Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors.

OBJECTIVES: Hepatitis B reactivation (HBVr) constitutes a side effect of the treatment of autoimmune rheumatic diseases. Even though HBVr risk of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) and anti-tumor necrosis factor (anti-TNF) agents has long been established, the risk of targeted synthetic (ts)DMARDs and anti-interleukin (anti-IL) agents remains largely unknown. METHODS: We conducted a SLR (PubMed, Scopus and EMBASE) and metanalysis to examine the HBVr risk for the following: anti-IL17, anti-IL12/23, anti-IL23 and JAK-inhibitors in patients with chronic HBV infection (HBsAg presence or detectable HBV-DNA) and in patients with prior HBV infection (HBcAb-positive and HBsAg-negative). Meta-analysis was performed using both the fixed and random effects method and was conducted using the R computing language. RESULTS: Overall, our study revealed a low HBVr risk of < 6% in all agents; the risk was significantly higher for people having chronic compared with those with resolved HBV (14,4% vs 5.1%, respectively p< 0.01). There was no difference among different drugs in the HBVr rates [anti-IL-17: 4% (95% CI: 1-9%), anti-IL-12/IL-23: 2% (95% CI: 0-5%), JAK-inhibitors: 4% (95% CI: 1-8%), anti-IL23: 0%]. Of note, HBVr rate reached 28% in patients with chronic HBV who did not receive anti-viral treatment. For patients with resolved hepatitis the respective percentage was 4.7%. CONCLUSION: Overall, our meta-analysis shows that patients with chronic HBV receiving anti-IL-17, anti-IL-12/23, anti-IL-23 and JAK-inhibitors have significant risk for HBVr, especially if they are not under anti-viral treatment. In contrast, resolved HBV seems to offer minor risk for HBVr even without anti-viral treatment.

Outcomes of COVID-19 Omicron variant in patients with rheumatoid arthritis: a nationwide Greek cohort study.

OBJECTIVES: Patients with RA were at increased risk for COVID-19-associated hospitalization and death during the first year of the pandemic in Greece. We aimed to examine their outcomes after the SARS-Cov-2 Omicron, a more contagious but with milder clinical impacts variant, prevailed. METHODS: A retrospective, nationwide study was conducted between 1 January 2022 and 30 June 2022 in all RA patients under treatment and matched (1:5) on age, sex and region of domicile random general population comparators. Confirmed SARS-CoV-2 infections, hospitalizations and deaths, anti-rheumatic medications, prior COVID-19, vaccinations and anti-viral medications were recorded. RESULTS: Among 34 182 RA patients, infections (n = 5569, 16.29%), hospitalizations (n = 489, 1.43%) and deaths (n = 106, 0.31%) were more frequent than among comparators. Incidence rates per 1000 person/years of infection [IRR (95% CI):1.19 (1.16, 1.23)], hospitalization [IRR (95% CI):2.0 (1.82, 2.24)], and death [IRR (95% CI):1.81 (1.44, 2.27)] were increased in RA despite better vaccination coverage (89% vs 84%) and more frequent use of anti-viral medications (2.37% vs 1.08). Logistic regression analysis after correcting for age, sex, vaccinations, prior COVID-19, and anti-viral medications in SARS-CoV-2 infected RA patients and comparators revealed increased risk of hospitalization (OR: 2.02, 95% CI: 1.79, 2.27) and death [OR: 1.73, (95% CI: 1.36, 2.20)] in RA. Among infected RA patients, rituximab treatment conferred increased risks for hospitalization [OR: 6.12, (95% CI: 2.89, 12.92)] and death [OR: 12.06 (95% CI: 3.90, 37.31)], while JAK inhibitors increased only hospitalization risk [OR: 2.18 (95% CI: 1.56, 3.06)]. CONCLUSION: RA remains a risk factor for hospitalization and death in an era of a relatively low COVID-19 fatality rate, pointing to the need of perseverance in vaccination programs and wider use of anti-viral medications.

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) 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 one conventional synthetic DMARD and at least two biologic DMARDs/targeted synthetic DMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA (Disease Activity index in PSoriatic Arthritis) >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 IBD (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.

Familial mediterranean fever in a patient with ankylosing spondylitis: could familial mediterranean fever explain a typical eight-year ankylosing spondylitis?

