Background:Giant cell arteritis (GCA) is an inflammatory condition of medium- and large-sized arteries. Prospective clinical trials have demonstrated the efficacy of tocilizumab (TCZ) for treatment of patients with GCA (1). However, there is a limited data on the use of TCZ in routine clinical practice.Objectives:To evaluate the efficacy and safety of TCZ in a retrospective cohort study of patients with GCA treated with TCZ.Methods:Patients with GCA treated with TCZ at 4 clinical centers of a single tertiary care institution (2000-2020) were identified. The diagnosis of GCA was confirmed by at least one of the following modalities: 1. Arterial biopsy 2. Large vessel imaging 3. Clinical diagnosis of GCA meeting ACR classification criteria and established by a rheumatologist. Patient demographics, clinical presentation, laboratory studies, treatment course and adverse events were abstracted from the medical record; only patients with at least 6 months of follow-up after TCZ initiation were included. Kaplan-Meier methods were used to estimate time to TCZ discontinuation and time to first relapse after TCZ discontinuation. Poisson regression models were used to compare relapse rates before and after TCZ initiation.Results:The study cohort included 119 patients [61% female; mean (SD) age at GCA diagnosis 70.3 (8.2) years]. The majority of patients (89%) had a biopsy-proven and/or imaging-based diagnosis of GCA, while 13 (11%) had a clinical diagnosis of GCA. In addition to glucocorticoids, 40 (34%) patients received other immunosuppressive agents prior to TCZ. The method of initial TCZ administration was subcutaneous (162mg/ml) weekly in 48 (41%), subcutaneous every other week in 20 (17%), monthly 4mg/kg infusions in 34 (29%), monthly 8mg/kg infusions in 14 (12%) and non-standard dosing in 3 remaining patients. The median (IQR) duration from GCA diagnosis to TCZ initiation was 4.8 (1.2-22.0) months and the median (IQR) duration of TCZ treatment was 18 (11-28) months. The mean (SD) dose of prednisone at TCZ initiation was 31 (19) mg/day and was reduced to a mean (SD) dose of 3.9 (6.7) mg/day at TCZ discontinuation/last follow-up visit. The relapse rate per year decreased 43% from 0.77 to 0.44 after the initiation of TCZ (RR=0.57; 95% CI: 0.44-0.75; p<0.001). The mean (SD) ESR and CRP decreased from 22 (20) mm/hour to 6 (9.2) mm/hour and from 19.1 (25) mg/L to 5.4 (16.6) mg/L, respectively from TCZ initiation to TCZ discontinuation/last follow-up visit. At 2 years of follow-up, 67% of patients had discontinued glucocorticoids. At last follow up, 46 patients had discontinued TCZ, only 14 of which were due to adverse events. The median time to TCZ discontinuation was 2.9 years. Only 17% (95%CI: 10-24%) had discontinued by 1 year after TCZ initiation and 38% (95% CI: 26-47%) had discontinued by 2 years. The most common adverse events were infections and cytopenias. While on TCZ, 1 patient developed new onset vision loss related to GCA and 1 patient, without history of diverticulitis, had bowel perforation. Among those discontinuing TCZ, 61% had relapsed at least once by 1 year after TCZ discontinuation.Conclusion:In this large single institution cohort of patients with GCA, TCZ use resulted in a significantly reduced relapse rate and reduction in glucocorticoid dosage. Overall, patients tolerated long-term use with only 12% discontinuing due to adverse events. However, over half of patients stopping TCZ had a subsequent flare; highlighting ongoing use may be required beyond two years in several patients with GCA to maintain remission.References:[1]Stone JH, et al. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017 Jul 27;377(4):317-328. doi: 10.1056/NEJMoa1613849. PMID: 28745999.[2]Calderón-Goercke M, et al. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin Arthritis Rheum. 2019 Aug;49(1):126-135. doi: 10.1016/j.semarthrit.2019.01.003. Epub 2019 Jan 5. PMID: 30655091.Disclosure of Interests:Jigisha Rakholiya: None declared, Matthew Koster: None declared, Hannah Langenfeld: None declared, Cynthia S. Crowson: None declared, Andy Abril: None declared, Pankaj Bansal: None declared, Lester Mertz: None declared, Alicia Rodriguez-Pla: None declared, Rahul Sehgal: None declared, Benjamin Wang: None declared, Kenneth J Warrington Grant/research support from: Research support: Kiniksa, Eli Lilly
Efficacy of lower dose Pirfenidone for idiopathic pulmonary fibrosis in real practice: a retrospective cohort study
