Huizinga T W, Dijkmans B A, van der Velde E A, van de Pouw Kraan T C, Verweij C L, Breedveld F C
Department of Rheumatology, University Hospital Leiden, The Netherlands.
Ann Rheum Dis. 1996 Nov;55(11):833-6. doi: 10.1136/ard.55.11.833.
Dysregulation of tumour necrosis factor alpha (TNF alpha) production is thought to be important in rheumatoid arthritis. Since pentoxifylline and thalidomide inhibit endotoxin induced TNF production in vitro, these drugs were tested in an open study in rheumatoid arthritis patients to assess toxicity, the effect on TNF production, and the antiarthritic effects.
12 patients with active rheumatoid arthritis were treated with 1200 mg pentoxifylline and 100 mg thalidomide a day during 12 weeks. In addition, TNF production was assessed by ex vivo whole blood cultures stimulated with endotoxin.
Adverse events such as xerostomia, drowsiness, and constipation occurred in almost all patients, which led to discontinuation in three. The drugs halved the TNF production capacity during treatment (ANOVA, P < 0.03) whereas production capacity of interleukin (IL) 6, IL-10, and IL-12 was not affected. Of the nine patients who completed the study, five fulfilled the ACR-20% response criteria after 12 weeks of treatment.
Although pentoxifylline/thalidomide reduced the production capacity of TNF, the benefit/side effects ratio was poor due to multiple adverse effects, while clinical observation suggests limited efficacy.
肿瘤坏死因子α（TNFα）生成失调被认为在类风湿性关节炎中起重要作用。由于己酮可可碱和沙利度胺在体外可抑制内毒素诱导的TNF生成，因此在一项针对类风湿性关节炎患者的开放性研究中对这些药物进行了测试，以评估其毒性、对TNF生成的影响及抗关节炎作用。
12例活动期类风湿性关节炎患者在12周内每天接受1200mg己酮可可碱和100mg沙利度胺治疗。此外，通过用内毒素刺激的全血体外培养来评估TNF生成。
几乎所有患者均出现口干、嗜睡和便秘等不良事件，其中3例患者因此停药。治疗期间，药物使TNF生成能力减半（方差分析，P<0.03），而白细胞介素（IL）-6、IL-10和IL-12的生成能力未受影响。完成研究的9例患者中，5例在治疗12周后达到美国风湿病学会（ACR）20%反应标准。
尽管己酮可可碱/沙利度胺降低了TNF的生成能力，但由于多种不良反应，其效益/副作用比不佳，而临床观察表明疗效有限。
