Relapses and serious adverse events during rituximab maintenance therapy in ANCA-associated vasculitis: a multicentre retrospective study.

OBJECTIVES: There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission-maintenance agent in microscopic-polyangiitis (ΜPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well serious-adverse-events (SAEs) in MPA/GPA patients during RTX-maintenance. METHODS: Retrospective cohort of newly-diagnosed/relapsing GPA/MPA patients who received RTX-maintenance (≥1 RTX-cycle, ≥6 months follow-up) following complete-remission (Birmingham-Vasculitis-Activity-Score-version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious-infections, COVID-19-associated hospitalizations, deaths, cardiovascular-events, malignancies and hypogammaglobulinemia. Incidence-rates (IR) and relapse-free survival through Kaplan-Meier plots were estimated. Cox-regression was conducted to investigate factors associated with the time-to-relapse. RESULTS: 101 patients were included; 48% females, 69% GPA, 53% newly diagnosed, median age: 63 years. During follow-up (294.5 patient-years, median: 3 RTX-cycles), 30 relapses (57% major) occurred among 24 patients (24%, IR 10.2/100 patient-years). Kidney involvement (adjusted-Hazard-Ratio/aHR: 0.20; 95% CI: 0.06-0.74, p= 0.016), prior induction with RTX plus cyclophosphamide (vs RTX monotherapy: aHR = 0.02; 95% CI: 0.001-0.43, p= 0.012) and shorter time-interval until complete-remission (aHR = 1.07; 95% CI: 1.01-1.14, p= 0.023) were associated with decreased relapse-risk. We recorded 17 serious-infections (IR 5.8/100 patient-years), 11 COVID-19-associated hospitalizations (IR 3.7/100 patient-years), 4 malignancies (IR 1.4/100 patient-years), 6 cardiovascular-events (IR 2/100 patient-years) and 10 deaths (IR 3.4/100 patient-years). CONCLUSION: In this real-world study, relapses during RTX-maintenance occurred in approximately in 1 out of 4 patients. Kidney involvement, induction with RTX plus cyclophosphamide and earlier achievement of complete-remission were associated with lower relapse-risk. Serious-infections rate was consistent with previous reports, whereas an increased rate of COVID19-associated hospitalizations was observed.

Urine Nephrin and Podocalyxin Reflecting Podocyte Damage and Severity of Kidney Disease in Various Glomerular Diseases-A Cross-Sectional Study.

Background/Objectives: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, characterized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels (p = 0.001 and p = 0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p < 0.05). In addition, the PDC and NEP demonstrated statistically significant correlations with interstitial inflammation (p = 0.018/p = 0.028). Regarding electron microscopy evaluation, PDC levels were correlated with distinct characteristics, such as fibrils and global podocyte foot process fusion, whereas the NEP/CR ratio was uniquely significantly associated with podocyte fusion only in non-immune-complex-mediated glomerulonephritis (p = 0.02). Among the other clinical and histological parameters included in our study, a strong correlation between proteinuria >3 g/24 h and diffuse fusion of podocyte foot processes (p = 0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine are markers of podocyte dysfunction, and in our study, they were associated both with serum creatinine and histological chronicity indices.

Renal Vein Thrombosis Secondary to Pyelonephritis: Targeting a Thrombo-Inflammatory Entity.

Renal vein thrombosis (RVT) is a relatively uncommon condition that is most frequently observed in individuals with nephrotic syndrome. While rare, pyelonephritis (PN) may serve as a predisposing factor for secondary RVT. In such cases, one should consider the possibility of RVT when patients fail to respond to appropriate antibiotic treatment. Typically, these patients require additional anticoagulation therapy for a duration of 3 to 6 months, with a generally favorable prognosis. In this report, we present the case of a 74-year-old female who developed RVT due to Klebsiella pneumoniae PN. Additionally, we reviewed 11 cases of PN complicated by RVT, which were documented in the PubMed database over a span of 40 years, emphasizing key elements in diagnostic and therapeutic approaches. Lastly, we elaborated upon the role of thrombo-inflammation, especially in the context of sepsis.

Identification and characteristics of patients with potential difficult-to-treat Psoriatic Arthritis: exploratory analyses of the Greek PsA registry.

