Welcome to the CORA 2023
Interactive Program

Background and Aims

Rituximab (RTX) achieved high remission-induction and sustained maintenance rates in patients with ANCA-associated vasculitis (AAV). However, RTX is expensive and may potentially lead to serious side effects. Defining the best maintenance regimen in AAV is still an unmet need

Methods

Consecutive AAV patients (classified as GPA and MPA) who successfully achieved disease remission (BVASv3=0) with conventional RTX regimen were included. Patients received at least three maintenance RTX infusions with either 1000 mg or 500 mg, twice per year (standard low dose) or once per year (ultra-low dose). The patients were compared after 18 months

Results

A total of 83 AAV patients (51±16 years, 49.4% female, 95.2% ANCA positive, 65.8% anti-PR3, 61 GPA, 22 MPA) achieved complete disease remission with conventional induction regimen. After 7 [6-9] months, 29.9% patients started maintenance treatment with ultra-low dose RTX, while 70.1% with standard low dose, for 18 months. No significant differences at baseline were noted. At the end of observation period, relapse-free survival was comparable between the two group (22.7% vs 21.2%, log-rank p=0.818).

No differences were noted in ANCA negative rate (p=0.262), B-cells depletion rate (p=0.725), serum IgG (p=0.367), VDI (4 [1-5] vs 2 [1-4], p=0.098).

Although not significant, patients treated with ultra-low dose had lower severe infection rate (10.5% vs 26.8%, p=0.154), lower severe hypogammaglobulinaemia (31.8% vs 36.5%, p=0.697) and less deaths (4.5% vs 5.8%, p=0.831).

Conclusions

Reduced RTX exposurewas not associated with an impaired efficacy in maintenance therapy in AAV patients. Remission maintenance with ultra-low dose RTX is a safe and more cost-effective option

Background and Aims

Takayasu’s arteritis (TAK) is widely thought to affect predominantly young Asian women. However, little is known regarding the clinical profile of late-onset TAK. This study investigated the clinical profile of patients with TAK with a focus on late-onset TAK.

Methods

We retrospectively enrolled patients with TAK who were hospitalized in Fuwai Hospital between January 2010 and December 2019. Demographic, clinical characteristics, vascular involvement, and biochemical findings were compared between those with early-onset TAK (<40 years) and with late-onset TAK (>=40 years).

Results

One hundred and forty-two (20.2%) of 704 patients with TAK were aged >=40 years when they experienced their earliest TAK-related symptoms. Late-onset TAK patients experienced more cardiac symptoms, were more likely to have cardiovascular risk factors and coronary artery involvement, and were less likely to have neurologic symptoms than those with early-onset TAK. Late-onset TAK patients had a lower estimated glomerular filtration rate (96.64 [84.60–106.98] vs. 110.37 [94.58–122.61]; p<0.001) and higher blood urea nitrogen (5.43 [4.39–7.05] vs. 4.97 [4.10–6.15]; p=0.002). Late-onset TAK patients tended to have more inflammatory biomarker activity, including a higher frequency of elevated erythrocyte sedimentation rate (44.3% vs. 25.9%; p<0.001) and higher levels of C-reactive protein (4.47 [2.25–11.80] vs. 3.35 [1.82–8.65]; p=0.013) and high-sensitivity C-reactive protein (4.01 [1.12–10.72] vs. 2.12 [0.88–7.97]; p=0.009).

Conclusions

Patients with late-onset TAK are more likely to have cardiac symptoms, cardiovascular risk factors, and coronary artery involvement, less likely to have neurologic symptoms, and tend to have more inflammatory activity and renal impairment than those with early-onset TAK.

Background and Aims

Management of immune-related adverse events (irAEs) is challenging as using corticosteroids as first-line therapy can lead to significant morbidity. Our preliminary results suggested a role for interleukin-6/Th17 pathway in both irAEs and immunotherapy resistance. Therefore, we evaluated the safety and efficacy of tocilizumab plus combination immune checkpoint inhibitors (ipilimumab/nivolumab) in previously untreated metastatic melanoma patients.

Methods

Phase II, open-label, single center study (NCT04940299). Participants (n=35) receive subcutaneous tocilizumab 162 mg weekly or bi-weekly for up to 12 weeks as approved for rheumatoid arthritis plus ipilimumab/nivolumab per the standard dosing for melanoma. Objectives: 1) assess grade 3 or higher irAEs; 2) estimate objective response rate (ORR) by RECIST 1.1 and overall survival; and 3) explore biomarkers of toxicity and tumor response/resistance. Safety assessments continue for up to 2 years in participants who discontinue therapy for any reason.

Results

To date, 25 participants have been enrolled; duration of treatment ranged from 6 to 41 weeks. Eleven patients (44%) had grade III/IV irAEs: colitis (20%), hepatitis (16%), pancreatitis (8%), and polymyalgia rheumatica-like and type I diabetes (4% each). Median time to irAE onset was 8.3 weeks (2.7-17.3) and irAEs led to study discontinuation in 4%. There have been no treatment-related deaths. The ORR was 60% including 44% in patients with elevated LDH and disease control rate (CR+PR+SD) was 75%.

