Welcome to the CORA 2023
Interactive Program

Background and Aims

In rheumatoid arthritis (RA) around two-thirds of patients are autoantibody-positive for rheumatoid factor, anti-citrullinated protein antibodies (ACPA) and/or anti-carbamylated protein antibodies (anti-CarP). The remaining seronegative subgroup of RA is clinically heterogeneous and thus far, biomarkers predicting the disease course in these patients are lacking. Therefore, we analysed the value of new autoantibodies in RA directed against malondialdehyde acetaldehyde adducts (MAA) and advanced glycation end-products (AGE).

Methods

In sera of 648 RA patients and 538 non-RA arthritis patients from the Leiden Early Arthritis Clinic anti-MAA and anti-AGE IgG antibody levels were measured using ELISA. Associations between genetic risk factors, acute phase reactants, radiological joint damage and anti-PTM positivity were investigated using regression and correlation analyses.

Results

Anti-AGE and anti-MAA were most prevalent in RA (44.6% and 46.1% respectively) but were also present in non-RA arthritis patients (32.9% and 30.3% respectively). Within seronegative RA patients the presence of anti-AGE and anti-MAA antibodies is associated with HLA-DRB1*03 (OR=1.98, p=0.003, and 2.37, p<0.001, respectively). HLA-DRB1*03 associates with anti-AGE in non-RA patients (OR=2.34, p<0.001) independent of anti-MAA. Presence of anti-MAA antibodies associated significantly with markers of inflammation, ESR and CRP, in both groups independent of anti-AGE. Interestingly, the presence of both anti-AGE and anti-MAA antibodies associated with radiologic progression in seronegative RA patients.

Conclusions

Anti-AGE and anti-MAA are present in around 50% of RA patients and 30% of non-RA patients, and although not specific for RA they associate with HLA risk factors and clinical outcomes especially in RF-, ACPA- and anti-CarP-negative patients.

Background and Aims

The JAK-1 inhibitor filgotinib has been recently licensed for Rheumatoid Arthritis (RA), thus real-world evidence is lacking. Our aim was to assess efficacy and safety of filgotinib in a real-world setting.

Methods

In this prospective monocentric study, we included all patients with RA (ACR/EULAR 2010 criteria) regularly followed-up (every 2-6 months), undergoing therapy with filgotinib (reimbursed in our Region since September 2021). Data were captured in the Regional Biologic Registry between 09/2021 and 10/2022. Disease activity was measured by DAS28-CRP, CDAI, and SDAI; concomitant cDMARDs and glucocorticoid therapy, and all adverse events (AE) experienced during filgotinib treatment were recorded

Results

We enrolled 42 RA patients, 4 (9.5%) b/tsDMARD naïve, 9 (21.4%) monotherapy, mean±SD follow-up 7.5±4.5 months (Table1). Twenty-three patients (54.8%) had ≥6month follow-up: mean±SD DAS28-CRP, CDAI, and SDAI significantly decreased from baseline (Table2). Fifteen (65.2%) and one (4.3%) patients achieved DAS28-CRP remission and LDA at 6 months, respectively. Patients with failure to >2 classes of bDMARDs (18) or those failing a JAK-i (6) prior to filgotinib initiation showed a response similar to that observed in other patients.

Overall, 17 patients (40.5%) experienced ≥1 AE, of whom 2 (4.8 %) were SAE (1 ILD progression, 1 death). 5/42 patients discontinued Filgotinib: 2 due to primary inefficacy (4.8%), 3 for AE/SAE (7.1%).

Within the first 6 months of treatment, no change in mean glucocorticoid dose was observed.

Conclusions

Real-world treatment with filgotinib was associated with clinical improvement and low AE rate. Multi-failure RA patients and those failing a previous JAK-i benefited from Filgotinib therapy.

Background and Aims

Remission in rheumatoid arthritis (RA) is the optimal goal but,even when it is reached,the “residual pain” can persist.The aims of this study were (i) to characterize the size and perception of residual pain and (ii) to evaluate the synovitis impact on residual pain in remission RA patients.

Methods

One hundred twenty-seven RA patients,of which 68 in clinical and ultrasound remission (REM-RA) and 29 in high disease activity (HDA-RA),were enrolled in the study.Thirty fibromyalgia patients were enrolled as control group (FIBRO).Upon enrolled,demographic,clinical,ultrasound features and PROs (RAID,FACIT,GHQ and VAS-pain questionnaires) were collected.RA patients underwent biopsy of the synovial membrane of the knee in order to assess the degree of synovitis,according to the Krenn Score (KSS).

Results

Considering the RA group,DAS28-CRP inversely correlated with FACIT (R2=-0.506,p<0.0001) while total GHQ score (R2=0.407;p<0.0001) and VAS-pain (R2=0.402,p<0.0001) are directly correlated to DAS28-CRP.Moreover a GHQ higher score was found in 26% of REM-RA patients compared to 52% (p=0.004) and 77% (p<0.0001) of HDA-RA and FIBRO groups respectively while the REM-RA patients had lower VAS-pain values ​​(20) compared to HDA-RA (50;p<0.0333) and FIBRO (70;p<0.0001).Moreover REM-RA patients presented lower RAID scores (3.34) than HDA-RA (5.56;p=0.0003) and FIBRO patients (7.63;p<0.0001).Finally,the presence of subclinical synovitis (KSS≥2) in REM-RA patients (50%) was not associated with a VAS-pain higher score.

