A post-hoc analysis of phase II and III trials published in the Journal of Rheumatology revealed that tofacitinib (TOF) was more effective than placebo in treating ankylosing spondylitis (AS), regardless of baseline C-reactive protein (CRP) levels, with patients showing higher CRP levels (≥ 5 mg/L) experiencing more pronounced improvements in disease activity and patient-reported outcomes.
The study analyzed 372 patients, stratifying them by CRP levels to assess the relationship between baseline inflammation and TOF efficacy. Patients with elevated CRP (≥ 5 mg/L and ≥ 10 mg/L) showed greater improvements in Assessment of SpondyloArthritis International Society (ASAS20 and ASAS40), and BASDAI50 at week 12, compared to those with normal CRP levels. The findings indicate that baseline CRP levels could serve as a predictive biomarker for response to TOF in AS patients. Additionally, the safety analysis found that treatment-emergent adverse events (TEAEs), including infections, were slightly higher in the group with lower baseline CRP levels, although TOF was generally well-tolerated across all subgroups. Despite these variations, the overall safety and efficacy of TOF remained consistent with its established profile in rheumatology.
Tofacitinib is an oral Janus kinase (JAK) inhibitor that modulates immune responses and reduces inflammation by inhibiting direct and indirect cytokine signaling pathways. It preferentially targets JAK3 and/or JAK1 signaling, with selective inhibition over JAK2-dependent pathways. This affects cytokines such as IL-17, IL-21, and IL-23, which are implicated in the pathology of AS. The post-hoc subanalysis of phase II trial data, stratified by baseline CRP (≥/< 0.287 mg/dL), showed that response rates for 20% and 40% improvement in the Assessment of ASAS20 and ASAS40 at week 12 were higher for patients receiving tofacitinib compared to placebo, regardless of baseline CRP levels. Notably, the difference in ASAS40 response rates between tofacitinib and placebo was more pronounced in the high CRP group (≥ 0.287 mg/dL) compared to the low CRP group (< 0.287 mg/dL).
Elevated C-reactive protein (CRP) is a well-established marker of inflammation in ankylosing spondylitis (AS). Previous studies have demonstrated that higher CRP levels can predict both clinical response and structural radiographic progression in AS patients treated with tumor necrosis factor inhibitors (TNFi) and interleukin-17 (IL-17) inhibitors. For instance, patients with elevated baseline CRP levels showed better clinical responses to treatments like etanercept, infliximab, and adalimumab. Conversely, elevated CRP levels at baseline or at weeks 14 or 24 were associated with an increased risk of structural radiographic progression in patients receiving golimumab.
For rheumatologists, this analysis highlights the importance of using baseline CRP levels to guide treatment decisions for AS patients. Those with elevated CRP may benefit more significantly from TOF, experiencing rapid improvements in both clinical and patient-reported outcomes. Given the established safety profile of TOF, the study suggests that CRP stratification could help optimize treatment plans, ensuring that patients receive the most appropriate therapy based on their inflammatory status. Further long-term studies, including real-world data, are needed to corroborate the role of CRP in personalizing AS treatment.
References
- Deodhar A, Baraliakos X, Magrey M, Gensler LS, Thorat AV, Pemmaraju SK, Cadatal MJ, Nash P. Efficacy and Safety of Tofacitinib in Ankylosing Spondylitis by Baseline C-Reactive Protein Level: Post Hoc Analysis of Phase II and Phase III Clinical Trials. J Rheumatol. 2024 Aug 1;51(8):772-780.
- van der Heijde D, Deodhar A, Wei JC, Drescher E, Fleishaker D, Hendrikx T, Li D, Menon S, Kanik KS. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2017 Aug;76(8):1340-1347.