Barnett M L, Kremer J M, St Clair E W, Clegg D O, Furst D, Weisman M, Fletcher M J, Chasan-Taber S, Finger E, Morales A, Le C H, Trentham D E
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Arthritis Rheum. 1998 Feb;41(2):290-7. doi: 10.1002/1529-0131(199802)41:2<290::AID-ART13>3.0.CO;2-R.
Oral administration of cartilage-derived type II collagen (CII) has been shown to ameliorate arthritis in animal models of joint inflammation, and preliminary studies have suggested that this novel therapy is clinically beneficial and safe in patients with rheumatoid arthritis (RA). The present study was undertaken to test the safety and efficacy of 4 different dosages of orally administered CII in patients with RA.
Two hundred seventy-four patients with active RA were enrolled at 6 different sites and randomized to receive placebo or 1 of 4 dosages (20, 100, 500, or 2,500 microg/day) of oral CII for 24 weeks. Efficacy parameters were assessed monthly. Cumulative response rates (percentage of patients meeting the criteria for response at any time during the study) were analyzed utilizing 3 sets of composite criteria: the Paulus criteria, the American College of Rheumatology criteria for improvement in RA, and a requirement for > or = 30% reduction in both swollen and tender joint counts.
Eighty-three percent of patients completed 24 weeks of treatment. Numeric trends in favor of the 20 microg/day treatment group were seen with all 3 cumulative composite measures. However, a statistically significant increase (P = 0.035) in response rate for the 20 microg/day group versus placebo was detected using only the Paulus criteria. The presence of serum antibodies to CII at baseline was significantly associated with an increased likelihood of responding to treatment. No treatment-related adverse events were detected. The efficacy seen with the lowest dosage is consistent with the findings of animal studies and with known mechanisms of oral tolerance in which lower doses of orally administered autoantigens preferentially induce disease-suppressing regulatory cells.
Positive effects were observed with CII at the lowest dosage tested, and the presence of serum antibodies to CII at baseline may predict response to therapy. No side effects were associated with this novel therapeutic agent. Further controlled studies are required to assess the efficacy of this treatment approach.
口服软骨来源的II型胶原蛋白（CII）已被证明可改善关节炎症动物模型中的关节炎，初步研究表明，这种新型疗法对类风湿关节炎（RA）患者具有临床益处且安全。本研究旨在测试4种不同剂量口服CII对RA患者的安全性和有效性。
274例活动期RA患者在6个不同地点入组，随机接受安慰剂或4种剂量（20、100、500或2500μg/天）之一的口服CII，为期24周。每月评估疗效参数。使用3套综合标准分析累积缓解率（研究期间任何时间达到缓解标准的患者百分比）：保卢斯标准、美国风湿病学会RA改善标准，以及肿胀和压痛关节计数均减少≥30%的要求。
83%的患者完成了24周的治疗。在所有3种累积综合测量中均观察到有利于20μg/天治疗组的数值趋势。然而，仅使用保卢斯标准时，检测到20μg/天组与安慰剂组相比缓解率有统计学显著增加（P = 0.035）。基线时存在抗CII血清抗体与治疗反应增加的可能性显著相关。未检测到与治疗相关的不良事件。最低剂量时观察到的疗效与动物研究结果以及口服耐受的已知机制一致，即较低剂量的口服自身抗原优先诱导抑制疾病的调节细胞。
在测试的最低剂量下观察到CII有积极作用，基线时存在抗CII血清抗体可能预测治疗反应。这种新型治疗药物未发现副作用。需要进一步的对照研究来评估这种治疗方法的疗效。
