Rheumatologists know that patients with axial spondyloarthritis (axSpA) experience chronic back pain, spinal stiffness, reduction in mobility and quality of life. Over time, permanent damage to spinal mobility and function can occur due to new bone formation in the spine.
The current standard of care for axSpA is non-steroidal anti-inflammatory drugs (NSAIDs). If there is an insufficient response or intolerance to NSAIDs, the next line of treatment is tumor necrosis factor (TNF)–alpha targeted therapies that have demonstrated efficacy in recent trials in non-radiographic axSPA (nr-axSpA) patients. TNF-blocking agents have been approved for this indication in the EU and other countries, but are not yet approved in the U.S.
In this randomized double-blind placebo-controlled clinical trial (GO-AHEAD), we investigated the effect of treatment every four weeks with subcutaneously administered golimumab (GLM), a fully human anti-TNF antibody over 16 weeks in patients with active nr-axSpA. The primary endpoint was ASAS 20 response at Week 16.
Patients were 18–45 years old with a physician’s diagnosis of active nr-axSpA, a disease duration of five years or less since diagnosis and chronic back pain of three months or longer duration. All patients were required to meet either the ASAS classification criterion for a positive MRI and have one of the spondyloarthritis features, or be HLA-B27 positive and have two or more spondyloarthritis features. Patients had active disease at both screening and baseline defined by a total back pain assessment of ≥40 and a BASDAI of ≥4.0 on a visual analog scale (VAS) of 0–10. An additional inclusion requirement was inadequate response or intolerance to at least one NSAID or inability to tolerate a maximal dose of NSAID therapy for 30 days.
Treatment with GLM every four weeks resulted in significant and sustained improvements in signs and symptoms of nr-axSpA through Week 16, with improvement apparent after the first injection of GLM. In this study, GLM was safe, generally well tolerated and consistent with the known safety profile of GLM in other indications.
In total, 71.1% of patients in the GLM group achieved the primary endpoint, the ASAS 20 response, at Week 16 compared with 40.0% in the PBO group. Improvement in ASDAS and BASDAI were already notable by the first post-baseline assessment (Week 4) and were maintained and increased slightly between four and 16 weeks. Treatment effects with GLM were also significant for the key secondary efficacy measures that included the ASAS 40 response, the BASDAI 50 response, ASAS partial remission and SPARCC MRI SI joint score change from baseline to Week 16. Clinically meaningful improvements were observed in multiple other measures of disease activity, physical function and quality of life.