N‐[4‐hydroxyphenyl] retinamide in rheumatoid arthritis: A pilot study

Abstract

Objective. To evaluate the efficacy and tolerability of N‐[4 hydroxyphenyl] retinamide (4‐HPR), a synthetic retinoid, in the treatment of rheumatoid arthritis (RA). Methods. An uncontrolled, open clinical trial with synovial biopsy pre‐ and postmedication to evaluate the clinical effects of 4‐HPR as well as its effects on metalloproteinase gene expression. Results. Twelve patients with severe, longstanding RA were enrolled in this study. Six patients withdrew before study completion, 2 because of drug toxicity, 2 because of a flare of RA, and 2 because of intercurrent medical problems. No patient met predetermined Paulus criteria for treatment response, and there was no improvement in the laboratory parameters, except for a modest decrease in C‐reactive protein. No decrease in messenger RNA for the metalloproteinases collagenase and stromelysin was seen in the 2 patients in whom paired synovial biopsies were obtained. Conclusion. No beneficial clinical effect was observed with the retinoid 4‐HPR in the treatment of severe, longstanding RA at the 300 mg/day dosage studied. The use of higher dosages is precluded by the observed toxicities. The effect of this drug in patients with early or mild disease was not studied. Although this particular retinoid was not effective in this pilot study, the use of other retinoids in RA should still be considered.

Effect of Synthetic Retinoid, TAC-101, on Experimental Autoimmune Disease

“…Acitretin, etretinate and Am-80 are reported to be effective in the suppression of experimented multiple serositis [19,20] and psoriasis [4,[21][22][23][24]. In addition, N-[4-hydroxyphenyl] retinoid, and 13-cis retinoic acid are effective in the treatment of experimental rheumatoid arthritis [25]. In our previous studies, Am-80 showed a potent inhibition for the development of CIA in mice by interfering with the production of IL-6 [20].…”

Biologic agents for treating rheumatoid arthritis. Concepts and progress

“…Approaches in vitro and in animal models thus far have included exogenous administration of tissue inhibitor of metalloproteinases (TIMP) (113), agents that can increase local production of TIMP such as retinoids (114), and synthetic peptides that inhibit MMPs (115,116). A small pilot study evaluating a synthetic analog of vitamin A as a treatment for RA did not reveal significant clinical improvement (117). Antibiotics such as tetracycline and related compounds, which are inhibitors of MMPs (118)(119)(120), have been shown to be superior to placebo in controlled trials in RA patients.…”