OBJECTIVE: To present the characteristics of patients with potential difficult-to-treat (D2T) psoriatic arthritis (PsA). METHODS: We used data from the Greek multicentre registry of PsA patients. D2T-PsA was defined as follows: patients with at least 6-months disease duration, who have failed to at least 1 csDMARD and at least 2 bDMARDs/tsDMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA > 14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. RESULTS: Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (p< 0.0001) and were more likely to have higher BMI (p= 0.023) and a history of inflammatory bowel disease (p= 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (p= 0.001 and p= 0.008, respectively). Moreover, female gender (p= 0.034) in the MODA analysis and axial disease (p= 0.040) in the MDA analysis were independent variables for D2T PsA. CONCLUSION: Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial-disease, and history of IBD were also associated with D2T PsA.

Autoimmune polyglandular syndrome with shock and high anion gap metabolic acidosis.

Autoimmune polyglandular syndrome (APS) is a rare group of immune-mediated disorders, which are typically, but not exclusively, related to the presence of endocrine abnormalities. APS type 2 is the most common subtype of the syndrome, more often observed in adulthood, with a characteristic clinical triad, which includes adrenal insufficiency, autoimmune thyroiditis and diabetes mellitus type 1. Adrenal insufficiency is an essential and necessary clinical manifestation of the syndrome, as it is observed in 100 % of the cases, while it can be accompanied by hyperchloremic metabolic acidosis. Herein, we present a 23 years-old patient with adrenal insufficiency in the context of autoimmune polyglandular syndrome type 2 with coexisting autoimmune thyroiditis and metabolic acidosis with an increased anion gap attributed to prolonged malnutrition. Additionally, we analyze the main clinical features of adrenal insufficiency, which is a central component of autoimmune polyglandular syndrome; highlight characteristics that differentiate the major APS subtypes.

EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update.

BACKGROUND: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. METHODS: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. RESULTS: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. CONCLUSIONS: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.

Pneumocystosis in a patient with rheumatoid arthritis on adalimumab therapy: a case-based review.

Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal type of pneumonitis, which may have devastating consequences. Typically, it occurs in immunocompromised patients, with the natural history varying depending on the presence or not of HIV infection. Staining and polymerase chain reaction (PCR) testing in induced sputum or bronchoalveolar lavage (BAL) is the cornerstone of the diagnosis, while trimethoprim-sulfamethoxazole is the treatment of choice. The etiological association of biologic agents with the occurrence of PJP is not entirely clear. Adalimumab is a fully human monoclonal anti-TNF-alpha antibody, which has been introduced relatively recently in the treatment of autoimmune inflammatory diseases, such as rheumatoid arthritis. In contrast to other biologic agents, such as Alemtuzumab or Infliximab, there are a small number of reports that support the drug's ability to trigger the occurrence of PJP. Hereby, we present a 53-year-old female patient with a medical history of rheumatoid arthritis on Adalimumab therapy, who developed PJP and we will discuss the main characteristics of PJP and the possible contribution of biologics to the occurrence of the infection.

Health-related quality of life in patients with ANCA vasculitides compared to rheumatoid arthritis: a cross-sectional comparative study.

OBJECTIVES: There are limited data regarding health-related quality of life (HRQoL) in patients with ANCA-associated vasculitides (AAVs). We aimed to evaluate the HRQoL in patients with AAVs and compare it to another chronic inflammatory disease like RA and to healthy controls (HC). METHODS: This was a multicentre, cross-sectional study of patients with AAVs and RA recruited from three tertiary rheumatology clinics. HRQoL was assessed with the Short Form 36 Health Survey, which included the physical and mental component summary scores (PCS and MCS). Data from 1007 HC served as historical controls. RESULTS: Sixty-six patients with AAVs and 71 with RA were included. Both AAV and RA patients had significantly lower PCS and MCS scores compared with HC (P < 0.05). HRQoL in AAV patients was worse in patients with microscopic polyangiitis compared with granulomatosis with polyangiitis (physical components) and those with high (VDI ≥ 3) vs low (VDI < 3) damage scores while it did not differ between those with active (BVASv3 ≥ 1) vs. inactive (BVASv3 < 1) disease. In contrast, in RA patients, HRQoL correlated both with disease activity (assessed by the DAS28-ESR) and functional impairment/damage (assessed by the HAQ). Although overall patients with RA had similar HRQoL compared with those with AAVs, those with active RA had worse HRQoL compared with those with active AAV. CONCLUSIONS: In patients with AAVs, HRQoL correlated more with organ damage and less with disease activity whereas in RA patients, it correlated with both. These data emphasize the need for AAV therapies aiming at preventing organ damage and thus improving HRQoL.

Pulmonary-Renal Syndrome During COVID-19 Pandemic Revealed a Rare Case of Anti-GBM Disease.

