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The vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a newly identified autoinflammatory disorder related to somatic UBA1 mutations. Up to 72% of patients may show lung involvement.What are the pleuropulmonary manifestations in VEXAS syndrome?One hundred fourteen patients were included in the French cohort of VEXAS syndrome between November 2020 and May 2021. Each patient included in the study who had an available chest CT scan was discussed in an adjudication multidisciplinary team and classified as showing potentially pleuropulmonary-specific involvement of VEXAS syndrome or others.Fifty-one patients had a CT scan available for review and 45 patients (39%) showed pleuropulmonary abnormalities on chest CT scan that were considered related to VEXAS syndrome after adjudication. Most patients were men (95%) with a median age 67.0 years at the onset of symptoms. Among these 45 patients, 44% reported dyspnea and 40% reported cough. All 45 patients showed lung opacities on chest CT scan (including ground-glass opacities [87%], consolidations [49%], reticulation [38%], and septal lines [51%]) and 53% of patients showed pleural effusion. Most patients showed improvement with prednisone, but usually required20 mg/d. The main clinical and biological features as well the median survival did not differ between the 45 patients with pleuropulmonary involvement and the rest of the cohort, suggesting that the prevalence of pleuropulmonary involvement might have been underdiagnosed in the rest of the cohort.Pulmonary manifestations are frequent in VEXAS syndrome, but rarely are at the forefront. The initial outcome is favorable with prednisone and does not seem to lead to pulmonary fibrosis.

ObjectiveTo identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy.MethodsWe conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment.ResultsWe included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P 100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone.ConclusionIn patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.

Introduction Giant cell arteritis (GCA) is a frequent granulomatous vasculitis. In the diagnosis of large vessel GCA, FDG-PET/CT imaging has been recommended and its use has steadily increased. The objective of this prospective study was to evaluate the diagnostic performance of digital FDG-PET imaging with a head and neck dedicated protocol, especially to detect cranial arteries involvement, using different visual grading scores, and to assess the inter-reader agreement. Material and Methods FDG-PET/CT scans with a 10-min acquisition time on the head and neck were performed in patients suspected of having recent GCA. A score including 20 segments due to the inclusion of cranial segments and a score established only for the cranial segments were compared to the Total Vascular Score (TVS) established on 7 arterial segments. These scores were assessed by two nuclear medicine physicians on a blinded manner and, in case of disagreement, a consensus was established with a third nuclear medicine physician. Results GCA diagnosis was retained for 15 of the 52 patients included. Sensitivity and specificity of the 20-segment or the cranial scores were higher than those of TVS (sensitivity and specificity of 80% of 97% for both scores vs 73% and 89% for TVS, respectively). The inter-reader agreement was substantial in the 20-segment score (weighted kappa = 0.68) but better in the cranial segments than other segments. Conclusion This study shows the usefulness of grading scores able to highlight involvement of cranial arteries in GCA with a better inter-reader agreement in cranial segments than other segments.

Resume L’arterite a cellules geantes (ACG) est la plus frequente des vascularites affectant l’artere temporale (AT). Neanmoins, d’autres types de pathologies vasculaires, qu’il s’agisse de vascularite ou non, peuvent toucher l’AT. Parmi les vascularites, on peut citer les vascularites necrosantes, en particulier les vascularites associees aux anticorps anti-cytoplasme des polynucleaires neutrophiles (ANCA) qui peuvent affecter les petits vaisseaux peri-adventitiels de la paroi de l’AT et mimer certains symptomes de l’ACG, ces derniers n’etant generalement pas isoles, ce qui doit faire rechercher les ANCA. Certaines vascularites infectieuses peuvent egalement toucher l’AT comme l’infection par le virus varicelle-zona (VZV) dont l’aspect histologique est tres proche de l’ACG a tel point que certains auteurs ont suggere un role du VZV dans le declenchement de l’ACG. Une vascularite de l’AT peut egalement etre secondaire a une maladie associee aux IgG4 ou d’origine medicamenteuse (inhibiteurs de checkpoint immunitaire). En dehors des vascularites, l’AT peut etre le siege d’autres vasculopathies non inflammatoires comme la maladie atheromateuse, l’arteriolopathie uremique calcifiante ou encore les atteintes post-traumatiques comme les faux-anevrysmes ou les fistules arterioveineuses de l’AT. Dans cette revue, nous decrivons ces differents types d’atteinte pouvant toucher l’AT.

