The role of corticosteroids in the treatment of rheumatoid arthritis has changed substantially since their introduction in the late 1940s. The powerful anti-inflammatory agent was initially perceived as a miracle drug because of its dramatic clinical effects in individuals with severe, debilitating disease. The fervor diminished as evidence of adverse effects associated with long-term glucocorticoid therapy began to accumulate. The development of seemingly less toxic drugs for chronic treatment further limited their appeal, according to Dr. Simon Carette, head of the division of rheumatology at Mount Sinai Hospital at the University of Toronto. "Millions of patients with rheumatoid arthritis worldwide have been treated with corticosteroids, yet controversy still surrounds their use," he said, noting, however, that the accumulation of well-designed studies addressing the issue of long-term efficacy, disease-modifying properties, and safety of corticosteroids should be enough to put the controversy to rest.
For this month’s column, Dr. Carette answered questions about the current role of corticosteroids in the management of rheumatoid arthritis.
Question: How has the availability of other disease-modifying antirheumatic drugs (DMARDs) and biologic agents in recent years changed the role of corticosteroids in rheumatoid arthritis?
Dr. Carette: I believe that the role of corticosteroids in the management of our patients with rheumatoid arthritis changed many years ago when we started using methotrexate as a disease-modifying drug. In contrast to the gold salts, antimalarials, and D-penicillamine that were used in the 60s and 70s, methotrexate worked faster – within 2-3 months rather than 6-12 months – and better. The need to rely on steroids decreased even further with the introduction of biologic agents in the 1990s, as these agents work even faster than methotrexate, often producing an initial response within a few weeks.
Question: In your opinion, when and how should corticosteroids be used in treatment of rheumatoid arthritis and for how long?
Dr. Carette: All patients with rheumatoid arthritis should receive corticosteroids as part of their management. What I mean by this provocative statement is that steroids should be used as bridge therapy in all patients while waiting for safer disease-modifying antirheumatic drugs to work. While patients in the COBRA trial received 60 mg of prednisone a day tapered over 6 weeks to 7.5 mg/day and discontinued after a year (Lancet 1997;350:309-18), I use 10 mg/day tapered by 2.5 mg every 2 weeks until cessation. I may repeat this same protocol at the end of 2 months in patients not achieving a significant clinical response with the other DMARD prescribed.
Question: When, or in whom, should use of corticosteroids be avoided?
Dr. Carette: Because I recommend using corticosteroids for a relatively short period of time (2-4 months), I cannot think of many situations when they should not be used. The only hesitation I would have is using steroids in patients with poorly controlled diabetes and in those with an active infection.
Question: Given some of the recognized safety concerns associated with long-term use of systemic corticosteroids, such as osteoporosis, infection, vascular issues, cataracts, and hyperglycemia, what is the best way to optimize the potential benefits while minimizing the risks?
Dr. Carette: While there is accumulating evidence that corticosteroids have disease-modifying properties, there are so many alternatives in our armamentarium that their long-term use should be restricted to a very small segment of the RA population. One of my guiding principles is that I never start corticosteroids alone but rather, only in combination with other disease-modifying agents. If a patient flares while on a disease-modifying agent, I will treat him or her with either intra-articular corticosteroids or with a short course of oral corticosteroids to reduce their symptoms. However, in that context, I will also modify their background therapy, such as increasing the dosage of the DMARD and/or adding another agent.
Question: Evidence suggests that corticosteroids are disease-modifying agents in RA, yet they are often not characterized that way. Why do you think that is? Also, is the disease-modifying potential enough to justify their long term use?
Dr. Carette: The evidence that corticosteroids are disease-modifying agents is relatively recent. While it was well accepted that corticosteroids can provide significant symptomatic relief, it wasn’t until the mid-1990s that a large trial suggested that corticosteroids also had disease-modifying properties (N. Engl. J. Med. 1995;333:142-6). A number of excellent studies have since been published confirming the observations made in this initial trial.
The major limitation to their long-term use has always been concerns about their safety. In trials assessing the long-term use of low (7.5-10 mg) or very-low (5 mg) dosage of prednisolone, weight gain has been the most striking side effect observed, with patients on prednisolone gaining an average of 3-4 kg, compared with patients on placebo. Interestingly, infections and bone mineral density loss were not observed to be different between patients on corticosteroids and those on placebo (Ann. N. Y. Acad. Sci. 2006;1069:275-88).