The methotrexate therapeutic response in rheumatoid arthritis

OBJECTIVE: Methotrexate (MTX) is used frequently as a disease modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), and patients tend to continue taking this drug for longer periods than alternative single agents. The shape of the therapeutic response beyond one or 2 years, however, has not been fully studied. We examined the properties of the pure MTX "therapeutic segment," that period that begins with start of MTX and terminates when MTX is discontinued or another DMARD is added, by observational study. METHODS: We studied new MTX starts for the period 1988 through 1996 for 437 patients from a parent cohort of 4253 patients. Patients were drawn from 8 Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) data centers: 2 community based populations; 2 private rheumatological practices; 2 university referral practices; and 2 university clinics for underserved minority urban populations. Health Assessment Questionnaire (HAQ) Disability Index scores (0-3) were obtained prospectively each 6 months. RESULTS: At MTX start, patients had relatively long average disease duration of 16.7 years, and had moderately severe disability, with an initial HAQ mean disability score of 1.48. Over the 10 year period examined in the parent cohort of 4253 patients (and thus irrespective of therapy), the prevalence of MTX use rose from 19% to 45%, while mean HAQ disability declined from 1.34 to 1.11. This correspondence is consistent with an accrual of benefits from more frequent use of MTX and other DMARD over this period. The MTX therapeutic segment revealed a distinct shape. HAQ-Disability Index values began at 1.48 at baseline and declined to a maximal improvement of 1.23 at 30 months. This long period to maximum benefit may have been partly driven by a slow titration upward to an optimal dosage. After 42 months, disability for this population began to re-progress and reached 1.39 at 84 months, still below the pretreatment baseline. Re-progression to baseline was about 8 or more years. Cumulative disability averted with MTX treatment for this population was roughly 1.30 disability-unit-years. CONCLUSION: MTX treatment of RA in practice differs substantially from common perception and appears suboptimal by being too little, too late, and too long to treatment change. A modification of the "sawtooth strategy" in which the disease is "ratcheted down" by change of MTX therapy at 3 years or when re-progression has proceeded halfway to baseline, rather than waiting for return to baseline, is suggested by these data. Also suggested is the need for more rapid upward dosage titration and longer maintenance of an optimal or highest tolerated dosage. "Therapeutic segment" data provide insights into strategic approaches to management of RA since they allow estimation of population aggregate properties such as time to maximum benefit and the time to return to baseline.     

类风湿关节炎亚甲基四氢叶酸还原酶基因多态性与甲氨蝶呤疗效和不良反应的关系

目的 探讨类风湿关节炎(RA)患者亚甲基四氢叶酸还原酶(MTHFR)基因677CDT[rs1801133)、1298A/C(rs1801131)单核苷酸多态性(SNP)及其与甲氨蝶呤(MTX)治疗的疗效和不良反应相关性.方法 收集RA患者184例.分为单用MTX组、MTX联用其他改善病情抗风湿药(DMARD)组、非MTX的DMARD组,于治疗前及治疗后24周检查临床及实验室指标,评价疗效及不良反应.采用实时荧光定量聚合酶链反应(FQ-PCR)方法检测RA患者及100名健康对照组的MTHFR基因677C/T及1298A/C多态性,比较两组间基因型分布及等位基因频率.结果 677CC/CT/TT基因型分布在RA组(19%、67%、14%)与健康对照组(27%、56%、17%)基因型分布频率差异无统计学意义(P>0.05);1298AA/AC/CC基因型分布在RA组(66%、31%、3%)健康对照组(70%、30%、0%)基因型分布频率差异无统计学意义(P>0.05).677CC/CT/TT基因型分布在RA有心血管并发症组(6%、75%、19%)与正常对照组(27%、56%、17%)差异有统计学意义(P<0.05).在单用MTX治疗者巾,1298AA/AC/CC在MTX治疗有效组(54%、44%、2%)和无效组(90%、10%、O%)中差异有统计学意义(P<0.05),677CC/CT/TT在MTX有不良反应组(13%、71%、16%)和无不良反应组(48%、48%、4%)中差异有统计学意义(P<0.05).在MTX联用其他DMARD组,677CC/CT/TT在有不良反应组(9%、78%、13%)和无不良反应组(35%、50%、15%)中差异有统计学意义(P<0.05).结论 MTHFR基因677C/T及1298A/C多态性与RA发病无关;677 C/T多态性与RA心血管并发症的出现有关、与MTX治疗后的不良反应相关,1298 A/C多态性与MTX的疗效相关.     

Intra-articular methotrexate in the treatment of rheumatoid arthritis and psoriatic arthritis: a clinical and sonographic study

The aim of our study was to evaluate the effects of intra-articular methotrexate (MTX) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Twenty-three consecutive patients, 10 with RA and 13 with PsA, with prevalent or unique arthritic involvement of one knee, were treated with intra-articular injections of MTX 10 mg every 7 days for 8 weeks. Before the beginning of the treatment and after 9 and 17 weeks, the patients underwent a clinical evaluation measuring maximal knee flexion angle, visual analog scale (VAS) and erythrocyte sedimentation rate (ESR). On the same days, an ultrasonographic examination of the involved knee was performed by two independent experienced operators. Synovial thickness in the suprapatellar bursa and the presence of joint effusion and Bakers cyst were assessed. An increase of the mean value of maximal knee flexion angle and a reduction of the mean values of ESR and VAS between T0, T9 and T17 were demonstrated. Ultrasonographic evaluation showed significant reduction of synovial thickness and joint effusion. No differences were detected for the presence of Bakers cyst. We may conclude that repeated intra-articular injections of MTX resulted in a decrease of local as well as systemic inflammatory signs. As far as we know, this is the first study that explores the effects of intra-articular MTX in RA and PsA both clinically and by ultrasonography.     

