Is Predisone 3 mg/day an Appropriate Dose for Patients with Rheumatoid Arthritis?

1. Documented efficacy in clinical trials of 5 mg/day, and 3 mg/day in a withdrawal clinical trial.^3,11,13
2. Doses of 5 mg/day or less generally are well tolerated.
3. Doses of 5 mg/day are physiologic rather than pharmacologic, are incremental to normal endogenous production of glucocorticoids to maintain homeostasis, and do not lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis.³¹ Therefore, discontinuation does not lead to adrenal insufficiency or possible adrenocortical crisis.
4. A prescription of 1–4 mg/day in 1-mg tablets allows a patient to titrate her/his own dosage to find an optimum level, with a minor (1- or 2-mg) increase when needed. Ironically, 1-mg tablets are more expensive than 5-mg prednisone tablets, but even prednisone 1 mg is one of the least expensive medications for a patient with RA.
5. Over long periods, adverse events associated with 5 mg/day in clinical care are no greater, and may even be lower than expected.²⁰

The case against prednisone in doses greater than 5 mg/day includes:

1. Short-term doses of greater than 5 mg/day, especially of 20 mg/day even briefly, may be associated acutely in some patients, albeit infrequently, with adverse events including restlessness, irritability, insomnia, increased appetite, weight gain, and psychosis—effects almost never seen with 5 mg/day, which provides similar efficacy.²⁵
2. Although doses of 7.5–10 mg/day appear to have no more, and in some cases even fewer, adverse events than placebo in short-term studies over two years or less, over 5 years or longer, doses greater than 5 mg/day are associated with higher rates of hypertension and diabetes, infection, and increased mortality rates.^{7,10-12,15,16,20-22,32}
3. Doses greater than 5 mg/day taken over two to three weeks led to suppression of the HPA axis, requiring “coverage” if the patient experiences surgery, trauma, and/or other stressful events.

Discussion

The use of 3 mg/day in RA appears to provoke as much controversy as whether or not patients should take glucocorticoids at all. Advocates of glucocorticoids in RA suggest that 3 mg/day is an inadequate “placebo” dose which is within physiologic production under normal circumstances. By contrast, opponents of glucocorticoids in RA suggest that any glucocorticoid is harmful, so why expose a patient to 3 mg prednisone per day, particularly if regarded as a “placebo-type” dose? Perhaps, as in many compromises, if neither side finds the compromise satisfactory, it might be worthy of consideration.

The efficacy, safety, and tolerability of 3 mg/day prednisone (or any medication) might ideally be documented in a randomized controlled trial protocol. However, it is not feasible or ethical to conduct a randomized study in RA over longer than two years, while effectiveness and safety data over five to 15 years are needed. Therefore, observational data are needed.