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ObjectiveTo evaluate the safety and efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) in a large North American cohort.MethodsPatients with GCA treated with TCZ between January 1, 2010, and May 15, 2020, were retrospectively identified. 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 annualized relapse rates before, during, and after TCZ use. Age- and sex-adjusted risk factors associated with relapse on and off TCZ and development of adverse events of significant interest (AESIs) were examined using Cox models.ResultsOne hundred fourteen patients (60.5% female) were included with mean (SD) age 70.4 (8.2) years. Median duration from GCA diagnosis to TCZ start was 4.5 months. Median overall duration of TCZ treatment was 2.3 years. Relapse rate prior to TCZ start (0.84 relapses/person-year) was 3-fold reduced while on TCZ (0.28 relapses/person-year;P< 0.001) but increased to 0.64 relapses/person-year after TCZ discontinuation. Fifty-two patients stopped TCZ after a median of 16.8 months; 27 relapsed after discontinuation (median: 8.4 months; 58% relapsed within 12 months). Only 14.9% of patients stopped TCZ because of AESIs. Neither dose/route of TCZ, presence of large-vessel vasculitis, nor duration of TCZ therapy prior to discontinuation predicted relapse after TCZ stop.ConclusionTCZ is well tolerated in GCA, with low rates of discontinuation for AESIs. However, relapse occurred in > 50% despite median treatment > 12 months. Since the duration of TCZ prior to discontinuation did not significantly affect subsequent risk of GCA recurrence, further research is needed to determine the optimal duration of therapy.

ObjectiveTo assess the frequency of comorbidities and metabolic risk factors at and prior to GCA diagnosis.MethodsRetrospective case-control study of patients with incident GCA between 1/1/2000 and 12/31/2019 in Olmsted County, MN. Two age- and sex-matched controls were identified, and each assigned an index date corresponding to an incidence date of GCA. Medical records were manually abstracted for comorbidities and laboratory data at incidence date, 5-years, and 10-years prior to incidence date. Twenty-five chronic conditions using ICD-9 diagnosis codes were also studied at incidence date and 5 years prior to incidence date.Results129 patients with GCA (74% female) and 253 controls were identified. At incidence date, the prevalence of diabetes mellitus (DM) was lower among GCA patients (5% vs 17%; p=0.001). At 5 years prior to incidence date, patients were less likely to have DM (2% vs 13%; p<0.001) and hypertension (27% vs 45%; p=0.002) and had a lower mean number (SD) of comorbidities [0.7 (1.0) vs [1.3 (1.4)] (p<0.001)] compared to controls. Moreover, patients had significantly lower median fasting blood glucose (FBG) (96 vs 104 mg/dL; p <0.001) and body mass index (BMI) (25.8 vs 27.7 kg/m2p=0.018) compared to controls. Multivariable logistic regression analysis revealed negative associations for FBG with GCA at 5 and 10 years prior to diagnosis/index date.ConclusionDM prevalence and median FBG and BMI were lower in patients with GCA up to 5 years prior to diagnosis, suggesting that metabolic factors influence the risk of GCA.

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