Although glucocorticoids at low dosages can be of great benefit to patients with rheumatoid arthritis and other rheumatic diseases, higher dosages can cause long-term adverse effects. Guidelines about glucocorticoid therapy in rheumatologic care exist, but many clinicians are apt to shy away from prescribing glucocorticoids due to uncertainty about the actual benefit-risk ratio.

To identify the conditions under which the benefits of long-term use may outweigh the risks, an international team of researchers conducted a systematic review of glucocorticoid safety. They found that harms associated with glucocorticoid use may depend as much on patient-specific factors as on dosage.

The multidisciplinary European League Against Rheumatism (EULAR) task force consisted of rheumatologists, epidemiologists, an endocrinologist, infection disease specialist, pharmacist, and patients with rheumatic disease. It divided itself to smaller groups to each analyze evidence on 1 of 4 major adverse effects of glucocorticoid therapy—osteoporosis, hyperglycemia, cardiovascular disease, and infection.


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Among the participants of each break-out group were a patient and 3 health professionals—one a proponent, one an opponent, and one having neutral views about use of glucocorticoids in rheumatologic disease management. Findings were shared among the groups, and a structured questionnaire was completed by task force members before they all met for a final discussion and drafting of a consensus.

Task force members found that strong evidence of the risks of long-term glucocorticoid therapy is lacking in the literature. They reported that studies on harm generally are of low quality, consisting of observational designs with high risk of bias, poor documentation of glucocorticoid exposure, and lacking standardization regarding risk attribution. Examination of clinical trial data did not much help in shedding light on the matter, either. Most trials of glucocorticoids have been small, short, and limited in their assessment of adverse events, according to the EULAR task force.

However, the group agreed that, except for patients at elevated risk for cardiovascular disease, the risk of harm is low for patients who are on low-dose (≤5 mg/d) long-term glucocorticoid therapy for management of a chronic inflammatory rheumatic disease.

Those on a high-dose (>10 mg/d) regimen are at high risk for a range of adverse effects. For those receiving dosages between 5 and 10 mg/d, the team concluded that patient-specific characteristics as well as dosage likely determine the degree of risk of harm.

“As a general rule, early diagnosis, low disease activity, low cumulative glucocorticoid dosage, and monitoring and treatment of additional risk factors and comorbidities reduce the glucocorticoid-associated risk of harm,” the researchers commented.

The consensus was that glucocorticoid use may be additive to predispositions to and preexisting risks of osteoporosis, hyperglycemia, cardiovascular disease, or infection. Therefore, patients and clinicians need to manage modifiable risk factors to ameliorate potential harms in patients who may otherwise benefit from glucocorticoid therapy.

Summary and Clinical Applicability    

A multidisciplinary EULAR task force reviewed the literature on dose-dependent risks related to glucocorticoid therapy in the management of chronic inflammatory rheumatic disease. They found that robust data on risks and benefits was lacking; however, they concluded that benefit outweighs risk for low-dose (≤5 mg/d) long-term glucocorticoid therapy and that risk of harm is high for patients receiving regimens at dosages in excess of 10 mg/d.

For those receiving dosages between 5 and 10 mg/d, patient-specific characteristics, including modifiable risk factors, likely factor into the degree of harm.

With this in mind, clinicians should prescribe glucocorticoids judiciously and manage modifiable risk factors in patients who would otherwise benefit from glucocorticoid therapy.

Reference

Strehl C, Bijlsma JW, de Wit M, et al. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis. 2016 Mar 1 [Epub ahead of print]