Janssen Research & Development, LLC (Janssen) announced today new findings from PSUMMIT II, a Phase 3 investigational study.
The study showed that patients with active psoriatic arthritis, including those previously treated with one to five tumor necrosis factor (TNF) inhibitors, receiving the interleukin (IL)-12/23 inhibitor STELARA® (ustekinumab) demonstrated significant improvements in signs and symptoms of the disease.
Significantly more patients receiving either STELARA 45 mg or 90 mg achieved at least a 20 percent improvement in signs and symptoms according to American College of Rheumatology criteria (ACR 20) at week 24, the primary endpoint, than did patients receiving placebo regardless of background methotrexate use.
During a late-breaker session of PSUMMIT 1, the initial Phase 3 study, investigators will present 52-week data that showed improvement in efficacy of STELARA over time in treating signs and symptoms of the disease. These data are being presented at the 2012 Annual Meeting of the American College of Rheumatology.
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 Including Those Previously Treated with Biologic Anti-TNF-alpha Agent(s) (PSUMMIT II) study, patients with active psoriatic arthritis despite treatment with disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs) and/or anti-TNF-alpha therapy (not intended as a superiority or comparative claim versus TNF inhibitors) 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, the primary endpoint was met as statistically significantly greater proportions of patients achieving ACR 20 responses (a standard measure of improvement in disease activity) were observed in patients receiving STELARA 45 mg (43.7 percent of patients) or STELARA 90 mg (43.8 percent of patients) compared with 20.2 percent of patients receiving placebo (P < 0.001 for both comparisons).
Among patients previously treated with TNF inhibitors, 36.7 percent of patients and 34.5 percent of patients receiving STELARA 45 mg or 90 mg, respectively, achieved ACR 20 at week 24 compared with 14.5 percent of patients receiving placebo (P = 0.006 for STELARA 45 mg, P = 0.011 for STELARA 90 mg).
"TNF inhibitors are the only approved biologic treatment option for psoriatic arthritis, but not all patients benefit from these currently available treatments," said Christopher Ritchlin, MD, MPH, Professor of Medicine and Director of the Rheumatology Fellowship Program and the Clinical Immunology Research Center at the University of Rochester Medical Center, and lead study investigator.
"A biologic therapy with a different mechanism of action, like ustekinumab, which has shown benefit in the treatment of psoriatic arthritis in two Phase 3 studies, is exciting for the rheumatology community."
In PSUMMIT II, significantly greater proportions of patients receiving STELARA 45 or 90 mg achieved ACR 50 at week 24 compared with placebo (17.5 and 22.9 percent vs. 6.7 percent, P = 0.018 for STELARA 45 mg, P = 0.001 for STELARA 90 mg). ACR 70 responses for both STELARA groups were greater, though not significantly, than for the placebo group at week 24.
Of patients with at least three percent body surface involvement of psoriasis at the start of PSUMMIT II, 51.3 percent and 55.6 percent of patients receiving STELARA 45 mg and 90 mg achieved at least a 75 percent improvement in psoriasis, respectively, as measured by the Psoriasis Area Severity Index (CASI 75), compared with five percent of patients receiving placebo (P < 0.001 for both comparisons).
Significant improvements from baseline to week 24 were also observed in physical function, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI), in the STELARA 45 mg and 90 mg treatment groups compared with placebo-treated patients (P = 0.001 for STELARA 45 mg, P < 0.001 for STELARA 90 mg).
Similar proportions of patients experienced at least one adverse event (AE) through week 16, the placebo-controlled period, among those receiving STELARA 45 mg (63.1 percent), STELARA 90 mg (60.6 percent) and placebo (54.8 percent) with infections being the most common AE. Serious AEs reported among the groups were: STELARA 45 mg (zero percent), STELARA 90 mg (1.0 percent) and placebo (4.8 percent).
No cases of tuberculosis (TB), opportunistic infections, major adverse cardiovascular events (MACE) or deaths occurred. Through week 24, one serious infection due to complications of pre-existent interstitial lung disease was reported in the placebo group and one skin malignancy (squamous cell carcinoma in situ) occurred in the STELARA 90 mg group.
