Association between serine proteinase activity and response to intra-articular corticosteroid injections in psoriatic arthritis

Objective: Intra-articular corticosteroid (IAS) injections are often used for the immediate relief of pain and inflammation in the joint of psoriatic arthritis (PsA) patients. However, studies identifying factors that can predict response to IAS injections are lacking. We aimed to assess the usefulness of serine proteinase activity measurements in PsA synovial fluid (SF) samples obtained at the time of injection in predicting clinical response. Methods: PsA patients with available SF samples from the knee joint were identified from the University of Toronto PsA cohort. Clinical response was defined as an absence of tenderness or swelling in the injected joint at the first post-injection visit, at either 3 or 6 months. Proteinase activity was determined by measuring cleavage of fluorogenic tri-peptide substrates for trypsin-like (VPR-AMC and VLK-AMC) and chymotrypsin-like (AAPF-AMC) serine proteinases. Generalized estimating equation (GEE) models were used to investigate which factors were associated with response. Results: A total of 32 patients with 60 injected joints and data available for follow-up at 3 or 6 months were included in the analysis, with 25 (41.7%) injected joints resulting in clinical response. Age, sex, active joint count, medications and serine proteinase activity at the time of injection were included as covariates. Only treatment with biologics was significantly associated with response at 3 or 6 months in the multivariate reduced model (OR 3.02, p = 0.027). Conclusion: We could not demonstrate an association between SF serine proteinase activity and response to IAS injection. Biologic agents significantly improve the likelihood of achieving clinical response.

研究目标：关节腔内糖皮质激素（intra-articular corticosteroid, IAS）注射常被用于快速缓解银屑病关节炎（psoriatic arthritis, PsA）患者关节的疼痛与炎症，但目前尚缺乏可预测IAS注射临床疗效的相关因素研究。本研究旨在评估注射时采集的PsA患者滑液（synovial fluid, SF）样本中的丝氨酸蛋白酶活性检测，对其临床疗效的预测价值。

研究方法：本研究从多伦多大学PsA队列中筛选出留存膝关节滑液样本的PsA患者。本研究将临床疗效定义为：在注射后首次随访（3个月或6个月时），注射关节无压痛或肿胀。通过检测类胰蛋白酶样（VPR-AMC、VLK-AMC）与类胰凝乳蛋白酶样（AAPF-AMC）荧光三肽底物的裂解情况，测定丝氨酸蛋白酶活性。采用广义估计方程（generalized estimating equation, GEE）模型，探究与疗效相关的影响因素。

研究结果：本研究共纳入32例患者，共计60个接受注射的关节，且均获取了3个月或6个月的随访数据，其中25个（41.7%）注射关节达到临床疗效。研究将年龄、性别、活动关节计数、用药情况及注射时的丝氨酸蛋白酶活性作为协变量。在多因素精简模型中，仅生物制剂治疗与3个月或6个月时的临床疗效呈显著相关性（优势比odds ratio, OR 3.02，P=0.027）。

研究结论：本研究未证实滑液丝氨酸蛋白酶活性与IAS注射疗效之间存在关联，生物制剂可显著提升患者获得临床疗效的概率。