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.

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.

Incidence, risk factors and validation of the RABBIT score for serious infections in a cohort of 1557 patients with rheumatoid arthritis.

OBJECTIVES: Predicting serious infections (SI) in patients with rheumatoid arthritis (RA) is crucial for the implementation of appropriate preventive measures. Here we aimed to identify risk factors for SI and to validate the RA Observation of Biologic Therapy (RABBIT) risk score in real-life settings. METHODS: A multi-centre, prospective, RA cohort study in Greece. Demographics, disease characteristics, treatments and comorbidities were documented at first evaluation and one year later. The incidence of SI was recorded and compared with the expected SI rate using the RABBIT risk score. RESULTS: A total of 1557 RA patients were included. During follow-up, 38 SI were recorded [incidence rate ratio (IRR): 2.3/100 patient-years]. Patients who developed SI had longer disease duration, higher HAQ at first evaluation and were more likely to have a history of previous SI, chronic lung disease, cardiovascular disease and chronic kidney disease. By multivariate analysis, longer disease duration (IRR: 1.05; 95% CI: 1.005, 1.1), history of previous SI (IRR: 4.15; 95% CI: 1.7, 10.1), diabetes (IRR: 2.55; 95% CI: 1.06, 6.14), chronic lung disease (IRR: 3.14; 95% CI: 1.35, 7.27) and daily prednisolone dose ≥10 mg (IRR: 4.77; 95% CI: 1.47, 15.5) were independent risk factors for SI. Using the RABBIT risk score in 1359 patients, the expected SI incidence rate was 1.71/100 patient-years, not different from the observed (1.91/100 patient-years; P = 0.97). CONCLUSION: In this large real-life, prospective study of RA patients, the incidence of SI was 2.3/100 patient-years. Longer disease duration, history of previous SI, comorbidities and high glucocorticoid dose were independently associated with SI. The RABBIT score accurately predicted SI in our cohort.

Teriparatide Treatment in Patients with Pregnancy- and Lactation-Associated Osteoporosis.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20 µg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24 months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24 months. Patients in group A had sustained a median of 4.0 VFs (3-9) vs. 2.5 VFs (1-10) in group B (p = 0.02). At 12 months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9  ±  11.9% vs. 6.2  ±  4.8% at the LS (p < 0.001), 10.0  ±  11.6% vs. 5.8  ±  2.8% at the TH (p = 0.43), and 6.7  ±  6.9% vs. 0.9  ±  3.7% in TBS (p = 0.09), respectively. At 24 months, seven patients on TPTD and six controls achieved a mean LS aBMD increase of 32.9  ±  13.4% vs. 12.2  ±  4.2% (p = 0.001). P1NP levels during the first month of TPTD treatment were positively correlated with the 1-year LS aBMD change (r = 0.68, p = 0.03). No new clinical fractures occurred while on-treatment. In patients with PLO, TPTD treatment resulted in significantly greater increases in LS aBMD compared with calcium and vitamin D supplementation at 12 and 24 months.

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 Comparison of EQ-5D-3L, EQ-5D-5L, and SF-6D Utilities of Patients with Musculoskeletal Disorders of Different Severity: A Health-Related Quality of Life Approach.

This study compares EQ-5D-3L, EQ-5D-5L, and SF-6D utilities in patients with different musculoskeletal (MSK) disorders, also differing in disease severity as defined by valid clinical indexes. Utilities were measured from a cross-sectional sample of rheumatoid arthritis (N = 114), psoriatic arthritis (N = 57), ankylosing spondylitis (N = 49), and osteopenia/osteoporosis (N = 95) patients. For the first three groups, disease activity (severity) was measured with the DAS-28, DAPSA, and BASDAI clinical indexes, respectively. Mean differences and effect sizes were measured, and agreement between utilities was estimated with the intraclass correlation coefficient and Bland−Altman plots. Higher agreement was observed between EQ-5D-5L and SF-6D, compared to EQ-5D-3L and SF-6D, in all MSK disorder groups and severity levels. In groups with moderate to high severity, agreement between EQ-5D-3L/SF-6D and EQ-5D-5L/SF-6D was between low and fair, and both EQ-5D-3L and 5L utilities were lower than SF-6D (p < 0.001). On the other hand, in remission or low activity groups, agreement was excellent, and SF-6D utilities were again typically higher than EQ-5D-3L/5L, but not significantly. In more severe patients, SF-6D generated significantly higher utilities than EQ-5D-3L and 5L, which is consistent with most previous studies. Such discrepancies could have implications on economic evaluations of interventions targeting patients with MSK disorders.

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.

Treatment patterns and achievement of the treat-to-target goals in a real-life rheumatoid arthritis patient cohort: data from 1317 patients.

