The effects of glucocorticoids are mediated by cytosolic glucocorticoid receptors and result from both genomic and nongenomic mechanisms that also have a role in the therapeutic effects of these agents [ 1-3 ]. The AEs appear to result largely from transactivation that leads to increased expression of regulatory and antiinflammatory proteins [ 2 ]; by contrast, many of the clinically desirable effects appear to result primarily from transrepression, which results in the decreased production of proinflammatory proteins. Nongenomic effects of glucocorticoids include rapid, nonspecific interactions of glucocorticoids with cellular membranes, nongenomic effects medicated by cytosolic glucocorticoid receptors, and specific interactions with membrane-bound glucocorticoid receptors [ 2 ].
Three head to head trials involving 148 patients (74 systemic corticosteroids; 74 comparator drugs) were included. Placebo-controlled trials were not found. In the studies, different kinds of systemic corticosteroids and different kinds of control drugs were used, both administered in different routes. Intramuscular triamcinolone acetonide was compared respectively to oral indomethacine, and intramuscular adrenocorticotropic hormone (ACTH); oral prednisolone (together with a single intramuscular diclophenac injection) was compared to oral indomethacine (together with a single placebo injection). Outcome measurements varied: average number of days until total relief of signs, mean decrease of pain per unit of time in mm on a visual analogue scale (VAS) - during rest and activity. In the triamcinolone-indomethacine trial the clinical joint status was used as an additional outcome . Clinically relevant differences between the studied systemic corticosteroids and the comparator drugs were not found; important safety problems attributable to the used corticosteroids were not reported. The quality of the three studies was graded as very low to moderate. Statistical pooling of results was not possible.