甲氨喋呤与甲氨喋呤联合羟氯喹治疗类风湿性关节炎的临床观察

20世纪 90年代以来 ,甲氨喋呤 (ＭＴＸ)对类风湿性关节炎 (ＲＡ)的疗效已受到国内外学者的广泛肯定[1 ] ,抗疟药治疗ＲＡ目前也逐渐受到重视 ,抗疟药不但与ＭＴＸ有协同作用 ,而且可以降低后者的肝毒性[2 ] ,ＭＴＸ加羟氯喹 (ＨＣＱ)已成为目前国内外治疗ＲＡ常用的联合治疗方案之一。本文应用随机对照临床试验方法 ,比较单用ＭＴＸ和ＭＴＸ +ＨＣＱ治疗ＲＡ的疗效及不良反应 ,以探讨ＲＡ的合理治疗。1　资料和方法1.1　一般资料　选择 19992 0 0 1年在我院住院的活动期ＲＡ患者 90例 ,分为两组 :ＭＴＸ组 60例 ,其中女性 49例 ,男性11例 ;…     

Lack of association between HLA-DR2 and clinical response to methotrexate in patients with rheumatoid arthritis

Recent studies have indicated an association between the HLA-DR2 phenotype and substantial response to methrotrexate in patients with rheumatoid arthritis (RA). To further resolve this issue, we analyzed this relationship. Our data, obtained from a multicenter, double-blind study of rigorously assessed patients with RA, demonstrated that neither HLA-DR2 nor any other HLA-DR specificity is significantly associated with a substantial clinical response to methotrexate in patients with RA.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

目的 探讨类风湿关节炎(RA)患者氨基咪唑氨甲酰转移酶(ATIC)基因347C/G(rs2372536)单核苷酸多态性(SNP)与甲氨蝶呤(MTX)疗效和不良反应的相关性.方法 收集RA患者359例,分为单用MTX组、MTX联用其他改善病情药(DMARDs)组、非MTX的DMARDs组,于治疗前和治疗后12、24周检查患者临床及实验室指标,评价疗效(采用ACR20)及不良反应.采用实时荧光定量聚合酶链反应(PCR)法检测RA患者及340名健康对照组的ATIC基因C347G多态性,比较2组间基因型分布及等位基因频率.结果 RA与健康对照组ATIC基因347C/G基因型分布频率差异无统计学意义(P>0.05).单用MTX治疗组的有效率为72%(77/107例),有效组ATIC 347CC,CG,GG基因型与无效组间差异无统计学意义(P>0.05),不良反应发生率为32.7%,且携带ATIC G等位基因型患者的不良反应发生率(22.4%)明显高于CC基因型组(10.3%)(OR=2.67,95%可信区间为1.27～5.59),差异有统计学意义(P<0.05).MTX联用其他DMARDs(128例)组及非MTX的DMARDs组(90例),ATIC基因多态性与其疗效及不良反应无关(P>0.05).结论 ATIC基因347C/G多态性在RA患者与健康对照组间差异无统计学意义;与MTX治疗RA的疗效无明显相关性,但ATIC G等位基因与MTX的不良反应密切相关.因此ATIC基因347C/G多态性可能作为患者使用MTX的出现不良反应的预测指标.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.     

氨基咪唑氨甲酰转移酶基因多态性在类风湿关节炎患者甲氨蝶呤治疗中的研究

Objective To investigate the relationship between the single nucleotide polymorphism of aminoimidazole carbexamide ribonucleotide transformylase gene and the efficacy and toxicity of methotrexate treatment in rheumatoid arthritis. Methods Total of 359 patients with RA were divided into mono-therapy with MTX group, combination therapy with other DMARDs group and other DMARDs combination with no MTX treatment group. The clinical and laboratory measurements were evaluated before therapy and 12, 24 weeks after therapy. Efficacy (evaluated by ACR20) and side effects of the drugs were also assessed. Real-time fluorescent quantitative PCR was conducted to test ATIC 347C/G mutation in RA patients and 340 healthy controls. Results There was no statistical significant difference in 347 CC, CG, GG between RA patients and healthy controls. In the MTX mono-therapy group (n=107), 72% (n=77) there was no statistical significant difference in 347CC, CG, GG between patients with good response and patients without efficacy. 32.7%(n=35) of these patients experienced adverse drug reactions. The ATIC G allele carriers (22.4%) experienced a greater frequency of side effects than the CC carriers (OR=2.672, 95%CI, 1.27～5.59, P<0.05). In MTX combined with other DMARDs group (n=128) and other DMARDs combination without MTX group (n=90), the polymorphism in the ATIC gene was not associated with good clinical response and adverse events (P>0.05). Conclusion There is no statistical significant difference between RA and healthy controls in the ATIC347 gene. Polymorphism in the ATIC gene is not associated with clinical response to MTX treatment, but the ATIC347 G allele is associated with MTX toxicity. It maybe used to predict the adverse drug reactions of patients who take MTX.