Clinical Edge Journal Scan

Commentary: Glucocorticoid use and progression in RA, February 2023

Dr. Jayatilleke scans the journals, so you don't have to!

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Arundathi Jayatilleke, MD

Several recent studies have assessed the use of glucocorticoids, a frequent companion to disease-modifying antirheumatic drug (DMARD) and biologic therapy. Many patients are treated with glucocorticoids early in their disease course as a bridging therapy to long-term treatment, and others receive glucocorticoid therapy chronically or intermittently for flares. Van Ouwerkerk and colleagues performed a combined analysis of seven clinical trials, identified in a systematic literature review, that included a glucocorticoid taper protocol for the treatment of newly diagnosed rheumatoid arthritis (RA), undifferentiated arthritis, or "high-risk profile for persistent arthritis." These studies encompassed intravenous, intramuscular, and oral glucocorticoid regimens, and the continued use of glucocorticoids after bridging. These regimens, including cumulative doses, were examined and found to result in a low probability of ongoing use, especially in patients with lower initial doses and shorter bridging schedules. However, though reassuring as to the early use of glucocorticoids in clinical practice, this finding can be affected by patient characteristics not examined in detail in the aggregated results, including whether the patients were classified as having RA, undifferentiated arthritis, or a "high-risk profile."

Adami and colleagues also looked at tapering of glucocorticoids in patients with RA (though not necessarily early RA) in order to determine risk for flare associated with different tapering schedules. They examined the characteristics of patients with RA experiencing a flare (defined as an increase in Disease Activity Score 28 for Rheumatoid Arthritis with C-reactive protein [DAS28-CRP] > 1.2) and their glucocorticoid therapy in the preceding 6 months and found that tapering to a prednisone equivalent ≤ 2.5 mg daily was associated with a higher risk for flare but that doses > 2.5 mg daily were not. Though this finding is perhaps expected, it does not provide further insight into a strategy to minimize the associated adverse effects of glucocorticoid therapy.

Adding further weight to this point is a study performed in Denmark by Dieperink and colleagues examining risk for Staphylococcus aureus bacteremia (SAB) using a nation-wide registry of over 30,000 patients with RA. They found 180 cases of SAB and examined the patient characteristics. Patients who were currently using or previously used a biologic DMARD had an increased risk for SAB as well as those with moderate to high RA disease activity. Study participants who were currently using a prednisone-equivalent of ≤ 7.5 mg daily had an adjusted odds ratio (aOR) of 2.2 and those using > 7.5 mg daily had an aOR of 9.5 for SAB. This concerning finding suggests that even a relatively "low" dose of prednisone use is not benign for patients with RA, and these studies bring to light the need to research optimal strategies for disease control and balancing immunosuppression with the risk for infection and other adverse events.

Heckert and colleagues looked at another aspect of RA disease control, namely, local progression in a single affected joint. Their prior work has suggested that patients with RA may be prone to recurrent inflammation in a single joint despite systemic treatment, a finding that aligns with common clinical observations. This study evaluates radiographic progression in susceptible joints via post hoc analysis using data from the BeSt study including tender and swollen joints, hand and foot radiographs, and disease activity scores. Despite systemic treatment to a target low disease activity or remission state (as per the BeSt protocol), the study found an association between recurrent joint inflammation and radiographic progression (ie, erosions). However, because they only looked at hand and foot joints, the strength of this association in other joints is unknown, as is the use of local treatment, such as steroid injection to minimize inflammation, though both questions may be difficult to evaluate in a small prospective study.

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