Dénarié Delphine, Rinaudo-Gaujous Mélanie, Thomas Thierry, Paul Stéphane, Marotte Hubert
Department of Rheumatology, CHU Saint-Etienne, Saint-Etienne, France.
Immunology and Immunomonitoring Department, CHU de Saint-Etienne, Saint-Etienne, France.
Mediators Inflamm. 2017;2017:3708250. doi: 10.1155/2017/3708250. Epub 2017 Mar 2.
To evaluate methotrexate effect on tumor necrosis factor (TNF) alpha bioactivity during infliximab (IFX) therapy in rheumatoid arthritis (RA) patients and to correlate TNF bioactivity with antibody towards IFX (ATI) development and RA clinical response. Thirty-nine active women RA patients despite conventional synthetic disease modifying antirheumatic drugs (csDMARDs) requiring IFX therapy were enrolled, and clinical data and blood samples were recorded at baseline (W0) and at 6 weeks (W6), W22, and W54 of IFX treatment. TNF bioactivity as well as IFX trough and ATI concentrations were assessed on blood samples. TNF bioactivity decreased from W0 to W54 with a large range from W22 at the time of ATI detection. From W22, TNF bioactivity was lower in presence of methotrexate as csDMARD compared to other csDMARDs. IFX trough concentration increased from W0 to W54 with a large range from W22, similarly to TNF bioactivity. Methotrexate therapy prevented ATI presence at W22 and reduced TNF bioactivity compared to other csDMARDs ( = 0.002). This suggests that methotrexate plays a key role in TNF bioactivity and against ATI development.
评估甲氨蝶呤对类风湿关节炎（RA）患者英夫利昔单抗（IFX）治疗期间肿瘤坏死因子（TNF）α生物活性的影响，并将TNF生物活性与抗IFX抗体（ATI）的产生及RA临床反应相关联。纳入39名尽管使用传统合成改善病情抗风湿药（csDMARDs）仍需IFX治疗的活动性女性RA患者，并在IFX治疗的基线期（W0）、6周（W6）、22周（W22）和54周（W54）记录临床数据和采集血样。对血样评估TNF生物活性以及IFX谷浓度和ATI浓度。TNF生物活性从W0至W54降低，在检测到ATI时的W22有较大范围变化。从W22起，与其他csDMARDs相比，联合使用甲氨蝶呤作为csDMARD时TNF生物活性更低。IFX谷浓度从W0至W54升高，在W22有较大范围变化，与TNF生物活性类似。与其他csDMARDs相比，甲氨蝶呤治疗可防止在W22时出现ATI并降低TNF生物活性（ = 0.002）。这表明甲氨蝶呤在TNF生物活性及对抗ATI产生方面起关键作用。
