Developing Personalized Steroid-Free Regimens in Patients with RA and Other ARD

Speaker: Dr. Beth Wallace - Michigan Medicine, VA Ann Arbor Healthcare System

Key Highlights:

Historical Context and Current Perspectives on Steroid Use in RA:

Steroids offer significant symptom relief in rheumatoid arthritis (RA), but long-term use is linked to serious side effects such as cardiovascular disease, osteoporosis, and diabetes. Despite their disease-modifying potential, the ACR guidelines (2021) now advise against routine steroid use.

Challenges in Steroid Tapering:

Steroid tapering is complicated by factors like disease flares, adrenal insufficiency, and steroid withdrawal syndrome (SWS). These complications hinder successful tapering and require careful management.

Dr. Wallace explained that Steroid Withdrawal Syndrome (SWS) occurs when patients taper steroids, leading to symptoms like disease flare or adrenal insufficiency, with no clear underlying cause. Up to 75% of RA patients experience this during tapering. The mechanism is not well understood, and treatment still involves increasing the steroid dose until symptoms subside. However, the lack of a clear mechanism for SWS complicates diagnosis and management, making it difficult to differentiate from other causes like disease activity or adrenal insufficiency. More research is needed to understand and better manage this common issue.

Emerging Data from Trials:

Recent trials, such as SAMIRA (2020) and STAR (2023), show varying degrees of success with steroid tapering, with persistent adrenal insufficiency and withdrawal symptoms noted in some patients. 

The SAMIRA trial (2020) examined a 1 mg/month prednisone taper vs. placebo in RA patients maintained on Tocilizumab. Its primary endpoint was flare occurrence at 24 weeks, with 25% of the taper group experiencing flares, similar to lupus. The study monitored adrenal insufficiency symptoms (GI issues, fatigue, unexplained weight loss), but no objective findings (e.g., orthostatic hypotension, pallor) or abnormal cort stimulation tests were reported. No significant evidence of adrenal insufficiency or withdrawal symptoms was found in the taper group. 

The STAR trial (2023) compared 6-month prednisone and hydrocortisone tapers in RA patients, followed by 6 months without steroids. Its primary endpoint was steroid discontinuation at 12 months, with about 50% of participants in each arm successfully discontinuing steroids. Secondary outcomes included patient-reported outcomes and universal cort stim screening, with hydrocortisone supplementation for abnormal tests. Although both taper groups had similar outcomes, small increases in flare frequency, fatigue, and disease impact were observed during tapering, especially in the prednisone group. At 4 months, 43% of hydrocortisone patients and 29% of prednisone patients had abnormal cort stim tests. By 7 months, these values decreased, and abnormal results at 12 months were still noted in 50-75% of patients who had initial abnormalities.

Personalized Approaches for Steroid-free Regimens:

The future of tapering strategies lies in personalized medicine. Adaptive interventions based on patient phenotyping (immune markers, endocrine function, central sensitization) could guide tailored tapering strategies, minimizing steroid toxicity while maintaining disease control.

Conclusion:

The shift towards minimizing steroid exposure in RA is essential due to the risks associated with long-term use. However, the complexities of steroid tapering necessitate a more personalized approach that considers individual patient characteristics to develop effective, steroid-free regimens for RA and related diseases. Further trials focused on these strategies are needed to refine the approach and improve patient outcomes.

American College of Rheumatology Convergence 2024, November 14–19, Washington, D.C.