from PSUMMIT II
The phase 2, multicenter, randomized, double-blind, placebo-controlled PSUMMIT II trial evaluated 2 doses of ustekinumab given subcutaneously to patients with active PsA who were uncontrolled by 1 to 5 disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and/or TNF inhibitors.
Patients were randomized to receive subcutaneous ustekinumab 45 mg or 90 mg, or placebo, at weeks 0 and 4, and then every 12 weeks.
At week 24, the primary end point of achieving at least the ACR 20% criteria for improvement (ACR20) in the signs and symptoms of PsA was reached in 43.7% of the patients who received the 45-mg dose of ustekinumab and in 43.8% of the patients who received the 90-mg dose, versus 20.2% of the patients who received placebo (P <.001 for both comparisons with placebo).
Among the patients who were previously treated with a TNF inhibitor, 36.7% in the ustekinumab 45-mg group and 34.5% in the ustekinumab 90-mg group met the ACR20 criteria, versus 14.5% of the patients who were given placebo (P <.001 for both comparisons with placebo).
The percentage of patients who achieved at least ACR50 at week 24 was 17.5% for ustekinumab 45 mg and 22.9% for ustekinumab 90 mg, versus 6.7% for placebo (P = .018 for the 45-mg dose versus placebo, and P = .001 for the 90-mg dose versus placebo).
Significant improvements from baseline to week 24 also were seen in physical function as measured by the Health Assessment Questionnaire Disability Index for both dosage levels of ustekinumab versus placebo.
Christopher Ritchlin, MD, Professor of Medicine and Director of the Rheumatology Fellowship Program and the Clinical Immunology Research Center at the University of Rochester Medical Center, NY, was the lead investigator of PSUMMIT II.
Week 52 Data from PSUMMIT I
Ustekinumab was superior to placebo in patients with active PsA despite treatment with DMARDs and NSAIDs (but not a TNF inhibitor) at 24 weeks, according to results from the PSUMMIT I trial. New 52-week data from PSUMMIT I showed that this improvement persisted from 24 to 52 weeks in patients who were treated with ustekinumab versus placebo.