Cipriani Paola, Ruscitti Piero, Carubbi Francesco, Liakouli Vasiliki, Giacomelli Roberto
Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, School of Medicine, University of L'Aquila, L'Aquila, Italy.
Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, School of Medicine, University of L'Aquila, L'Aquila, Italy.
Clin Ther. 2014 Mar 1;36(3):427-35. doi: 10.1016/j.clinthera.2014.01.014. Epub 2014 Mar 5.
Methotrexate (MTX) is currently considered the drug of choice, among the disease-modifying antirheumatic drugs, for the treatment of rheumatoid arthritis (RA) because of its favorable risk/benefit ratio, good safety profile, and low costs. Despite MTX's widespread use and large experience accumulated over the many years since its introduction into clinical practice, specific guidelines have not been published.
We report here the available research regarding the optimal dosage and route of MTX administration.
MEDLINE and the Cochrane Library were systematically searched for articles published between 1990 and 2013, using terms related to RA and MTX. The search was conducted by using both MeSH terms and free text. The references of the retrieved studies were also screened manually for additional articles.
For the treatment of rheumatic diseases, the antimetabolite drug MTX can be administered weekly by different routes: oral, subcutaneous, or intramuscular. One of the goals of treatment is to minimize acute and chronic toxicity. A starting dose of 15 mg/week orally, escalating to 25 to 30 mg/week or the highest tolerable dose (with a subsequent switch to parenteral administration in cases of insufficient response), seems to be the optimal evidence-based strategy for MTX treatment of RA. Oral MTX is widely preferred because of its low costs and patient preferences; the bioavailability of parenteral MTX is higher, however. This is supported by data from observational studies, in which patients switching from parenteral to oral MTX at an equal dose had disease exacerbations. In several trials, the subcutaneous formulation of MTX was considered, by both physicians and patients, to be more advantageous in terms of discomfort and compliance. In addition, a significant proportion of patients reported that this formulation led to greater independence, with a resulting improvement in quality of life.
Although MTX treatment can be initiated by using the oral administration route, parenteral administration of MTX is indicated in those patients with poor compliance toward the oral form. The subcutaneous route seems to be more effective than the oral route for MTX administration based on the results of several studies, and this route may be preferred because of better usability and absence of pain at the infusion site.
甲氨蝶呤（MTX）由于其良好的风险/效益比、良好的安全性和低成本，目前被认为是改善病情抗风湿药中治疗类风湿关节炎（RA）的首选药物。尽管MTX自引入临床实践以来已广泛使用并积累了多年的丰富经验，但尚未发布具体指南。
我们在此报告有关MTX给药的最佳剂量和途径的现有研究。
系统检索MEDLINE和Cochrane图书馆中1990年至2013年发表的文章，使用与RA和MTX相关的术语。检索通过使用医学主题词（MeSH）和自由文本进行。还手动筛选了检索到的研究的参考文献以查找其他文章。
对于风湿性疾病的治疗，抗代谢药物MTX可以通过不同途径每周给药：口服、皮下或肌肉注射。治疗的目标之一是将急性和慢性毒性降至最低。口服起始剂量为15mg/周，逐步增加至25至30mg/周或最高耐受剂量（如果反应不足则随后改为胃肠外给药），似乎是MTX治疗RA的最佳循证策略。口服MTX因其低成本和患者偏好而被广泛青睐；然而，胃肠外MTX的生物利用度更高。观察性研究的数据支持了这一点，在这些研究中，同等剂量从胃肠外MTX改为口服MTX的患者病情加重。在几项试验中，医生和患者都认为MTX的皮下制剂在不适和依从性方面更具优势。此外，相当一部分患者报告说这种制剂带来了更大的独立性，从而改善了生活质量。
虽然MTX治疗可以通过口服途径开始，但对于口服剂型依从性差的患者，建议胃肠外给药MTX。基于多项研究的结果，皮下途径似乎比口服途径在MTX给药方面更有效，并且由于更好的可用性和输液部位无疼痛，该途径可能更受青睐。
