A recent study published in RMD Open indicates that while certolizumab pegol (CZP) effectively reduces inflammation in patients with active axial spondyloarthritis (axSpA), this reduction does not always translate into significant clinical improvements. The findings come from a post hoc analysis of the phase 3 RAPID-axSpA trial, suggesting that clinical trial endpoints relying on patient-reported symptoms may not fully capture the anti-inflammatory effects of treatments.
The RAPID-axSpA trial, a double-blind, multicenter study, involved 315 patients with axSpA who were randomized to receive subcutaneous CZP 200 mg every 2 weeks, CZP 400 mg every 4 weeks, or placebo until week 12. The trial continued with a dose-blind design up to week 48, followed by an open-label phase until week 204. Researchers assessed improvements in objective inflammation measures using magnetic resonance imaging (MRI) and C-reactive protein (CRP) levels, and correlated these with changes in clinical composite outcome measures such as the Axial Spondyloarthritis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).
Discrepancies Between Inflammation Reduction and Clinical Improvement
Of the 315 patients, 136 underwent MRI assessments both before and after 12 weeks of CZP treatment. Results showed that 100% of these patients experienced at least a 50% reduction in CRP levels, indicating a strong anti-inflammatory response. Furthermore, 53.7% achieved at least a 50% reduction in the Berlin MRI score, and 52.2% in the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI score.
However, clinical improvements were less consistent. Only 47.1% of patients demonstrated at least a 50% reduction in BASDAI scores, and 48.5% in ASDAS scores. This discrepancy suggests that while CZP effectively reduces inflammation, the clinical benefits as measured by standard composite scores may not fully reflect this reduction.
Impact of Pretreatment Inflammation Levels
In a subset of 117 patients with significant pretreatment inflammation, 100% achieved at least a 50% reduction in CRP levels following CZP treatment. Additionally, 58.1% and 53.8% showed similar reductions in Berlin and SPARCC scores, respectively. Clinical improvements in this subgroup were observed in approximately half of the patients, with 47.9% achieving at least a 50% reduction in BASDAI scores and 51.3% in ASDAS scores.
Correlation with ASAS40 Response
Patients who achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40) scores demonstrated greater clinical improvements. Among these responders, 75.4% achieved at least a 50% reduction in ASDAS scores, compared to only 21.2% of nonresponders. Similarly, 73.8% of ASAS40 responders achieved at least a 50% reduction in BASDAI scores, compared to 15.4% of nonresponders.
Limitations and Implications
The study's limitations include its focus on a clinical trial population, which may not fully represent real-world conditions. Additionally, the use of a nonstandard CRP threshold and the 12-week treatment window could affect the generalizability of the findings.
Despite these limitations, the researchers concluded that "the use of only clinical measures of disease activity as clinical trial endpoints may underestimate objective anti-inflammatory treatment effects. This could have important implications for the clinical evaluation of patients with axSpA."
