Ustekinumab for Patients with Active PsA Long-Term

San Diego—The efficacy and safety of ustekinumab as treatment for active psoriatic arthritis (PsA) is maintained at 100 weeks follow-up, according to long-term data presented at the ACR/ARHP meeting.

PSUMMIT 1 (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) is a phase 3, large, multicenter, double-blind, placebo-controlled trial. In this study, adult patients with PsA were randomized to receive subcutaneous ustekinumab 45 mg (n=205), ustekinumab 90 mg (n=240), or placebo (n=206). All patients had active disease as defined by > 5 swollen joint count (SJC), >5 tender joint count (TJC), C-reactive protein >0.3 mg/dL, and had received prior treatment with disease-modifying antirheumatic drugs and/or nonsteroidal anti-inflammatory drugs therapy. Patients who received prior treatment with an anti-tumor necrosis factor therapy were excluded from the study.

At week 16 during the trial, patients with <5% improvement in TJC and SJC were entered into blinded early escape where patients treated by placebo received ustekinumab 45 mg, patients treated by ustekinumab 45 mg received ustekinumab 90 mg, and patients who received ustekinumab 90 mg remained on that treatment dose. Patients on placebo crossed over to ustekinumab 45 mg at week 24.

Prior results at 24 weeks showed the efficacy of ustekinumab in reducing clinical signs and symptoms of PsA compared to placebo, with significantly larger proportions of patients receiving ustekinumab at either dose having ACR20/ACR50/ACR70 responses and greater improvements in Health Assessment Questionnaire Disability Index score. Results at 24 weeks also showed that ustekinumab was associated with a significant inhibition of radiographic progression compared to placebo based on change from baseline in total modified van der Heijde-Sharp (vdH-S) score.

Arthur Kavanaugh, MD, division of rheumatology, allergy and immunology, University of California, San Diego, California, reported the long-term clinical and radiographic efficacy of the trial at week 100. Overall, patients received 12 weeks of dosing to week 88, with this final efficacy evaluation at week 100.

At week 100, the study showed that the clinical and radiographic improvements seen in week 24 were maintained. For example, ACR70 response was seen in 18.6% of patients treated with placebo and then switched to ustekinumab 45 mg, 24.7% of ustekinumab 45 mg, and 22.2% of ustekinumab 90 mg.

The study also examined 440 patients with >3% body surface area involvement at baseline. A higher proportion of patients treated with ustekinumab 45 mg and ustekinumab 90 mg achieved a Psoriasis Area and Severity Index score of 75 at week 100 compared to patients receiving placebo and then switched to ustekinumab 45 mg (72.5% and 71.3% vs 63.9%, respectively).

Similarly, radiographic progression was maintained at week 100 as shown by the change in total modified vdH-S score among patients treated by placebo and then switched to ustekinumab 45 mg, ustekinumab 45 mg, and ustekinumab 90 mg (0.77 vs 0.48 and 0.63, respectively).

The final analysis also evaluated safety at week 108. With an average of 91.9 weeks of follow-up, the reported rate of adverse events was 160.60 and 7.10 for serious adverse events patients treated by ustekinumab (combined group). Rates (per 100 patient-years of follow-up) of other adverse events reported by patients treated by ustekinumab (combined group) included serious infections (1.23), malignancies (0.38), and major adverse cardiovascular events (0.66). Among patients who received ustekinumab, 0.4% reported injection-site reactions.

Based on these data, the investigators emphasized that ustekinumab at either dose maintained substantial benefit over time by reducing the clinical signs and symptoms of arthritis, improving physical function and health-related quality of life, and being generally well tolerated.