A Randomized, Double‐Blind, Placebo‐Controlled, Sixteen‐Week Study of Subcutaneous Golimumab in Patients With Active Nonradiographic Axial Spondyloarthritis

Abstract

ObjectiveAxial spondyloarthritis (SpA) is a chronic inflammatory disease characterized by back pain and stiffness. The objective of this study was to determine whether golimumab is superior to placebo in patients with nonradiographic axial SpA.MethodsThis phase III, double‐blind, randomized, placebo‐controlled trial was performed to evaluate subcutaneous golimumab (50 mg) versus placebo in patients ages ≥18 years to ≤45 years who had active nonradiographic axial SpA according to the Assessment of SpondyloArthritis international Society (ASAS) criteria for ≤5 years since diagnosis, high disease activity, and an inadequate response to or intolerance of nonsteroidal antiinflammatory drugs. Patients were randomized 1:1 to receive golimumab or placebo subcutaneously every 4 weeks. The primary end point was 20% improvement according to the ASAS criteria (ASAS20) at week 16. Key secondary end points were an ASAS40 response, ASAS partial remission, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and change in the Spondyloarthritis Research Consortium of Canada (SPARCC) magnetic resonance imaging (MRI) index for sacroiliac (SI) joint inflammation (SPARCC score).ResultsOf the 198 patients randomized, 197 were treated (97 received golimumab, and 100 received placebo). The mean age of the patients was 31 years, and 57.1% were male. At baseline, the mean ± SD BASDAI was 6.5 ± 1.5, the mean ± SD ASDAS was 3.5 ± 0.9, and the mean ± SD SPARCC score was 11.3 ± 14.0. The primary end point, an ASAS20 response, was achieved by significantly more patients in the golimumab group compared with the placebo group (71.1% versus 40.0%; P < 0.0001). An ASAS40 response was also achieved by significantly more patients in the golimumab group compared with the placebo group (56.7% versus 23.0%; P < 0.0001). The incidence of adverse events did not differ meaningfully between groups.ConclusionPatients with active nonradiographic axial SpA treated with golimumab had significantly greater improvement in symptoms compared with patients treated with placebo. Golimumab was well tolerated and had a favorable risk/benefit profile.

Imaging Findings Suggestive of Axial Spondyloarthritis in Diffuse Idiopathic Skeletal Hyperostosis

“…In addition, their mean SPARCC score was similar, if not higher, to what has been observed in axial SpA in randomized controlled trials (30,31). By contrast, SI joint lesions were more scarce in DISH patients, and SPARCC SI joint scores were much lower.…”

Cost-effectiveness Analysis of Golimumab in the Treatment of Non-Radiographic Axial Spondyloarthritis in Scotland

“…The mean age of the trial population was 31.2 years (SE = 0.51 years) and 57.1% were male. As expected, disease activity was high for this group of patients (mean BASDAI = 6.5) [18]. Golimumab was associated with better clinical outcomes than conventional therapy, as demonstrated by significantly higher proportions of patients in the golimumab group achieving BASDAI50, ASAS20, and ASAS40 responses (median OR = 3.2, 3.6, and 6.0, respectively).…”

“…GO-AHEAD, a 16-week, phase 3, placebo-controlled randomized trial, demonstrated the efficacy and tolerability of golimumab in patients with nr-axSpA who were not responding to NSAIDs [18]. Significantly more patients in the golimumab group achieved ASAS 20% response criteria (ASAS20), compared with the placebo group at week 16 (71.1 vs. 40.0%, P \ 0.0001), when looking at the full analysis set.…”

“…Significantly more patients in the golimumab group achieved ASAS 20% response criteria (ASAS20), compared with the placebo group at week 16 (71.1 vs. 40.0%, P \ 0.0001), when looking at the full analysis set. In part 2 of GO-AHEAD, where patients in the golimumab group continued to receive golimumab, and patients in the placebo group crossed over to receive golimumab, the proportion of ASAS20 responders in the golimumab/golimumab group continued to increase from week 16 to week 32, and in the placebo/golimumab group, there was a notable increase in patients achieving ASAS20 after switching to golimumab [18].…”

Challenges and Advances in Targeting Remission in Axial Spondyloarthritis

“…In 2001, the Assessment of Spondyloarthritis international Society (ASAS) developed a preliminary definition of clinical remission-ASAS partial remission (ASAS PR), which includes assessment of 4 domains: patient global, spinal pain, physical function, and "inflammation" (a proxy for true inflammation, based on morning stiffness) 5 . In clinical trials, 12-15% 5,6 of patients with ankylosing spondylitis (AS) receiving nonsteroidal antiinflammatory drugs (NSAID) achieve partial remission; a ceiling of ~15-40% at 6 months also exists with biologic therapies, including tumor necrosis factor (TNF) inhibitors and secukinumab 7,8 (Table 1 [9][10][11][12][13][14][15][16][17][18][19][20] ). Treating patients with short symptom duration may increase the proportion of patients reaching clinical remission to ~50% 9,21,22 .…”