Several trials, including CAPRA-1 and -2, conceived by Dr. Buttgereit from Germany, have investigated a modified-release (MR) form of prednisone that patients take at bedtime and that then delivers the steroid around 2 a.m., and these studies have also established the MR prednisone as safe and not harmful to the HPA axis. It has been suggested that this type of chronotherapy could be applied to other agents, such as methotrexate.8,9,10
Dr. Saag thinks this approach may work for certain patients, but the questions are still somewhat unsettled. “It makes some pathophysiologic sense to better mimic the circadian patterns of glucocorticoids with a product that can be released at night,” he says. “It’s good to have this choice to provide a tailored therapy for individuals; the question is really, ‘Who should get this more expensive therapy?’”
Dr. Cutolo concludes, “For sure, the approach of chronotherapy is applicable at best for the medium- to long-term, low-dose glucocorticoid treatments in chronic inflammatory diseases, like polymyalgia rheumatica and, of course, rheumatoid arthritis.”
Setting a Dangerous Precedent?
Dr. Russell remains unconvinced that steroids should still have a role in RA management. He was on the EULAR committee that published recommendations on management of systemic glucocorticoids seven years ago.11 “I was the only one who was antisteroids on that committee,” he reports. He was able to persuade fellow committee members, however, to insert language about obtaining informed consent whenever patients were prescribed glucocorticoids. That informed consent should include discussing with patients the potential adverse effects of glucocorticoid therapy, from cardiovascular to gastrointestinal to ophthalmologic to psychological effects. He wonders, though, how many patients are thoroughly apprised of the possible consequences of the therapy before the treatment begins.
What about the use of glucocorticoids as bridging therapy, to bring symptoms under control while methotrexate or biologics take hold? “I don’t believe that 5 mg a day for three months is going to cause any serious problems for a particular patient,” he says. But this practice, he believes, will cause serious problems “to the management of RA patients in general.” The reason for this belief, Dr. Russell explains, is that family and internal medicine colleagues will continue to assume, because rheumatologists have prescribed glucocorticoids, that the practice is acceptable. He has observed that patients then arrive at his office after having seen their family doctors who kept them on steroids for a year, “with terrible erosive disease” and no complementary DMARD therapy.