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Disease modifying and immunomodulatory effects of high dose 1a(OH) D3 in rheumatoid arthritis patients

Z. Andjelkovic¹, J. Vojinovic³, N. Pejnovic², M. Popovic¹, A. Dujic², D. Mitrovic¹, Lj. Pavlica¹, D. Stefanovic¹

¹Department of Rheumatology and ²Department of Clinical and Experimental Immunology, Institute of Medical Research, Military Medical Academy, Belgrade and ³Department of Pediatrics, University Clinical Center, Nis, Yugoslavia.

ABSTRACT
Objective
Vitamin D analogues such as 1a(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.

Methods
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 mg/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.

Results
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.

Conclusion
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.

Key words
Vitamin D3 analogues, rheumatoid arthritis, immunomodulation, therapy.

This study was financially supported by Zdravlje-Leskovac, Yugoslavia.

Please address correspondence and reprint requests to: Ass. Prof. Jelena Vojinovic, MD, Department of Pediatrics, University Clinical Center, Nade Tomic 15/6, 18 000 Nis, Yugoslavia.