Background 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 (pts) 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
Objectives Determine long-term safety and explore maintenance of efficacy in GCA pts in a 2-year long-term extension (part 2) of this trial.
Methods At the end of the double-blind period, pts 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. GCA therapy, which could include initiation/termination of open-label TCZ and/or GC, was at the 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 pts 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 pts in CR at wk 52, 38 (47%) and 13 (36%) pts, respectively, maintained CR during part 2. Of these 51 original TCZ pts, 33 (65%) were treatment-free (no TCZ and no GC treatment), which was higher than the treatment-free proportion of original PBO pts who maintained CR in part 2 (17/38; 45%). Median time to first flare while not receiving TCZ was longer for pts in the original TCZ groups (TCZ QW, 575 days; TCZ Q2W, 428 days) than for pts in the original PBO groups (PBO+26, 162 days; PBO+52, 295 days); TCZ QW pts 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-year study was lowest in the TCZ QW group (median dose [mg/day]: TCZ QW, 2372.8; TCZ Q2W, 2863.0; PBO+26, 5006.0; PBO+52, 5322.5). Rates of serious adverse events per 100 pt-years over 3 years (double-blind period + part 2) were comparable for pts who never received TCZ (23.2) and who did receive ≥1 dose of TCZ (25.4), and rates of serious infections were 4.6 and 3.5 per 100 pt-years, respectively. Additional results will be presented for original PBO pts.
Conclusion Nearly half the pts treated with TCZ QW maintained CR for the entirety of part 2, though flares still occurred in the remaining pts once they discontinued TCZ treatment. Among pts 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 pts who experienced flare. Cumulative GC doses over 3 years were lower in pts originally assigned to TCZ than in those originally assigned to PBO. No new safety signals were observed with TCZ exposure in GCA pts during the 3-year study.
References  Stone JH, et al. N Engl J Med. 2017;377:317-328.
Disclosure of Interests John H. Stone Grant/research support from: F. Hoffmann-La Roche, Genentech, Xencor, Consultant for: Chugain, F. Hoffmann-La Roche, Genentech, Xencor, Min Bao Shareholder of: F. Hoffmann-La Roche Ltd., Employee of: Genentech, Jian Han Shareholder of: F. Hoffmann-La Roche Ltd., Employee of: Genentech, Martin Aringer Grant/research support from: Roche, Consultant for: AstraZeneca and Eli Lilly, Daniel Blockmans: None declared, Elisabeth Brouwer Speakers bureau: Dr. Brouwer as an employee of the UMCG received speaker fees and consulting fees from Roche which were paid to the UMCG, Maria C. Cid Grant/research support from: Kiniksa Pharmaceuticals, Consultant for: Roche, GSK, Janssen, Abbvie, Speakers bureau: Boehringer-Inhelheim, Vifor, Bhaskar Dasgupta Consultant for: Roche, GSK, Sanofi, BMS, Abbvie, Speakers bureau: Roche, Jürgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Carlo Salvarani: None declared, Robert Spiera Grant/research support from: Roche-Genentech, GlaxoSmithKline, Bristol-Myers Squibb, Boehringer Ingelheim, Cytori, Chemocentryx, Corbux, Consultant for: Roche-Genentech, GlaxoSmithKline, CSL Behring, Sanofi Aventis, Sebastian Unizony Grant/research support from: F. Hoffmann-La Roche, Genentech, Consultant for: Kiniksa, Sanofi, GSK
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