Tocilizumab vs prednisone in established rheumatoid arthritis patients (TOPIRA): an investigator-initiated randomized clinical trial.

Abstract

In rheumatoid arthritis (RA) patients with an insufficient response to conventional synthetic DMARDs (csDMARDs), both biologic DMARDs and low-to-moderate dose glucocorticoids are effective treatment options. However, direct comparative evidence on their relative effectiveness and safety is lacking. This investigator-initiated, open-label, randomized trial compared 10 mg daily prednisone to weekly subcutaneous tocilizumab (TCZ, 162 mg), both added to stable csDMARD therapy, in a 12-month treat-to-target strategy. If treatment response was inadequate at 3 months, patients switched to the alternative arm. The primary end point was Clinical Disease Activity Index (CDAI) averaged over months 6-12. Secondary outcomes included the Glucocorticoid Toxicity Index (GTI), TCZ-related adverse events and radiographic progression. Sixty-five patients with established RA were included in the intention-to-treat population. TCZ was superior in reducing CDAI over months 6-12 (mean difference on square root scale: -0.64; 95% CI: -1.18 to -0.09). Treatment was switched in 28% (TCZ) and 52% (prednisone). No significant differences were observed in toxicity (GTI: P = 0.922; TCZ-related adverse events: P = 1.00) or in radiographic progression (P = 0.376). On-treatment analyses yielded similar results. TCZ led to greater improvement in disease activity than prednisone. There was no significant difference in joint damage progression over 12 months and there were no major differences in adverse events. EudraCT Number: 2017-003037-28.