Previously, the GiACTA study demonstrated the superiority of subcutaneous (SC) tocilizumab (TCZ) plus prednisone vs prednisone alone in achieving sustained glucocorticoid (GC)-free remission in patients with giant cell arteritis (GCA).1
Objectives
To evaluate the effectiveness and safety of SC and intravenous TCZ in real-world clinical practice.
Methods
We performed a retrospective analysis of GCA patients treated with TCZ at a single center (MGH) between 2010-2018. Annual relapse rate, time to disease relapse, number of relapses, prednisone use, and adverse events (AE) before and after TCZ initiation were assessed. Disease relapse was defined as the re-appearance of clinical manifestations of GCA (e.g., cranial symptoms) that required treatment modification.
Results
A total of 60 GCA patients were included in the analysis. Table 1 depicts the baseline characteristics and the treatments received by this cohort. The median (IQR) disease duration before TCZ use was 0.6 (0.2-1.6) years. Fifty-eight patients (96.7%) received concomitant prednisone (mean [SD] dose: 30 [18.3] mg daily) at the time of TCZ initiation. Patients received TCZ for a median (IQR) period of 0.5 (0.3-1.4) years. Before TCZ treatment, 43 patients (71.7%) had ≥1 relapse (median [IQR] time to relapse 0.5 [0.3-0.7] years). After TCZ initiation, 18 patients (30.0%) had ≥1 relapse (estimated median [IQR] time to relapse 2.1 [0.6-2.3] years). The annual rate of relapse was lower on TCZ than while off TCZ (RR=0.40 [95% CI, 0.25-0.63]; P=0.0001) (Table 2). Twenty-seven patients (46.6%) successfully tapered off prednisone during TCZ treatment. The incidence of AEs and serious AEs (SAE) was similar before and after TCZ initiation (Table 2). During TCZ treatment, however, 38 of 81 AEs were considered related or possibly related to prednisone. An AE led to TCZ discontinuation in 5 patients. No deaths occurred during the study period.
Conclusion
In this retrospective analysis, TCZ improved clinical outcomes in patients with GCA as indicated by a reduced incidence of relapses and by the ability to discontinue prednisone. The occurrence of AEs and SAEs (many due to GC) did not differ substantially while patients were on or off TCZ. These real-world findings support the previously reported efficacy and safety profile of TCZ in patients with GCA.
Reference
[1] Stone JH, et al. N Engl J Med. 2017;377(4):317-328.
Disclosure of Interests
Sebastian Unizony Grant/research support from: F. Hoffmann-La Roche, Genentech, Consultant for: Kiniksa, Sanofi, GSK, Jinglan Pei Employee of: Genentech, Paris Sidiropoulos Employee of: Genentech, Jennie H. Best Shareholder of: Genentech, Employee of: Genentech, Christine Birchwood Employee of: Genentech, John H. Stone Grant/research support from: F. Hoffmann-La Roche, Genentech, Xencor, Consultant for: Chugain, F. Hoffmann-La Roche, Genentech, Xencor
Abstract Background Filgotinib (FIL), an oral preferential Janus kinase 1 inhibitor, was evaluated for the treatment of ulcerative colitis in the phase 2b/3 double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522). Clinical, histological and endoscopic remission rates at week 58 were significantly greater with FIL 200 mg than with PBO (p < 0.025 for all comparisons). Here, we identify disease characteristics contributing to histo-endoscopic mucosal healing (HEMH; Geboes histological remission and endoscopic subscore ≤ 1) at week 58. FIL 100 mg data are excluded from by-treatment summaries because histological and endoscopic remission rates were not significantly different from PBO in SELECTION. Methods Eligible patients (18–75 years old) with moderately to severely active ulcerative colitis were enrolled in Induction Study A (biologic-naïve) or B (biologic-experienced) and randomized to receive FIL 200 mg, FIL 100 mg or PBO (2:2:1) once daily for up to 11 weeks, with response assessed at week 10. At week 11, FIL responders were re-randomized 2:1 to continue their induction FIL dose or to receive PBO for the 47-week maintenance study. PBO responders continued receiving PBO. For the maintenance study, univariate logistic regression was used to identify baseline and week 10 disease characteristics associated with HEMH (defined as achieving both Geboes histological remission [Grade 0 of ≤0.3, Grade 1 of ≤ 1.1, Grade 2a of ≤ 2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0] and an endoscopic subscore of 0 or 1) at week 58 for patients receiving FIL 200 mg; variables with p < 0.05 in the univariate analysis were included in a multivariate analysis. Results Patients had similar characteristics across the treatment groups for both the induction (Table 1) and maintenance studies (Table 2). HEMH was achieved in a greater proportion of patients receiving FIL 200 mg than those receiving respective PBO at week 58 (32.7% vs 10.2%; p < 0.0001). No associations between disease characteristics (at baseline and week 11) and HEMH at week 58 were found (Table 3). Conclusion FIL 200 mg was effective at establishing HEMH compared with PBO at week 58; there were no baseline characteristics identified to be associated with HEMH at week 58.
Background: The GiACTA study demonstrated the superiority of subcutaneous tocilizumab (TCZ) plus prednisone vs prednisone alone in achieving sustained glucocorticoid (GC)-free remission in patients with giant cell arteritis (GCA) 1.We aimed to evaluate the effectiveness and safety of subcutaneous and intravenous TCZ in real-world clinical practice.Methods: We performed a retrospective analysis of GCA patients treated with TCZ at a single center (MGH) between 2010-2018.Time to disease relapse, number of relapses, prednisone use, and adverse events (AE) before and after TCZ initiation were assessed.Disease relapse was defined as the re-appearance of clinical manifestations of GCA (e.g., cranial symptoms) that required treatment modification.Results: A total of 60 GCA patients were included in the analysis (mean [SD] age of 69.3 [9.4] years; 71.7% female).The median (IQR) disease duration before TCZ use was 0.6 (0.2-1.6) years.Fifty-eight patients (96.7%) received concomitant prednisone (mean [SD] dose: 30 [18.3] mg daily) at the time of TCZ initiation.Patients received TCZ for a median (IQR) period of 0.5 (0.3-1.4) years.While not on TCZ treatment, 43 patients (71.7%) had 51 relapse (median [IQR] time to relapse 0.5 [0.3-0.7]years).On TCZ, 18 patients (30.0%) had 51 relapse (median [IQR] time to relapse 2.1 [0.6-2.6]years) (Table 1).Time to relapse was significantly longer after TCZ initiation than before TCZ (HR ¼ 0.22; 95% CI: 0.10 to 0.50; P ¼ 0.0003).Twenty-seven patients (46.6%) successfully tapered off prednisone during TCZ treatment.The incidence of AEs and serious AEs (SAE) was similar before and after TCZ initiation (Table 1).During TCZ treatment, however, 38 out of 81 AEs were considered related or possibly related to prednisone.An AE led to TCZ discontinuation in 5 patients.No deaths occurred during the study period. Conclusion:In this retrospective analysis, TCZ improved clinical outcomes in patients with GCA as indicated by a reduction in the incidence of relapses and by the ability to discontinue prednisone.The occurrence of AEs and SAEs (many due to GC) did not differ substantially while patients were on or off TCZ.These real-world findings support the previously reported efficacy and safety profile of TCZ in patients with GCA.
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