Atzeni Fabiola, Rotondo Cinzia, Siragusano Cesare, Corrado Addolorata, Cauli Alberto, Caporali Roberto, Chimenti Maria Sole, Conti Fabrizio, Picerno Valentina, Gremese Elisa, Camarda Federica, Guiducci Serena, Ramonda Roberta, Idolazzi Luca, Semeraro Angelo, Sebastiani Marco, Lapadula Giovanni, Ferraccioli Gianfranco, Iannone Florenzo
Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, 98168 Messina, Italy.
Rheumatology Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria Policlinico Riuniti di Foggia, Università degli Studi di Foggia, 71122 Foggia, Italy.
J Clin Med. 2025 Jun 10;14(12):4111. doi: 10.3390/jcm14124111.
: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). : This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) ( = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) ( = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) ( = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3-44.8, = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1-1.5; = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10-10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1-1.1, = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1-1.03, = 0.05). Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients.
银屑病关节炎（PsA）是一种主要影响肌肉骨骼系统和皮肤的慢性炎症性疾病。虽然生物制剂和靶向合成的改善病情抗风湿药（DMARDs）已使治疗有所进展，但许多患者仍无法实现病情缓解。与肿瘤坏死因子抑制剂（TNFi）不同，TNFi与传统合成改善病情抗风湿药（csDMARDs）联合使用有益，而将csDMARDs与生物（b）DMARDs或靶向合成（ts）DMARDs联合使用，相比使用白细胞介素-17、白细胞介素-23抑制剂或JAK抑制剂单药治疗并无额外益处。古塞库单抗（GUS）和司库奇尤单抗（RKZ）对白细胞介素-23具有高特异性靶向作用。随机对照试验（DISCOVER 1和2、COSMOS）已证实，无论是否使用甲氨蝶呤（MTX），GUS均有效，不过MTX使用时肝毒性更高。关于GUS的真实世界数据仍然有限，在了解其长期有效性和药物留存率方面存在差距。本研究的目的是在一个接受古塞库单抗（GUS）治疗并随访12个月的意大利多中心PsA患者真实队列中评估以下三点：（1）GUS的有效性和安全性；（2）药物留存率（DRR）及停药原因；（3）合并症对实现最小疾病活动度（MDA）的影响。 本研究利用了GISEA注册中心的数据，该中心包括意大利不同地区（北部、中部、南部和岛屿）的中心，纳入了根据CASPAR标准诊断为PsA的18岁及以上患者。收集了170例接受GUS治疗的PsA患者的数据。在最初6个月，与基线相比，所有临床指标均观察到迅速的平均百分比改善。在6个月随访时，总体组中60%的患者达到美国风湿病学会（ACR）20改善，30%达到ACR 50改善，15%达到ACR 70改善，28%达到MDA，50%的患者疾病活动度银屑病关节炎疾病活动指数（DAPSA）<14。在未使用过bDMARDs的组中ACR 50改善率为50%，与一名bDMARDs无反应者（NR）（8%）相比存在显著差异（P = 0.021）。在12个月随访时，未使用过bDMARDs的患者（60%）与一名bDMARDs NR患者（22%）（P = 0.035）以及未使用过bDMARDs的患者（60%）与≥2名bDMARDs NR患者（22%）（P = 0.024）之间，在达到MDA的患者比例上观察到显著差距。通过多变量二元逻辑回归分析，12个月随访时达到MDA的预测因素为未使用过bDMARDs（比值比：7.9，95%置信区间：1.3 - 44.8，P = 0.019）以及基线时较高的医师全面评估（pGA）值（比值比：1.1，95%置信区间：1 - 1.5；P = 0.046）。包括纤维肌痛和肥胖在内的合并症的存在似乎并未影响达到MDA。在12个月随访时，GUS留存率为76%，平均存活时间为
10.5个月±0.2（95%置信区间：10 - 10.9）。在未使用过bDMARDs的患者、一名bDMARDs NR患者和≥2名bDMARDs NR患者之间（在后者中，无论先前的作用机制：TNFi或其他机制），以及在接受GUS单药治疗的患者和与csDMARDs联合治疗的患者之间，未发现GUS存活时间有显著差异。发现因原发性NR和继发性NR导致的停药率较低（17%）。记录了GUS的高安全性。实际上，仅4% 的患者因不良事件（均定义为轻度）停药。通过COX回归多变量分析，与较高的GUS停药风险相关的因素为基线银屑病面积和严重程度指数（PASI）更严重（风险比：1.05，95%置信区间：1 - 1.1，P =
0.038）和较高的基线红细胞沉降率（ESR）（风险比：1.06，95%置信区间：1 - 1.03，P = 0.05）。在未使用过生物制剂的患者以及先前bDMARDs治疗失败的患者（无论先前药物的作用机制：TNFi或非TNFi）中均观察到GUS的良好疗效，即使作为第三种作用机制使用，在治疗中也具有良好的持续性。其高安全性特征使得GUS即使在特别复杂的患者中也可使用。
