IL-17 inhibitor takes on axial spondyloarthritis in Asians

Jairia Dela Cruz
26 Apr 2021
IL-17 inhibitor takes on axial spondyloarthritis in Asians

Interleukin (IL)-17 inhibition with brodalumab has demonstrated therapeutic potential for Asian patients with active axial spondyloarthritis (axSpA) in a phase III trial.

“Over 16 weeks, the Assessment of SpondyloArthritis International Society (ASAS) 40 response rate ... consistently improved with brodalumab and was significantly higher vs placebo,” according to the investigators.

“IL-17 cytokines play a pathophysiological role in axSpA, and clinical trials have demonstrated the efficacy and safety of IL-17 inhibitors in the treatment of [both subtypes, namely] ankylosing spondylitis (AS) and nonradiographic axSpA,” they added. [Curr Opin Rheumatol 2016;28:359-367; Arthritis Rheumatol 2019;71:599-611; RMD Open 2019;5:e001005; ACR Open Rheumatol 2020;2:119–27; Lancet 2020;395:53–64]

Compared with other selective IL-17 inhibitors, the fully human anti-IL-17 receptor A (IL-17RA) monoclonal antibody brodalumab has a broader inflammation-blocking activity, suppressing the production of several other cytokines, including IL-17A and IL-17F. Evidence shows that inhibition of IL-17A and IL-17F can prevent inflammation and pathological and new bone formation. [Arthritis Rheumatol 2019;71:612-625; RMD Open 2020;6:e001306]

The current trial examined the efficacy and safety of brodalumab 210 mg (n=80) against placebo (n=79) in patients with axSpA across Japan, Korea, and Taiwan. Treatment was given subcutaneously at baseline, weeks 1 and 2, and every 2 weeks thereafter, for 16 weeks.

At week 16, more patients treated with the IL-17 blocker versus placebo achieved the primary endpoint of ASAS 40 response (43.8 percent vs 24.1 percent; rate difference, 19.7 percent, 95 percent confidence interval [CI], 5.3–34.1; p=0.018). [Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2020-219406]

Results for the ASAS 20 response followed the same pattern, with the rate being higher in the brodalumab than in the placebo group (67.5 percent vs 41.8 percent).

In subgroups defined by axSpA subtypes, the ASAS 40 response rates were higher with brodalumab vs placebo both in patients with AS (46.0 percent vs 25.8 percent) and those with nr-axSpA (35.3 percent vs 18.8 percent).

Furthermore, the IL-17 inhibitor produced a greater decrease in disease activity, as measured by ASDAS with C-reactive protein (ASDAS-CRP; least squares mean change, –1.127 vs –0.672). The proportion of patients with major and clinically important improvement at week 16 was 15.0 percent and 41.3 percent, respectively, with brodalumab vs 6.3 percent and 25.3 percent, respectively, with placebo.

Other outcomes, including Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), enthesitis count, swollen joint count, and Patient Global Assessment of spinal pain and axSpA were slightly higher in the active treatment group.

“The incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo and brodalumab groups, with no new safety signals identified with [the IL-17 inhibitor] over 16 weeks. Importantly, no TEAEs related to suicidal ideation or behaviour were reported, as cautioned in the brodalumab label,” according to the investigators. []

Currently, brodalumab 210 mg is approved for the treatment of plaque psoriasis in North America, Canada, Europe, Japan, and other Asian countries. The findings of the current trial highlight the drug's potential for treating patients with axSpA, the investigators said.

However, they acknowledged that the generalizability of results is limited to Japan, Korea, and Taiwan. Also, the current data demonstrate only the short-term efficacy and safety of brodalumab in axSpA. “The 52-week (weeks 16–68) results from the open-label extension of this study will further confirm the long-term efficacy and safety of brodalumab.”

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