Conclusions

Remission status in RA is associated with a better psycho-physical state but,despite that,there is the persistence of a certain degree of residual pain,regardless of the subclinical synovitis degree,suggesting different underlying biological mechanisms in residual pain in RA remission status.

Background and Aims

Subclinical myocardial dysfunction is frequent in inflammatory rheumatic diseases. We explored the potential association of adipokines and pro-inflammatory cytokines with subclinical myocardial dysfunction of patients with active psoriatic arthritis (PsA).

Methods

Fifty-five PsA patients without cardiovascular risk factors and 25 controls underwent standard and speckle tracking echocardiography with GLS calculated. Standard anthropometric data, disease specific data and DAPSA scores were recorded. Patients with DAPSA score <15 were defined as mild while patients with DAPSA score >15 were defined as moderate to severe. Standard biochemistry, serum adipokines levels (adiponectin, resistin, leptin) and pro-inflammatory cytokines (TNFα, IL-17, BLC and MIG) were analysed.

Results

Median age was 53.0 (46.0 - 61.0), median PsA duration 6.0 (4.0 – 13.0) years and median DAPSA score 25.5 (13.0 – 41.5). Lower GLS, TAPSE and LVEF were found in moderate to severe PsA compared to mild disease and controls. PsA patients with GLS≤20 had higher BMI, DAPSA score and uric acid levels, and lower adiponectin levels. Although PsA patients with GLS≤20 had higher IL-17 levels, it was not statistically significant (P=0.056). When analysis included healthy controls and assessed differences between subjects with GLS>20 and GLS≤20, the difference in IL-17 became statistically significant, 0.17 pg/mL (0.06-0.32) vs. 0.43 pg/mL (0.23-0.65), P=0.017.

Conclusions

Moderate to severe PsA patients without cardiovascular risk have more frequently reduced myocardial function. PsA patients with impaired myocardial function might have lower adiponectin and higher IL-17 levels compared to PsA patients with normal myocardial function and healthy controls.

Background and Aims

Biologic disease modifying anti-rheumatic drugs (bDMARDs) have dramatically improved the outcome of patients affected by chronic inflammatory arthritis. However, a satisfactory disease control is not achieved in a proportion of patients.

While a “difficult-to-treat” (D2T) definition has been validated in rheumatoid arthritis (RA), it was only recently suggested for psoriatic arthritis (PsA) (Perrotta FM et al, Rheumatol Ther 2021). Based on this definition, we aimed to assess prevalence and characteristics of D2T-PsA in our cohort.

Methods

We conducted a single-center, cross-sectional study: consecutive, adult PsA patients receiving bDMARDs at a tertiary care, dedicated outpatient clinic were enrolled.

Demographic, clinical, and clinimetric data, and the Health Assessment Questionnaire (HAQ) were gathered.

Comparison between D2T and non-D2T patients was performed with univariate analysis.

Results

Among 269 PsA patients, only 8 (3%) fulfilled D2T definition. In bivariate analysis, D2T patients presented higher rate of osteoarthritis (62.5% vs 24.9%; p=0.03), fibromyalgia (62.5% vs 14.94%; p<0.004), and therapy with steroids (50% vs 12.1%; p=0.008). Furthermore, D2T patients presented significantly higher patient global assessment (PGA 0-10) (7.5 vs 2.00; p<0.001) and VAS pain 0-10 (8.00 vs 2.00; p<0.001). Among non-D2T patients, 24 were in moderate disease activity (9.19%).

Due to the unbalance between the groups numerosity, multivariate analysis was not feasible.

Conclusions

Only few patients satisfied the PsA-D2T definition in our cohort; application of a RA-like D2T definition to a heterogeneous disease as PsA should be discussed more broadly in the future.

Background and Aims

Whether glucocorticoids (GC) may affect the efficacy and safety of Janus kinases inhibitors (JAKi) is unknown.

Methods

We evaluated the use of GC in a cohort of patients with rheumatoid arthritis (RA) who started treatment with JAKi between 03/2018 and 10/2021. The primary outcome was the EULAR response (moderate/good) after 6 months; secondary outcomes were EULAR response at 12 months and drug discontinuation. Patients who discontinued JAKi were imputed as non-responders for efficacy outcomes. We expressed the associations between outcomes and covariates as odds ratio (OR) and 95% confidence interval (CI).

Results

We included 149 patients (mean age 59 years, RA duration 16 years; females 89%) treated with JAKi (tofacitinib 34%, baricitinib 43%, upadacitinib 16%, filgotinib 7%). 66% of patients took GC (mean 4.5 mg/d), decreasing to 48% after 6 months. GC dose was transiently reduced in responders (56%) at 6 months (-1.8 mg/d, p<0.001; Figure), but it was neither associated with response nor drug retention at 12 months; 6% of patients restarted GC between 6 and 12 months. In multiple logistic regression, GC use had no association with the response at 6 months, which was significantly related to the male sex (OR 2.9;1.6-5.3), no extra-articular disease (OR 2.6;1.7-4.0) and no rheumatoid factor (OR 1.7;1.2-2.4). 20% of patients discontinued JAKi within 6 months (59% adverse events, 41% inefficacy), and 26% within 12 months (31% adverse events, 69% inefficacy), regardless of GC use.

Conclusions

JAKi allowed a slight decrease in GC use. The efficacy and safety of JAKi were independent of GC use.