BACKGROUND: Data regarding the real-life predictors of low disease activity (LDA) in rheumatoid arthritis (RA) patients are limited. Our aim was to evaluate the rate and predictors of LDA and treatment patterns in RA. METHODS: This was a multicenter, prospective, RA cohort study where patients were evaluated in two different time points approximately 12 months apart. Statistical analysis was performed in order to identify predictors of LDA while patterns of disease-modifying anti-rheumatic drug [DMARDs; conventional synthetic (csDMARD) or biologic (bDMARD)] and glucocorticoid (GC) use were also recorded. RESULTS: The total number of patients included was 1317 (79% females, mean age: 62.9 years, mean disease duration: 10.3 years). After 1 year, 57% had achieved LDA (DAS28ESR<3.2) while 43% did not (34%: moderate disease activity: DAS28ESR ⩾3.2 to <5.1, 9%: high disease activity, DAS28ESR ⩾5.1). By multivariate analysis, male sex was positively associated with LDA [odds ratio (OR) = 2.29 p < 0.001] whereas advanced age (OR = 0.98, p = 0.005), high Health Assessment Questionnaire (HAQ) score (OR = 0.57, p < 0.001), use of GCs (OR = 0.75, p = 0.037) or ⩾2 bDMARDs (OR = 0.61, p = 0.002), high co-morbidity index (OR = 0.86, p = 0.011) and obesity (OR = 0.62, p = 0.002) were negative predictors of LDA. During follow-up, among active patients (DAS28ESR >3.2), 21% initiated (among csDMARDs users) and 22% switched (among bDMARDs users) their bDMARDs. CONCLUSION: In a real-life RA cohort, during 1 year of follow-up, 43% of patients do not reach treatment targets while only ~20% of those with active RA started or switched their bDMARDs. Male sex, younger age, lower HAQ, body mass index and co-morbidity index were independent factors associated with LDA while use of GCs or ⩾2 bDMARDs were negative predictors.

Antithyroid drug induced syndrome that lies in between ANCA vasculitis and lupus-like syndrome in a 40-year-old female with Graves' disease under methimazole therapy: A Case report.

We report the case of a 40-year-old Greek female with symptoms of polyarthritis, pruritic rash and positive p-ANCA antibodies, undergoing treatment with Methimazole therapy for Graves' disease. The rash and the arthritis symptoms promptly disappeared after withdrawal of methimazole, but p-ANCA antibodies remained positive for 6 weeks. By the time that p-ANCA became negative, anti-dsDNA antibodies presented and remained at high titers for 3 months, with no clinical or specific organ disease symptoms. The patient was under close monitoring for the case of potentially life-threating vasculitis of the lung or the kidney and was treated with methylprednisolone. We diagnosed the patient with Antithyroid drug Syndrome, which in our patient presented with arthritis symptoms and had serological features which are commonly found to Antithyroid drug pANCA vasculitis and Antithyroid drug lupus-like syndrome. Physician's awareness is essential for the diagnosis and treatment of this syndrome in clinical practice, taking into consideration the high frequency of the use of antithyroid agents.

Multicenter Cross-sectional Study of Patients with Rheumatoid Arthritis in Greece: Results from a cohort of 2.491 patients.

AIM OF THE STUDY: To evaluate the current disease characteristics, treatment and comorbidities of rheumatoid arthritis (RA) in Greece. METHODS: Multicenter, cross-sectional study with a 9-month recruitment period between 2015 and 2016. Demographics, disease characteristics, treatment and comorbidities were collected via a web-based platform. RESULTS: 2.491 RA patients were recruited: 96% from tertiary referral centers, 79% were females with a mean age of 63.1 years and disease duration of 9.9 years. Fifty-two percent were rheumatoid factor and/or anti-CCP positive, while 41% had erosive disease. Regarding treatment, 82% were on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), 42% on biologic DMARDs (TNFi: 22%, non-TNFi: 20%) and 40% on corticosteroids (mean daily dose: 5.2 mg). Despite therapy, 36% of patients had moderate and 12% high disease activity. The most frequent comorbidities were hypertension (42%), hyperlipidemia (33%), osteoporosis (29%), diabetes mellitus (15%) and depression (12%). Latent tuberculosis infection (positive tuberculin skin test or interferon gamma release assay) was diagnosed in 13 and 15.3% of patients, respectively. Regarding chronic viral infections, 6.2% had history of herpes zoster while 2% and 0.7% had chronic hepatitis B and C virus infection, respectively. A history of serious infection was documented in 9.6%. Only 36% and 52% of the participants had ever been vaccinated against pneumococcus and influenza virus, respectively. CONCLUSION: This is one of the largest epidemiologic studies providing valuable data regarding the current RA characteristics in Greece. Half of patients were seropositive but despite therapy, half displayed residual disease activity, while preventive vaccination was limited.

Clinical Case: Pregnancy lactation osteoporosis.

Pregnancy-lactation osteoporosis (PLO) is a rare condition with most cases appearing during the third trimester of pregnancy or early in the post-partum period, especially in primigravid women. Our knowledge concerning its pathogenesis is scarce although it seems that most women who experience fragility fractures during this period have a pre-existing bone disease which is further burdened by the mechanical and metabolic changes during pregnancy and lactation. Breastfeeding produces an obligatory loss of maternal skeletal mineral which contributes to the decline of bone density. Little is known whether pharmacological treatments exert a beneficial role upon the situation of PLO since there is lack of firm evidence and bone density seems to recumb spontaneously during weaning.