International audience; BACKGROUND: Cardiovascular risk is increased in giant cell arteritis (GCA). We aimed to characterize myocardial infarction (MI) in a GCA cohort, and to compare the GCA and non-GCA population affected by MI. METHODS: In patients with a biopsy-proven diagnosis of GCA between 1 January 2001 and 31 December 2016 in Côte D'Or (France), we identified patients with MI by crossing data from the territorial myocardial infarction registry (Observatoire des Infarctus de Côte d'Or) database. Five controls (non-GCA + MI) were paired with one case (GCA + MI) after matching for age, sex, cardiovascular risk factors and prior cardiovascular disease. MI were characterized as type 1 MI (T1MI), resulting from thrombus formation due to atherothrombotic disease, or type 2 MI (T2MI), due to a myocardial supply/demand mismatch. GCA-related MI was defined as MI occurring within 3 months of a GCA flare (before or after). RESULTS: Among 251 biopsy-proven GCA patients, 13 MI cases were identified and paired with 65 controls. MI was GCA-related in 6/13 cases, accounting for 2.4% (6/251) of our cohort. T2MI was more frequently GCA-related than GCA-unrelated (80% vs. 16.7%, p = 0.080), and GCA diagnosis was the only identified triggering factor in 75% of GCA-related T2MI. GCA-unrelated MI were more frequently T1MI and occurred in patients who had received a higher cumulative dose of prednisone (p = 0.032). GCA was not associated with poorer one-year survival. CONCLUSIONS: GCA-related MI are mainly T2MI probably caused by systemic inflammation rather than coronaritis. GCA-unrelated MI are predominantly T1MI associated with atherothrombotic coronary artery disease.

OBJECTIVE Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. METHODS Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. RESULTS Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up-regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3- Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/β TCR repertoire. CONCLUSION We established the presence of a specific Tfh cell signature in both circulating and aorta-infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK.

Giant cell arteritis (GCA) is the most common primary large-vessel vasculitis. Glucocorticoids (GC) therapy remains the standard of care for GCA despite frequent side effects (SEs). However, treatment modality changes, prophylactic treatment of osteoporosis, or vaccinations might have decreased the frequency of GC-related SEs. This study aims to describe GCA treatment and GC-related SEs in a recent cohort.Patients with a diagnosis of GCA between May 2009 and March 2018 were included in this multicentric retrospective study. Characteristics of patients, treatment modalities and GC-related SEs were collected and analysed. Risk factors associated with the occurrence of SE were studied.We analysed the files from 206 patients (153 women, 53 men; median age 74 years). Median follow-up was 34 months. Patients received GC for a median of 25 months, starting at 0.7 mg/kg/day, with tapering to 5 mg/day after 11 months follow-up. Flares occurred in 83/201 (41%) patients. Among the 132 patients who stopped GC, 29 (22%) experienced a relapse. SEs occurred in 129 (64%) patients: bone fractures and infections in 13% each and hypertension onset in 9%. Age75 years, treatment duration2 years, past medical history of diabetes were risk factors associated with GC-related SEs.Flares occur in 41% of patients during GC withdrawal. As much as 64% of patients had treatment related SEs. An age75 year and a past medical history of diabetes were predictive of SEs during follow-up.

