New Data on Vunakizumab in Radiographic Axial Spondyloarthritis Trial

Key Takeaways

• Vunakizumab 120 mg was associated with a higher week 16 ASAS20 response than placebo in adults with active radiographic axial spondyloarthritis.
• ASAS40 and ASAS5/6 results also favored vunakizumab at week 16, and responses were sustained or increased through week 32, including after placebo switch to vunakizumab 120 mg.
• Adverse-event rates were broadly similar during the placebo-controlled period, most events were mild or moderate, and no new safety signals were identified through week 32.

In a vunakizumab trial in radiographic axial spondyloarthritis, week 16 ASAS20 responses reached 65.6% with vunakizumab 120 mg versus 42.5% with placebo. The between-group difference was 23.2 percentage points (95% CI, 11.8% to 34.0%; P<.001). The double-blind, placebo-controlled, adaptive phase 2 to 3 trial randomized 548 adults across 38 hospitals in China between June 9, 2021 and March 30, 2023.

Eligible participants were adults aged 18 years or older with documented radiographic sacroiliitis meeting modified New York criteria and active symptoms at screening and baseline. Active disease required BASDAI and total back pain scores of at least 4, plus inadequate response to at least 2 NSAIDs or NSAID intolerance or contraindication. Stage 1 of the study compared subcutaneous vunakizumab 120 mg, vunakizumab 240 mg, and placebo, and stage 2 compared 120 mg with placebo. Stable NSAIDs, selected analgesics, methotrexate, sulfasalazine, and low-dose oral glucocorticoids were permitted if doses were unchanged.

At week 16, ASAS40 responses were 46.3% with vunakizumab 120 mg and 24.0% with placebo, a 22.3-point difference (95% CI, 13.3%-31.3%; nominal P<.001). ASAS5/6 responses were 55.4% and 22.6%, respectively, for a 32.8-point difference (95% CI, 24.0%-41.7%; nominal P<.001). Disease activity, function, spinal mobility, quality of life, and inflammatory measures also moved in the same direction at week 16. Median ASDAS-CRP was 1.7 in the vunakizumab group and 2.6 in the placebo group. ASAS20 responses appeared by weeks 2 and 4, and subgroup patterns at week 16 were generally consistent by BASDAI, CRP, and prior anti-TNF exposure.

Among patients who continued vunakizumab 120 mg, week 32 response rates were 77.0% for ASAS20 and 62.2% for ASAS40. The corresponding ASAS5/6 response rate at week 32 was 65.4% during the extension period. Patients who switched from placebo to vunakizumab 120 mg during the extension improved to week 32 values similar to those in the continuous-treatment group. Benefits in other efficacy measures were also maintained or increased through the 32-week observation period.

During the 16-week placebo-controlled period, adverse events occurred in 83.7% of the vunakizumab group and 81.5% of the placebo group, and most events were mild or moderate. Serious adverse events occurred in 1.0% and 0.7%, while discontinuation because of adverse events occurred in 0.7% and 1.4%, respectively. Across 32 weeks, serious adverse events were reported in 13 of 538 patients receiving at least 1 dose of vunakizumab, with 2 considered possibly treatment related. No new safety signals were identified through week 32, and no deaths, serious infections, opportunistic infections, or malignant neoplasms were reported.

Reported limitations included 32 weeks of follow-up, no active comparator, enrollment only in China, and use of ASAS20 rather than the currently recommended ASAS40 as the primary endpoint. Imaging outcomes for progression were not collected, and radiographic progression remained unestablished.