Disease modifying and immunomodulatory effects of high dose 1 alpha(OH) D3in rheumatoid arthritis patients

Objective Vitamin D analogues such as 1 alpha(OH) D3 (alphacalcidiol) have a possible physiological paracrine effect on cell proliferation and differe ntiation. Experimentally established possibilities to prevent autoimmune di seases suggest that alphacalcidiol may have therapeutic value as an immunom odulatory agent in patients with rheumatoid arthritis. Methods We organized a 3-month open-label trial on 19 patients being treate d with standard DMARD therapy for acute RA. They were divided into 2 subgro ups, those with highly active R4 and those with moderately active RA. Their regular drug regimen was maintained during the trial and oral alphacalcidi ol 2 mu g/day was added. Therapy results were evaluated by ESR, CRI:,mornin g 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 m edium. Results After 3 months, high dose oral alphacalcidiol therapy showed a posi tive effect on disease activity in 89% of the patients (45% or 9pts. with c omplete remission and 44% or 8 pts. with ed satisfactory effect). Only two patients 11% showed no improvement, but no new symptoms occurred. No side e ffects were observed Conclusion These results suggest that alphacalcidiol is a powerful immunomo dulatory agent,vith 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 accordin g to the prior cell activation state. Alphacalcidiol could therefore possib ly be used as an adjunct therapy with DMARDs in patients with rheumatoid ar thritis.