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.

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.

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.

Use of conventional synthetic and biologic disease-modifying anti-rheumatic drugs in patients with rheumatic diseases contracting COVID-19: a single-center experience.

To examine whether patients with inflammatory arthritis (IA) treated with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and/or biologic (b) DMARDs, could be affected from SARS-CoV-2 infection and to explore the COVID-19 disease course and outcome in this population. This is a prospective observational study. During the period February-December 2020, 443 patients with IA who were followed-up in the outpatient arthritis clinic were investigated. All patients were receiving cs and/or bDMARDs. During follow-up, the clinical, laboratory findings, comorbidities and drug side effects were all recorded and the treatment was adjusted or changed according to clinical manifestations and patient's needs. There were 251 patients with rheumatoid arthritis (RA), 101 with psoriatic arthritis (PsA) and 91 with ankylosing spondylitis (AS). We identified 32 patients who contracted COVID-19 (17 RA, 8 PsA, 7 AS). All were in remission and all drugs were discontinued. They presented mild COVID-19 symptoms, expressed mainly with systemic manifestations and sore throat, while six presented olfactory dysfunction and gastrointestinal disturbances, and all of them had a favorable disease course. However, three patients were admitted to the hospital, two of them with respiratory symptoms and pneumonia and were treated appropriately with excellent clinical response and outcome. Patients with IA treated with cs and/or bDMARDs have almost the same disease course with the general population when contract COVID-19.

Comparable or higher prevalence of comorbidities in antiphospholipid syndrome vs rheumatoid arthritis: a multicenter, case-control study.

OBJECTIVES: Evidence on comorbidity prevalence in antiphospholipid syndrome (APS) and its difference from high comorbidity burden rheumatic diseases is limited. Herein, we compare multiple comorbidities between APS and RA. METHODS: A total of 326 patients from the Greek APS registry [237 women, mean age 48.7 (13.4) years, 161 primary APS (PAPS), 165 SLE-APS] were age/sex matched (1:2 ratio) with 652 patients from a Greek multicentre RA cohort of 3115 patients. Prevalence of cardiovascular (CV) risk factors, stroke, coronary artery disease (CAD), osteoporosis, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), depression and neoplasms were compared between APS and RA patients using multivariate regression analysis. RESULTS: Ηyperlipidemia and obesity (ΒΜΙ ≥ 30 kg/m2) were comparable while hypertension, smoking, stroke and CAD were more prevalent in APS compared with RA patients. Osteoporosis and depression were more frequent in APS, while DM, COPD and neoplasms did not differ between the two groups. Comparison of APS subgroups to 1:2 matched RA patients revealed that smoking and stroke were more prevalent in both PAPS and SLE-APS vs RA. Hypertension, CAD and osteoporosis were more frequent only in SLE-APS vs RA, whereas DM was less prevalent in PAPS vs RA. Hyperlipidaemia was independently associated with CV events (combined stroke and CAD) in PAPS and SLE-APS, while CS duration was associated with osteoporosis in SLE-APS. CONCLUSION: Comorbidity burden in APS (PAPS and SLE-APS) is comparable or higher than that in RA, entailing a high level of diligence for CV risk prevention, awareness for depression and CS exposure minimization.

Therapeutic Options and Cost-Effectiveness for Rheumatoid Arthritis Treatment.

PURPOSE OF REVIEW: During the last two decades, the therapeutic decisions and strategies for rheumatoid arthritis (RA) management have improved dramatically. Today, the therapeutic armamentarium is significantly augmented, and by using both old and new drugs, remission or low disease activity is a reasonable goal. The use of conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) in combination with biologic (b) or targeted synthetic (ts) DMARDs has revolutionized RA treatment. Methotrexate administration is considered fundamental among other csDMARDs for the treatment of RA. It is recommended as the initial drug (monotherapy), or in combination with other csDMARDs, bDMARDs, and tsDMARDs in a step-up strategy. Furthermore, it can be used with other csDMARDs as initial combination-therapy. On the other hand, despite the fact that bDMARDs and ts DMARDs are highly efficacious and can also be used as monotherapy in certain cases, cost-effectiveness is still questionable when compared with csDMARDs. In this direction, the classic argument of utmost importance has to do with the most appropriate treatment strategy that shall be initially applied: csDMARD combination-therapy versus monotherapy, or step-up combinationtherapy with bDMARDs, especially tumor necrosis factor-α (TNFa) blockers. For this reason, a literature review of the most important csDMARDs combination and bDMARDs combination studies has been deployed. RECENT FINDINGS: The results showed that the triple csDMARDs therapy approach is more effective and less expensive. In addition, workers' productivity is higher than any other treatment options for RA. Triple-therapy constitutes a smart, efficacious, and significantly cheaper choice for RA therapeutic management.

