A. Deodhar, MD, Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, Oregon, USA.
X. Baraliakos, MD, Rheumazentrum Ruhrgebiet Herne, Ruhr University Bochum, Bochum, Germany.
J Rheumatol. 2024 Aug 1;51(8):772-780. doi: 10.3899/jrheum.2023-1198.
This post hoc analysis assessed the effect of baseline C-reactive protein (CRP) on the efficacy and safety of tofacitinib (TOF) use in ankylosing spondylitis (AS), as well as patient-reported outcomes (PROs).
Phase II (ClinicalTrials.gov: NCT01786668) and phase III (ClinicalTrials.gov: NCT03502616) data from patients with active AS were used. Endpoints (weeks 12, 16, and 48), including 20% and 40% improvement in Assessment of SpondyloArthritis international Society (ASAS), AS Disease Activity Score with CRP low disease activity, 50% improvement in Bath AS Disease Activity Index (BASDAI50), and PROs (pain and fatigue), were stratified by baseline CRP (mg/L) as follows: < 5 (normal), ≥ 5 (elevated), < 10, and ≥ 10. Safety outcomes were evaluated between < 5 and ≥ 5 mg/L subgroups.
Overall, 372 patients were included (69.6% ≥ 5mg/L; 50.8% ≥ 10 mg/L). At baseline in the < 5mg/L group, more placebo-treated than TOF-treated patients received concomitant nonsteroidal antiinflammatory drugs (NSAIDs) or sulfasalazine (SSZ). Week 12 efficacy and PRO responses were generally higher for TOF vs placebo, regardless of baseline CRP. The treatment effect (placebo-adjusted response) at week 12 was generally numerically higher in ≥ 5 mg/L and ≥ 10 mg/L vs < 5 mg/L and < 10 mg/L groups. Incidence rates for treatment-emergent adverse events (TEAEs) and "all infections" were numerically higher for TOF vs placebo in patients in the < 5 mg/L group, but similar for TOF vs placebo in patients in the ≥ 5 mg/L group.
Regardless of baseline CRP, TOF was more efficacious vs placebo at week 12. The placebo-adjusted efficacy and PRO responses were generally numerically higher in patients with CRP ≥ 5 mg/L and ≥ 10 mg/L vs < 5 mg/L and < 10 mg/L. The higher concomitant NSAID/SSZ exposure may have improved efficacy responses in the baseline < 5 mg/L placebo group, and ultimately affected the TOF treatment effect. Safety was consistent with previous studies of TOF use in AS, with numerically higher incidence rates for TEAEs and "all infections" for TOF vs placebo in patients with CRP < 5 mg/L.
本事后分析评估了基线 C 反应蛋白 (CRP) 对托法替布 (TOF) 治疗强直性脊柱炎 (AS) 的疗效和安全性的影响，以及患者报告的结局 (PROs)。
使用来自活动性 AS 患者的 II 期 (ClinicalTrials.gov：NCT01786668) 和 III 期 (ClinicalTrials.gov：NCT03502616) 数据。终点 (第 12、16 和 48 周)，包括 ASAS20%和 40%改善、CRP 低疾病活动度的 AS 疾病活动评分、Bath AS 疾病活动指数 (BASDAI50) 改善 50%以及 PROs(疼痛和疲劳)，按基线 CRP(mg/L)分层如下：<5(正常)、≥5(升高)、<10 和≥10。在<5mg/L 和≥5mg/L 亚组之间评估安全性结果。
总体而言，纳入了 372 名患者(69.6%≥5mg/L;50.8%≥10mg/L)。在<5mg/L 组中，与 TOF 治疗组相比，更多接受安慰剂治疗的患者同时接受非甾体抗炎药 (NSAIDs) 或柳氮磺胺吡啶 (SSZ)。无论基线 CRP 如何，TOF 治疗的第 12 周疗效和 PRO 反应通常高于安慰剂。在≥5mg/L 和≥10mg/L 组中，第 12 周的治疗效果(安慰剂调整反应)通常高于<5mg/L 和<10mg/L 组。在<5mg/L 组中，TOF 治疗的患者发生治疗出现的不良事件 (TEAE) 和“所有感染”的发生率高于安慰剂，但在≥5mg/L 组中，TOF 与安慰剂的发生率相似。
无论基线 CRP 如何，TOF 在第 12 周的疗效均优于安慰剂。在 CRP≥5mg/L 和≥10mg/L 的患者中，与<5mg/L 和<10mg/L 的患者相比，安慰剂调整后的疗效和 PRO 反应通常更高。基线<5mg/L 安慰剂组中 NSAID/SSZ 联合治疗的高暴露率可能改善了疗效反应，并最终影响了 TOF 的治疗效果。安全性与 TOF 治疗 AS 的先前研究一致，在 CRP<5mg/L 的患者中，TOF 治疗的 TEAE 和“所有感染”发生率高于安慰剂。
