WASHINGTON — New phase 3 data show that ustekinumab, an inhibitor of interleukin (IL)-12 and IL-23, is safe and effective in patients with psoriatic arthritis.
The PSUMMIT II study, presented here at ACR 2012, showed significant improvements in the signs and symptoms of psoriatic arthritis in patients with active disease treated with ustekinumab, including those previously treated with 1 to 5 tumor necrosis factor (TNF) inhibitors. In addition, 52-week data from the PSUMMIT I study, also presented here, showed improvement in signs and symptoms of the disease with ustekinumab.
Ustekinumab is approved by the US Food and Drug Administration (FDA) for the treatment of psoriasis; about 20% of patients with psoriasis will develop autoimmune inflammatory arthritis. Ustekinumab is the first new biologic agent for the treatment of psoriatic arthritis in phase 3 studies.
"TNF inhibitors are the only biologic agents currently approved by the FDA for the treatment of psoriatic arthritis, but these drugs are not universally effective and there is a need for new treatments," said Arthur Kavanaugh, MD, professor of medicine and director of the Center for Innovative Therapy at the University of California at San Diego, who is coprincipal investigator of the PSUMMIT II study. "The data for this biologic therapy in psoriatic arthritis are promising," he noted.
PSUMMIT II
The PSUMMIT II study is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ustekinumab given subcutaneously to patients with active psoriatic arthritis despite previous treatment with disease-modifying anti-rheumatic 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 week 0, week 4, and every 12 weeks thereafter.
The primary end point was improvement in the signs and symptoms of psoriatic arthritis of at least 20% (i.e., ACR20) at week 24. It was reached in 43.7% of patients treated with ustekinumab 45 mg, 43.8% treated with ustekinumab 90 mg, and 20.2% treated with placebo (P < .001 for both doses vs placebo).
Of the patients previously treated with a TNF inhibitor, 36.7% treated with ustekinumab 45 mg (P = .006 vs placebo), 34.5% treated with ustekinumab 90 mg (P = .011 vs placebo), and 14.5% treated with placebo met the ACR20 criteria.
The percentage of patients achieving at least a 50% improvement in signs and symptoms of psoriatic arthritis (i.e., ACR50) at week 24 was 17.5% for ustekinumab 45 mg (P = .018 vs placebo), 22.9% for ustekinumab 90 mg (P = .001 vs placebo), and 6.7% for placebo.
Significant improvements at week 24 from baseline were seen in physical function, measured by the Health Assessment Questionnaire–Disability Index, for ustekinumab 45 mg (P = .001) and ustekinumab 90 mg (P < .001), compared with placebo.
"Not all patients benefit from TNF inhibitors.... A biologic therapy with a different mechanism of action, like ustekinumab...is exciting for the rheumatology community," said lead PSUMMIT II investigator 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 in New York.
PSUMMIT I: Improvement Continues
Twenty-four week data from PSUMMIT I, previously reported at EULAR 2012, showed that ustekinumab is superior to placebo for patients with active psoriatic arthritis despite treatment with DMARDs and NSAIDs, but not with TNF inhibitors. The 52-week PSUMMIT I data presented here showed that the signs and symptoms of psoriatic arthritis continued to improve from weeks 24 to 52 in patients treated with ustekinumab.
"Long-term management of the signs and symptoms of disease is essential in the treatment of psoriatic arthritis, a systemic inflammatory disease that can be marked by chronic pain and dysfunction. These results build on previously reported 24-week data from the PSUMMIT I trial of ustekinumab, and demonstrate efficacy and improvements in disease activity at 1 year for patients living with psoriatic arthritis," said Dr. Kavanaugh.
"Ustekinumab represents a hopeful development for the treatment of psoriatic arthritis," said Eric L. Matteson, MD, chair of the Department of Rheumatology at the Mayo Clinic in Rochester, Minnesota.
"This drug seems to address the specific pathophysiology of psoriasis via a cell-signaling mechanism — inhibition of IL 12/23 — that is upregulated in psoriasis but not in other autoimmune diseases. Preliminary studies suggest that the drug also addresses the arthritis component of psoriatic arthritis by alleviating signs and symptoms," Dr. Matteson explained.
Dr. Ritchlin reports receiving research funding from Janssen. Dr. Kavanaugh reports receiving research funding for studies of psoriatic arthritis from Janssen, UCB, Bristol-Myers Squibb, Abbott, and Amgen. Dr. Matteson reports financial ties with Centecor/Johnson & Johnson, Genentech and Biogen Idec, Hoffman-La Roche, Human Genome Sciences, Pfizer, Novartis Pharmaceutical Corporation, Roche Pharmaceuticals, UCB Group, and Horizon Pharma.
ACR 2012: Abstracts 2557 and 2562. Presented November 13, 2012.
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Cite this: Psoriatic Arthritis Improved With Ustekinumab - Medscape - Nov 15, 2012.
