Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis
Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis
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DOI：
10.1136/ard.58.2.79
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发表时间：
1999-02-01
影响因子：
27.4
通讯作者：
van de Putte, LBA
中科院分区：
文献类型：
--
作者：
Haagsma, CJ;Blom, HJ;van de Putte, LBA
目的：研究柳氮磺胺吡啶（SSZ）、氨甲喋呤（MTX）及二者联合应用（COMBI）对早期类风湿关节炎（RA）患者血浆同型半胱氨酸（Hcy）的影响，并探讨其与临床疗效的关系。（2-3 g/天），MTX（7.5-15 mg/周）和COMBI（相同剂量范围），并在52周期间进行双盲评估。测定血浆同型半胱氨酸、血清叶酸浓度和维生素B12。的酶亚甲基四氢叶酸还原酶（MTHFR）基因的C677 T突变的影响进行了analysed.Results-A轻微的趋势，增加疗效和轻微的胃肠道毒性的发生率增加，目前在COMBI组，SSZ和MTX之间的临床上没有差异。SSZ组血浆同型半胱氨酸仅出现轻微和暂时性升高，而MTX组持续升高，COMBI组升高幅度更大。MTHFR基因突变纯合子患者的基线同型半胱氨酸水平显著高于无突变患者，MTHFR基因杂合子患者在第52周时血浆同型半胱氨酸水平显著高于无突变患者。临床疗效变量与同型半胱氨酸之间无相关性。胃肠道毒性的患者有一个显着更大的增加在homocystein.Conclusion-A血浆同型半胱氨酸浓度的持续增加，观察单独与MTX治疗的患者，更显着的SSZ相结合，与SSZ单独。血浆同型半胱氨酸的增加与MTHFR中的C677 T突变有关。同型半胱氨酸浓度的变化与胃肠道毒性有关，与临床疗效无关。
Objective-To study the influence of sulphasalazine (SSZ), methotrexate (MTX), and the combination (COMBI) of both on plasma homocysteine and to study the relation between plasma homocysteine and their clinical effects.Methods-105 patients with early rheumatoid arthritis (RA) were randomised between SSZ (2-3 g/day), MTX (7.5-15 mg/week), and the COMBI (same dose range) and evaluated double blindly during 52 weeks. Plasma homocysteine, serum folate concentrations, and vitamin B12 were measured. The influence of the C677T mutation of the enzyme methylenetetrahydrofolatereductase (MTHFR) gene was analysed.Results-A slight trend towards increased efficacy and an increased occurrence of minor gastrointestinal toxicity was present in the COMBI group, no differences existed clinically between SSZ and MTX. Only a slight and temporary increase in plasma homocysteine was found in the SSZ group, in contrast with the persistent rise in the MTX group and the even greater increase in the COMBI patients. Patients homozygous for the mutation in the MTHFR gene had significantly higher baseline homocysteine, heterozygous MTHFR genotype induced a significantly higher plasma homocysteine at week 52 compared with no mutation. No correlation was found between clinical efficacy variables and homocysteine. Patients with gastrointestinal toxicity had a significantly greater increase in homocysteine.Conclusion-A persistent increase in plasma homocysteine concentrations was observed in patients treated with MTX alone and more pronounced in combination with SSZ, in contrast with SSZ alone. An increase in plasma homocysteine is related to the C677T mutation in MTHFR. A relation in the change in homocysteine concentrations with (gastrointestinal) toxicity was found, no relation with clinical efficacy existed.