THU0128 GLUCOCORTICOID TAPERING IN MONTHLY 1-MG DECREMENTS DOES NOT RESULT IN CLINICALLY MANIFEST ADRENAL INSUFFICIENCY IN PATIENTS WITH RHEUMATOID ARTHRITIS: LEARNINGS FROM THE PHASE 3/4 SEMIRA STUDY. (June 2019)

• Record Type: Journal Article
• Authors: Buttgereit, Frank; Michael Nebesky, J.; Burmester, Gerd Rüdiger; Hochberg, Marc; Bernasconi, Corrado; John, Markus R.; Donath, Marc Y.
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 2
• Page Start: 336
• Page End: 336
• Publication Date: 2019-06
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2019-eular.2113
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: 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 (AI), especially in patients receiving GCs long-term. The expectation of AI 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 Objectives: To determine whether GC tapering in the SEMIRA trial resulted in any cases of AI. Methods: Eligible patients 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 AI. Confirmatory testing was recommended for patients with suspected AI, 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 AI 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 AI 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 patients 2 and underscores the potential to further reduce glucocorticoid burden. Clinical AI 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. Disclosure of Interests: Frank Buttgereit: None declared, J. Michael Nebesky Shareholder of: F. Hoffmann-La Roche, Employee of: F. Hoffmann-La Roche, Gerd Rüdiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme, Marc Hochberg Shareholder of: BriOri Biotech, Theralogix LLC., Consultant for: Bristol Myers Squibb, Eli Lilly, EMD Serono, Novartis Pharma AG, Pfizer Inc., Samumed LLC, Symic Bio Inc., Theralogix LLC, TissueGene Inc., TLC Biopharmaceuticals, Inc., Zynerba, Galapagos, IQVIA, Hoffman LaRoche., Corrado Bernasconi Consultant for: Roche, Markus R. John Shareholder of: Roche, Employee of: Roche, Marc Y. Donath Consultant for: Roche