Conclusions

Our preliminary data showed a numerically lower rate of grade III/IV irAEs compared to similarly designed ipilimumab/nivolumab melanoma trials without negative impact on efficacy. Ongoing immune analysis will be presented to help further interpret these results.

Background and Aims

Few biomarkers are currently available for monitoring of idiopathic inflammatory myopathies (IIM). Extracellular vesicles (mEVs) are small lipid-bilayer particles involved in modulation of immune response. We aim to investigate correlates between plasma mEVs and clinical and laboratory features of IIM.

Methods

Adult IIM patients (EULAR 2017) and age-/sex-matched healthy controls (HD) were included. mEVs were isolated through size exclusion chromatography and ultra-filtration. Particles morphology, concentration and surface marker characterization were assessed via transmission electron microscopy, nanoparticle tracking analysis and imaging flow cytometry respectively. Data were cross-sectionally analyzed; parametric Student-t test and one-way ANOVA with Bonferroni correction or non-parametric tests were used.

Results

We included 45 IIM patients (F:M 2:1; mean age±SD 59.2±13.5y) and 45 HD. The specific IIM diagnosis was identified. 39 (86.7%) patients were receiving glucocorticoids and/or immunosuppressants at the time of blood sampling.

Immunophenotyping revealed a significantly increased proportion of CD19+ mEVs, indicating a likely B cell origin.
IIM patients displayed significantly increased mEV concentrations compared to HD (mean±SD [mEVs/mL], 1.95x10¹⁰±1.47x10¹⁰ vs. 1.45x10¹⁰ ± 7.82x10⁹, p=0.025). mEVs concentrations were significantly higher in treatment-naïve patients and decreased upon treatment. Patients with IIM onset ≤6 months displayed higher circulating levels of mEVs (3.20x10¹⁰±2.42x10¹⁰ vs. 1.80x10¹⁰±1.80x10¹⁰, p=0.042), as did seropositive patients against seronegative (2.09x10¹⁰±1.63x10¹⁰ vs. 1.49x10¹⁰±0.43x10¹⁰, p=0.063). Cancer associated myositis patients displayed the highest levels of circulating mEVs.

Conclusions

Circulating, B cell-derived mEVs are significantly increased in IIM, especially in recent-onset, seropositive, treatment-naïve disease.

Our findings reinforce the potential role of mEVs as biomarkers for early diagnosis, treatment response and disease monitoring in IIM.

Background and Aims

To assess the long-term outcome in inflammatory idiopathic myopathies (IIM) patients using Artificial intelligence (AI) and focusing on clinical and laboratory features and treatment.

IIM are a group of rare heterogeneous diseases classified into dermatomyositis (DM), inclusion body myositis (IBM), anti-synthase syndrome (ASS), immune-mediated necrotizing myopathy (IMNM), overlap syndromes. The clinical course can be highly variable with systemic involvement of different organs and patients can have a rapidly progressive, remitting, or periodic relapsing course.

Machine learning (ML) allows to analyze great information and evaluating decision-making processes, deep learning (DL) analyzes data through neural networks and learns from them. Both processes are increasingly used in medical research.

Methods

We evaluate the long-term outcome of 107 patients affected by IIM. All patients had a diagnosis based on Bohan and Peter criteria or EULAR/ACR criteria for IIM and had at least a 2-year follow-up period.

We considered different parameters, including clinical manifestations and organ involvement, number and type of treatments, serum creatine kinase levels, muscle strength (MMT8 score), disease activity (MITAX score), disability (HAQ-DI score), disease damage (MDI score), and physician and patient global assessment (PGA).

Results

The database collects data that will be analyzed, applying, with R, supervised ML algorithms such as lasso, ridge, elastic net, classification, and regression trees (CART) and random forest to find the factors that best predict disease outcome.

Conclusions

The use of artificial intelligence (AI) algorithms will allow us to identify the parameters that best correlate with the disease outcome in IIM.

Background and Aims

Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab (RTX). Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking. This abstract reports on a prospective single-Center open study aimed at evaluating the clinical presentation and effects of RTX administered alone in patients (pts) with severe non HCV-related cryoglobulinemic syndrome

Methods

We analyzed all pts with a previous diagnosis of non HCV-related cryoglobulinemia and biopsy-proven renal involvement. Inclusion criteria for the study were the presence of cryoglobulins on at least 2 determinations and the absence of HCV infection. They were all treated with 4 once-weekly doses of RTX (375 mg/m²) plus two more doses, administered 1 and 2 months later (improved protocol)

Results

All 11 pts presented with biopsy-proven renal involvement, 4/11 with leukocytoclastic vasculitis, and 8 with involvement of the peripheral nervous system. Mean cryocrit was 2.5%. 4/11 pts had symptomatic sicca complex. After 6 months we observed a remarkable improvement in the necrotizing skin ulcers and a substantial amelioration of the electrophysiological parameters of motor and sensory peripheral neuropathy. Improvement in both renal function (from 2.8 to 1.4 mg/dl, p<0.001) and proteinuria (from 4.2 to 0.4 g/24 hours, p<0.001) was found in 10/11 pts. Good renal response was confirmed at the end of follow-up (38.4 months).

Conclusions

In our cohort the administration of 4 once-weekly infusions of RTX followed by 2 more infusions after 1 and 2 months proved to be effective in the management of these rare pts.