THE COMPARATIVE EFFICACY AND TOXICITY OF 2ND-LINE DRUGS IN RHEUMATOID-ARTHRITIS - RESULTS OF 2 METAANALYSES
THE COMPARATIVE EFFICACY AND TOXICITY OF 2ND-LINE DRUGS IN RHEUMATOID-ARTHRITIS - RESULTS OF 2 METAANALYSES
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DOI：
10.1002/art.1780331001
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发表时间：
1990-10-01
影响因子：
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通讯作者：
MEENAN, RF
中科院分区：
文献类型：
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作者：
FELSON, DT;ANDERSON, JJ;MEENAN, RF
我们对安慰剂对照试验和对比临床试验进行了两项荟萃分析，以检验甲氨蝶呤(MTX)、可注射金、D-青霉胺(DP)、柳氮磺吡啶(SSZ)、金诺芬(Auranofin)和抗疟疾药物的相对疗效和毒性，这些药物最常用于治疗类风湿性关节炎(RA)。在疗效研究中，我们应用了一套纳入标准，并专注于提供关节压痛计数、血沉或握力信息的试验。我们发现了66项临床试验，包含117个感兴趣的治疗组，对于每种药物，我们将这些治疗组结合在一起。对于每种结果，结果显示AUR往往比其他二线药物更弱。将3种结果指标的结果综合成一个综合结果指标，AUR显著弱于甲氨蝶呤(P=0.006)、可注射金(P<；0.0001)、DP(P<；0.0001)和SSZ(P=0.009)，略弱于抗疟药(P=0.11)。我们还发现抗疟疾药物之间的异质性，氯喹治疗的患者比羟基氯喹治疗的患者效果更好。我们发现甲氨蝶呤、可注射金、DP和SSZ之间的疗效差别不大。一项功效分析表明，一项试验应该至少包含每个治疗组170名患者，以成功区分更有效和更低效(例如AUR)的二线药物。我们回顾的已报道的药物间比较试验中，没有一个是这么大的。对于毒性研究，我们的纳入标准包括RA试验，这些试验报告了因药物毒性而停止治疗的患者的比例和退出的总比例。我们发现了71项临床试验，包含129个治疗组。计算每种药物的平均辍学比例和因药物毒性而辍学的平均比例。总体而言，在这些试验中，30.2%的患者退出了；其中50%的患者退出是因为药物毒性。可注射GOLD的毒副作用(P<；0.05)和总脱落率(P<；0.01)高于任何其他药物；接受GOLD治疗的患者中有30%的患者因副作用而退出，而所有试验患者的这一比例为15%。抗疟疾药物和AUR的毒性比率相对较低；MTX的比率由于试验之间的差异而不准确。因此，在常用的二线药物中，AUR是最弱的，注射金是毒性最大的。未来引入的药物将与这些药物进行比较。如果没有找到治愈药物，可能需要进行大型多中心试验或从多个药物试验中综合数据，以确定有希望的新治疗方案。
We performed 2 metaanalyses of placebo-controlled and comparative clinical trials to examine the relative efficacy and toxicity of methotrexate (MTX), injectable gold, D-penicillamine (DP), sulfasalazine (SSZ), auranofin (AUR), and antimalarial drugs, the second-line drugs most commonly used to treat rheumatoid arthritis (RA). For the efficacy study, we applied a set of inclusion criteria and focused on trials which provided information on tender joint count, erythrocyte sedimentation rate, or grip strength. We found 66 clinical trials that contained 117 treatment groups of interest, and for each drug, we combined the treatment groups. For each outcome, results showed that AUR tended to be weaker than other second-line drugs. The results of the 3 outcome measures were synthesized into a composite measure of outcomes, and AUR was significantly weaker than MTX (P = 0.006), injectable gold (P < 0.0001), DP (P < 0.0001), and SSZ (P = 0.009) and was slightly, but not significantly, weaker than antimalarial agents (P = 0.11). We also found heterogeneity among antimalarial agents, in that patients treated with chloroquine did better than those treated with hydroxychloroquine. We found little difference in efficacy between MTX, injectable gold, DP, and SSZ. A power analysis showed that a trial should contain at least 170 patients per treatment group to successfully differentiate between more effective and less effective (e.g., AUR) second-line drugs. None of the reported interdrug comparative trials we reviewed were this large. For the toxicity study, our inclusion criteria captured RA trials which reported the proportion of patients who discontinued therapy because of drug toxicity and the total proportion who dropped out. We found 71 clinical trials that contained 129 treatment groups. The average proportion who dropped out and the average proportion who dropped out because of drug toxicity were computed for each drug. Overall, 30.2% of the patients in these trials dropped out; 50% of them did so because of drug toxicity. Injectable gold had higher toxicity rates (P < 0.05) and higher total dropout rates (P < 0.01) than any other drug; 30% of gold-treated patients dropped out because of side effects versus 15% of all trial patients. Antimalarial drugs and AUR had relatively low rates of toxicity; the rate for MTX was imprecise because of discrepancies between trials. Thus, of the commonly used second-line drugs, AUR is the weakest, and injectable gold is the most toxic. Agents introduced in the future will be compared with these drugs. If a curative drug is not found, large multicenter trials or data synthesis from multiple drug trials may be necessary to identify new treatment regimens that have promise.