Post-hoc analysis demonstrates the efficacy of tofacitinib in ankylosing spondylitis regardless of baseline C-reactive protein levels

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A recent post hoc analysis published in The Journal of Rheumatology showed that TOF significantly improved efficacy compared to placebo across various baseline CRP levels. The study findings further support the tailored use of TOF in AS, emphasizing the influence of baseline inflammation levels on treatment outcomes. 

The analysis involving 372 patients with AS evaluated the efficacy and safety of TOF compared to placebo across different baseline CRP levels (<5 mg/L, ≥5 mg/L, <10 mg/L, and ≥10 mg/L). At week 12, TOF consistently outperformed placebo in improving disease activity measures (ASAS 20/40, ASDAS with CRP, BASDAI50) and patient-reported outcomes (PROs) such as pain and fatigue. Patients with elevated CRP (≥ 5 mg/L and ≥ 10 mg/L) demonstrated a greater magnitude of placebo-adjusted improvement compared to those with lower CRP levels (<5 mg/L and <10 mg/L). In the low CRP (< 5 mg/L) group, placebo efficacy was likely enhanced by higher NSAID and sulfasalazine (SSZ) usage, potentially affecting the observed treatment effect of TOF. The safety profile of TOF remained consistent with previous studies, with slightly higher rates of treatment-emergent adverse events and infections observed in the <5 mg/L CRP group for TOF, while adverse event rates were comparable between TOF and placebo in the elevated CRP groups. These findings confirm the efficacy of TOF across different CRP levels, with particularly pronounced benefits in patients with higher baseline inflammation. 

TOF is an oral Janus kinase (JAK) inhibitor that exerts its therapeutic effects by targeting JAK enzymes, which play a key role in regulating immune responses in immune-mediated inflammatory diseases (IMIDs), including AS. By inhibiting JAK1, JAK2, JAK3, and Tyk2, TOF blocks the competitive binding of these enzymes to the adenosine triphosphate (ATP) kinase domain, preventing phosphorylation and subsequent activation of signal transducers and activators of transcription (STATs). This mechanism disrupts the inflammatory pathways that contribute to disease activity in AS and other IMIDs. In AS, TOF helps reduce inflammation, improve disease outcomes, and alleviate symptoms such as pain and fatigue. The inhibition of JAK enzymes also plays a role in modulating immune cell function and cytokine production, which are central to the inflammatory process in conditions like AS. Additionally, TOF’s oral administration offers a convenient alternative to injectable biologics, making it an attractive option for patients with AS. 

Supporting the current study findings, another post-hoc analysis by Navarro-Compán et al. found that tofacitinib led to faster improvements in AS core domains compared to placebo. Within the first month, half of tofacitinib-treated patients experienced significant pain relief and ASDAS improvements. By month 2, nocturnal pain and enthesitis had improved, with morning stiffness reducing by month 3. Early treatment initiation showed quicker results than delayed therapy. 

Overall, the present study reinforces the potential of TOF as a treatment option for AS and highlight the importance of baseline CRP levels in predicting treatment response. 

 

Reference 

  1. Deodhar A, Baraliakos X, Magrey M, Gensler LS, Thorat AV, Pemmaraju SK, et al. 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. The Journal of Rheumatology. 2024 Aug 1;51(8):772–80. 
  2. Padda IS, Bhatt R, Parmar M. Tofacitinib. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Nov 28]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK572148/ 
  3. Wollenhaupt J, Lee EB, Curtis JR, Silverfield J, Terry K, Soma K, et al. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther. 2019 Apr 5;21(1):89. 
  4. Navarro-Compán V, Deodhar A, Bahiri R, Bushmakin AG, Cappelleri JC, Rammaoui J. Time to improvement of pain, morning stiffness, fatigue, and disease activity in patients with ankylosing spondylitis treated with tofacitinib: a post hoc analysis. Arthritis Res Ther. 2024 May 24;26(1):105. 

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