Improvement of Signs and Symptoms by STELARA in Patients with Active Psoriatic Arthritis: Week 52 Results of the Phase 3, Multicenter, Double-blind, Placebo-controlled PSUMMIT I Study
Findings from 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 are the focus of a late breaker oral presentation.
PSUMMIT I is evaluating the efficacy and safety of STELARA in patients with active psoriatic arthritis despite treatment with conventional therapy (anti-TNF-alpha naive) through 108 weeks. Patients 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, 42.4 percent and 49.5 percent of patients receiving STELARA 45 mg and 90 mg, respectively, achieved ACR 20, the primary endpoint, compared with 22.8 percent of patients receiving placebo (P < 0.001 for both comparisons).
Patients who qualified for early escape at week 16 were considered non-responders for the primary and major secondary analyses at week 24. Following week 24 assessment, patients receiving STELARA 45 mg and 90 mg continued to receive every-12-week maintenance therapy, and placebo patients were crossed over to receive STELARA 45 mg induction (at weeks 24 and 28) and maintenance therapy every 12 weeks thereafter.
Observed data showed that signs and symptoms continued to increase between weeks 24 and week 52, with 55.7 percent, 60.3 percent and 65.2 percent of patients in the STELARA 45 mg, STELARA 90 mg and placebo crossover groups, respectively, demonstrating ACR 20 response.
"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," said Arthur Kavanaugh, MD, Professor of Medicine, and Director of the Center for Innovative Therapy at the University of California, San Diego, and co-principal investigator.
"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 one year for patients living with psoriatic arthritis."
ACR 50 and ACR 70 response rates increased from week 24 through week 52 among patients receiving STELARA maintenance therapy. At week 24, among patients receiving STELARA 45 mg, 24.9 percent achieved ACR 50 compared with 8.7 percent in the placebo group (P < 0.001), which increased to 31.4 percent at week 52, and 12.2 percent achieved ACR 70 compared with 2.3 percent in the placebo group (P < 0.001) at week 24, which increased to 18 percent at week 52.
Similar changes were observed in the STELARA 90 mg group at week 24 as 27.9 percent achieved ACR 50 compared with 8.7 percent in the placebo group (P < 0.001), which increased to 37 percent at week 52, and 14.2 percent achieved ACR 70 compared with 2.3 percent in the placebo group (P < 0.001) at week 24, which increased to 21.2 percent at week 52.
Investigators also reported continued improvements in physical function and skin symptoms through the end of the study, with nearly half of patients demonstrating clinically meaningful change from baseline in HAQ-DI scores, and more than two-thirds of patients achieving PASI 75 at week 52.
Among study participants affected with enthesitis (inflammation of the entheses, the sites where tendons or ligaments attach to bone, n=425) or dactylitis (inflammation of the finger or toe, n=286) at baseline, patients receiving STELARA achieved clinically relevant improvements in both measures at week 24 and week 52.
At week 24, median percent changes in enthesitis scores (-42.9 for STELARA 45 mg and -50.0 for STELARA 90 mg) and dactylitis scores (-75.0 for STELARA 45 mg and -70.8 for STELARA 90 mg) were significantly higher than those seen for patients receiving placebo (P < 0.001 for all comparisons). Improvements in enthesitis scores (-83.3, -74.2 and -87.5) and dactylitis scores (-100 in all patients) in the STELARA 45 mg, 90 mg and crossover groups, respectively, continued through week 52.
A similar proportion of patients experienced at least one AE or serious AE through week 16, the placebo-controlled period of PSUMMIT I. Safety through week 52 was consistent with that observed during the placebo-controlled period between STELARA 45 mg and 90 mg groups in the incidence of AEs (66.8 percent and 64.7 percent, respectively) and serious AEs (5.9 percent and 3.4 percent, respectively).
No malignancies, cases of TB, opportunistic infections or deaths occurred through week 52. Investigators reported three MACE in STELARA-treated patients in patients with multiple pre-existing cardiovascular risk factors.