Background/Purpose: Tocilizumab (TCZ) 162 mg administered subcutaneously weekly (QW) or every-other-week (Q2W) plus 26-wk prednisone tapering resulted in higher rates of sustained glucocorticoid (GC)–free remission in patients with giant cell arteritis (GCA) than placebo plus 26-wk (PBO+26) or 52-wk (PBO+52) prednisone tapering in the 52-wk, double-blind, randomized controlled GiACTA trial.¹ The objective of this analysis was to determine long-term safety and explore maintenance of efficacy in GCA patients in a 2-year long-term extension (part 2) of this trial.

Methods: At the end of the double-blind period, patients in clinical remission (CR) were instructed to stop double-blind TCZ treatment upon entering part 2. CR was defined as absence of flare per investigator assessment without requirement for normalization of CRP < 1 mg/dL. GCA therapy, which could include initiation/termination of open-label TCZ and/or GC, was administered at investigator’s discretion per disease status. Outcomes included maintenance of CR (no flare during part 2), flare, time to first flare, treatments received, cumulative GC dose, and safety. Treatment groups refer to originally assigned treatment (PBO or TCZ). Results: Among 250 patients treated in the double-blind period, 215 entered part 2 and 197 (92%) completed 3 years in the trial. Among the 81 TCZ QW and 36 TCZ Q2W patients in CR at wk 52, 38 (47%) and 13 (36%) patients, respectively, maintained CR during part 2. Of these 51 original TCZ patients, 33 (65%) were treatment-free (no TCZ or GC treatment), which was higher than the treatment-free proportion of original PBO patients who maintained CR in part 2 (17/38; 45%). Median time to first flare while not receiving TCZ was longer for patients in the original TCZ groups (TCZ QW, 575 days; TCZ Q2W, 428 days) than for patients in the original PBO groups (PBO+26, 162 days; PBO+52, 295 days); TCZ QW patients remained flare-free the longest (Figure 1). Retreatment with TCZ (with or without GC) for flare was effective for restoring CR in part 2. Cumulative GC dose over the 3 years was lowest in the TCZ QW group (median dose [mg/day]: TCZ QW, 2647; TCZ Q2W, 3782; PBO+26, 5248; PBO+52, 5323). Rates of serious adverse events per 100 patient-years over 3 years (double-blind period + part 2) were comparable for patients who never received TCZ (23.2) and those who did receive ≥1 dose of TCZ (25.4), and rates of serious infections were 4.6 and 3.5 per 100 patient-years, respectively. Additional results will be presented for original PBO patients.

Conclusion: Nearly half of patients treated with TCZ QW maintained CR for the entirety of part 2, but flares still occurred in the remaining patients once they discontinued TCZ treatment. Among patients who maintained CR in part 2, higher proportions of those originally assigned to TCZ were treatment-free compared with those originally assigned to PBO. Retreatment with TCZ restored CR in patients who experienced flare. Cumulative GC dose over 3 years was lower in patients originally assigned to TCZ than in those originally assigned to PBO. No new safety signals were observed with TCZ exposure in GCA patients during the 3-year study.

Reference: 1. Stone JH et al. N Engl J Med 2017;377:317-328.

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-outcome-of-tocilizumab-for-patients-with-giant-cell-arteritis-results-from-part-2-of-a-randomized-controlled-phase-3-trial/