de Groot K, Reinhold-Keller E, Tatsis E, Paulsen J, Heller M, Nölle B, Gross W L
Medizinische Universität Lübeck, Abteilung Klinische Rheumatologie, Bad Bramstedt, Germany.
Arthritis Rheum. 1996 Dec;39(12):2052-61. doi: 10.1002/art.1780391215.
To compare the efficacy of low-dose intravenous (IV) methotrexate (MTX; 0.3 mg/kg once weekly), both with and without concomitant prednisone, versus daily oral trimethoprim/sulfamethoxazole (T/S; 160 mg of trimethoprim + 800 mg of sulfamethoxazole twice a day), with and without prednisone, in maintaining remission in patients with generalized Wegener's granulomatosis (WG).
In this study, 65 patients with generalized WG whose disease had entered remission with cyclophosphamide (CYC) and prednisone therapy were started on one of the following remission-maintenance regimens: MTX alone (group A; n = 22), T/S alone (group B; n = 24), MTX plus concomitant prednisone (group C; n = 11), and T/S plus concomitant prednisone (group D; n = 8). Clinical, radiographic, and seroimmunologic data were evaluated to assess the efficacy of the 4 regimens and to seek possible predictive factors concerning outcome in each group.
Partial or complete remission was maintained in 86% of the patients in group A, but in only 58% of those in group B (P < 0.05). In group C, 91% of patients remained in remission, which is in sharp contrast to group D, in which all patients experienced a relapse after a median of 14.5 months (P < 0.005). Side effects occurred twice as often with MTX (n = 12) as with T/S (n = 6) treatment and could usually be resolved by supplemental folinic acid. Two patients taking MTX and 3 patients taking T/S were withdrawn from the study medication because of side effects. In none of the patients were the adverse effects life threatening. No statistically significant factors predictive of poor outcome emerged in any group.
Low-dose MTX was found to be superior to T/S for the safe and effective maintenance of remission in patients with generalized WG. The use of concomitant prednisone was not associated with a worse outcome with MTX treatment. Since T/S, especially with concomitant prednisone, seemed to increase the chance of relapse, neither T/S alone nor T/S plus prednisone can be recommended for the maintenance of remission in patients with generalized WG.
比较低剂量静脉注射甲氨蝶呤(MTX;0.3mg/kg,每周一次)单独使用及联合泼尼松与每日口服甲氧苄啶/磺胺甲恶唑(T/S;160mg甲氧苄啶+800mg磺胺甲恶唑,每日两次)单独使用及联合泼尼松,在维持全身性韦格纳肉芽肿(WG)患者缓解方面的疗效。
在本研究中,65例全身性WG患者在接受环磷酰胺(CYC)和泼尼松治疗后病情进入缓解期,开始采用以下缓解期维持方案之一进行治疗:单独使用MTX(A组;n=22)、单独使用T/S(B组;n=24)、MTX联合泼尼松(C组;n=11)、T/S联合泼尼松(D组;n=8)。对临床、影像学和血清免疫学数据进行评估,以评估这4种方案的疗效,并寻找每组中可能影响预后的预测因素。
A组86%的患者维持部分或完全缓解,而B组仅58%的患者维持缓解(P<0.05)。C组91%的患者维持缓解,这与D组形成鲜明对比,D组所有患者在中位时间14.5个月后均复发(P<0.005)。MTX治疗的副作用发生率(n=12)是T/S治疗(n=6)的两倍,通常补充亚叶酸后可缓解。2例服用MTX的患者和3例服用T/S的患者因副作用退出研究药物治疗。所有患者的不良反应均未危及生命。任何一组均未出现预测预后不良的统计学显著因素。
发现低剂量MTX在安全有效地维持全身性WG患者缓解方面优于T/S。联合使用泼尼松与MTX治疗的不良结局无关。由于T/S,尤其是联合泼尼松,似乎增加了复发几率,因此不推荐单独使用T/S或T/S联合泼尼松来维持全身性WG患者的缓解。