Anti-GBM disease is a rare, life-threatening small vessel vasculitis caused by circulating anti-GBM antibodies resulting to rapidly progressive glomerulonephritis and/or pulmonary haemorrhage. The gold standard for the diagnosis is the renal biopsy with the pathognomonic finding of linear deposition of IgG along the glomerular capillaries. Early diagnosis and intervention are key determinants of the response to therapy and long-term prognosis of these patients. However, during COVID-19 pandemic recognizing a pulmonary-renal syndrome caused by autoimmune diseases has become challenging. Herein, we aimed to describe a rare case of anti-GBM disease with pulmonary haemorrhage and rapidly progressive glomerulonephritis in a young man in a tertiary referral hospital in Greece, while COVID-19 pandemic was at its peak. Although the patient presented high level of creatinine and crescents, the early diagnosis and start of treatment resulted to favourable renal prognosis.

The Role of Myositis-Specific and Myositis-Associated Autoantibodies and the Activation of Type I Interferon Pathway in the Generation of Clinical Phenotypes of Inflammatory Myopathies.

Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous autoimmune diseases with a prevalence of 20 cases per 100000 of population. Despite their diversity, IMMs are characterised by several common clinical features such as muscle inflammation, proximal muscle weakness, abnormal electromyography and/or muscle biopsy. Over the last years, it has been increasingly recognised that an array of autoantibodies known as myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are associated with distinct clinical phenotypes and diverse prognosis. Although the exact underlying mechanism of IIMs is not fully understood, accumulating data suggest that the activation of type I interferon pathway plays a central role in disease development. Previous studies have reported the upregulation of type I interferon (IFN) induced genes in peripheral blood and muscle biopsies derived from myositis patients. Given the heterogeneity of inflammatory myopathies along with the central role of type I IFN pathway in disease pathogenesis, the aim of the current study is to elucidate the link between distinct clinical phenotypes of inflammatory myopathies with the presence of serum MSAs or MAAs, as well as with type I IFN activation.

Real-world effectiveness of golimumab in adult patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis and an inadequate response to initial TNFi therapy in Greece: the GO-BEYOND prospective, observational study.

The impact of golimumab (GLM) on remission or low disease activity (LDA) was evaluated in patients with moderate-to-severe rheumatoid arthritis (RA), progressive psoriatic arthritis (PsA), or severe axial spondyloarthritis (axSpA), who failed previous treatment for their rheumatic disease with one initial tumor necrosis factor α inhibitor (TNFi). This is a multicenter, prospective, real-world observational 18-month study, conducted in Greece. The primary endpoint, assessed at 6 months, included the proportion of patients attaining LDA and/or remission (Disease Activity Score for 28 joints based on C-reactive protein [DAS28-CRP] ≤ 3.2), minimal disease activity (MDA; MDA criteria), and moderate disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] score 4-7), respectively. Other endpoints evaluated the persistence to GLM treatment and its impact on patients' work productivity (Work Productivity and Activity Impairment [WPAI] instrument) and quality of life (QoL; EuroQoL5 dimensions 3 levels [EQ-5D-3L] questionnaire). Descriptive statistics, the Wilcoxon signed-rank test, and Kaplan-Meier method were used for analyses. At 6 months, LDA was achieved by 46.4% of patients with RA, MDA by 57.1% of patients with PsA, and BASDAI 4-7 by 24.1% of patients with axSpA. For all study patients, persistence rates on GLM were high (85.1-93.7%) over 18 months; all WPAI domain scores and the EQ-5D-3L index score improved significantly (p < 0.001) from baseline to 18 months. GLM treatment was effective in patients with RA, PsA, or axSpA who had failed previous treatment with one TNFi and led to significant WPAI and QoL improvements. Persistence rates were high. Trial registration number and date of registration: As per the local regulations the study has been registered at the national registry for non-interventional studies https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=MK8259-6995 .

Impact of CDK4/6 Inhibitors on Aromatase Inhibitor-Associated Musculoskeletal Syndrome (AIMSS) in the Adjuvant Setting.

