I asked the fellow his choice, and he surprised me by suggesting a switch from etanercept to rituximab. Although rituximab is an effective agent, I have a general reluctance to kill healthy cells to treat a benign, albeit serious, disease. I especially worry about eliminating circulating B cells for months and the effects on adaptive immune responses, including those to vaccines.
I then asked the fellow if he believes rituximab is safer than 5 mg prednisone and the response was a qualified yes. The fellow then enumerated the usual litany of steroid problems: hypertension, hyperglycemia, osteoporosis, depression, mania and so on. Cardiovascular disease also received mention.
I tried to assure the fellow that, with a low-dose glucocorticoid (i.e., 5 mg of prednisone or prednisolone), those dreaded side effects should be very limited, as shown by studies like the GLORIA trial.8 Nevertheless, the teaching against glucocorticoids is so strong that the fellow seemed unconvinced.
One article I read stated the medical community has been “inept” in developing an evidence base on glucocorticoid therapy.9 While inept is a strong word, the gaps in knowledge about glucocorticoids remain surprisingly large after 70 years.
In Sum
Because glucocorticoids are going to be part of RA treatment for the foreseeable future, rheumatologists should continue to ask salient questions about their risks and benefits. Hopefully, the answers will be substantive and provide evidence to satisfy even the most demanding attending-cum-Socrates in the clinic.
David S. Pisetsky, MD, PhD, is a professor of medicine and immunology at Duke University School of Medicine, Durham, N.C., and a staff rheumatologist at the Durham VA Medical Center. He also served as the first physician editor of The Rheumatologist.
References
- Benedek TG. History of the development of corticosteroid therapy. Clin Exp Rheumatol. 2011 Sep–Oct;29(5 Suppl 68):S-5-12.
- Burmester GR, Buttgereit F, Bernasconi C, et al. Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): A double-blind, multicentre, randomised controlled trial. Lancet. 2020 Jul 25;396(10246):267–276.
- Research Sub-Committee of the Empire Rheumatism Council. Gold therapy in rheumatoid arthritis: Final report of a multicentre controlled trial. Ann Rheum Dis. 1961 Dec;20(4):315–334.
- Kirwan JR. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. New Engl J Med. 1995 Jul 20;333(3):142–146.
- Stone JH, McDowell PJ, Jayne DRW, et al. The glucocorticoid toxicity index: Measuring change in glucocorticoid toxicity over time. Semin Arthritis Rheum. 2022 Aug;55:152010.
- Black RJ, Joseph RM, Brown B, et al. Half of U.K. patients with rheumatoid arthritis are prescribed oral gluco- corticoid therapy in primary care: A retrospective drug utilisation study. Arthritis Res Ther. 2015 Dec 24;17:375.
- Spies CM, Cutolo M, Straub RH, et al. Prednisone chronotherapy. Clin Exp Rheumatol. 2011 Sep–Oct;29(5 Suppl 68):S42–S45.
- Boers M, Hartman L, Opris-Belinski D, et al. Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic randomised, double-blind placebo-controlled GLORIA trial. Ann Rheum Dis. 2022 Jul;81(7):925–936.
- Palmowski Y, Buttgereit T, Dejaco C, et al. ‘Official view’ on glucocorticoids in rheumatoid arthritis: A systematic review of international guidelines and consensus statements. Arthritis Care Res (Hoboken). 2017 Aug;69(8):1134–1141.
