Read the complete EBM Focus and earn CME
Reference: PSUMMIT 1 trial (Lancet 2013 Aug 31;382(9894):780) (level 1 [likely reliable] evidence)
Psoriatic arthritis is common in patients with psoriasis, with estimated prevalence ranging from about 7% to 20% or more in this population. Usual treatments include NSAIDs for mild disease and tumor necrosis factor inhibitors or disease-modifying antirheumatic drugs (DMARDs) for more severe disease. Ustekinumab, an anti-interleukin monoclonal antibody, is FDA approved for the treatment of moderate-to-severe plaque psoriasis in adults. The PSUMMIT 1 trial evaluated the efficacy of ustekinumab for psoriatic arthritis in 615 adult patients previously treated with or intolerant to NSAIDS and DMARDs.
Patients (median age 48 years) with active psoriatic arthritis for ≥ 6 months were randomized to ustekinumab (45 mg vs. 90 mg) subcutaneously vs. placebo at baseline and at 4 weeks, then once every 12 weeks for up to 1 year. At baseline, all patients had ≥ 5 tender joints and ≥ 5 swollen joints and all had been previously treated with either ≥ 3 months of DMARDs and/or ≥ 4 weeks of NSAIDs or had intolerance to both. At 16 weeks, patients who had < 5% improvement in both tender joint and swollen joint counts were switched from the placebo group to ustekinumab 45 mg and from the ustekinumab 45 mg to ustekinumab 90 mg. At 24 weeks, all patients still receiving placebo were switched to ustekinumab 45 mg.
The primary outcome was the proportion of patients achieving an American College of Rheumatology 20% response (ACR20) at 24 weeks. ACR 20 requires at least 20% improvement in tender and swollen joint counts and 20% improvement in 3 of 5 measures: patient global assessment, physician global assessment, self-reported physical disability, an acute phase reactant, and patient pain assessment. ACR50 response (50% improvement) was a secondary outcome. For patients who changed treatment at 16 weeks, the 16-week response was carried forward to 24 weeks.
ACR20 response was achieved in 49.5% with ustekinumab 90 mg, 42.4% with ustekinumab 45 mg, and 22.8% with placebo (p < 0.0001 for each ustekinumab dose vs. placebo), with a number needed to treat (NNT) of 4 with the higher dose and 6 with lower dose of ustekinumab. ACR50 response was achieved in 27.9% with ustekinumab 90 mg, 24.9% with ustekinumab 45 mg, and 8.7% with placebo. (p < 0.0001 for each ustekinumab dose vs. placebo). Both doses of ustekinumab were associated with significant reductions in dactylitis and enthesitis and significant improvements in physical function and health-related quality of life. There were no significant differences among groups in adverse events at 16 weeks. The most common adverse events with ustekinumab were nasopharyngitis, upper respiratory tract infection, and headache. Treatment responses with ustekinumab were maintained at 1 year (ACR20 in 58% for 2 doses combined).
For more information, see the Psoriatic arthritis topic in DynaMed.