Tofacitinib demonstrates greater efficacy than placebo in treating ankylosing spondylitis, irrespective of baseline C-reactive protein (CRP) levels, according to a post-hoc analysis of Phase 2 and 3 trial data published in The Journal of Rheumatology. The study, supported by Pfizer Inc., suggests that baseline CRP levels do not diminish the effectiveness of tofacitinib in patients with this chronic inflammatory condition.
Background and Study Design
Elevated CRP levels in ankylosing spondylitis patients can indicate treatment response and disease progression. However, the influence of baseline CRP levels on the efficacy and safety of Janus kinase (JAK) inhibitors like tofacitinib has not been thoroughly investigated. The analysis combined data from a Phase 2 trial (NCT01786668) and a Phase 3 trial (NCT03502616) to evaluate tofacitinib's efficacy and safety in active ankylosing spondylitis patients, focusing on baseline CRP levels.
In the Phase 2 trial, patients were randomized to receive placebo or tofacitinib at 2 mg, 5 mg, or 10 mg twice daily for 12 weeks, followed by a 4-week washout period. The Phase 3 trial involved patients receiving tofacitinib 5 mg twice daily or placebo for 16 weeks, followed by an open-label extension of tofacitinib 5 mg twice daily for up to 48 weeks.
Key Findings
The analysis included 372 patients, with 185 receiving tofacitinib and 187 receiving placebo. Patients were stratified into two categories based on baseline CRP levels: <5 mg/L (normal) or ≥5 mg/L (elevated), and <10 mg/L or ≥10 mg/L. The primary outcomes assessed were the Assessment of SpondyloArthritis international Society (ASAS20/40) response rates, Ankylosing Spondylitis Disease Activity Scores with CRP (ASDAS-CRP), and 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores.
Tofacitinib treatment showed greater efficacy compared to placebo across all endpoints, regardless of baseline CRP levels. At 12 weeks, 70.9% of patients with CRP levels ≥5 mg/L who received tofacitinib achieved an ASAS20 response, compared to 26.5% in the placebo group. Among patients with CRP levels ≥10 mg/L, response rates were 70.5% and 26.7% for the tofacitinib and placebo groups, respectively.
Improvements in ASDAS-CRP and BASDAI scores were also significantly greater with tofacitinib than with placebo, particularly among patients with higher baseline CRP levels. These improvements were generally sustained up to 48 weeks.
Safety Profile
Safety analyses indicated that tofacitinib was associated with a higher incidence of treatment-emergent adverse events and infections compared to placebo, especially among patients with baseline CRP levels below 5 mg/L.
Expert Commentary
Researchers concluded that elevated baseline CRP levels in ankylosing spondylitis patients could predict a rapid treatment response to tofacitinib. However, the study's limitations include its post-hoc design, short follow-up period, and small sample sizes, warranting further investigation.
