LOW IMMUNOGENICITY IN PATIENTS WITH GIANT CELL ARTERITIS TREATED WITH TOCILIZUMAB: 3-YEAR RESULTS FROM THE RANDOMIZED CONTROLLED PORTION AND OPEN-LABEL FOLLOW-UP OF A PHASE 3 TRIAL

Background: Tocilizumab (TCZ) has low immunogenicity in patients with rheumatoid arthritis.1 The risk for immunogenicity remains to be determined in patients with giant cell arteritis (GCA) treated with TCZ. TCZ administered subcutaneously every week (QW) or every other week (Q2W) with 26-week prednisone tapering was superior to placebo (PBO) plus 26-week (PBO+26) or 52-week (PBO+52) prednisone tapering for the achievement of sustained remission in patients with GCA in the 52-week, double-blind part 1 of the GiACTA trial.2 Part 2 was a 2-year open-label, long-term follow-up in which patients were treated at the investigators’ discretion; part 2 treatment could include initiation/termination of TCZ QW with or without glucocorticoids or methotrexate. Objectives: To investigate immunogenicity of TCZ QW and Q2W regimens in patients with GCA in combination with a 26-week prednisone taper regimen versus PBO+26 or PBO+52 over the course of the GiACTA study in the randomized controlled part 1 and long-term follow-up part 2. Methods: In parts 1 and 2 combined, anti–TCZ antibodies (ADA) and corresponding pharmacokinetic (PK) parameters were assessed in serum samples taken at scheduled times at weeks 0, 8, 24, 36, 52, 76, 100, 136, and 156 or at early withdrawal. Additional assessments were made for patients who interrupted blinded TCZ treatment for ≥4 weeks in part 1 and those who withdrew from the study because of anaphylaxis/hypersensitivity. All samples were tested by screening assay, and samples that were ADA positive were further analyzed by a confirmation assay to verify specificity. If the confirmation assay was positive, 2 additional tests were performed to characterize the detected ADA: a neutralizing assay to test the neutralizing potential of ADAs and an assay to determine whether the detected ADA were of the IgE isotype. Proportions of patients in whom ADA developed were summarized for the safety population. Results: Among evaluable patients (had baseline and ≥1 postbaseline ADA assessments and received ≥1 dose of study treatment) in part 1, ADA developed in 1 of 95 (1.1%) and 3 of 46 (6.5%) patients after TCZ QW and Q2W dosing, respectively. One of 49 (2.0%) and 1 of 47 (2.1%) in the PBO+26 and PBO+52 groups, respectively, tested positive for ADA but had not received TCZ and were considered false positives. In parts 1 and 2 combined, among 199 patients who received ≥1 dose of TCZ, 193 (97%) were evaluable (Table); TCZ-induced ADA developed in 13 of these patients (6.7%) postbaseline (4 during part 1, 9 during part 2). Of these 13 patients, 8 (4.1%) had ADA with neutralizing potential and 1 (0.5%) had IgE ADA. Most TCZ-induced ADA were transient. There was no clear impact of TCZ-induced ADA on TCZ PK (Figure). No patients with TCZ-induced ADA experienced anaphylaxis, hypersensitivity reactions, or injection site reactions, and none withdrew because of lack of efficacy Conclusion: In patients with GCA, treatment-induced ADA developed in a minority of patients and had no impact on TCZ PK, efficacy, or safety. The immunogenicity of subcutaneous TCZ treatment was low, consistent with that observed in patients with RA. References: [1]Burmester GR et al. Ann Rheum Dis 2017;76:1078-85. [2]Stone JH et al. N Engl J Med 2017;377:317-28. Disclosure of Interests: Min Bao Shareholder of: Roche, Employee of: Genentech, Navita L. Mallalieu Shareholder of: Roche, Employee of: Roche, John H. Stone Grant/research support from: Roche, Consultant of: Roche