# Impact of Long-Term Glucocorticoid Therapy on the Response to Biologic Agents in Rheumatoid Arthritis: A Prospective Observational Study

## TL;DR

Long-term use of glucocorticoids in rheumatoid arthritis patients reduces the effectiveness of biologic treatments and increases health risks.

## Contribution

This study provides real-world evidence on how glucocorticoid dose affects biologic therapy outcomes in rheumatoid arthritis.

## Key findings

- Higher glucocorticoid doses correlate with worse clinical responses to anti-TNF and anti-IL-6 therapies.
- JAK inhibitors and rituximab show partial effectiveness even with high glucocorticoid exposure.
- Prolonged glucocorticoid use increases risks of diabetes, hypertension, and osteoporosis.

## Abstract

Background

Prolonged glucocorticoid use remains common in rheumatoid arthritis (RA), particularly in resource-limited settings. However, long-term exposure may reduce the effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) and increase the risk of metabolic and skeletal complications. This prospective observational study evaluated the association between cumulative glucocorticoid dose and clinical response to biologic therapies in patients with RA.

Methodology

Adults with RA fulfilling the 2010 ACR/EULAR classification criteria and treated with biologic therapy were prospectively included. Sociodemographic data, disease duration, Disease Activity Score in 28 joints (DAS28), radiographic erosions, inflammatory markers, background and concomitant therapies, and major cardiometabolic and skeletal comorbidities were recorded. Glucocorticoid exposure was analyzed according to treatment duration and cumulative prednisone-equivalent dose. Treatment effectiveness and safety were assessed at 6 and 12 months.

Results

A total of 153 patients were included, predominantly women (75.8%), with a mean age of 57.5 ± 13.7 years and a mean RA duration of 15.2 ± 9.3 years. At baseline, 70.6% were receiving glucocorticoids. Compared with non-exposed patients, glucocorticoid-exposed patients had higher disease activity (mean DAS28-CRP: 4.08 vs 3.09; p = 0.019), a less favorable clinical response at 12 months (DAS28-CRP: 3.92 vs 2.92; p = 0.005), and more radiographic erosions (74.0% vs 35.5%; p = 0.008). The effectiveness of anti-TNF and anti-IL-6 therapies decreased with increasing cumulative glucocorticoid dose, with no good clinical response observed beyond 20,000 mg, whereas response was partially preserved with Janus kinase (JAK) inhibitors (20%) and rituximab (25%). Diabetes (relative risk [RR] = 4.05), hypertension (RR = 4.02), and osteoporosis (RR = 2.48) were more frequent in glucocorticoid-exposed patients.

Conclusions

Prolonged glucocorticoid exposure in RA was associated with a lower likelihood of achieving a good clinical response to biologic therapies targeting cell surface receptors and with higher rates of metabolic and skeletal complications. These real-world data support rational, time-limited glucocorticoid use and careful selection of biologic class in patients with high cumulative exposure.