OP0307 Efficacy and safety of risankizumab, a selective il-23p19 inhibitor, in patients with active psoriatic arthritis over 24 weeks: results from a phase 2 trial

Abstract

BackgroundInterleukin-23 (IL-23), a key regulator of multiple effector cytokines, has been implicated in the pathogenesis of psoriatic lesions, synovitis, enthesitis, and bone erosion. Risankizumab (RZB) is a humanised IgG1 monoclonal antibody that binds to p19 subunit of IL-23, selectively inhibiting this critical cytokine.ObjectivesTo report the efficacy and safety of different doses of RZB in patients (pts) with active psoriatic arthritis (PsA) over 24 weeks.MethodsIn this double-blind, parallel-design, dose-ranging Phase 2 study, pts with active PsA (stratified by prior TNFi use and concurrent MTX use) were randomised in a 2:2:2:1:2 ratio to receive RZB (150 mg at weeks [Wks] 0, 4, 8, 12, and 16 [Arm 1], 150 mg at Wks 0, 4, and 16 [Arm 2], 150 mg at Wks 0 and 12 [Arm 3], 75 mg single dose at Wk 0 [Arm 4]) or matching placebo (PBO, Arm 5). Pts completing Wk 24 visit had an option to enter a separate open-label extension (OLE) study; pts not entering the OLE were followed until Wk 32. Efficacy assessments included ACR20/50/70, PASI, minimal disease activity (MDA), DAS28(CRP), dactylitis count, SPARCC enthesitis index, pain-VAS, HAQ-DI, and mTSS scores.ResultsOf the 185 pts who received the study drug, 173 (93.5%) completed 16 Wks of treatment and 145 (78.4%) entered OLE at Wk 24. The primary endpoint of ACR20 response at Wk 16 was achieved by pts in each of the RZB arms.1 At Wk 24, ACR20/50/70 responses were significantly higher in pts receiving RZB (pooled across all RZB arms) compared with PBO (table 1). PASI75/90/100 responses at Wk 24 were significantly higher in RZB-treated pts compared with PBO. At Wk 24, RZB-treated pts achieved significantly higher MDA responses as well as greater improvements in DAS28(CRP) and Pain–VAS. Improvements in HAQ-DI and enthesitis from BL were numerically greater in RZB arms. At Wk 24, RZB-treated pts (pooled across all RZB arms) showed significant improvement from BL in mTSS compared with PBO. Treatment-emergent adverse events (TEAEs), collected up to Wk 32, were comparable across treatment arms (table 2); the most common TEAE was infection. There were no deaths or cases of tuberculosis in RZB-treated pts; 2 adjudicated major adverse cardiovascular events were reported in RZB arms.Abstract OP0307 – Table 1Summary of efficacy results at week 24*Abstract OP0307 – Table 2Overview of treatment-emergent adverse events (TEAEs) over 32 weeksConclusionsPts with active PsA treated with RZB maintained improvement in joint and skin symptoms through 24 wks. RZB-treated pts (pooled across all RZB arms) showed evidence for inhibition of radiographic progression. RZB was well-tolerated with no new or unexpected safety findings.Reference[1] Mease PJ, et al. Arthritis Rheumatol2017;69(suppl 10).AcknowledgementsAbbVie and Boehringer Ingelheim (BI) funded the study (NCT02719171); BI contributed to its design and participated in data collection and both participated in data analysis and interpretation of the data, and in writing, review, and approval of the publication. AbbVie, BI, and the autho...

Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naïve active psoriatic arthritis patients with physician-reported spondylitis: pooled results from two phase 3, randomised, controlled trials

“…Given that multiple immunological functions can be altered by a myriad of genetic polymorphisms, it is not surprising that individual SpA disorders have demonstrated heterogeneity in responses to biologic agents targeting the IL-23/IL-17 axis. IL-12/23p409–11 and IL-23p19 inhibitors are effective in PsA22 23 but not AS,13 24 while IL-17 inhibition is effective in AS and PsA, inclusive of axial manifestations 25 26. Specific to AS and PsA, it has been postulated that differing biologic mechanisms in the spine, where IL-23-independent production of IL-17 may occur, versus the periphery results in differential responses to IL-23 inhibition 27 28.…”

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

“…Two studies in subjects with active PsA have both shown that ustekinumab improves enthesitis scores . Similarly, risankizumab has also shown to improve enthesitis scores when compared to placebo …”

“…243,244 Similarly, risankizumab has also shown to improve enthesitis scores when compared to placebo. 245 Other therapies, such as tofacitinib, act as an inhibitor of JAK1 and JAK3, and JAK2 to a lesser extent. While IL-23 signals through JAK2, and not JAK1 and JAK3, any benefits of tofacitinib could be attributed to the blockade of IL-23 signaling.…”

ALIGN PsA: Advancing a Multidisciplinary Approach in PsA

“…Many of the emerging therapies for PsA target pathways that are similar to the currently established treatment. Agents that are currently under investigation in PsA include brodalumab (IL-17 inhibitor), bimekizumab (IL-17 inhibitor), 102 risankizumab (IL-23 inhibitor), 103 guselkumab (IL-23 inhibitor), upadacitinib (JAK inhibitor), 104 and BCD-085 (IL-17 inhibitor). 105 As the treatment options for PsA expand over the coming years, the dermatology-rheumatology overlap has more therapeutic implications than ever.…”