Ixekizumab treatment improves MRI structural lesions in sacroiliac joints of patients with radiographic axial spondyloarthritis, post hoc analysis finds
Presenter: Walter P. Maksymowych, FRCP, Professor of Medicine, University of Alberta, Edmonton, AB, Canada
Effect of Ixekizumab Treatment on MRI Structural Lesions in the Sacroiliac Joints of Patients with Radiographic Axial Spondyloarthritis; A Post-hoc Analysis of a Placebo and Active Controlled RCT. Abstract 2549. Presented Nov 14, 2023.
In patients with biologic-naive radiographic axial spondyloarthritis (axSpA), ixekizumab treatment for 16 weeks improved structural lesions of the sacroiliac joints viewed on magnetic resonance imaging (MRI), according to a post hoc analysis of a phase 3 study presented at ACR Convergence 2023.
The findings suggest that ixekizumab may have an impact on progression of structural damage and healing in patients with radiographic axSpA, according to investigator Walter P. Maksymowych, FRCP, professor of medicine, University of Alberta, Edmonton, AB, Canada.
“We see an unequivocal effect on treatment of structural lesions, and this suggests that there is an effect of ixekizumab that goes beyond its effect on inflammation,” Dr Maksymowych said in his podium presentation of the study results.
Results showed that treatment decreased erosion scores and increased backfill and fat lesion scores, with further improvements in the erosion and backfill scores continuing through week 52 of the study.
In an interview with the Cleveland Clinic Journal of Medicine, Dr Maksymowych said patients with radiographic axSpA are concerned by knowing that their disease may progress to disability caused by ankylosis of the spine.
“Consequently, we must provide evidence that our therapies can prevent or ameliorate the progression of structural joint damage,” he said.
However, demonstrating the impact of therapy on structural damage progression or healing is very difficult in the context of a randomized clinical trial, he added. That’s because ankylosis on x-rays develops very slowly and may not be captured in the shorter placebo-controlled portion of axSpA studies.
“We have to look for other outcomes that might be affected by treatment in the first 12 to 16 weeks of a randomized, controlled trial,” said Dr Maksymowych.
In this study, Dr Maksymowych and co-investigators performed a post hoc analysis of COAST V, a multicenter, randomized, double-blind, placebo- and active-controlled phase 3 study in 341 biologic-naive adults with active radiographic axSpA. Patients were randomized to one of four treatment groups: ixekizumab 80 mg every 2 weeks, ixekizumab 80 mg every 4 weeks, adalimumab 40 mg every 2 weeks, or placebo.
The post hoc analysis included 325 patients in COAST V with baseline and week 16 MRI data. Across the four treatment groups, mean ages ranged from 40.8 to 41.7 years, 76.9% to 83.3% were male, and 89.3% to 92.3% were HLA-B27 positive.
Investigators scored changes in MRI structural lesions using the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint structural scores for erosion, backfill, fat lesion, and ankylosis.
Results showed the approved dose of ixekizumab 80 mg every 4 weeks was very comparable to adalimumab in preventing joint damage.
For the non-FDA approved, higher dose of ixekizumab 80 mg every 2 weeks, the effects were numerically greater. However, this was a post hoc study, and it was not designed to test superiority, Dr Maksymowych noted.
Erosion scores were significantly decreased in the active treatment groups by week 16. The least squares mean change from baseline for erosion scores was -0.56 for adalimumab (P ≤ .01), -0.57 for ixekizumab every 4 weeks (P ≤ .01), and -0.91 for ixekizumab every 2 weeks (P ≤ .001). For placebo, the change was plus 0.10.
Similarly, backfill scores increased by week 16 in the active treatment arms, but the difference was significant only in the higher-dose ixekizumab group, with a least square mean change from baseline of plus 0.52 (P ≤ .001).
In a subgroup analysis, men fared better than women, the data suggest. Erosion scores decreased significantly among men in the ixekizumab and adalimumab groups. By contrast, backfill scores improved significantly only among men in the ixekizumab every 2 weeks group. The improvements in erosion and backfill scores continued to improve through week 52.
After week 16 in the COAST V trial, patients on ixekizumab continued treatment through week 52, while patients receiving placebo or adalimumab crossed over to ixekizumab. By week 52, there was a further reduction in erosion scores in both the ixekizumab arms, the adalimumab crossover arm, and the placebo crossover arm.
“The effects of treatment on structural lesions on MRI occur very quickly, as soon as 16 weeks when compared to placebo, and this data supports a possible disease-modifying effect,” Dr Maksymowych said.
Upcoming studies will evaluate the impact of these MRI changes on the future development of ankylosis on x-rays, he added.
Disclosures
Walter P. Maksymowych, FRCP, reported disclosures related to AbbVie, BMS, Boehringer-Ingelheim, CARE Arthritis Ltd, Celgene, Eli Lilly, Galapagos, Gilead, Janssen Pharmaceuticals, Novartis, Pfizer, and UCB.
References:
van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. Lancet 2018; 392(10163):2441-2451. doi:10.1016/S0140-6736(18)31946-9
Dougados M, Wei JC, Landewé R, et al. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W) [published correction appears in Ann Rheum Dis. 2020 Jun;79(6):e75]. Ann Rheum Dis 2020; 79(2):176-185. doi:10.1136/annrheumdis-2019-216118