A recent phase 2 study published in the Rheumatology (Oxford) evaluated the efficacy and safety of vunakizumab (SHR-1314), a novel humanized monoclonal antibody targeting interleukin (IL)-17A, in patients with active psoriatic arthritis (PsA). The study demonstrated that vunakizumab significantly improved clinical outcomes compared with placebo and was well tolerated.
Vunakizumab is a recombinant, humanized IgG1/κ monoclonal antibody administered subcutaneously, designed to selectively neutralize IL-17A. By inhibiting IL-17A binding to its receptor, it suppresses downstream pro-inflammatory signaling pathways implicated in the pathogenesis of PsA and other IL-17–mediated diseases, including psoriasis and ankylosing spondylitis. Given the central role of the IL-17 axis in synovial inflammation, enthesitis, and structural damage, targeted inhibition represents a well-established therapeutic strategy in PsA.
This multicentre, randomized, double-blind, placebo-controlled phase 2 trial enrolled adults aged 18–75 years with active PsA. Participants were randomized in a 1:1:1 ratio to receive subcutaneous vunakizumab 120 mg (n = 38), vunakizumab 240 mg (n = 37), or placebo (n = 37) at weeks 0, 2, 4, and 8. At week 12, patients receiving placebo were re-randomized to vunakizumab (120 mg or 240 mg) and continued treatment through week 20, while those initially assigned to vunakizumab maintained their dosing regimen. The primary endpoint was the proportion of patients achieving at least a 20% improvement according to the American College of Rheumatology criteria (ACR20) at week 12.
At week 12, ACR20 response rates were significantly higher with vunakizumab 120 mg (47.4%; P = 0.02) and 240 mg (59.5%; P = 0.001) compared with placebo (21.6%). Higher-dose therapy demonstrated a numerically greater response, suggesting a dose–response relationship. Clinical improvements were sustained through week 24 and were also observed in patients who switched from placebo, indicating consistent efficacy across treatment sequences. Although not powered for secondary endpoints, trends toward improvement in additional domains of PsA (including joint counts and patient-reported outcomes) were reported.
The safety profile of vunakizumab was favorable. Treatment-emergent adverse events (TEAEs) occurred at comparable rates across groups during the 12-week placebo-controlled period (120 mg: 73.7%; 240 mg: 64.9%; placebo: 70.3%), with no severe TEAEs or unexpected safety signals identified. The overall tolerability is consistent with the known safety profile of IL-17 inhibitors, with no apparent increase in serious infections or discontinuations during the study period.
These findings position vunakizumab as a promising addition to the IL-17 inhibitor class, which includes established agents such as secukinumab and ixekizumab. While the observed efficacy and safety outcomes are encouraging, the relatively small sample size and short duration of the phase 2 study warrant confirmation in larger, adequately powered phase 3 trials. Further evaluation is also needed to assess long-term efficacy, structural outcomes, and comparative effectiveness against existing biologic and targeted synthetic DMARDs.
In conclusion, vunakizumab demonstrated significant clinical efficacy and a favorable safety profile in patients with active PsA, supporting its continued clinical development as a targeted therapy for IL-17–mediated inflammatory diseases.
References
- Xue Y, Sun L, Zhang N, Chen H, Shi X, Liu S, Chen L, Ma X, Wei H, Jiang Z, Li X, Fan H, Li H, Li J, Wu R, Shi G, Zhu J, Kong X, Lu Y, Liu P, Zheng Q, Bai X, Zhang S, Wan W, Zou H. Vunakizumab in patients with active psoriatic arthritis: a multicentre, randomized, double-blind, placebo-controlled, phase 2 study. Rheumatology (Oxford). 2026 Feb 4;65(2):keag060.
- Keam SJ. Vunakizumab: First Approval. Drugs. 2024 Nov;84(11):1481-1485.