Effects of ustekinumab versus tumor necrosis factor inhibition on enthesitis: Results from the enthesial clearance in psoriatic arthritis (ECLIPSA) study.

OBJECTIVES: To date, all studies addressing on anti-inflammatory drugs in PsA have been carried out in psoriatic arthritis (PsA) patients with polyarticular disease. Specific studies on enthesitis are missing. IL-23 is considered to play a central role in the development of enthesitis. We therefore speculated that therapeutic inhibition of IL-12/IL-23 is particularly effective in enthesitis-driven PsA patients. METHODS: Enthesial CLearance In PSoriatic Arthritis (ECLIPSA) is a prospective randomized-controlled open-label study. Patients with PsA with active enthesitis were randomized 1:1 to receive either ustekinumab (UST; arm 1) or tumor necrosis factor inhibitors (TNFi; arm 2). Primary endpoint was complete clearance of enthesitis, defined by Spondyloarthritis Research Consortium of Canada (SPARCC) index equal to zero at 24 weeks. RESULTS: 51 patients (UST = 25; TNFi = 26) were screened, 47 enrolled (UST = 23; TNFi = 24) and 46 completed the study. Mean ±â€¯SD SPARCC index at baseline was 4.8 ±â€¯2.6 in the UST group and 3.5 ±â€¯2.3 in the TNFi group with no significant difference. After 24 weeks, 73.9% of UST patients and 41.7% of TNFi patients reached the primary endpoint (SPARCC = 0) indicating clearance from enthesitis (p = 0.018). UST achieved superior responses as compared to TNFi with respect to enthesitis (p = 0.007) and psoriatic skin disease (p = 0.030) but not for arthritis (p = 0.95). CONCLUSION: These results indicate that p40-IL-12/IL-23 inhibition is superior to TNFi in the clearance of enthesitis. Future stratified therapeutic approaches in PsA patients may therefore consider the presence or absence of enthesitis as a discriminator of response between different cytokine blocking modalities.