Correlation of patient preferences to treatment outcomes in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors in Greece.

OBJECTIVES: To investigate possible associations between rheumatoid arthritis (RA) patient-expressed preferences over anti-tumour necrosis factor (anti-TNF) treatment and clinical and patient-reported outcomes. METHODS: PANORAMA was a non-interventional, prospective, multicentre, cohort study of 12 months duration, in patients with moderate-to-severe RA who initiated or switched to anti-TNF treatment. After initiation of anti-TNF, patients completed a preferences questionnaire on attributes related to anti-TNF treatment. Satisfaction with treatment was assessed with the Treatment Satisfaction Questionnaire for Medication (TSQM); compliance and persistence to treatment were recorded via a patient diary. Univariate and multivariate analyses were applied to assess correlations between patients' preferences over treatment with clinical and patient-reported outcomes. RESULTS: A total of 254 patients were enrolled; 66.1% (168/254) had highly active disease (DAS28-ESR > 5.1), while 65.4% (166/254) were biological-naïve. The 12-month drug-survival rate was 72.3%, while the respective rates of good EULAR response and remission (DAS28-ESR < 2.6) were 56.5% and 40.8%, respectively. By univariate analysis, fulfilment of patient preferences over treatment was associated with increased probability of remaining on therapy (p = 0.019), good EULAR response (p < 0.001) and satisfaction with treatment (p < 0.001). By multivariate analysis, fulfilment of patient preferences was the most important predictor for good EULAR response (OR 5.56, p < 0.001; finding confirmed and after propensity scoring matching), while seropositivity (HR 1.18, p = 0.047) and a high ESR (> 35 mm/h, HR 1.16, p = 0.071) predicted drug survival. CONCLUSIONS: In anti-TNF-treated RA patients, fulfilment of treatment preferences was independently associated with a good EULAR response and correlated with drug persistence at 12 months, emphasising the importance of patient preferences in treatment outcomes. Key Points • In anti-TNF treated RA patients, fulfilment of patients' treatment preferences is associated with a good clinical response at 12 months. • A shared decision-making process can maximise treatment's outcome in anti-TNF treated patients.

The impact of temporal artery biopsy for the diagnosis of giant cell arteritis in clinical practice in a tertiary university hospital.

BACKGROUND: Temporal artery biopsy (TAB) is useful in assisting with giant cell arteritis (GCA) diagnosis but lacks sensitivity. The aim of our study was to assess the diagnostic impact of TAB histology in patients with suspected GCA on hospital admission. METHODS: A prospectively maintained database was queried for all TABs performed between 1-1-2000 until 31-12-2017 at the University Hospital of Ioannina. Thus, inclusion criteria were made on the grounds of every patient that underwent a TAB during the above-mentioned period, regardless of demographic, clinical and laboratory data. RESULTS: Two hundred forty-five TABs were included (149 females and 96 males), with a mean age of 64.5 (±3.5) years. The mean symptoms duration until admission to the hospital was 8.6 (±1.3) weeks and all had elevated acute phase reactants on admission. The reasons of admission were fever of unknown origin (FUO) in 114 (46.5%) patients, symptoms of polymyalgia rheumatica (PMR) in 84 (34.3%), new headache in 33 (13.5%), anemia of chronic disease (ACD) in 8 (3.32%) and eye disturbances in 6 (2.5%) patients. Positive results were found in 49 (20%) TABs. More specifically, in 14% of patients with FUO, 21% in those with PMR, while in patients with a new headache the percentage was 27%. Finally, 5 out of 6 (83.3%) of patients with ocular symptoms and only one (12.5%) of those suffering from ACD. Visual manifestations and FUO are correlated with a positive TAB. CONCLUSION: It seems that TAB is useful in assisting with GCA diagnosis, but lacks sensitivity.

