2016精准医学：风湿免疫指南之后的治疗路径.ppt

2、激素暴露时间与股骨头坏死的关系 Glucocorticoid exposure was associated with osteonecrosis regardless of how recent the drug use was: Within 1 to 90 days, OR 5.8 (95% CI 1.6 to 21.2) Between 180 and 365 days earlier, OR 8.9 (95% CI 2.5 to 32.5) More than 730 days earlier, OR 4.3 (95% CI 2 to 9) When the researchers conducted a separate analysis limited to remote users – patients whose exposure was more than a year before the index date – they found persistent high risks: Between 30 and 90 days, OR 9.3 (95% CI 2.5 to 34.9) Between 90 and 180 days, OR 4.1 (95% CI 0.4 to 47.9) More than 365 days, OR 165.4 (95% CI 7 to 999.9) Primary source: American College of RheumatologyVlad S, et al Short periods of glucocorticoid use are associatd with a prolonged risk of osteonecrosis ACR 2011; Abstract 802. 1、纤溶酶原激活物抑制物-1（PAI-1）： 4G4G allele carriers always have higher plasma PAI-1 activity than 4G5G and 5G5G carriers 2、ABCB1 3435： p糖蛋白家族，药物转运蛋白，MDR1基因 基因型 ON（20例） freq（%） NO-ON（52例） freq（%） 4G5G-CC 8 40 6 11.5 4G5G-TT 4 20 13 25 4G5G-CT 3 15 6 11.5 4G4G-CC 2 10 4 7.7 5G5G-CC 1 5 2 4 4G4G-TT 1 5 4 8 4G4G-CT 1 5 6 11.5 5G5G-TT 3 5.8 5G5G-CT 8 15.4 SARS患者基因型与股骨头坏死发生 PAI-1与ABCB1 3435基因型组合在ON与NO-ON中的频率 基因型与股骨头坏死发生概率 风险度 基因型 ON发生率%（ON/NO-ON） 4 4G5G-CC 57.1 4 4G4G-CC 50.0 4 5G5G-CC 50.0 3 4G5G-CT 33.3 2 4G5G-TT 26.7 2 4G4G-TT 25.0 1 4G4G-CT 14.3 0 5G5G-TT 0 0 5G5G-CT 0 基因型风险度与股骨头坏死发生概率 风险度 风险较高： PAI-1及ABCB1均突变，即高风险。 需高度关注骨骼反应，同时配伍用预防性的药物：抗凝及抗凋亡。 降低激素剂量并换用其他药物。 风险度中等：PAI-1及ABCB1中有一个突变，则风险度中等， 需要关注骨骼反应，针对性使用预防性药物。 风险度低：PAI-1及ABCB1均未突变，则风险度低。 但仍需关注骨骼反应。 Robert S. Glucocorticoid-induced osteonecrosis. Endocrine 2011. DOI 10,1007/s 12020-011-9580-0 2、 DMARDs （1）硫唑嘌呤、6MP Azathioprine, cyclosporine, minocycline and gold were considered but not included in these guidelines due to their infrequent use in RA and/ or lack of new data since 2012. 【2015 ACR guildline】 在我