Achieving Axial Spondyloarthritis Disease Activity Score Inactive Disease Status in Axial Spondyloarthritis in Clinical Trials: A Systematic Review and Metaanalysis.

Abstract

The Axial Spondyloarthritis Disease Activity Score (ASDAS) is a composite score that measures disease activity in axial spondyloarthritis (axSpA) and is based on patient-reported outcomes and objective measures of inflammation. An ASDAS score < 1.3 indicates inactive disease (ID; ASDAS-ID) in axSpA clinical trials and is considered equivalent to clinical remission. We hypothesized that achieving ASDAS < 1.3 represents a stringent target that may be difficult to attain in randomized controlled trials (RCTs). We aimed to evaluate the proportion of patients with axSpA achieving ID compared to low disease activity (LDA; ie, ASDAS < 2.1 [ASDAS-LDA]) in clinical trials. A comprehensive literature search was conducted in MEDLINE, Embase, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and the EU Clinical Trials Register to identify eligible studies published from inception through August 2025. Clinical trials reporting ASDAS-ID or ASDAS-LDA were included. Eligible studies enrolled patients with radiographic or nonradiographic axSpA treated with biologic therapies, including tumor necrosis factor inhibitors (TNFi), interleukin 17 inhibitors (IL17i), or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) such as Janus kinase inhibitors (JAKi). Risk of bias (ROB) was assessed using the Cochrane ROB tool, and 2 independent reviewers screened all records, with disagreements resolved by a senior author. A metaanalysis was performed, and data were synthesized using forest plots to calculate pooled odds ratios with 95% CIs. Study heterogeneity was assessed using the <i>I ²</i> statistic. A total of 41 unique studies were included; 19 RCTs were identified with 6171 patients included in the metaanalysis. Additionally, 22 open-label extension (OLE) studies were included. Several OLE publications originated from the same parent RCT and therefore did not represent independent studies. The pooled proportion of patients achieving ID status in the treatment group was 0.24 (95% CI 0.18-0.31) at 12-24 weeks, and in the OLE phases 0.22 (95% CI 0.17-0.28) during weeks 48-52 and 0.35 (95% CI 0.25-0.43) during weeks 96-156. The odds of achieving ID were 0.30 (95% CI 0.17-0.51) compared to LDA in the treatment group. This study demonstrates that attainment of ASDAS-ID in axSpA clinical trials is consistently low, reflecting the stringency of this remission threshold within trial designs. These findings underscore the importance of interpreting ASDAS-ID alongside ASDAS-LDA, which may represent a more attainable and clinically meaningful disease state when remission is not achieved.