Background/Purpose: Systemic glucocorticoids (GCs) are used to treat serious inflammatory diseases but are associated with adverse events. Guidelines recommend tapering GCs to the lowest possible dose and discontinuing them as soon as possible. Physicians have concerns that reductions, even from low doses, may increase disease symptoms or cause adrenal insufficiency, especially in patients receiving GCs long term. The expectation of adrenal insufficiency risk may be inflated by false positives in cortisol testing of patients without relevant symptoms and by a lack of robustly designed GC taper trials. The international, multicenter SEMIRA trial evaluated a taper scheme in rheumatoid arthritis (RA) patients receiving tocilizumab (TCZ) ± conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).¹ The objective of this analysis was to determine whether GC tapering in the SEMIRA trial resulted in any cases of adrenal insufficiency.

Methods: Eligible patients, diagnosed per revised 1987 ACR criteria, had low disease activity or remission for ≥4 weeks and were receiving a stable prednisone regimen (5 mg/day) + TCZ ± csDMARDs for ≥4 weeks. Patients had to have received ≥6 months’ total TCZ + GCs (prednisone equivalent 5-15 mg/day). Patients were randomly assigned (1:1) to double-blind continued prednisone 5 mg/day (n = 128) or prednisone taper (n = 131). TCZ ± csDMARDs remained stable during the 24-week study. The prednisone taper consisted of 1-mg decrements every 4 weeks starting at randomization and ending at GC discontinuation (week 16). RA flares were treated with prednisone 5 mg/day for 2 weeks. The primary assessment was maintenance of disease control with GC discontinuation. The protocol provided evidence-based guidance for diagnosis and management of adrenal insufficiency. Confirmatory testing was recommended for patients with suspected adrenal insufficiency, but routine precautionary ACTH stimulation testing was not mandated.

Results: In the taper arm, 65% of patients achieved “treatment success” by meeting all key secondary end point components (maintained low disease activity, experienced no flares, and had no confirmed adrenal insufficiency necessitating replacement therapy) at week 24 versus 77% of continued patients (risk ratio for treatment success, 0.833 [95% CI, 0.714-0.972]; p = 0.021). None of the taper patients required ACTH stimulation testing, and no cases of adrenal insufficiency were reported.

Conclusion: SEMIRA demonstrated the usefulness of a new standardized GC dose taper scheme. Two-thirds of patients receiving TCZ underwent successful tapering and could stop GCs entirely, which is higher than the spontaneous 35% discontinuation rate observed in real-world RA patients² and underscores the potential to further reduce glucocorticoid burden. Clinical adrenal insufficiency was not observed; thus, routine laboratory testing may be unnecessary in real-world applications of this taper scheme.

References: 1. Burmester GR et al. Arthritis Rheumatol 2018;70(suppl 10):L18. 2. Yagız B et al. Arthritis Rheumatol 2018;70(suppl 10):627.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/glucocorticoid-tapering-in-monthly-1-mg-decrements-does-not-result-in-clinically-manifest-adrenal-insufficiency-in-patients-with-rheumatoid-arthritis-learnings-from-a-phase-3-4-study/