Unmet needs in the treatment of ankylosing spondylitis: a long-term observational study from a single university center.

Despite the progress in the treatment of ankylosing spondylitis (AS), a significant number of patients do not achieve low disease activity (LDA). The aim of the study is to estimate the size of unmet needs in the treatment of AS in a long-term observational study. Between January 2003 and December 2017, 220 patients with radiographic SpA were evaluated fulfilling the ASAS criteria. They were followed up at predefined times and were naive to biological treatment with anti-tumor necrosis factor agents (anti-TNFs) and the interleukin (IL)-17 inhibitor. NSAIDs, all anti-TNFs and the IL-17 inhibitor secukinumab were used according to the European, United States and Canadian guidelines for AS. During follow-up, several clinical parameters including disease activity scores were recorded. All 220 patients had an active disease and received at least two NSAIDs for 3 months. The anti-TNF of first choice was infliximab-51%, followed by adalimumab-27% and etanercept-22%. During follow-up, 22 patients were excluded from the study (18 lost, 4 never received anti-TNF due to comorbidities). From the rest (198), 12 did not receive anti-TNFs (8 due to sustained LDA on NSAIDs solely and 4 due to treatment denial). Finally, 186 (94%) were treated with anti-TNFs demonstrating sustained long-term LDA. However, 16 patients never achieved LDA despite they received two or three anti-TNFs or the IL-17 inhibitor. Thus, a total of 20 (10.1%) patients never achieved LDA. This is the first study aiming to estimate the gap and the size of unmet needs in AS patients using the international guidelines and recommendations for AS treatment, which is 10.1%.

High 3-year golimumab survival in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: real world data from 328 patients.

OBJECTIVES: Our primary objective was to study the long-term survival on drug (SOD) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) treated with golimumab (GLM) in real life settings. METHODS: This was a retrospective, observational study of all patients treated with GLM in 4 Academic Centres in Greece during a 4-year period (09/2010-06/2014). SOD was analysed using Kaplan-Meier survival analysis, while Cox regression analysis estimating hazard ratios (HRs) for different baseline variables associated with drug discontinuation was performed for each disease. RESULTS: 328 patients (RA: 166, PsA: 82, AS: 80) were included. The estimated SOD at 2 and 3 years was 68% and 62% overall and was better for AS (79% and 76%) compared to RA (69% and 60%, p=0.067) and PsA (58% and 53%, p=0.001) patients; no difference was noted between RA and PsA patients (p=0.204). There was no difference in SOD between biologic-naïve and experienced nor between non-biologic co-treated or GLM monotherapy treated patients. Seropositivity (rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) was associated with a lower risk for GLM discontinuation by multivariate analysis (HR=0.5, 95% CI=0.0.25-1.1, p=0.05) in RA patients. During 606 patient-years of follow-up, 11 (3.3%) patients discontinued GLM due to adverse events (AE), accounting for 11% of treatment discontinuations. The rates of serious AEs and serious infections were 2.3 and 1.0/100-patient-years, respectively. CONCLUSIONS: In this real-life study, GLM showed a high 3-year SOD in patients with inflammatory arthritides with a low rate of discontinuation due to AEs.

Neurological adverse events in patients receiving anti-TNF therapy: a prospective imaging and electrophysiological study.