Objectives GCA is a large vessel vasculitis for which triggering factors remain unknown. Clonal haematopoiesis (CH) was associated with atherosclerosis through the induction of inflammation in myeloid cells, and data suggest that CH expansion and inflammation may support each other to induce a pro-inflammatory loop. Our objective was to describe the impact of JAK2p.V617F-mutated myeloproliferative neoplasms (MPNs) on GCA and to screen MPN-free patients for CH mutations. Methods We performed a retrospective case–control study comparing the characteristics of 21 GCA patients with MPN and 42 age- and gender-matched GCA patients without MPN. Also, 18 GCA patients were screened for CH through next-generation sequencing (NGS). Results The most frequent associated MPN was essential thrombocythaemia (ET; n = 11). Compared with controls, GCA patients with MPN had less-frequent cephalic symptoms (71.4 vs 97.6%; P = 0.004) and higher platelet counts at baseline [485 × 109/l (interquartile range 346–586) vs 346 (296–418); P = 0.02]. There was no difference between groups for other clinical features. Overall survival was significantly shorter in patients with MPN compared with controls [hazard ratio 8.2 (95% CI 1.2, 56.6); P = 0.03]. Finally, screening for CH using NGS in 15 GCA patients without MPN revealed CH in 33%. Conclusion GCA patients with MPN display higher platelet counts and shorter overall survival than controls. This association is not fortuitous, given the possible pathophysiological relationship between the two diseases. CH was found in one-third of GCA patients, which may be higher than the expected prevalence for a similar age, and should be confirmed in a larger cohort.

Background Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype. Aims This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis. Methods Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death. Results Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29–7.34), performance status (OR 1.40, 1.05–1.87), use of morphine (OR 2.51, 0.87–7.24), abdominal guarding (OR 3.08, 1.01–9.37), ileus (OR 2.29, 0.98–5.32), melena (OR 2.74, 1.17–6.42), increased leukocytes (per G/L, OR 1.05, 1.00–1.10), low hemoglobin (per g/dL, OR 0.80, 0.71–0.91) and increased CRP (log mg/L, OR 1.21, 0.94–1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well. Conclusions Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death.

This study aimed to identify markers of disease worsening in patients hospitalized for SARS-Cov2 infection.Patients hospitalized for severe recent-onset (1 week) SARS-Cov2 infection were prospectively included. The percentage of T-cell subsets and plasma IL-6 at admission (before any steroid therapy) were compared between patients who progressed to a critical infection and those who did not.Thirty-seven patients (18 men, 19 women) were included; 11 (30%) progressed to critical infection. At admission, the critical infection patients were older (P = 0.021), had higher creatinine levels (P = 0.003), and decreased percentages of circulating B cells (P = 0.04), T cells (P = 0.009), and CD4+ T cells (P = 0.004) than those with a favorable course. Among T cell subsets, there was no significant difference between the two groups except for the percentage of Th17 cells, which was two-fold higher in patients who progressed to critical infection (P = 0.028). Plasma IL-6 at admission was also higher in this group (P = 0.018). In multivariate analysis, the percentage of circulating Th17 cells at admission was the only variable associated with higher risk of progression to critical SARS-Cov2 infection (P = 0.021).This study suggests that an elevated percentage of Th17 cells in patients hospitalized for SARS-Cov2 infection is associated with an increased risk of progression to critical disease. If these data are confirmed in a larger study, this marker could be used to better target the population of patients in whom tocilizumab could decrease the risk of progression to critical COVID-19.

Objectives To investigate the performance of cranial PET/CT for the diagnosis of GCA. Methods All patients with a suspected diagnosis of GCA were prospectively enrolled in this study and had a digital PET/CT with evaluation of cranial arteries if they had not started glucocorticoids >72 h previously. The diagnosis of GCA was retained after at least 6 months of follow-up if no other diagnosis was considered by the clinician and the patient went into remission after at least 6 consecutive months of treatment. Cranial PET/CT was considered positive if at least one arterial segment showed hypermetabolism similar to or greater than liver uptake. Results For cranial PET/CT, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were 73.3%, 97.2%, 91.7% and 89.7%, respectively. For extracranial PET/CT, diagnostic performance was lower (Se = 66.7%, Sp = 80.6%, PPV = 58.8%, NPV = 85.3%). The combination of cranial and extracranial PET/CT improved overall sensitivity (Se = 80%) and NPV (NPV = 90.3%) while decreasing overall specificity (Sp = 77.8%) and PPV (PPV = 60%). Conclusion Cranial PET/CT can be easily combined with extracranial PET/CT with a limited increase in examination time. Combined cranial and extracranial PET/CT showed very high diagnostic accuracy for the diagnosis of GCA. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT05246540.

