Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial

• Published in: The Lancet (British edition) Vol. 373; no. 9664; pp. 633 - 640
• Main Authors: Gottlieb, Alice, Dr, Menter, Alan, MD, Mendelsohn, Alan, MD, Shen, Yaung-Kaung, PhD, Li, Shu, MS, Guzzo, Cynthia, MD, Fretzin, Scott, MD, Kunynetz, Rod, MD, Kavanaugh, Arthur, MD
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 21.02.2009; Elsevier; Elsevier Limited
• Subjects: Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Arthritis, Psoriatic - classification; Arthritis, Psoriatic - drug therapy; Arthritis, Psoriatic - physiopathology; Biological and medical sciences; Clinical trials; Cross-Over Studies; Cytokines; Dermatology; Diseases of the osteoarticular system; Double-Blind Method; Drug therapy; Endpoint Determination - methods; Female; Follow-Up Studies; General aspects; Hospitals; Humans; Inflammatory joint diseases; Internal Medicine; Light therapy; Male; Medical sciences; Middle Aged; Monoclonal antibodies; Placebo effect; Psoriasis; Psoriasis. Parapsoriasis. Lichen; Skin diseases; Ustekinumab; Human; Skin disease; Psoriasis; Diseases of the osteoarticular system; Cytokine; Interleukin 12; Interleukin 23; Inflammatory joint disease; Monoclonal antibody; Psoriatic arthritis; Spondylarthropathy; Medicine; Chronic; Randomization; Double blind study
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(09)60140-9

Summary Background Since some patients with psoriatic arthritis do not respond to typical drug treatments, alternatives are needed. Findings suggest that interleukins 12 and 23 might affect clinical symptoms and pathological joint changes of psoriatic arthritis. Ustekinumab is a human monoclonal antibody that inhibits receptor-binding of these cytokines. We aimed to assess the efficacy and safety of ustekinumab for psoriatic arthritis in this phase II study. Methods We undertook a double-blind, randomised, placebo-controlled, crossover study at 24 sites in North America and Europe. Patients with active psoriatic arthritis were randomly allocated via interactive voice response system to either ustekinumab (90 mg or 63 mg) every week for 4 weeks (weeks 0–3) followed by placebo at weeks 12 and 16 (n=76; Group 1) or placebo (weeks 0–3) and ustekinumab (63 mg) at weeks 12 and 16 (n=70; Group 2). The first 12 weeks of the study were placebo-controlled. Masking was maintained to week 16 infusion, and patients were followed up to week 36. The primary endpoint was ACR20 response at week 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00267956. Findings At week 12, 32 (42%) patients in Group 1 and ten (14%) in Group 2 achieved the primary endpoint (difference 28% [95% CI 14·0–41·6]; p=0·0002). Of 124 (85%) participants with psoriasis affecting 3% or more body surface area, 33 of 63 (52%) in Group 1 and three of 55 (5%) in Group 2 had a 75% or greater improvement in psoriasis area and severity index score at week 12 (47% [33·2–60·6]; p<0·0001). During the placebo-controlled period (weeks 0–12), adverse events arose in 46 (61%) patients in Group 1 and 44 (63%) in Group 2; serious adverse events were recorded in three (4%) Group 2 patients (none in Group 1). Interpretation Ustekinumab significantly reduced signs and symptoms of psoriatic arthritis and diminished skin lesions compared with placebo, and the drug was well tolerated. Larger and longer term studies are needed to further characterise ustekinumab efficacy and safety for treatment of psoriatic arthritis. Funding Centocor.