In the pre-methotrexate or pre-biologic era, glucocorticoids were often the only way to prevent a patient from going up in smoke— another term from times past. Unlike the SAARD experience, clinical experience with prednisone inspired confidence that inflammation could be quelled. Further, studies showed that glucocorticoids have DMARD action and could attenuate progression of erosion;4 nevertheless, glucocorticoids are not usually categorized as DMARDs. For persistently painful joints, intra- articular steroids were often the only way short of surgery (including synovectomy, another relic) to reduce symptoms. Indeed, some patients had multiple injections to provide some comfort over time.
As is now well recognized, gluco- corticoids have a significant short- term and long-term toxicity that can be assessed quantitatively by a glucocorticoid toxicity index.5 Without careful dosing (less than 5 to 7.5 mg of prednisone daily), the toxicity can be substantial, especially if higher doses are used for too long a time. Chronic use nevertheless remains a reality, even if guidelines recommend only short-term use for flares or as bridge therapy when starting DMARDs.6
The concern about glucocorticoid toxicity has led to an interesting term: steroid-sparing agents. As the name indicates, the desired pharmacologic actions of these agents is to allow glucocorticoids to be reduced or discontinued. I would be reluctant, however, to define effective agents in terms of their activity on other agents. I would not refer to tumor necrosis factor (TNF) inhibitors as methotrexate-sparing agents any more than I would call methotrexate a TNF-inhibitor sparing agent.
Among many older rheumatologists, I find less concern over toxicity than among younger rheumatologists who don’t have to rely on prednisone for treatment benefits. Interestingly, although I prescribe prednisone to be taken in the morning, a colleague (older like me) splits the dose between morning and night, which he claims is more effective. I do wince a bit because I was taught to give prednisone in the morning to mimic the diurnal variation. Chronotherapy is, nevertheless, a concept worth exploring if the usual morning steroid dose is too late to abate the morning burst of cytokines.7
The differing perceptions about glucocorticoid safety recently became clear to me when I discussed a patient with one of our fellows. The patient was a man in his 50s who had seropositive RA and persistent disease activity despite 25 mg of methotrexate and 50 mg of etanercept each week. With an elevated Disease Activity Score-28 (DAS28) and a plethora of tender and swollen joints, another agent was clearly indicated.