Background: Third-generation aromatase inhibitors (AIs) are the mainstay of treatment in hormone receptor (HR)-positive breast cancer. Even though it is considered to be a well-tolerated therapy, AI-induced musculoskeletal symptoms are common and may be accused for treatment discontinuation. Recently, selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors changed the therapeutic setting, and currently, ribociclib, palbociclib, and abemaciclib are all approved in combination with nonsteroidal AIs in patients with ER-positive, HER2-negative advanced or metastatic breast cancer. This systematic review aims to identify the frequency of aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) in the adjuvant setting in patients under AI monotherapy compared to patients under combination therapy with AIs and CDK4/6 inhibitors and demonstrate the underlying mechanism of action. Methods: This study was performed in accordance with PRISMA guidelines. The literature search and data extraction from all randomized clinical trials (RCTs) were done by two independent investigators. Eligible articles were identified by a search of MEDLINE and ClinicalTrial.gov database concerning the period 2000/01/01-2021/05/01. Results: Arthralgia was reported in 13.2 to 68.7% of patients receiving AIs for early-stage breast cancer, while arthralgia induced by CDK4/6 inhibitors occurred in a much lower rate [20.5-41.2%]. Bone pain (5-28.7% vs. 2.2-17.2%), back pain (2-13.4% vs. 8-11.2%), and arthritis (3.6-33.6% vs. 0.32%) were reported less frequently in patients receiving the combination of CDK4/6 inhibitors with ET. Conclusions: CDK4/6 inhibitors might have a protective effect against joint inflammation and arthralgia occurrence. Further studies are warranted to investigate arthralgia incidence in this population.

The genomic landscape of ANCA-associated vasculitis: Distinct transcriptional signatures, molecular endotypes and comparison with systemic lupus erythematosus.

Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) present with a complex phenotype and are associated with high mortality and multi-organ involvement. We sought to define the transcriptional landscape and molecular endotypes of AAVs and compare it to systemic lupus erythematosus (SLE). Methods: We performed whole blood mRNA sequencing from 30 patients with AAV (granulomatosis with polyangiitis/GPA and microscopic polyangiitis/MPA) combined with functional enrichment and network analysis for aberrant pathways. Key genes and pathways were validated in an independent cohort of 18 AAV patients. Co-expression network and hierarchical clustering analysis, identified molecular endotypes. Multi-level transcriptional overlap analysis to SLE was based on our published data from 142 patients. Results: We report here that "Pan-vasculitis" signature contained 1,982 differentially expressed genes, enriched in leukocyte differentiation, cytokine signaling, type I and type II IFN signaling and aberrant B-T cell immunity. Active disease was characterized by signatures linked to cell cycle checkpoints and metabolism pathways, whereas ANCA-positive patients exhibited a humoral immunity transcriptional fingerprint. Differential expression analysis of GPA and MPA yielded an IFN-g pathway (in addition to a type I IFN) in the former and aberrant expression of genes related to autophagy and mRNA splicing in the latter. Unsupervised molecular taxonomy analysis revealed four endotypes with neutrophil degranulation, aberrant metabolism and B-cell responses as potential mechanistic drivers. Transcriptional perturbations and molecular heterogeneity were more pronounced in SLE. Molecular analysis and data-driven clustering of AAV uncovered distinct transcriptional pathways that could be exploited for targeted therapy. Discussion: We conclude that transcriptomic analysis of AAV reveals distinct endotypes and molecular pathways that could be targeted for therapy. The AAV transcriptome is more homogenous and less fragmented compared to the SLE which may account for its superior rates of response to therapy.

Apremilast for biologic-naïve, peripheral psoriatic arthritis, including patients with early disease: results from the APROACH observational prospective study.

To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast's safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0-29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient's health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.

Ixekizumab therapy following secukinumab inadequate response in psoriatic arthritis: a case series focusing on axial disease.

There are limited data regarding cycling between interleukin-17 (IL-17) inhibitors in psoriatic arthritis (PsA). We aimed to report the efficacy of an IL-17 inhibitor (ixekizumab-IXE) after inadequate response (IR) of another one (secukinumab-SEC) in patients with PsA. Case series of PsA patients who received IXE after SEC-IR in four rheumatology centers between 1/9/2021 and 1/9/2022 were included. Peripheral arthritis was assessed with disease activity in psoriatic arthritis score (DAPSA) and skin involvement with body surface area (BSA). Axial disease was defined as having both imaging and clinical features and its activity was measured with the ankylosing spondylitis disease activity score (ASDAS). Twenty-four patients (54.2% female, mean [SD] age: 51.6 [14.1]) who were SEC-IR and received IXE either immediately (n = 11) or after ≥ 1 interposed biologic disease modifying anti-rheumatic drug (bDMARD) (n = 13) were included. Patients were followed on IXE for a mean [SD] period of 9.6 [4.9] months. Among patients with peripheral arthritis (n = 24), the mean [SD] DAPSA decreased from 22.8 [8.6] to 13.6 [7.8] during follow-up (p = 0.0001) with 62.5% of patients showing improvement in the DAPSA disease activity categories. For patients with axial involvement (n = 16), a clinically meaningful improvement (Δ ≥ 1.1 in ASDAS) was noted in 50% (8/16), while dactylitis and enthesitis resolution was observed in 60% (3/5) and 83% (5/6) of patients, respectively. Regarding psoriasis, the mean [SD] BSA of involved skin decreased from 8.7 [8.7] to 2.4 [3.3] (p = 0.001). In this case series, treatment with IXE after inadequate response to another IL-17 inhibitor (SEC) was efficacious in a real-world setting in patients with PsA, including axial disease.

