早期类风湿关节炎联合治疗与单药治疗的比较：一项随机试验。芬兰类风湿关节炎联合治疗试验组

Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group.

作者信息

Möttönen T, Hannonen P, Leirisalo-Repo M, Nissilä M, Kautiainen H, Korpela M, Laasonen L, Julkunen H, Luukkainen R, Vuori K, Paimela L, Blåfield H, Hakala M, Ilva K, Yli-Kerttula U, Puolakka K, Järvinen P, Hakola M, Piirainen H, Ahonen J, Pälvimäki I, Forsberg S, Koota K, Friman C

机构信息

Division of Rheumatology, Turku University Central Hospital, Finland.

出版信息

Lancet. 1999 May 8;353(9164):1568-73. doi: 10.1016/s0140-6736(98)08513-4.

DOI:10.1016/s0140-6736(98)08513-4

PMID:10334255

Abstract

BACKGROUND

The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis.

METHODS

199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat.

FINDINGS

87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0.011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0.003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0.028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0.058) had clinically improved. The frequencies of adverse events were similar in both treatment groups.

INTERPRETATION

Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.

摘要

背景

类风湿关节炎的治疗应以临床缓解为目标。这项为期2年随访的多中心随机试验旨在探寻联合治疗（柳氮磺胺吡啶、甲氨蝶呤、羟氯喹和泼尼松龙）与单一改善病情抗风湿药物治疗（无论是否联用泼尼松龙）相比，在早期类风湿关节炎治疗中的疗效和耐受性证据。

方法

199例患者被随机分配至两个治疗组。195例开始治疗（97例接受联合治疗，98例接受单一药物治疗）。所有患者单一药物治疗均起始于柳氮磺胺吡啶；51例患者随后换用甲氨蝶呤。63例患者需要口服泼尼松龙。主要结局指标为诱导缓解。分析采用意向性分析。

结果

联合治疗组87例患者和单一治疗组91例患者完成试验。1年后，联合治疗的97例患者中有24例达到缓解，单一药物治疗的98例患者中有11例达到缓解（p = 0.011）。2年时的缓解频率分别为97例中的36例和98例中的18例（p = 0.003）。联合治疗的68例（75%）患者和单一药物治疗的56例（60%）患者在1年后实现临床改善（美国风湿病学会50%临床反应标准）（p = 0.028），而在2年随访时分别为69例和57例（71%对58%，p = 0.058）实现临床改善。两个治疗组不良事件发生频率相似。