ObjectiveTo develop a score assessing the probability of relapse in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).MethodsLong-term follow-up data from GPA and MPA patients included in five consecutive randomised controlled trials were pooled. Patient characteristics at diagnosis were entered into a competing-risks model, with relapse as the event of interest and death the competing event. Univariate and multivariate analyses were computed to identify variables associated with relapse and build a score, which was then validated in an independent cohort of GPA or MPA patients.ResultsData collected from 427 patients (203 GPA, 224 MPA) at diagnosis were included. Mean±SD follow-up was 80.6±51.3 months; 207 (48.5%) patients experienced ≥1 relapse. Relapse risk was associated with proteinase 3 (PR3) positivity (HR=1.81 (95% CI 1.28 to 2.57); pConclusionThe FRS can be used at diagnosis to assess the relapse risk in patients with GPA or MPA. Its value for tailoring the duration of maintenance therapy should be evaluated in future prospective trials.

Background Biannual rituximab infusions over 18 months effectively maintain remission after a "standard" remission induction regimen for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Objective To evaluate the efficacy of prolonged rituximab therapy in preventing AAV relapses in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who have achieved complete remission after completing an 18-month maintenance regimen. Design Randomized controlled trial. (ClinicalTrials.gov: NCT02433522). Setting 39 clinical centers in France. Patients 68 patients with GPA and 29 with MPA who achieved complete remission after the first phase of maintenance therapy. Intervention Rituximab or placebo infusion every 6 months for 18 months (4 infusions). Measurements The primary end point was relapse-free survival at month 28. Relapse was defined as new or reappearing symptoms or worsening disease, with a Birmingham Vasculitis Activity Score greater than 0. Results From March 2015 to April 2016, 97 patients (mean age, 63.9 years; 35% women) were randomly assigned, 50 to the rituximab and 47 to the placebo group. Relapse-free survival estimates at month 28 were 96% (95% CI, 91% to 100%) and 74% (CI, 63% to 88%) in the rituximab and placebo groups, respectively, an absolute difference of 22% (CI, 9% to 36%) with a hazard ratio of 7.5 (CI, 1.67 to 33.7) (P = 0.008). Major relapse-free survival estimates at month 28 were 100% (CI, 93% to 100%) versus 87% (CI, 78% to 97%) (P = 0.009), respectively. At least 1 serious adverse event developed in 12 patients (24%) in the rituximab group (with 9 infectious serious adverse events occurring among 6 patients [12%]) versus 14 patients (30%) in the placebo group (with 6 infectious serious adverse events developing among 4 patients [9%]). No deaths occurred in either group. Limitation Potential selection bias based on previous rituximab response and tolerance. Conclusion Extended therapy with biannual rituximab infusions over 18 months was associated with a lower incidence of AAV relapse compared with standard maintenance therapy. Primary funding source French Ministry of Health and Hoffmann-La Roche.

OBJECTIVE The relapse rate of patients with giant cell arteritis (GCA) treated with glucocorticoids (GCs) alone varied widely in observational series and randomized controlled trials (RCTs). The purpose of this systematic review was to evaluate the prevalence of relapse and predisposing factors in patients receiving GCs alone. METHODS We searched Medline up to December 2017. The prevalence of relapse was pooled using a random-effects model. RESULTS A total of 34 studies (2,505 patients), comprising 8 RCTs, were included. The overall prevalence of relapse was 47.2% (95% confidence interval 40.0, 54.3) with a high heterogeneity (I2 = 93%). Prevalence of relapse was significantly higher for patients included in an RCT compared to those included in an observational study (P < 0.0001), but was not significantly different according to design (P = 0.06). The relapse rate was associated with year of publication (34 studies, rate increase of 8.3% for 1 decade; P < 0.0001) and with shorter GC regimens (17 studies, rate decrease of 1.7% for 1 additional month; P < 0.001), the duration of scheduled GC therapy being shorter in RCTs (12.8 months) compared to observational studies (28.8 months). The effective duration of GC therapy (P = 0.23), initial GC dose (P = 0.49), duration of follow-up (P = 0.14), sex (P = 0.29), and age (P = 0.43) were not associated with the prevalence of relapse. CONCLUSION GCA relapses occur in half of patients and without improvement across decades in patients receiving GC alone, and the relapse rate is more related to short duration of GC administration than to the initial dose at induction. These results advocate for trial design with at least 12 months of GC therapy.