Herpes zoster in patients with inflammatory arthritides or ulcerative colitis treated with tofacitinib, baricitinib or upadacitinib: a systematic review of clinical trials and real-world studies.

JAK inhibitors (JAKi) are new targeted-synthetic drugs, approved for various immune-mediated inflammatory diseases (IMIDs), including inflammatory arthritides (rheumatoid arthritis-RA, psoriatic arthritis-PsA, ankylosing spondylitis-AS) and ulcerative colitis (UC). JAKi have been associated with increased risk for herpes zoster (HZ), but the relative risk among different JAKi in these IMIDs remains unclear. We aimed to systematically review the incidence of HZ among RA, PsA, AS and UC patients treated with the approved doses of tofacitinib (TOFA), baricitinib (BARI) or upadacitinib (UPA). PubMed, Embase, Scopus, Cochrane and Web-of-Science were searched up to 30 March 2022. Clinical trials and real-world studies (RWS) were included. Outcomes assessed were the incidence rate (/100 patient-years) or/and cumulative incidence of HZ. From 1710 records, 53 clinical trials and 25 RWS were included (RA: 54, PsA: 8, AS: 4, and UC: 12). In clinical trials, the HZ-incidence was higher in TOFA-treated patients with RA (2.2-7.1/100 patient-years) or UC (1.3-7.6/100 patient-years) compared to PsA (1.7/100 patient-years), and with higher doses of TOFA in UC (10 mg/twice daily: 3.2-7.6/100 patient-years vs. 5 mg/twice daily: 1.3-2.3/100 patient-years). Evidence for HZ-risk in JAKi-treated patients with AS and in UPA-treated patients was limited. The HZ-incidence between TOFA and BARI groups in 2 RA RWS did not differ significantly. Concomitant glucocorticoid, but not methotrexate, use in RA increased the HZ-risk. This systematic review showed higher HZ-risk in RA or UC than PsA patients treated with TOFA, in those treated with higher TOFA doses or with concomitant glucocorticoids. Preventive measures and monitoring of JAKi-treated patients with IMIDs are essential in daily practice.

Disease Profile and Achievement of Therapeutic Goals in a Modern, Nationwide Cohort of 923 Patients with Psoriatic Arthritis.

Background: Psoriatic arthritis (PsA) is a heterogenous chronic inflammatory disease affecting skin, joints, entheses, and spine with various extra-musculoskeletal manifestations and comorbidities. The reported patient, disease and treatment characteristics in the modern therapeutic era are limited. Methods: In this cross-sectional, multi-centre, nationwide study, we recorded the demographic, clinical, and therapeutic characteristics as well as the comorbidities of patients with PsA seen for 1 year (1/1/2022-31/12/2022). Results: 923 patients (55% females) with a median (IQR) age of 57 (48-65) years and a mean disease duration of 9.5 years were enrolled. Family history of psoriasis and PsA was noted in 28.3% and 6.3%, respectively. Most patients had limited psoriasis (BSA<3: 83%) while enthesitis, dactylitis, nail and axial involvement reported in 48.3%, 33.2%, 43% and 25.9% of patients, respectively. Regarding comorbidities, approximately half of patients had dyslipidaemia (42%) or hypertension (45.4%), 36.8% were obese and 17% had diabetes while 22.7% had a depressive disorder. Overall, 60.1% received biologics and among them more patients treated with anti-IL-17 or -12/23 agents were on monotherapy (64.2%) compared to those on TNFi monotherapy (49.4%, p=0.0001). The median PsA activity as assessed by the DAPSA score was 6 (IQR: 2.3 - 13.1) with 46% of patients reaching minimal disease activity status (MDA). Conclusion: In this large, real life, modern cohort of patients with PsA with frequent comorbidities who were treated mainly with biologics, almost half achieved minimal disease activity. These results show the value of existing therapeutic approaches while at the same time highlight the existing unmet needs.

