EULAR 2023: What Do CRP Levels Reveal About the Efficacy and Safety of Tofacitinib in Patients with Ankylosing Spondylitis?
What is the impact of baseline C-reactive protein (CRP) levels on the efficacy and safety of treating ankylosing spondylitis (AS) with the Janus kinase inhibitor (JAKi) tofacitinib? The authors of the cited study below sought to answer this question, with their results presented at this year’s annual EULAR congress, which took place in Milan, Italy, at the traditional turn of May and June.
Methodology, Objectives, and Assessed Patient Population
Elevated baseline CRP concentrations may predict treatment response in patients with ankylosing spondylitis (AS). The authors conducted a post hoc analysis of pooled data from 2 randomized double-blind placebo-controlled studies − a 16-week Phase II study (NCT01786668) and a 48-week Phase III study (NCT03502616) considering baseline CRP levels (normal: < 5 mg/L; elevated: ≥ 5 mg/L).
The outcomes of all participants who received at least one dose of tofacitinib or placebo were assessed. In the Phase III study, subjects initially on placebo were switched to active tofacitinib treatment after 16 weeks. Tofacitinib was administered at a dose of 5 mg twice daily (BID), and its efficacy was evaluated at week 12 and then at weeks 16-48 (in the Phase III study).
The primary endpoints included achieving ASAS (Assessment of Spondyloarthritis International Society) 20/40, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) 50, ASDAS-CRP ID – AS-Disease Activity Score − CRP Inactive Disease indicating inactive disease based on CRP levels, mean change in night-time spinal pain score from baseline, and fatigue score using the FACIT-F – Functional Assessment of Chronic Illness Therapy − Fatigue. Safety was assessed at weeks 16 and 48.
Results
Out of a total of 372 patients, 30.4% had normal baseline CRP levels and 69.6% had elevated levels. Both groups generally had similar baseline characteristics, with a higher proportion of males, active smokers, and individuals previously treated with biological disease-modifying anti-rheumatic drugs (bDMARDs) in the elevated CRP group.
At week 12, more patients in the tofacitinib group showed an ASAS 20 response compared to the placebo group in both CRP groups, with sustained efficacy observed up to week 48. The difference in response between placebo and tofacitinib at week 12 was numerically greater in the elevated CRP group (44.7% vs. 15.9% for ASAS 20; 34.6% vs. 17.3% for ASAS 40; 33.8% vs. 15.3% for BASDAI 50). Difference in ASDAS-CRP ID response compared to placebo was 9.5% in the elevated CRP group vs. 8.2% in the normal CRP group. The change in night-time spinal pain score was −2.1 vs. −1.4 and the change in FACIT-F score was 5.2 vs. 3.5.
Safety assessment indicated that the incidence of treatment-emergent adverse events (TEAEs) and infections up to week 16 was numerically higher in the tofacitinib group compared to placebo in patients with normal CRP levels, while in those with elevated CRP levels, it was similar between the active and placebo groups. A small number of serious adverse events (SAEs), serious infections, or herpes zoster virus infection were reported across all groups. No deaths occurred.
Conclusion
Regardless of baseline CRP levels, tofacitinib treatment was more effective than placebo at week 12. Across primary endpoints, the differences in response to tofacitinib compared to placebo were numerically greater in patients with elevated CRP levels. Safety risks associated with tofacitinib were comparable to placebo in patients with elevated CRP levels but higher in patients with normal CRP levels.
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Source: Deodhar A., Baraliakos X., Magrey M. et al. AB0937 Tofacitinib efficacy and safety in patients with ankylosing spondylitis by baseline C-reactive protein levels: a post hoc analysis. Ann Rheum Dis 2023; 82: 1685, doi: 10.1136/annrheumdis-2023-eular.2118.
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