Long-term effect of tocilizumab in patients with giant cell arteritis: open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial.

BACKGROUND

The combination of tocilizumab plus a glucocorticoid taper is effective in maintaining clinical remission without requiring additional glucocorticoid therapy in patients with giant cell arteritis, as shown in part one of the Giant Cell Arteritis Actemra (GiACTA) trial. However, the duration of the tocilizumab effect after discontinuation is unknown. Here, we explored the maintenance of efficacy 1 year after discontinuation of tocilizumab treatment, the effectiveness of retreatment with tocilizumab after relapse, and the long-term glucocorticoid-sparing effect of tocilizumab.

METHODS

In part one of the GiACTA trial, 251 patients were randomly assigned (2:1:1:1) to receive subcutaneous tocilizumab (162 mg) once a week or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. Patients in clinical remission stopped masked injections at 1 year (the conclusion of part one). In part two, treatment was at the investigators' discretion and could consist of no treatment, tocilizumab, glucocorticoids, methotrexate, or combinations of these, for two years. Maintenance of efficacy as assessed by clinical remission (defined as absence of relapse determined by the investigator), cumulative glucocorticoid dose, and long-term safety were exploratory objectives in part two of the trial. This trial is registered at ClinicalTrials.gov, NCT01791153.

FINDINGS

215 patients participated in part two of the trial; 81 patients who were randomly assigned to tocilizumab once a week in part one were in clinical remission after 1 year, of whom 59 started part two on no treatment. 25 of these 59 patients (42%) maintained tocilizumab-free and glucocorticoid-free clinical remission throughout part two. Median (95% CI) cumulative glucocorticoid doses over 3 years were 2647 mg (1987-3507) for tocilizumab once a week, 3948 mg (2352-5186) for tocilizumab-every-other-week, 5277 mg (3944-6685) for placebo with a 26-week prednisone taper, and 5323 mg (3900-6951) for placebo with a 52-week prednisone taper (van Elteren p≤0·001, tocilizumab once a week vs placebo groups; p<0·05, tocilizumab-every-other-week vs placebo groups). Tocilizumab-based regimens restored clinical remission among patients who experienced relapse in part two and were treated (median time to remission: 15 days for tocilizumab alone [n=17]; 16 days for tocilizumab plus glucocorticoids [n=36]; and 54 days for glucocorticoids alone [n=27]). No new or unexpected safety findings were reported over the full 3 years of the study.

INTERPRETATION

Giant cell arteritis remains a chronic disease that entails ongoing management and careful vigilance for disease relapse, but continuous indefinite treatment with immunosuppressive drugs is not required for all patients. A substantial proportion of patients treated with tocilizumab for one year maintain drug-free remission during the two years after tocilizumab cessation. For patients who experience relapse, tocilizumab can be used to manage relapses, but it remains prudent to include prednisone for patients who experience relapse because of the risk for vision loss.

FUNDING

F Hoffmann-La Roche.

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The GiACTA trial is supported by Roche and Genentech. JHS has received research grants and consulted for Roche and Genentech and Chugai on vasculitis, IgG4-related disease, Covid-19, and glucocorticoid toxicity, outside the submitted work. JH is an employee of Genentech. MA has received study site support from Roche for the GiACTA study site; and personal fees from Roche outside the submitted work. DB has received consulting and travel fees from Roche outside the submitted work. EB has received personal fees paid to her institution from Roche outside the submitted work. MCC received personal fees from Roche for the GiACTA trial; consulting fees from GlaxoSmithKline, Janssen, and AbbVie; a research grant from Kiniksa; and lecture fees from Vifor outside the submitted work. BD has received grants and personal fees from Roche, Chugai, and Sanofi Aventis; and personal fees from GlaxoSmithKline during the conduct of the study. JR has received consultancy or speaker fees from Roche, AbbVie, Biogen, Bristol Myers Squibb, Chugai, GlaxoSmithKline, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Sobi, and UCB. RS has received research funding from Roche and Genentech for the work under consideration; and research funding and consultancy fees from Roche and Genentech outside the submitted work. SHU has received grants and/or personal fees from Genentech, Janssen, Sanofi, and Kiniksa outside the submitted work. MB is an employee of Genentech and has a patent issued for subcutaneously administered anti-IL-6 receptor antibody. CS has no competing interests.