Ravelli A, Viola S, Migliavacca D, Ruperto N, Pistorio A, Martini A
Dipartimento di Scienze Pediatriche dell'Università, Laboratorio di Informatica Medica, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico, San Matteo, Pavia, Italy.
J Pediatr. 1999 Sep;135(3):316-20. doi: 10.1016/s0022-3476(99)70127-7.
To determine whether demographic, clinical, and laboratory variables measurable at baseline predict the clinical efficacy or major toxic effects of methotrexate (MTX) therapy in children with chronic arthritis.
Patient eligibility criteria: (1) monitored in our unit between 1986 and 1996 with a diagnosis of chronic arthritis and (2) treatment with MTX as the sole second-line agent and for at least 6 months. Outcomes investigated: (1) short-term (6-month) clinical response, (2) complete disease control, (3) disease relapse after MTX discontinuation after complete disease control, (4) aminotransferase elevation, (5) gastrointestinal toxicity. Independent variables that showed significant results with univariate tests or were clinically relevant for each outcome underwent multiple logistic or Poisson regression analyses.
Eighty patients were available for analysis. The disease onset subtype was systemic in 37 patients, polyarticular in 20 patients, and oligoarticular in 23 patients (all with polyarticular course: extended oligoarticular subtype). The extended oligoarticular subtype was the best predictor for both the short-term clinical response (odds ratio 6.80, P =.02) and, together with a better functional ability, the complete disease control (rate ratio 3.85, P =.03 and rate ratio 3.29, P =.006, respectively). Patients with this subtype of chronic arthritis tended to have earlier, and more frequently, a disease relapse after MTX discontinuation. Thrombocytosis was the only significant risk factor for liver biochemical abnormalities (rate ratio 2.94, P =.008), whereas no variable yielded significant results for gastrointestinal toxicity.
Patients with extended oligoarticular chronic arthritis were more likely to benefit from MTX therapy and to have a relapse after treatment discontinuation, suggesting that MTX is distinctly more effective in this subset of chronic arthritis.
确定在基线时可测量的人口统计学、临床和实验室变量是否能预测甲氨蝶呤(MTX)治疗慢性关节炎儿童的临床疗效或主要毒性作用。
患者入选标准:(1)1986年至1996年在我们单位接受监测,诊断为慢性关节炎;(2)以MTX作为唯一的二线药物治疗至少6个月。研究的结局指标:(1)短期(6个月)临床反应;(2)疾病完全控制;(3)疾病完全控制后停用MTX后的疾病复发;(4)转氨酶升高;(5)胃肠道毒性。在单变量检验中显示出显著结果或与每个结局指标临床相关的自变量进行多因素逻辑回归或泊松回归分析。
80例患者可供分析。疾病起病亚型为全身型37例,多关节型20例,少关节型23例(均为多关节病程:扩展性少关节亚型)。扩展性少关节亚型是短期临床反应(优势比6.80,P = 0.02)以及与更好的功能能力一起对疾病完全控制的最佳预测指标(发生率比分别为3.85,P = 0.03和3.29,P = 0.006)。这种慢性关节炎亚型的患者在停用MTX后往往更早且更频繁地出现疾病复发。血小板增多症是肝生化异常的唯一显著危险因素(发生率比2.94,P = 0.008),而没有变量对胃肠道毒性产生显著结果。
扩展性少关节型慢性关节炎患者更有可能从MTX治疗中获益,且在停药后会复发,这表明MTX在这一慢性关节炎亚组中明显更有效。