Background EULAR recommendations for the management of systemic glucocorticoid (GC) therapy in rheumatoid arthritis (RA) state that a reduction and even a discontinuation should be attempted once remission or low disease activity (LDA) has been reached1; however, a GC reduction schedule has not yet been standardized. This study was set-up to evaluate a predefined GC dose reduction schedule in tocilizumab (TCZ) treated RA patients with LDA (DAS28 [disease activity score] ≤3.2).
Objectives The primary objective of the study was to evaluate the proportion of RA patients with LDA able to discontinue oral GC within 20 weeks, with confirmation of the GC-free status and maintained LDA 4 weeks later.
Methods The ACT-Alone study was an open-label, multicentre, single-arm phase IV study consisting of 2 parts. First, a non interventional, observational phase of up to 6 months, during which adult RA patients were treated according to routine practice with oral GC and TCZ (8mg/kg IV perfusion every 4 weeks), with or without DMARDs, with the aim of achieving LDA. Once LDA was achieved, patients took part in a 28-week interventional phase, during which they were treated with oral methylprednisolone (MP, the investigational medicinal product, at a dose of ≥1 mg to ≤20 mg/day) and TCZ, with or without DMARDs. This part consisted of a 4 week GC run-in phase to confirm LDA under MP treatment, followed by a phase of up to 20 weeks where patients followed a fixed GC dose reduction schedule. GC-free status with maintained LDA was confirmed 4 weeks after discontinuation of MP.
Results 43 patients were analysed in the GC reduction phase of the study (ITT population). 58.1% of patients discontinued GC within 20 weeks with confirmation of LDA 4 weeks later, and 93.3% of study completers were able to reduce GC by ≥50% after 24 weeks. In general, disease activity and levels of pain and disability remained at a low level throughout the interventional phase of the study, despite reduction and discontinuation of oral MP. Mean DAS28 values remained <2.6 throughout the GC reduction phase and mean CDAI values remained <10. No major safety issues were observed during the study. During the GC reduction phase, 60.5% reported at least one AE and one SAE was reported by one patient (2.3%). AEs were considered as related to MP for 6 patients (14.0%) and as severe in intensity for 4 patients (9.3%).
Conclusions The ACT-Alone study shows that GC treatment can be safely reduced and often discontinued in patients reaching LDA with TCZ backbone therapy. Just over half (58.1%) of the patients following the fixed GC reduction schedule were able to discontinue GC within 20 weeks, with confirmation of GC-free status and maintained LDA 4 weeks later. Disease activity, pain and disability remained at low levels throughout the GC dose reduction phase and no safety issues were observed. Reduction of the cumulative GC dose is likely to decrease the long-term risk of infectious and metabolic adverse effects and as such could improve patients' quality of life.
Hoes JN et al. Ann Rheum Dis 2007;66:1560–7.
Acknowledgements The authors wish to acknowledge the Belgian investigators and medical staff who participated in the study and Keyrus Biopharma for performing statistical analysis and their support in preparing this communication.
Disclosure of Interest C. Ribbens: None declared, J. Vanhoof: None declared, M. Maertens: None declared, M. Van Steenberghe Grant/research support: NV Roche SA, Employee of: NV Roche SA, P. Verschueren: None declared