Long-term Brodalumab Treatment for axSpA Supported by Phase 3 Data
Injections of brodalumab safely reduced disease activity in 68-week study
Long-term treatment with under-the-skin injections of brodalumab safely and effectively reduced disease activity in people with axial spondyloarthritis (axSpA), according to final data from a Phase 3 trial.
axSpA is a type of chronic inflammatory arthritis affecting the joints of the spine, chest, and pelvis. Ankylosing spondylitis (AS) is a severe type that mainly affects the joints of the spine.
“We present the first long-term results of brodalumab in patients with axSpA,” the researchers wrote, adding that the data “demonstrated the long-term efficacy and safety of brodalumab in patients with axSpA.”
These findings further support the long-term benefits of brodalumab in axSpA patients, for whom it is approved in Japan.
The study, “Brodalumab, an anti-interleukin-17 receptor A monoclonal antibody, in axial spondyloarthritis: 68-week results from a phase 3 study,” was published in Rheumatology.
Blocking IL-17 signaling pathway emerges as promising treatment approach
Activation of the interleukin-17 (IL-17) immune signaling pathway is thought to underlie a number of autoimmune or inflammatory diseases. As such, blocking this pathway has emerged as a promising treatment approach for these diseases.
Two IL-17 pathway inhibitors are currently approved for the treatment of AS, namely Novartis’ Cosentyx (secukinumab) and Eli Lilly’s Taltz (ixekizumab). Both are designed to block IL-17A, a signaling molecule involved in the pathway.
Originally developed by Amgen and Aztrazeneca, brodalumab is an antibody-based treatment designed to block another critical component of the IL-17 pathway: the IL-17 receptor A (IL-17RA).
It is approved in several countries for psoriasis, an inflammatory disease that causes non-contagious patches of thick and reddened skin and silvery scales.
In Japan, the therapy — sold by Kyowa Kirin under the brand name Lumicef — is also approved for AS and non-radiographic axSpA, a form of axSpA in which patients experience symptoms, but no visible damage is seen on X-rays.
The 2020 approval was mainly based on the interim results of a Kyowa Kirin-sponsored Phase 3 clinical trial (NCT02985983), which assessed the therapy’s safety and efficacy against a placebo in 159 adults with active AS or non-radiographic axSpA.
Participants, recruited at sites in Japan, Korea, and Taiwan, were randomly assigned to receive under-the-skin injections of either brodalumab (210 mg; 80 patients) or a placebo (79 patients) for 16 weeks (about four months). Injections were given once a week for the first three weeks and every other week thereafter.
Those completing the 16-week period entered the study’s open-label extension portion, in which all received the therapy for one year.
Findings show more patients on brodalumab improved on tests
Interim findings showed the trial met its main goal, with a significantly higher proportion of brodalumab-treated patients achieving at least a 40% improvement on the Assessment of SpondyloArthritis International Society (ASAS40) criteria at week 16 relative to the placebo group (43.8% vs. 24.1%).
ASAS40 is a tool that assesses four domains: pain, function, inflammation, and a patient global assessment.
The researchers have now published the long-term safety and efficacy of brodalumab over the entire 68-week study.
Overall, 134 (84.3%) of the participants completed the trial: 91.3% of those originally assigned to the therapy and 77.2% of those originally on a placebo.
Data showed that the proportion of patients who had been on brodalumab from the start and who met ASAS40 criteria increased to 61.8% after 68 weeks. The rate of responders showing at least a 20% improvement (ASAS20) also increased, from 70.1% at week 16 to 78.1% at the end of the study.
For those originally on placebo, both response rates also showed a consistent increase after switching to the therapy, becoming comparable to the brodalumab group after about four months of treatment. At week 68, the ASAS40 response rate was 57.4%, and the ASAS20 response rate was 78.7%.
Subgroup analyses showed that among AS patients, ASAS40 and ASAS20 response rates were comparable between both groups by study’s end.
The proportion of patients with inactive disease increased from 50.6% at week 16 to 63% at week 68 in patients who consistently received brodalumab and from 31.9% to 62.3% among those who switched to the therapy when they entered the study’s extension.
Other measures of disease severity, patient perception of health status, inflammation, pain, and life quality also showed positive changes in both groups over the course of the study. For AS patients, signs of disease on MRI scans were also eased with treatment.
No new safety signals were observed in the trial, and the “safety profile of brodalumab was similar to that of other IL-17 inhibitors in previous AS studies,” the researchers wrote.
Adverse events were reported in 122 patients (76.7%), the most common being upper respiratory tract infections and cold-like symptoms.
Serious treatment-related adverse events were reported in five patients (3.4%). These included infection with the herpes zoster oticus virus, heart attack, bacterial skin infection, appendicitis, and intestinal inflammation (one patient each).
Antibodies that bound to the therapy were detected in one patient, but these could not neutralize its effects.
While a direct comparison with global studies testing IL-17 inhibitors in active AS patients “may not be feasible due to differences in study population ethnicity … ASAS responses achieved across the studies were similar,” the researchers wrote.
This suggests that IL-17RA-suppressing therapies such as brodalumab may be an effective alternative for reducing disease activity in people with axSpA, including AS.
Still, future studies involving patients from other regions are needed to confirm the therapeutic potential of brodalumab in the general axSpA patient population, the researchers noted.