Hayes Michael J, Stein Adam C, Sakuraba Atsushi
J Gastroenterol Hepatol. 2014 Jun;29(6):1177-85. doi: 10.1111/jgh.12517.
The association of concomitant immunosuppressant use with infliximab (IFX) and therapeutic outcomes in correlation with pharmacokinetic properties in ulcerative colitis (UC) remains unclear.
To assess the effect of concomitant immunosuppressant use on the duration of IFX therapy, and the pharmacokinetic properties of IFX in patients with UC.
A retrospective analysis of UC patients treated with IFX. Duration of efficacious IFX therapy, and serum IFX and antibody-to-IFX (ATI) levels were compared between those receiving IFX as monotherapy and in combination with an immunosuppressant.
Among the 85 UC patients who received IFX, 46 (54.1%) received concomitant immunosuppressants, and 38 (45.9%) received IFX monotherapy. Concomitant immunosuppressant use was associated with increased duration of IFX therapy as 90% of patients receiving immunosuppressants remained on therapy at 1 year versus 61% of patients on monotherapy (Log-rank, P = 0.016). Concomitant immunosuppressant use, as compared with monotherapy, was associated with greater IFX levels (20.4 mg/L vs 10.5 mg/L, P = 0.025) and less frequent ATI formation (4.5% vs 33.3%, P = 0.031). Patients receiving greater than 2.0 mg/kg of azathioprine had greater IFX lev l than those receiving less than 2.0 mg/kg (26.0 vs 10.6 mcg/mL, P = 0.03) and those receiving IFX monotherapy (26.0 vs 11.2 mcg/mL, P = 0.03). The duration of IFX therapy among patients receiving less than 2.0 mg/kg azathioprine was indistinguishable from patients on IFX monotherapy (Log-rank, P = 0.95).
Concomitant immunosuppressant therapy with IFX improves outcomes in UC as shown by increased duration of therapy, decreased immunogenicity against IFX, and increased blood levels of IFX. Our data suggest that this benefit may be dependent on the dose of concomitant immunosuppression.
在溃疡性结肠炎（UC）中，同时使用免疫抑制剂与英夫利昔单抗（IFX）的关联以及与药代动力学特性相关的治疗结果仍不清楚。
评估同时使用免疫抑制剂对IFX治疗持续时间的影响，以及UC患者中IFX的药代动力学特性。
对接受IFX治疗的UC患者进行回顾性分析。比较接受IFX单药治疗和联合免疫抑制剂治疗的患者中有效IFX治疗的持续时间、血清IFX水平和抗IFX抗体（ATI）水平。
在85例接受IFX治疗的UC患者中，46例（54.1%）同时接受免疫抑制剂治疗，38例（45.9%）接受IFX单药治疗。同时使用免疫抑制剂与IFX治疗持续时间延长相关，因为90%接受免疫抑制剂治疗的患者在1年时仍在接受治疗，而单药治疗患者为61%（对数秩检验，P = 0.016）。与单药治疗相比，同时使用免疫抑制剂与更高的IFX水平（20.4 mg/L对10.5 mg/L，P = 0.025）和更低的ATI形成频率（4.5%对33.3%，P = 0.031）相关。接受大于2.0 mg/kg硫唑嘌呤的患者比接受小于2.0 mg/kg硫唑嘌呤的患者具有更高的IFX水平（26.0对10.6 mcg/mL，P = 0.03），也高于接受IFX单药治疗的患者（26.0对11.2 mcg/mL，P = 0.03）。接受小于2.0 mg/kg硫唑嘌呤的患者中IFX治疗的持续时间与接受IFX单药治疗的患者无差异（对数秩检验，P = 0.95）。
如治疗持续时间增加、对IFX的免疫原性降低和IFX血药水平升高所示，IFX联合免疫抑制剂治疗可改善UC的治疗结果。我们的数据表明，这种益处可能取决于联合免疫抑制的剂量。
