Scott D L, Berry H, Capell H, Coppock J, Daymond T, Doyle D V, Fernandes L, Hazleman B, Hunter J, Huskisson E C, Jawad A, Jubb R, Kennedy T, McGill P, Nichol F, Palit J, Webley M, Woolf A, Wotjulewski J
Department of Rheumatology, King's College Hospital (Dulwich), East Dulwich Grove, London, UK.
Rheumatology (Oxford). 2000 Oct;39(10):1095-101. doi: 10.1093/rheumatology/39.10.1095.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat osteoarthritis (OA), though their long-term efficacy is uncertain. We report a comparison of the symptomatic responses to therapy with tiaprofenic acid, indomethacin and placebo over 5 yr.
A parallel-group, randomized, single-blind trial of patients with knee OA recruited 812 patients from 20 centres; 307 patients received tiaprofenic acid (300 mg b.d.), 202 indomethacin (25 mg t.d.s.) and 303 matching placebo for up to 5 yr. At the end of the parallel-group study, patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo, both given for 2 weeks. Assessments were at baseline, 4 weeks, then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study. They comprised pain scores, duration of morning stiffness, patients' global assessments, paracetamol consumption, adverse reactions, withdrawals and functional outcomes.
There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase. Thereafter there were no advantages favouring active therapy. In the cross-over phase, pain scores were significantly lower in patients receiving tiaprofenic acid than placebo. Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa. Adverse events were reported by 61% of patients receiving tiaprofenic acid, 63% on indomethacin and 51% on placebo. Potentially severe side-effects were rare; for example, there were only three cases of gastrointestinal bleeding on NSAIDs. The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study; at 48 weeks 53% of the patients remained on tiaprofenic acid, 50% on indomethacin and 54% on placebo.
NSAIDs significantly reduce overall pain over 4 weeks. This short-term responsiveness is retained, and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo. Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy.
非甾体抗炎药（NSAIDs）被广泛用于治疗骨关节炎（OA），但其长期疗效尚不确定。我们报告了一项关于替诺昔康、吲哚美辛与安慰剂治疗5年的症状反应比较。
一项平行组、随机、单盲试验，从20个中心招募了812例膝骨关节炎患者；307例患者接受替诺昔康（300mg，每日两次），202例接受吲哚美辛（25mg，每日三次），303例接受匹配的安慰剂，治疗长达5年。在平行组研究结束时，接受替诺昔康或安慰剂的患者进入一项为期4周的替诺昔康或安慰剂双盲交叉研究，两者均给药2周。评估在基线、4周时进行，然后在平行组研究中每6个月进行一次，长达5年，在交叉研究中每2周进行一次。评估内容包括疼痛评分、晨僵持续时间、患者总体评估、对乙酰氨基酚消耗量、不良反应、退出情况和功能结局。
在平行组阶段，与安慰剂相比，接受NSAIDs治疗的患者在4周时总体疼痛评分显著下降。此后，积极治疗并无优势。在交叉阶段，接受替诺昔康治疗的患者疼痛评分显著低于安慰剂组。长期接受替诺昔康治疗的患者在接受安慰剂治疗时疼痛评分显著升高，反之亦然。接受替诺昔康治疗的患者中有61%报告了不良事件，接受吲哚美辛治疗的为63%，接受安慰剂治疗的为51%。潜在的严重副作用很少见；例如，使用NSAIDs的患者中只有3例发生胃肠道出血。在平行组研究中，服用NSAIDs和安慰剂的患者退出模式相似；在48周时，53%的患者仍在服用替诺昔康，50%的患者仍在服用吲哚美辛，54%的患者仍在服用安慰剂。
NSAIDs在4周内可显著减轻总体疼痛。这种短期反应性得以保留，即使在使用替诺昔康治疗数年之后，改为安慰剂治疗2周时疼痛评分仍会升高。我们的结果并未显示在OA中使用NSAIDs有长期益处，并且大多数患者尽管接受了治疗仍持续存在疼痛和残疾。
