San Diego, October 28, 2013 -- New findings from two integrated Phase 3 Janssen Research & Development, LLC (Janssen)-sponsored studies showed treatment with STELARA (ustekinumab) resulted in significantly greater inhibition of structural damage in patients with active psoriatic arthritis compared with placebo. Pre-specified integrated analyses from the PSUMMIT I and II trials showed treatment with either STELARA 45 mg or 90 mg resulted in significantly less change from baseline at week 24 in total psoriatic arthritis modified van der Heijde-Sharp (vdH-S) scores compared with placebo. STELARA-treated patients from the combined data analysis of both trials demonstrated continued inhibition through one year and through two years according to findings from the PSUMMIT I trial. These results are being presented during the 2013 Annual Meeting of the American College of Rheumatology (ACR). STELARA recently received approval from the U.S. Food and Drug Administration (FDA) and approval from the European Commission for the treatment of signs and symptoms in adult patients with active psoriatic arthritis.
"Data from the integrated analysis of the Phase 3 clinical program show the efficacy of the interleukin-12/23 antibody STELARA in inhibiting the progression of structural damage in patients with active psoriatic arthritis," said Iain B. McInnes, PhD, FRCP, Professor of Medicine, and Director of the Institute of Infection, Immunity, and Inflammation, University of Glasgow, Scotland, lead study investigator. "These new findings are significant since impeding further joint damage is an important part of the long-term management of this chronic inflammatory disease."
According to a pre-specified integrated analysis of the two Phase 3 Multicenter, Randomised, Double-blind, Placebo-controlled trials of Ustekinumab, a Fully Human anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis (PSUMMIT I and II), 927 patients with active psoriatic arthritis despite treatment with disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs) and/or tumor necrosis factor (TNF)-alpha inhibitors were randomized to receive STELARA 45 mg, 90 mg or placebo at weeks 0, 4 and then every 12 weeks. Patients with no response to placebo (defined as less than 5 percent improvement in tender and swollen joint count from baseline) at week 16 were crossed over to receive STELARA 45 mg as early escape, and all remaining patients receiving placebo crossed over at week 24 to STELARA 45 mg. Patients receiving STELARA 45 mg who had no response began an increased dose of STELARA 90 mg starting at week 16. Inhibition of radiographic progression was assessed by the change from baseline in total psoriatic arthritis modified vdH-S scores, an X-ray measure of joint destruction, including joint erosion and joint space narrowing. With this method, higher scores indicate greater structural damage while lower scores indicate less structural damage.
In the integrated analysis, at week 24, patients receiving STELARA 45 mg or 90 mg had a mean change ( standard deviation) from baseline in total vdH-S score of 0.40 (2.11) and 0.39 (2.40), respectively, compared with a mean change of 0.97 (3.85) for patients receiving placebo (P = 0.017 and P < 0.001, respectively). Data through week 52 showed the continued inhibition of radiographic progression with a mean change from baseline of 0.58 ( 2.60) and 0.65 (3.68) for patients randomized to STELARA 45 mg or 90 mg, respectively. Patients initially randomized to receive placebo who crossed over to STELARA at week 16 or 24 had a mean change of 1.15 (5.41) from baseline to week 52. When evaluated alone, results from PSUMMIT I were consistent with the pre-specified integrated analysis demonstrating significant inhibition of structural damage at week 24 for both STELARA doses. The effect of STELARA on the inhibition of structural damage progression could not be discerned in the smaller PSUMMIT II study, though a high number of patients who received placebo were missing radiographs (23 percent).
In PSUMMIT I, effects on inhibition of radiographic progression were maintained through week 100 with a mean change from baseline of 0.95 (3.82), 1.18 (5.52) and 2.26 (12.58) for patients receiving STELARA 45 mg or 90 mg, and crossover placebo patients, respectively. Additional measures of clinical response through week 100, as measured by the ACR response criteria (ACR 20: STELARA 45 mg, 56.7 percent; STELARA 90 mg, 63.6 percent), improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI), and improvements in dactylitis and enthesitis indicate maintained clinical efficacy for patients treated with STELARA through week 100.
"Ustekinumab has demonstrated clinical efficacy across multiple areas of psoriatic arthritis disease activity, including not only joint and skin, but also in joint tissues, including dactylitis and enthesitis. Now there is data suggesting efficacy inhibiting the progression of joint damage as assessed on X-rays," said Arthur Kavanaugh, MD, Director of the Center for Innovative Therapy, and Professor of Medicine at the University of California, San Diego School of Medicine, and co-principal study investigator. "Long-term findings from the PSUMMIT I trial offer important insights into the efficacy and safety of ustekinumab as a new treatment option for patients with psoriatic arthritis."
In PSUMMIT I and PSUMMIT II, similar proportions of patients receiving STELARA or placebo experienced at least one adverse event (AE) or serious AE through week 16, the placebo-controlled period of both trials. Safety through week 52 among patients receiving STELARA 45 mg or 90 mg was consistent with that observed during the placebo-controlled period with AE incidence of 66.8 percent and 64.7 percent, respectively, in PSUMMIT I; 78.6 percent and 77.9 percent, respectively, in PSUMMIT II. The incidence of serious AEs among patients receiving STELARA 45 or 90 mg were 5.9 percent and 3.4 percent, respectively, in PSUMMIT I; 5.8 percent in both dose groups, in PSUMMIT II. STELARA continued to be well-tolerated through week 108 in PSUMMIT I, with a safety profile similar to that observed in the placebo-controlled portion of the trial and through week 52.
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