ObjectiveThe randomized, controlled MAINRITSAN2 trial was designed to compare the capacity of an individually tailored therapy [randomization day 0 (D0)], with reinfusion only when CD19+ lymphocytes or ANCA had reappeared, or if the latter’s titre rose markedly, with that of five fixed-schedule 500-mg rituximab infusions [D0 + D14, then months (M) 6, 12 and 18] to maintain ANCA-associated vasculitis (AAV) remissions. Relapse rates did not differ at M28. This ancillary study was undertaken to evaluate the effect of omitting the D14 rituximab infusion on AAV relapse rates at M12.MethodsMAINRITSAN2 trial data were subjected to post-hoc analyses of M3, M6, M9 and M12 relapse-free survival rates in each arm as primary end points. Exploratory subgroup analyses were run according to CYC or rituximab induction and newly diagnosed or relapsing AAV.ResultsAt M3, M6, M9 and M12, respectively, among the 161 patients included, 79/80 (98.8%), 76/80 (95%), 74/80 (92.5%) and 73/80 (91.3%) from D0, and 80/81 (98.8%), 78/81 (96.3%), 76/81 (93.8%) and 76/81 (93.8%) from D0+D14 groups were alive and relapse-free. No between-group differences were observed. Results were not affected by CYC or rituximab induction, or newly diagnosed or relapsing AAV.ConclusionsWe were not able to detect a difference between the relapse-free survival rates for up to M12 for the D0 and D0+D14 rituximab-infusion groups, which could suggest that omitting the D14 rituximab remission-maintenance dose did not modify the short-term relapse-free rate. Nevertheless, results at M12 may also have been influenced by the rituximab-infusion strategies for both groups.

Summary Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behcet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. Funding American College of Rheumatology and the European Alliance of Associations for Rheumatology.

Objectives An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA. Methods All patients with GCA and HM living in Côte d’Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d’Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018. Results Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients [standardized incidence ratios (SIR) = 2.71 and 5.16, respectively], with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56). Conclusions Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.

Objective The aim of this study was to describe the efficacy and safety of rituximab and MTX (RTX/MTX) combination therapy in ANCA-associated vasculitides (AAV). Methods A retrospective French nationwide study was conducted in patients with AAV who received RTX/MTX combination therapy for persistently active disease. Results Seventeen patients were included. All patients had granulomatosis with polyangiitis (GPA), with positive ANCA in 76% of them, mainly with PR3-ANCA specificity. Sixteen patients (94%) had priorly failed to achieve remission with RTX and 11 (65%) with CYC. Patients had experienced a median of 3 (2–4) flares. Manifestations requiring RTX/MTX combination therapy were subglottic or bronchial stenosis in 6 patients (35%), orbital mass in 6 (35%), disabling ENT involvement in 2 (12%), and epiduritis and pachymeningitis in 1 case (6%) each. The median follow-up duration for the RTX/MTX combination therapy was 11 months (11–26 months). At 6 months, global response had been achieved in 15 patients (88%), including partial response in 11 (65%) and complete response in 4 (24%). At last evaluation, global response had been achieved in 16 patients (94%). Seven patients (41%) experienced severe adverse events (grade 3 or 4), including infections in 4 (24%) and hepatitis in 2 (12%). Combination therapy was withdrawn in 4 patients (24%), but never for safety concerns. In contrast, the MTX dose was decreased in 2 patients (12%) because of adverse events. One patient died of an unknown cause. Conclusion RTX/MTX combination therapy could be an effective salvage therapy to treat persistently active GPA with granulomatous manifestations, with an acceptable safety profile.