Patients with active psoriatic arthritis receiving the interleukin (IL)-12/23 inhibitor Stelara (ustekinumab) experienced significant improvements in signs and symptoms of the disease, according to new findings presented from a Janssen Research & Development, LLC-sponsored investigational study. Data from the 615-patient Phase 3 trial presented at the European League Against Rheumatism (EULAR) Annual Congress showed patients receiving Stelara 45 mg and 90 mg achieved the primary endpoint of the study, a significant reduction in arthritis signs and symptoms at week 24. Investigators reported Stelara-treated patients also achieved significant improvements in physical function, including dactylitis and enthesitis (two common manifestations of psoriatic arthritis which cause pain and swelling), as well as in plaque psoriasis. Stelara is currently being investigated in a Phase 3 program for the treatment of active psoriatic arthritis and is approved for the treatment of moderate to severe plaque psoriasis in 65 countries. The EULAR press committee has selected the Stelara psoriatic arthritis study findings to be presented during the official EULAR press conference occurring Friday, June 8 from 9:00-9:45 CEST, which will take place in the Press Centre, Hall 6.3 at the congress.
“Some 15% of patients living with psoriasis of the skin will develop psoriatic arthritis. This is a challenging disease that causes great distress for those afflicted, for which we currently have too few treatment options. These new findings showing the efficacy of Stelara in improving the joint symptoms of the disease are therefore important for rheumatologists and dermatologists,” said Iain B. McInnes, Ph.D., Professor, Experimental Medicine and Rheumatology, Director of the Institute of Infection, Immunity, and Inflammation, University of Glasgow, Scotland, and study investigator. “We look forward to additional data from the Phase 3 psoriatic arthritis clinical development program to allow us to more fully assess the efficacy and safety of Stelara in the treatment of this complex inflammatory disease.”
In the Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled trial of Ustekinumab, a Fully Human anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis (PSUMMIT I) study, patients with active psoriatic arthritis, despite treatment with disease-modifying antirheumatic drugs (DMARDs) and/or nonsteroidal anti-inflammatory drugs (NSAIDs), were randomized to receive subcutaneous Stelara 45 mg or 90 mg or placebo at weeks 0, 4 and then every 12 weeks. At week 24 of the trial, 42% and 50% of patients receiving Stelara 45 mg and 90 mg, respectively, achieved at least a 20% improvement in signs and symptoms according to American College of Rheumatology (ACR) criteria (ACR 20), the primary endpoint, compared with 23% of patients receiving placebo (P < 0.001). ACR responses were greater with Stelara than placebo regardless of methotrexate use. As measured by the ACR response criteria, significantly higher proportion of patients in the Stelara 45 mg and 90 mg groups also achieved approximately 50% improvement in signs and symptoms (ACR 50) and approximately 70% improvement in signs and symptoms (ACR 70) versus patients receiving placebo (P < 0.001 for all comparisons).
Study participants receiving Stelara achieved clinically relevant improvements in physical function, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and enthesitis (inflammation of the entheses, the sites where tendons or ligaments attach to bone) and dactylitis (inflammation of the finger or toe) scores. Changes from baseline in HAQ-DI at week 24 were significantly greater in the Stelara groups, and significantly greater proportions of Stelara-treated patients had a clinically meaningful change from baseline in HAQ-DI (defined as a change of at least 0.3) compared with patients in the placebo group. Among study participants affected with enthesitis (n=425) or dactylitis (n=286) at baseline, significantly greater improvements in symptoms were observed in patients receiving Stelara 45 mg or 90 mg than in patients receiving placebo based on median% changes in the enthesitis score (-42.9 and -50.0 versus 0.0, respectively) and the dactylitis score (-75.0 and -70.8 vs. 0.0) [P < 0.001].
“These data provide important new insights into the efficacy of Stelara in the treatment of psoriatic arthritis across multiple disease measures,” said Alice B. Gottlieb, M.D., Ph.D., Dermatologist-in-Chief and Chair of Dermatology, Tufts Medical Center, Harvey B. Ansell Professor of Dermatology, Tufts University School of Medicine, and study investigator. “For physicians who treat patients living with active psoriatic arthritis, the potential of Stelara, an IL-12/23 monoclonal antibody, for the treatment of this chronic, inflammatory disease is a promising development.”
PSUMMIT I also assessed the efficacy of Stelara in the treatment of moderate to severe plaque psoriasis. Of 440 patients with at least three percent body surface involvement at the start of the study, 57% of patients receiving Stelara 45 mg and 62% of patients receiving Stelara 90 mg achieved at least a 75% improvement in psoriasis as measured by the Psoriasis Area Severity Index (PASI 75) score at week 24, compared with 11.0% of patients receiving placebo (P < 0.001).
Patients in the Stelara groups also reported statistically significant improvements in EULAR/Disease Activity Score (DAS) 28 C-reactive protein (CRP) responses. At week 24, 66% and 68% of patients receiving Stelara 45 mg and 90 mg, respectively, reported EULAR/DAS-CRP response compared with 34% of placebo patients (P < 0.001). The DAS 28 is a measure of disease activity in patients with arthritis that is calculated by assessing the number of tender and swollen joints (out of a total of 28), inflammation and the patient’s assessment of global health. CRP is a type of protein produced in the liver and expressed during episodes of acute inflammation associated with arthritic conditions.
Treatment with Stelara was generally well-tolerated with similar proportions of patients experiencing at least one adverse event (AE) through week 16, the placebo-controlled period, among those receiving Stelara (42%) and placebo (42%). Serious AEs were reported in two percent of Stelara-treated patients and two% of patients receiving placebo. No malignancies, cases of tuberculosis, serious infections, opportunistic infections, major adverse cardiovascular events (MACE) or deaths occurred through the placebo-controlled portion, week 16 of the study; one stroke occurred in the Stelara 45 mg group after the placebo-controlled period.
Date: June 6, 2012
Source: Janssen Research & Development LLC
Filed Under: Drug Discovery