A case of adenoviral covid-19 vector vaccine possibly linked to severe but reversible interstitial lung injury post-vaccination.

BACKGROUND: Several safe and effective vaccines against nCoV-19 have been developed to contain the pandemic with very few severe adverse-reactions reported. Vaccine-induced interstitial lung disease (ILD) is a very rare and difficult to recognise and diagnose adverse-reaction and is mostly associated with Influenza vaccines. METHODS: We report a 55-yr old male who presented with severe respiratory failure that required for several days oxygen supplementation with high flow nasal cannula, and myocardial infarction. Symptoms onset was eighteen days after the first shot of adenoviral AZD1222 vector vaccine. Possible SARS-CoV-2 natural infection post-vaccination was excluded with rigorous laboratory work-up including multiple nasopharengeal rt-qPCR tests for SARS-CoV-2 detection and close monitoring of his serum SARS-CoV-2 antibodies. Other potential infectious agents and alternate diagnoses were thoroughly investigated. RESULTS: Patient responded impressively to high dose steroids. A repeat chest CT nine days after the first one showed a remarkable resolution of the bilateral ground glass opacities. Except for his cardiology medication, no supplemental oxygen neither steroids were prescribed upon his discharge. On one month follow-up, no residual pulmonary dysfunction was noticed with patient preserving a SatO2 of 97-98% on ambient air. CONCLUSION: Vaccine-induced ILD might constitute a rare nCoV-19 post-vaccination adverse-event. According to current restricted data, when post-vaccination ILD is early suspected and recognised, then prompt implementation of steroid treatment reverses significantly the lung lesions without progression to fibrosis.

Patient characteristics, treatment patterns and disease outcomes in patients with psoriatic arthritis followed in a combined Dermatology-Rheumatology clinic: a retrospective real-world study.

The aim of this study was to assess the patient characteristics, treatment patterns and disease outcomes in patients with psoriatic arthritis (PsA) referred to a combined Dermatology-Rheumatology (Derm-Rheum) Clinic. This was a retrospective study of patients seen in a combined Derm-Rheum Clinic (February 2018 to June 2020) in a Tertiary University Hospital. Consecutive patients with suspicious musculoskeletal symptoms or a known diagnosis of PsA referred to the Derm-Rheum Clinic were examined and followed simultaneously by experienced dermatologists and rheumatologists. Among 151 patients with psoriasis (PSO) with suspicious musculoskeletal complaints, 129 (85%) with a final diagnosis of PsA were included (56% females, mean age: 55 years, median disease duration: 14.2 years). In 62% of these patients (n = 94), PsA was diagnosed for the 1st time. At initial evaluation, 95% had peripheral arthritis, 45% nail involvement, 23% axial involvement, 12% enthesitis and 6% dactylitis with a median DAPSA and PASI scores of 20.5 and 1.6, respectively. 31% of the patients were not receiving any systemic treatment, 45% were on biologics, 29% on non-biologics and 10% on targeted synthetic agents (apremilast). At last visit (median interval time: 15 months), only 8% did not receive any systemic therapy (p < 0.001 compared to 1st visit), 62% were on biologics (p = 0.009 compared to 1st visit), 46% on non-biologics (p = 0.01 compared to 1st visit) and 10% remained on apremilast. The median DAPSA and PASI scores decreased significantly to 5.3 and 0, respectively. In conclusion, about 2/3 of patients with PSO and musculoskeletal complaints referred to a combined Derm-Rheum Clinic were diagnosed for the 1st time with PsA. During follow-up, the percentage of PsA patients on systemic therapies significantly increased with major improvement of disease activity indices. These data emphasize the value of combined Derm-Rheum Clinics for earlier referral, diagnosis, and more effective treatment of PsA patients.

Patterns and factors associated with pneumococcal vaccination in a prospective cohort of 1,697 patients with rheumatoid arthritis.

Introduction: Patients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort. Materials and methods: Multi-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later. Results: One thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58-59.85), history of cancer (OR = 2.35, 95% CI: 1.09-5.06), bDMARD use (OR = 1.85, 95% CI: 1.29-2.65), seropositivity (OR = 1.47, 95% CI: 1.05-2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17-1.51). Male sex (OR = 0.65, 95% CI: 0.43-0.99) was a negative predictor for pneumococcal vaccination during follow-up. Discussion: Despite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a "vaccination culture" in RA patients.