To the Editor:
We note with interest that Dr. Lionel Roger has written concerning evening application of triamcinolone to treat rheumatoid arthritis (RA)1. Dr. Roger responded to our article on chronotherapy of RA with a new modified-release prednisone tablet with a special focus on the adrenal function tests2.
Indeed, in the CAPRA-1 study (Circadian Administration of Prednisone in Rheumatoid Arthritis) we found significantly better efficacy, particularly on morning symptoms such as joint stiffness, which had not been sufficiently controlled by previous treatments with the standard immediate-release prednisone tablet. There are no adverse effects of the nighttime administration of prednisone on HPA axis function. The results of the double-blind study phase comparing the modified-release and the immediate-release tablets and the subsequent 9-month open-label treatment phase with the modified-release tablet are reported in the 2 previous publications on the CAPRA-1 study3,4.
Dr. Roger’s experience with evening dosing of triamcinolone and his appeal that European League Against Rheumatism and American College of Rheumatology study groups should “request from the pharmaceutical industry” an immediate reintroduction of oral triamcinolone is understandable. But he refers to an earlier publication, an abstract of 1991, of a longitudinal study with triamcinolone (4 mg orally at 7:00 PM), which we could not trace and therefore are not able to comment on. Nor can we give an answer to his leading question, “where in the world is oral triamcinolone.” Triamcinolone plays an undisputed role in topical administration of glucocorticoids, such as in the form of crystalline suspensions for intraarticular injections. The longer half-life of oral triamcinolone, compared to prednisone, and its rather long biological action, over 48 hours, may not agree well with the 24-hour rhythm of the inflammatory mediators of RA and the symptoms.
The hypothesis behind the development of the modified-release prednisone was the established circadian rhythm of the proinflammatory cytokines, the endogenous cortisol release, and the RA symptoms. As we have outlined in our reports on the CAPRA-1 Study with the new modified-release prednisone, it is the innovative preparation of this prednisone tablet that adapts the release of prednisone to the circadian rhythm of RA symptoms and also mimics and thereby supports the intrinsic antiinflammatory hormonal response.