Elfishawi, Mohanad

Objective To evaluate the incidence and outcomes of large artery (LA) involvement among patients with giant cell arteritis (GCA) and to compare LA involvement to non-GCA patients. Methods The study included Olmsted County, Minnesota, USA residents with incident GCA between 1950 and 2016 with follow-up through 31 December 2020, death or migration. A population-based age-matched/sex-matched comparator cohort without GCA was assembled. LA involvement included aortic aneurysm, dissection, stenosis in the aorta or its main branches diagnosed within 1 year prior to GCA or anytime afterwards. Cumulative incidence of LA involvement was estimated; Cox models were used. Results The GCA cohort included 289 patients (77% females, 81% temporal artery biopsy positive), 106 with LA involvement. Reported cumulative incidences of LA involvement in GCA at 15 years were 14.8%, 30.2% and 49.2% for 1950–1974, 1975–1999 and 2000–2016, respectively (HR 3.48, 95% CI 1.67 to 7.27 for 2000–2016 vs 1950–1974). GCA patients had higher risk for LA involvement compared with non-GCA (HR 3.22, 95% CI 1.83 to 5.68 adjusted for age, sex, comorbidities). Thoracic aortic aneurysms were increased in GCA versus non GCA (HR 13.46, 95% CI 1.78 to 101.98) but not abdominal (HR 1.08, 95% CI 0.33 to 3.55). All-cause mortality in GCA patients improved over time (HR 0.62, 95% CI 0.41 to 0.93 in 2000–2016 vs 1950–1974) but remained significantly elevated in those with LA involvement (HR 1.89, 95% CI 1.39 to 2.56). Conclusions LA involvement in GCA has increased over time. Patients with GCA have higher incidences of LA involvement compared with non-GCA including thoracic but not abdominal aneurysms. Mortality is increased in patients with GCA and LA involvement highlighting the need for continued surveillance.

Abstract Objectives ANCA-associated vasculitis (AAV) is currently categorized under the small vessel vasculitides. There is limited knowledge about large vessel involvement in AAV (L-AAV), mainly described in case reports and small series. L-AAV can involve temporal arteries (TA-AAV), aorta (A-AAV), and periaortic soft tissue (PA-AAV). We sought to characterize the features of patients with L-AAV. Methods Patients older than 18 years at diagnosis of TA-AAV, A-AAV and PA-AAV seen at the Mayo Clinic, Rochester between 1 January 2000 and 31 December 2021 were identified through a proprietary medical text search algorithm. Patients were included if diagnosed with L-AAV, fulfilled 2022 ACR/EULAR classification criteria for GPA, MPA or EGPA, had positive ANCA test results, and had more than one outpatient or inpatient visit. Results The study cohort consists of 36 patients with L-AAV. Of those, 23 had p-ANCA and/or MPO-ANCA, and 13 had c-ANCA and/or PR3-ANCA. Mean (s.d.) age at AAV diagnosis was 63.4 (12.79) years; 20 (56%) were male. Seventeen patients had TA-AAV, 10 had A-AAV and 9 had PA-AAV. Most patients (n = 25, 69%) were diagnosed with large vessel vasculitis and AAV within a 1-year timespan. Twenty-five (69%) patients had histopathological confirmation of AAV diagnosis in a location other than temporal artery, aorta or periaortic soft tissue. Glucocorticoids (36/36), rituximab (19/36) and methotrexate (18/36) were the most frequent treatments. Conclusion This is the largest single-centre cohort of patients with L-AAV to date. AAV can involve large arteries, albeit infrequent. AAV-targeted therapy should be considered in patients with L-AAV.

ObjectiveThe objective of this study was to compare the efficacy and safety of two rituximab (RTX) regimens for the induction of remission in severe antineutrophil cytoplasm antibody‐associated vasculitis (AAV): the four‐dose (375 mg/m2 intravenously weekly) versus the two‐dose (1000 mg intravenously biweekly) regimen.MethodsA systematic review was performed to identify studies using the four‐ and/or two‐dose RTX regimens for induction of remission in severe AAV. Disease status 6 months after RTX infusion was required for inclusion. Patients were excluded if they received concomitant cyclophosphamide or plasma exchange. The primary end point was the proportion of patients in complete remission at 6 months. The pooled estimate was obtained by using meta‐analysis methods for proportions with random effects. Secondary end points included antineutrophil cytoplasm antibody status, number of patients with B‐cell depletion, mean prednisone dose, infections, and death.ResultsA total of 27 studies and 506 patients were included for analysis: 361 patients received the four‐dose regimen, and 145 patients received the two‐dose regimen. Most patients had relapsing disease at inclusion (83% and 92% of patients, respectively). There was no significant difference between the four‐ and two‐dose regimens, with a complete remission achieved in 85% (95% confidence interval [CI]: 70‐96) and 91% (95% CI: 79‐99) of patients, respectively. At 6 months, both regimens were associated with a similar mean daily prednisone dose (8.1 mg), infections (12% in both), and death (1% vs. 0%, respectively).ConclusionNo difference was found in terms of efficacy or safety between the four‐ and two‐dose RTX regimens for induction of remission in severe AAV.https://onlinelibrary.wiley.com/doi/10.1002/acr2.11274Bénard V, Farhat C, Zarandi‐Nowroozi M, Durand M, Charles P, Puéchal X, et al. Comparison of two rituximab induction regimens for antineutrophil cytoplasm antibody–associated vasculitis: systematic review and meta‐analysis. ACR Open Rheumatol 2021;3:484–94.

Summary Behçet disease is a multi-system disease associated with human leukocyte antigen (HLA) class I polymorphism. High-resolution next-generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behçet disease and 160 healthy geographic and ethnic-matched controls were genotyped for HLA class I loci (HLA-A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High-resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA-B*51:08 [odds ratio (OR) = 19·75, 95% confidence interval (CI) = 6·5–79; P < 0·0001], HLA-B*15:03 (OR = 12·15, 95% CI = 3·7–50·7; P < 0·0001), HLA-C*16:02 (OR = 6·53, 95% CI = 3–14; P < 0·0001), HLA-A*68:02 (OR = 3·14, 95% CI = 1·1–8·9; P < 0·01) were found to be associated with Behçet disease, as were HLA-DRB1*13:01 and HLA-DQB1*06:03 (OR = 3·39, 95% CI = 0·9–18·9; P = 0·04 for both). By contrast, HLA-A*03:01 (OR = 0·13, 95% CI = 0–0·8; P = 0·01) and HLA-DPB1*17:01 were found to be protective (OR = 0·27, 95% CI = 0·06–1·03; P = 0·02). We identified strong linkage disequilibrium between HLA-B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behçet disease. HLA-B*51:08 was significantly associated with legal blindness (OR = 2·98, 95% CI = 1·06–8·3; P = 0·01). In Egyptian Behçet patients, HLA-B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement.