Validation of the Italian version of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire.

Objectives: The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods: The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results: A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P < 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P < 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P < 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion: The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL.

Cutting-Edge Strategies for Renal Tumour-like Lesions in Granulomatosis with Polyangiitis: A Systematic Review.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterised by granulomatous inflammation and small-to-medium vessel necrotising vasculitis, mainly affecting respiratory tract and kidneys. Renal involvement presenting as tumour-like lesions poses diagnostic and treatment challenges. METHODS: Following the observation of a GPA patient presenting with multiple renal tumour-like lesions, we conducted a systematic literature review on MEDLINE/PubMed, EMBASE, and Cochrane databases. Data gathered from the literature were analysed to summarise the diagnostic approach, management, and outcome of renal GPA-related tumour-like lesions. RESULTS: a 49-year-old female presented with persistent constitutional symptoms and multiple bilateral renal lesions. Renal biopsy showed chronic interstitial inflammation with necrotising granulomas. Laboratory tests disclosed positive anti-proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) leading to a final diagnosis of GPA. She was effectively treated with high-dose glucocorticoids and rituximab. Literature search yielded 41 articles, concerning 42 GPA patients with renal masses, presenting bilaterally in 23.8% of the cases. Positive PR3-ANCA was observed in 86.5% of the cases. Half of 42 patients showed kidney abnormalities. Treatment with glucocorticoids (83.3%) and immunosuppressive agents (80.9%) resulted in an overall good remission rate and favourable prognosis. CONCLUSIONS: GPA should be considered in the differential diagnoses of kidney tumour-like lesions. The diagnosis is challenging, and histological examination greatly contributes to the diagnostic work-up.

Clinical Characteristics and Outcomes of Polyarteritis Nodosa: An International Study.

OBJECTIVE: We describe the demographics, clinical features, disease course, and survival of polyarteritis nodosa (PAN) through an international collaboration (GLOBAL-PAN). METHODS: Patients with PAN were recruited between 1990 and 2020 from observational cohorts of nine countries across Europe, Japan, and North America. Eligibility was retrospectively defined using the European Medicines Agency classification algorithm. Patients with PAN related to hepatitis B virus (n = 12) and two monogenic diseases mimicking PAN, deficiency of adenosine deaminase 2 enzyme (n = 16) or familial Mediterranean fever (n = 11), were excluded. Data regarding organ involvement, relapse, disease-related damage, and survival were analyzed. RESULTS: Three hundred fifty-eight patients (female:male ratio 174:184), including those with systemic PAN (sPAN, n = 282) and cutaneous PAN (n = 76), were included. Twenty-five were pediatric onset. Mean ± SD age at diagnosis was 44.3 ± 18.1 years. Constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and neurologic features (48.0%) were common manifestations. Among patients with sPAN, gastrointestinal involvement and proteinuria over 400 mg/day were reported in 52.2% and 11.2%, respectively. During a median (interquartile range) 59.6 (99.5) months of follow-up, relapse occurred in 48.5% of patients. One, 5- and 10-year survival rates for sPAN were 97.1%, 94.0%, and 89.0%, respectively. Predictors of death for sPAN included age ≥65 years at diagnosis, serum creatinine at diagnosis >140 µmol/L, gastrointestinal manifestations, and central nervous system (CNS) involvement. CONCLUSION: The spectrum of PAN remains a complex, multifaceted disease. Relapse is common. Age ≥65 years and serum creatinine >140 µmol/L at diagnosis, as well as gastrointestinal and CNS involvement, are independent predictors of death in sPAN.

Safety of dupilumab in T2 airways conditions: focus on eosinophilia across trials and real-life evidence.

INTRODUCTION: Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, effectively blocks both IL-4 and IL-13 mediated pathways. Its introduction has represented a significant advancement in the treatment of severe asthma and other Type 2 (T2) conditions, including nasal polyps, atopic dermatitis, and eosinophilic esophagitis. To date, Dupilumab has demonstrated optimal efficacy and safety profile. AREAS COVERED: The safety profile of dupilumab has been extensively studied, especially for its effects on blood eosinophil count. Transient eosinophil increase during treatment is typically insignificant from a clinical point of view and related to its mechanism of action. Rare cases of hyper-eosinophilia associated with clinical conditions like eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) have been reported. Those cases are often related to the drug's steroid-sparing effect or the natural trajectory of the underlying disease rather than a direct cause-effect relationship with dupilumab. EXPERT OPINION: The management of hyper-eosinophilia during dupilumab treatment requires comprehensive diagnostic work-up and strict follow-up monitoring for early detection of systemic disease progression in order to avoid unnecessary discontinuation of an effective treatment. This approach highlights the importance of a personalized treatment.

Combination of monoclonal antibodies targeting type 2 inflammation for severe asthma and eosinophilic granulomatosis with polyangiitis.

Monoclonal antibodies targeting type 2 inflammation are promising treatments for eosinophilic-associated diseases. There is growing interest in the potential benefits of combining two biologics to treat patients with poorly controlled conditions. We present a case of a 54-year-old female patient affected with a relapsing-refractory ANCA myeloperoxidase positive eosinophilic granulomatosis with polyangiitis (EGPA), presenting with difficult-to-treat asthma and rhino-sinusitis manifestations. She failed several biologics, including omalizumab 300 mg, mepolizumab 100 mg, and benralizumab 30 mg every 8 weeks. A switch to dupilumab led to significant eosinophilia (7.69 × 109/L) as well as systemic symptoms, and a deterioration of asthma control. Therefore, a combination of dupilumab-benralizumab was started, leading to better nasal and ear outcomes, asthma control and decrease in blood eosinophils. During the 12-month treatment, no adverse effects were observed. We conducted an extensive literature search in MEDLINE for original articles published until August 1st, 2023 reporting the combination of anti-type 2 biologics. A total of 51 cases were retrieved from the literature. Omalizumab was the most frequently combined drugs (34 cases). Combination therapy led to reduction of asthma exacerbations and glucocorticoid intake, though was ineffective only for one EGPA patient. Only one patient on omalizumab-mepolizumab therapy reported a mild adverse reaction. Combination biologic therapies for conditions which share pathogenic pathways appears to be both safe and effective. This approach may benefit patients with uncontrolled conditions and counter side effects of biologics, like dupilumab-related hypereosinophilia.

Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies.

BACKGROUND: The usefulness of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) for the assessment of idiopathic inflammatory myopathies (IIMs) is acknowledged, but laboratory standardization remains a challenge. We detected MSAs/MAAs by multi-analytic line immunoassay (LIA) and particle-based multi-analyte technology (PMAT) in a multicenter cohort of patients with IIMs. METHODS: We tested the sera from 411 patients affected with definite IIM, including 142 polymyositis (PM), 147 dermatomyositis (DM), 19 cancer-associated myositis, and 103 overlap myositis syndrome (OM), and from 269 controls. MSAs/MAAs were determined by 16Ags LIA in all sera, and anti-HMGCR by ELISA in 157/411 IIM sera and 91/269 control sera. The analytical specificity of LIA/HMGCR ELISA was compared with that of PMAT in 89 MSA+ IIM sera. RESULTS: MSAs/MAAs were positive in 307/411 (75%) IIM patients and 65/269 (24%) controls by LIA (Odds Ratio 9.26, 95% CI 6.43-13.13, p < 0.0001). The sensitivity/specificity of individual MSAs/MAAs were: 20%/100% (Jo-1), 3%/99.3% (PL-7), 4%/98.8% (PL-12), 1%/100% (EJ), 0.7%/100% (OJ), 9%/98% (SRP), 5.6%/99.6% (TIF1γ), 4.6%/99.6% (MDA5), 8%/96% (Mi-2), 1.5%/98% (NXP2), 1.7%/100% (SAE1), 4%/92% (Ku), 8.5%/99% (PM/Scl-100), 8%/96% (PM/Scl-75), and 25.5%/79% (Ro52). Anti-HMGCR was found in 8/157 (5%) IIM patients and 0/176 (0%) controls by ELISA (p = 0.007). Concordance between LIA/HMGCR ELISA and PMAT was found in 78/89 (88%) samples. Individual MSAs detected by LIA were associated with IIM subsets: Jo-1 with PM and OM, PL-12 with OM, Mi-2, TIF1γ, and MDA5 with DM, SRP with PM, and PM/Scl-75/100 with OM (p < 0.001 for all). CONCLUSIONS: Since MSAs are mostly mutually exclusive, multi-specific antibody profiling seems effective for a targeted clinical-serologic approach to the diagnosis of IIMs.

Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA. PATIENTS AND METHODS: We conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm3. RESULTS: Fifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268-4501) occurring at 13 weeks (IQR 4-36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab. CONCLUSION: These results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.

Might maintenance therapy be discontinued once clinical remission is achieved in ANCA-associated vasculitis?

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of rare, multisystem autoimmune disorders characterised by the occurrence of inflammation and damage to small blood vessels, leading to a wide range of clinical manifestations. They include granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Outcomes for patients with MPA and GPA have been transformed over recent years. However, the establishment of effective maintenance therapy aiming to balance the risks of disease relapse with those related to prolonged immunosuppression has become a clinical priority. This review aims to explore two differing perspectives on this unsolved problem. Pros and Cons of the following approaches will be discussed: "Biomarker-guided personalised approach on top of generic maintenance strategy guidelines" or "ANCA specificity-related personalised maintenance treatment after intensive B-cell depletion"?

Subclinical giant cell arteritis in polymyalgia rheumatica: Concurrent conditions or a common spectrum of inflammatory diseases?

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice. Subclinical GCA prevalence in newly diagnosed PMR patients ranges from 23 to 29%, depending on the screening method. Vessel wall imaging and temporal artery biopsy can detect subclinical GCA. Epidemiology and trigger factors show similarities between the two conditions, but PMR is more common than GCA. Genetic and pathogenesis studies reveal shared inflammatory mechanisms involving dendritic cells, pro-inflammatory macrophages, and an IL-6 signature. However, the inflammatory infiltrates differ, with extensive T cell infiltrates seen in GCA while PMR shows an incomplete profile of T cell and macrophage-derived cytokines. Glucocorticoid treatment is effective for both conditions, but the steroid requirements vary. PMR overall mortality might be similar to the general population, while GCA patients with aortic inflammatory aneurysms face increased mortality risk. The GCA-PMR association warrants further research. Considering their kinship, recently the term GCA-PMR Spectrum Disease (GPSD) has been proposed.

Characteristics and outcome of ANCA-associated vasculitides induced by anti-thyroid drugs: a multicenter retrospective case-control study.

OBJECTIVE: Data on ANCA-associated vasculitis (AAV) induced by anti-thyroid drugs (ATD) are scarce. We aimed to describe the characteristics and outcome of these patients in comparison to primary AAV. METHODS: We performed a retrospective multicenter study including patients with ATD-induced AAV. We focused on ATD-induced microscopic polyangiitis (MPA) and compared them with primary MPA by matching each case with 4 controls by gender and year of diagnosis. RESULTS: Forty-five patients with ATD-induced AAV of whom 24 MPA were included. ANCA were positive in 44 patients (98%), including myeloperoxidase (MPO)-ANCA in 21 (47%), proteinase 3 (PR3)-ANCA in 6 (13%), and double positive MPO- and PR3-ANCA in 15 (33%). Main clinical manifestations were skin involvement (64%), arthralgia (51%), and glomerulonephritis (20%). ATD was discontinued in 98% of cases, allowing vasculitis remission in 7 (16%). All the remaining patients achieved remission after glucocorticoids, in combination with rituximab in 11 (30%) or cyclophosphamide in 4 (11%). ATD were reintroduced in 7 cases (16%) without any subsequent relapse. Compared with 96 matched primary MPA, ATD-induced MPA were younger at diagnosis (48 vs. 65 years, P < 0.001), had more frequent cutaneous involvement (54 vs. 25%, P = 0.007), but less frequent kidney (38 vs. 73%, P = 0.02), and a lower risk of relapse (adjusted HR 0.07; 95%CI 0.01-0.65, P = 0.019). CONCLUSION: ATD-induced AAV were mainly MPA with MPO-ANCA, but double MPO- and PR3-ANCA positivity was frequent. The most common manifestations were skin and musculoskeletal manifestations. ATD-induced MPA were less severe and showed a lower risk of relapse than primary MPA.

Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients.

BACKGROUND: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. METHODS: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. RESULTS: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. CONCLUSIONS: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.

Validation of the 2022 American College of Rheumatology/EULAR classification criteria for Takayasu arteritis.

OBJECTIVES: The present study validates the 2022 ACR/European Alliance of Associations for Rheumatology (EULAR) classification criteria for Takayasu's arteritis (TAK), compared with the 1990 ACR TAK classification criteria. METHODS: The fulfilment of 2022 ACR/EULAR and 1990 ACR TAK criteria from four referral centres was assessed for TAK compared with extracranial giant cell arteritis (EC-GCA) and other controls. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio of a positive test (LR+) or negative test (LR-), and area under receiver operating characteristics curve (AUC) were calculated. RESULTS: Among 504 patients with TAK (404 females) and 222 controls (151 females, 144 patients with EC-GCA), the 2022 ACR/EULAR criteria had better sensitivity (95.83% vs 82.94%) and NPV, but poorer specificity (63.51% vs 90.54%), PPV, LR+, LR- and AUC at the pre-determined cut-offs than the 1990 ACR criteria. The 2022 ACR/EULAR criteria had greater specificity (76.06% vs 57.62%) and AUC (0.845 vs 0.771), with similar sensitivity (93% vs 96.53%) in males as in females. The 2022 ACR/EULAR criteria performed similarly with only EC-GCA as controls (sensitivity 95.83%, specificity 60.42%, AUC 0.781). Sensitivity remained similar, whereas specificity was higher for 40-60 years vs <40 years. Cut-offs of ≥6 (sensitivity 91.87%, specificity 82.88%) and ≥7 (sensitivity 86.71%, specificity 86.49%), or removing the point for female sex (sensitivity 92.64%, specificity 81.08%) greatly improved the balance between sensitivity and specificity. CONCLUSION: The poor specificity of the 2022 ACR/EULAR TAK criteria in real-life settings was improved by increasing the cut-off to 6 or 7, or removing the point for female sex.

COVID-19 vaccination rate and safety profile in a multicentre Italian population affected by mixed cryoglobulinaemic vasculitis.

OBJECTIVES: Mixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterised by heterogeneous clinical manifestations mainly involving lymphatic system, skin, kidney and peripheral nervous system. Although MCV patients have been included in priority programs for vaccination against SARS-CoV-2 in Italy, limited information is available for these patients. The aims of this multicentre Italian study were to investigate SARS-CoV-2 vaccination rate in MCV patients and its safety profile. METHODS: All MCV patients referring to participating centres were assessed with an interview-based survey about vaccination, reasons for not getting vaccinated, adverse events (AE), and disease flares within a month after vaccination. RESULTS: A total of 416 patients were included in the study. Among participants, 7.7% did not get vaccinated, mainly for fear related to vaccine side-effects (50%) or medical decision (18.8%). They were more frequently treated with chronic glucocorticoids or rituximab (p=0.049 and p=0.043, respectively). Mild and self-limiting AE were recorded in 31.7% of cases, while post-vaccination vasculitis flares were observed in 5.3% of subjects. Disease relapses were mainly observed in patients with peripheral neuropathy or skin vasculitis (40% and 25%, respectively). CONCLUSIONS: Vaccination against SARS-CoV-2 has been performed in a high percentage of MCV patients with encouraging safety profile. Vasculitis flares rate was in line with that observed for other autoimmune diseases, despite patients with purpura or peripheral neuropathy seem to be at risk for symptoms' exacerbation. Patients' hesitancy, rituximab and glucocorticoids treatment were the main reasons for delaying vaccination.

New onset and flare of rheumatic diseases following COVID-19 vaccination are mild and respond well to treatment: 9-month follow-up data from a single centre cohort.

OBJECTIVES: Anti-COVID-19 vaccines have proved to be effective and well tolerated. Great attention is now being paid to the characterisation of possible adverse events associated to their administration. We report a case series of suspected rheumatic diseases (RDs) following anti-COVID-19 vaccination. METHODS: We included patients evaluated at first-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padova University Hospital between May and September 2021 presenting with a RD within 30 days after an anti-COVID-19 vaccine dose. Our selection was in accordance with the World Health Organisation guidelines for adverse event following immunisation (AEFI) surveillance. Patients were regularly re-evaluated by telemedicine or face-to-face visit. RESULTS: We identified 30 cases of RD following vaccination: 24 (80.0%) new onsets and 6 (20.0%) flares. Most of patients (76.6%) received the BNT162b2 vaccine. The mean time to RD onset/flare was 12±9 days. The most common manifestations were inflammatory arthritis (40.0%), rheumatic polymyalgia (33.3%) and adult-onset Still's disease (13.3%). At the last FU visit (9.6±2.2 months), 83.3% of patients showed complete response to first- or second-line therapy, 13.3% a partial response and one patient (3.3%) was still experiencing an active disease. CONCLUSIONS: Considering the amount of vaccine doses administered during the evaluation period we overall detected a limited number of cases. We noted a clear prevalence of autoinflammatory conditions and seronegative manifestations. The great majority of patients had mild features and showed a good response to therapy.

Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology.

OBJECTIVES: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features. METHODS: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%). RESULTS: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex. CONCLUSIONS: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study.

BACKGROUND: Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA. METHODS: This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up. FINDINGS: 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab. INTERPRETATION: These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity. FUNDING: None.

Use of biologics to treat relapsing and/or refractory polyarteritis nodosa: data from a European collaborative study.

OBJECTIVES: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN). METHODS: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease. RESULTS: Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases. CONCLUSION: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings.

Biologic therapy in relapsing polychondritis: navigating between options.

INTRODUCTION: Relapsing polychondritis (RP) is a rare systemic inflammatory disease of unknown etiology, primarily affecting cartilaginous tissue and proteoglycan-rich structures. Clinical manifestations vary from mild symptoms to occasional organ or life-threatening complications. Treatment can be challenging and is mostly based on experience or case reports/series. AREAS COVERED: There is growing literature investigating the role of biologics in the management of RP. TNFα antagonists, abatacept, tocilizumab, rituximab, anakinra and tofacitinib have been prescribed in several RP patients, mainly as second-line treatment, after conventional immunosuppressive agents' failure. EXPERT OPINION: Glucocorticoids represent the gold standard treatment of RP. Conventional immunosuppressants should be administered in refractory patients or when a glucocorticoid-sparing effect is needed. Biologic therapy should be used after failure of conventional treatments or in severe manifestations. TNFα inhibitors are the most prescribed biologic agent, with partial or complete response in several cases, but loss of efficacy may occur over time. Infliximab and adalimumab should be preferred among TNFα antagonists. Abatacept and tocilizumab proved to be effective as second-line biologic agents, but infections are reported with the former. Data on anakinra and rituximab are controversial, therefore they are not recommended as first-line biologic drugs. The use of JAK inhibitors is still anecdotal.