Andjelkovic Z, Vojinovic J, Pejnovic N, Popovic M, Dujic A, Mitrovic D, Pavlica L, Stefanovic D
Department of Rheumatology, Military Medical Academy, Belgrade, Yugoslavia.
Clin Exp Rheumatol. 1999 Jul-Aug;17(4):453-6.
Vitamin D analogues such as 1 alpha (OH) D3 (alphacalcidiol) have a possible physiological paracrine effect on cell proliferation and differentiation. Experimentally established possibilities to prevent autoimmune diseases suggest that alphacalcidiol may have therapeutic value as an immunomodulatory agent in patients with rheumatoid arthritis.
We organized a 3-month open-label trial on 19 patients being treated with standard DMARD therapy for acute RA. They were divided into 2 subgroups, those with highly active RA and those with moderately active RA. Their regular drug regimen was maintained during the trial and oral alphacalcidiol 2 micrograms/day was added. Therapy results were evaluated by ESR, CRP, morning stiffness, the Richie index, and the Lee index. Immunomodulatory effects were investigated by measuring lymphocyte proliferation and apoptosis both in the patients and in vitro in 10 nM alphacalcidiol-supplemented culture medium.
After 3 months, high dose oral alphacalcidiol therapy showed a positive effect on disease activity in 89% of the patients (45% or 9 pts. with complete remission and 44% or 8 pts. with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred. No side effects were observed.
These results suggest that alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity. Clinical improvement was strongly correlated with the immunomodulating potential of this agent. We noticed dual effects on lymphocyte proliferation and apoptosis according to the prior cell activation state. Alphacalcidiol could therefore possibly be used as an adjunct therapy with DMARDs in patients with rheumatoid arthritis.
维生素D类似物，如1α（OH）D3（阿法骨化醇）对细胞增殖和分化可能具有生理旁分泌作用。实验证实的预防自身免疫性疾病的可能性表明，阿法骨化醇作为类风湿关节炎患者的免疫调节剂可能具有治疗价值。
我们对19例接受标准改善病情抗风湿药物（DMARD）治疗的急性类风湿关节炎患者进行了为期3个月的开放标签试验。他们被分为2个亚组，即高度活动型类风湿关节炎患者和中度活动型类风湿关节炎患者。在试验期间维持他们的常规药物治疗方案，并添加每日口服2微克阿法骨化醇。通过血沉（ESR）、C反应蛋白（CRP）、晨僵、里奇指数和李指数评估治疗结果。通过测量患者体内以及在添加10 nM阿法骨化醇的培养基中体外培养的淋巴细胞增殖和凋亡情况来研究免疫调节作用。
3个月后，高剂量口服阿法骨化醇治疗对89%的患者疾病活动度产生了积极影响（45%或9例完全缓解，44%或8例效果满意）。只有2例患者（11%）无改善，但未出现新症状。未观察到副作用。
这些结果表明，阿法骨化醇是一种强大的免疫调节剂，高钙血症活性相当低。临床改善与该药物的免疫调节潜力密切相关。我们注意到根据先前的细胞激活状态，阿法骨化醇对淋巴细胞增殖和凋亡有双重作用。因此，阿法骨化醇可能可作为类风湿关节炎患者DMARDs的辅助治疗药物。
