Fleischmann R M, Cohen S B, Moreland L W, Schiff M, Mease P J, Smith D B, Keenan G, Kremer J M
Radiant Research--Dallas, University of Texas, Southwestern Medical Center at Dallas, Dallas, TX 75235, USA.
Curr Med Res Opin. 2005 Aug;21(8):1181-90. doi: 10.1185/030079905X53261.
Infliximab plus methotrexate (MTX) is approved for the treatment of rheumatoid arthritis (RA). Based on the benefit/risk profile of this combination therapy, lower doses of MTX would be preferable when infliximab efficacy can be maintained. We evaluated the ability of patients receiving infliximab plus MTX to achieve and maintain a clinical response while the dose of MTX was tapered.
Infliximab infusions were administered at a minimum dosage of 3 mg/kg at 8-week intervals (following three loading doses at weeks 0, 2, and 6) to patients who had an inadequate response to MTX. MTX tapering was initiated at week 22 or later when at least a 40% improvement in the combined tender and swollen joint count was achieved; dosages were reduced by 5 mg every 8 weeks to a protocol-specified minimum dosage of 5 mg per week. If the required dosage of MTX after a flare was greater than the baseline dosage, the patient was considered a treatment failure.
Of the 210 patients enrolled, 159 (76%) achieved a 40% or better improvement in the combined tender and swollen joint count and had their MTX doses tapered. In these 159 responders, the median (mean) dose of MTX was reduced from 15 (16.5) mg per week at baseline to 5 (7.1) mg per week at week 54. From the time of initial response, 79% of these patients had a zero- or a one-vial increase in infliximab, corresponding to an approximate dose increase of 1 mg/kg, through week 54.
Approximately 75% of the patients participating in this trial achieved at least a 40% reduction in the combined swollen and tender joint count (correlating with an American College of Rheumatology 20% [ACR20] response in 83% of patients) while reducing the mean MTX dose by 57%.
英夫利昔单抗联合甲氨蝶呤（MTX）已被批准用于治疗类风湿关节炎（RA）。基于这种联合疗法的效益/风险状况，在能够维持英夫利昔单抗疗效的情况下，较低剂量的MTX更为可取。我们评估了接受英夫利昔单抗联合MTX治疗的患者在MTX剂量逐渐减少时实现并维持临床反应的能力。
对于对MTX反应不足的患者，每8周给予一次英夫利昔单抗输注，最低剂量为3mg/kg（在第0、2和6周给予三次负荷剂量后）。当联合压痛和肿胀关节计数至少改善40%时，在第22周或更晚开始逐渐减少MTX剂量；每8周将剂量减少5mg，直至方案规定的最低剂量每周5mg。如果病情复发后所需的MTX剂量大于基线剂量，则该患者被视为治疗失败。
在入组的210例患者中，159例（76%）的联合压痛和肿胀关节计数改善了40%或更多，并逐渐减少了MTX剂量。在这159例有反应的患者中，MTX的中位（平均）剂量从基线时的每周15（16.5）mg降至第54周时的每周5（7.1）mg。从初始反应时起，至第54周，这些患者中有79%的英夫利昔单抗增加量为零瓶或一瓶，相当于剂量增加约1mg/kg。
参与该试验的患者中约75%的联合肿胀和压痛关节计数至少减少了40%（83%的患者与美国风湿病学会20%[ACR20]反应相关），同时平均MTX剂量降低了57%。
