Milan Raymond, LeLorier Jacques, Brouillette Marie-Josée, Holbrook Anne, Litvinov Ivan V, Rahme Elham
Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Front Pharmacol. 2022 Feb 15;13:810309. doi: 10.3389/fphar.2022.810309. eCollection 2022.
Sex differences exist in psoriasis manifestation and expectations from treatment with systemic agents, including, conventional systemic agents (CSA) and tumor necrosis factor inhibitors or ustekinumab (TNFi/UST). However, sex differences in patterns of systemic agent use, such as CSA discontinuation and switch from CSA to TNFi/UST have not been examined. To assess sex differences in patterns of CSA use and identify factors associated with switch to (or add) a TNFi/UST and those associated with CSA discontinuation. We conducted a retrospective cohort study using the Quebec health administrative databases. We included patients with psoriasis initiating a CSA in 2002-2015. We excluded patients with a psoriasis diagnosis in the 3 years prior to the first diagnosis date between 2002 and 2015, and those with a systemic agent dispensation in the year prior to that date. We used Cox regression models with the Least Absolute Shrinkage and Selection Operator method to identify factors associated with Switch/add TNFi/UST, and those associated with CSA discontinuation. Separate analyses were performed for male and female patients. We included 1,644 patients (55.7% females, mean age 60.3 years), among whom 60.4% discontinued their CSA and 7.4%, switched/added TNFi/UST (3.4% switched and 4.0% added) within a median of 0.78 years of follow-up. Among male and female patients, rates of Switch/add TNFi/UST per 1,000 person-year were 49.1 and 41.0 and rates of CSA discontinuation were 381.2 and 352.8. Clinical obesity in male patients (HR 3.53, 95% CI 1.20-10.35), and adjustment/somatoform/dissociative disorders (HR 3.17, 95% CI 1.28-7.85) and use of nonsteroidal anti-inflammatory drugs (HR 2.70, 95% CI 1.56-4.70) in female patients were associated with Switch/add TNFi/UST. Male patients followed by a rheumatologist (HR 0.66, 95% CI 0.46-0.94) and those with a prior hospitalization (HR 0.70, 95% CI 0.57-0.87) were at lower risk of CSA discontinuation, while those initiated on acitretin (vs methotrexate) were at higher risk to discontinue their CSA (HR 1.61, 95% CI 1.30-2.01). Female patients with rheumatoid arthritis comorbidity (HR 0.69, 95% CI 0.51-0.93), those with a dispensed lipid-lowering agent (HR 0.72, 95% CI 0.59-0.88) and hypoglycemic agent (HR 0.75, 95% CI 0.57-0.98) and those initiated on methotrexate (vs all other CSAs) were less likely to discontinue their CSA. Male and female patients entering the cohort between 2011 and 2015 were at reduced risk of CSA discontinuation compared to those entering the cohort before 2011. Most male and female patients discontinued their CSA within 1 year of follow-up. Our study highlighted sex differences in patients' characteristics associated with switch/add a TNFi/UST and CSA discontinuation; treatment switch and discontinuation may be indications of treatment failure in most patients.
银屑病的临床表现以及对全身用药(包括传统全身用药(CSA)、肿瘤坏死因子抑制剂或乌司奴单抗(TNFi/UST))治疗的期望存在性别差异。然而,全身用药使用模式中的性别差异,如CSA停药以及从CSA转换为TNFi/UST,尚未得到研究。为了评估CSA使用模式中的性别差异,并确定与转换至(或加用)TNFi/UST以及与CSA停药相关的因素。我们使用魁北克省卫生管理数据库进行了一项回顾性队列研究。我们纳入了在2002年至2015年开始使用CSA的银屑病患者。我们排除了在2002年至2015年首次诊断日期前3年内被诊断为银屑病的患者,以及在该日期前一年有全身用药配药记录的患者。我们使用带有最小绝对收缩和选择算子方法的Cox回归模型来确定与转换/加用TNFi/UST相关的因素以及与CSA停药相关的因素。对男性和女性患者分别进行了分析。我们纳入了1644例患者(55.7%为女性,平均年龄60.3岁),其中60.4%的患者停用了CSA,7.4%的患者在中位随访0.78年内转换/加用了TNFi/UST(3.4%转换,4.0%加用)。在男性和女性患者中,每1000人年的转换/加用TNFi/UST率分别为49.1和41.0,CSA停药率分别为381.2和352.8。男性患者的临床肥胖(HR 3.53,95%CI 1.20 - 10.35)、女性患者的适应障碍/躯体形式障碍/分离性障碍(HR 3.17,95%CI 1.28 - 7.85)以及使用非甾体抗炎药(HR 2.70,95%CI 1.56 - 4.70)与转换/加用TNFi/UST相关。男性患者由风湿病学家随访(HR 0.66,95%CI 0.46 - 0.94)以及有过住院史(HR 0.70,95%CI 0.57 - 0.87)的患者CSA停药风险较低,而起始使用阿维A(对比甲氨蝶呤)的患者停用CSA的风险较高(HR 1.61,95%CI 1.30 - 2.01)。患有类风湿关节炎合并症的女性患者(HR 0.69,95%CI 0.51 - 0.93)、使用过降脂药(HR 0.72,95%CI 0.59 - 0.88)和降糖药(HR 0.75,95%CI 0.57 - 0.98)的女性患者以及起始使用甲氨蝶呤(对比所有其他CSA)的女性患者停用CSA的可能性较小。与2011年前进入队列的患者相比,2011年至2015年进入队列的男性和女性患者CSA停药风险降低。大多数男性和女性患者在随访1年内停用了CSA。我们的研究突出了与转换/加用TNFi/UST以及CSA停药相关的患者特征中的性别差异;治疗转换和停药在大多数患者中可能表明治疗失败。