INTRODUCTION: The aim was to investigate the frequency of neurological adverse events in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) treated with tumor necrosis factor (TNF) α antagonists. METHODS: Seventy-seven patients eligible for anti-TNFα therapy were evaluated. There were 36 patients with RA, 41 with SpA [24 psoriatic arthritis (PsA) and 17 with ankylosing spondylitis (AS)]. All patients had a complete physical and neurological examination. Brain and cervical spine magnetic resonance imaging (MRI) and neurophysiological tests were performed in all patients before the initiation of anti-TNFα therapy and after a mean of 18 months or when clinical symptoms and signs indicated a neurological disease. Exclusion criteria included hypertension, diabetes mellitus, dyslipidemia, heart arrhythmias, atherothrombotic events, vitamin B12 and iron deficiency, head and neck trauma and neurological surgeries. RESULTS: Two patients did not receive anti-TNFα therapy because brain MRIs at baseline revealed lesions compatible with demyelinating diseases. Thus, 75 patients received anti-TNFα (38 infliximab, 19 adalimumab and 18 etanercept). Three patients developed neurological adverse events. A 35-year-old man with PsA after 8 months of infliximab therapy presented with paresis of the left facial nerve and brain MRI showed demyelinating lesions. Infliximab was discontinued and he was treated with pulses of corticosteroids recovering completely after two months. The second patient was a 45-year-old woman with RA who after 6 months of adalimumab therapy presented with optic neuritis. The third patient was a 50-year-old woman with AS, whom after 25 months of infliximab therapy, presented with tingling and numbness of the lower extremities and neurophysiological tests revealed peripheral neuropathy. In both patients anti-TNF were discontinued and they improved without treatment after 2 months. The rest of our patients showed no symptoms and MRIs showed no abnormalities. The estimated rate of neurological adverse events in patients treated with anti-TNF therapy is 4% (3/75). CONCLUSIONS: Neurological adverse events after anti-TNFα therapy were observed in our patient. Brain MRI and neurophysiological tests are essential tools to discriminate neurological diseases.

Demyelination and other neurological adverse events after anti-TNF therapy.

Tumor necrosis factor (TNF) α inhibitors are an essential therapeutic option for several inflammatory diseases, like rheumatoid arthritis, spondyloarthropathies and inflammatory bowel diseases. As TNFα antagonists have become increasingly utilized, there have been a number of reports of neurological adverse events in patients receiving anti-TNFα therapy. The frequency of central nervous system adverse events after initiation of anti-TNFα therapy is unknown. However, questions have been raised about a possible causal association. Although several hypotheses have been proposed in an attempt to explain the possible relationship between TNFα antagonist and demyelination, none is considered to be adequate. Thus, in this report we deal with the implication of TNFα in multiple sclerosis and we discuss the possible relationship of TNFα antagonist and demyelinating diseases.

Fertility in male patients with seronegative spondyloarthropathies treated with infliximab.

OBJECTIVES: The majority of patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are affected during their peak reproductive years. Tumor necrosis factor (TNF)α plays a pivotal role in the pathogenesis of both diseases. Today, anti-TNFα blockers are an essential treatment for these patients. To identify male patients who achieved pregnancy development during their management with anti-TNFα blockers (infliximab). METHODS: We reviewed the data of 65 patients with AS and 30 patients with PsA who were followed-up in our rheumatology outpatients clinic and they were on infliximab therapy between January 2001 and December 2010. RESULTS: We identified overall seven male patients with AS and three male patients with PsA who had fathered 14 healthy infants. Moreover, we recognized one man with PsA who was on infliximab and on concomitant therapy with MTX at the time of conception, whose wife had to proceed to therapeutic abortion due to congenital abnormalities of the fetus (hydrocephalia), while she was on the first trimester of pregnancy. CONCLUSIONS: We described male patients with AS and PsA who demonstrated no fertility problems while they were on infliximab treatment. The data designated in this report provide some supportive evidence for the safe use of infliximab in male patients who are affected of those inflammatory diseases during their peak reproductive years.

Adalimumab in the treatment of rheumatoid arthritis.

Adalimumab (ADA), a fully human monoclonal antibody against TNF-α is indicated for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohn's disease, ulcerative colitis and psoriasis. In RA, it may be prescribed in combination with methotrexate or other disease-modifying antirheumatic drugs or as monotherapy. Studies comparing ADA with other TNF-α inhibitors are limited and are based mainly on meta-analyses of randomised controlled trials and large observational cohorts. In this study, the effectiveness and safety of ADA is compared with that of etanercept and infliximab.