Patients with familial mediterranean fever (FMF) often present with musculoskeletal involvement typical of spondyloarthropathy (SpA) or ankylosing spondylitis (AS), posing a diagnostic challenge for medical practitioners and leading to the description of the FMF-related SpA/AS clinical spectrum. Currently, the available data focuses on SpA diagnosis in patients with known FMF, while the contrary is rarely reported in the medical literature. We describe an unusual case of concomitant FMF diagnosis in a patient with an eight-year long history of typical, human leukocyte antigen-B27 positive AS on adalimumab treatment, who presented with recurrent febrile attacks and abdominal pain. The laboratory work-up revealed high titres of serum amyloid A while genetic testing was positive for the pathogenic M694V heterozygous variant in the MEFV gene. The patient was promptly treated with colchicine, showing complete remission of clinical symptoms and normalisation of inflammatory markers to date. We also performed a review of the available literature elaborating on the interrelationship of AS and FMF in terms of pathogenesis and clinical characteristics. Our case highlights the need for reporting of similar cases and further explores the association of AS and FMF as distinct clinical entities or as constituents of the same disease continuum model.

Progression of subclinical atherosclerosis in ankylosing spondylitis: a 10-year prospective study.

Chronic systemic inflammation contributes to increased CVD burden in Ankylosing Spondylitis (AS). Since long-term follow-up data on subclinical atherosclerosis acceleration are lacking, we examined its progression in contemporary AS patients during 10 years. Fifty-three (89% male, aged 50.4 (36.3-55.9) years,) non-diabetic, CVD-free AS patients and 53 age-sex-matched non-diabetic, control individuals were re-evaluated after 9.2-10.2 years by ultrasonography for carotid/femoral atheromatosis, pulse wave velocity (PWV) and intima-media thickness (IMT), performed by the same operator/protocol. New atheromatic plaque formation, PWV deterioration, and IMT increase were associated only with classical CVD risk factors, as reflected by the heartSCORE (age, gender, smoking status, blood pressure and cholesterol levels) by multivariate analysis, rather than disease presence. However, among AS patients, despite remission/low disease activity at follow-up end in 79%, atheromatosis progression was associated by multivariate analysis with higher BASDAI scores (p = 0.028), independently of biologic therapies administered in 2/3 of them. Moreover, in AS patients, but not in controls, PWV values at baseline were associated with plaque progression during the 10-year follow-up after taking into account baseline heartSCORE and plaque burden status (p = 0.033). Despite comparable prevalence of both hypertension and hypercholesterolemia at baseline between patients and controls, a lower percentage of AS patients had achieved "adequate" CVD risk factor control at follow-up end (11% vs 25% respectively, p = 0.076). Classical CVD risk factors and residual disease activity account for the progression of subclinical atherosclerosis in AS, pointing to the unmet needs in the contemporary management of these patients.

Increased prevalence of inflammatory arthritis, systemic lupus erythematosus and systemic sclerosis, during 2020-2023 versus 2016-2019 in a Nation-Wide Cohort Study.

Although several studies have explored the geoepidemiology of autoimmune rheumatic diseases (ARD), trends of their frequency overtime are under-investigated. Herein, in a nation-wide study, we examine trends in the prevalence of various ARD over-time, taking also into account the Covid-19 pandemic. In this retrospective study in the entire Greek adult population (approximately 10.000.000 people), we searched the electronic prescription database of the e-Government Centre for Social Security Services using prespecified ICD-10 codes to capture all adult patients with Psoriatic Arthritis (PsA), Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS), Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc) and Polymyalgia Rheumatica or Giant Cell Arteritis (PMR/GCA). Two sequential 4-year periods, namely 2016-2019 and 2020-2023 were compared. Prevalence of RA, PsA, AxSpA, SLE and SSc increased significantly during 2020-2023 compared to 2016-2019. This applies to both genders and to all age groups for RA, PsA and AxSpA, to female patients in SLE and SSc and to patients 18-39 years in SLE and ≥ 60 years in SSc. Overall, there was 47% increase in prevalence for AxSpA (0.100% in 2016-19 vs 0.147% in 2020-23), 36.5% for PsA (0.148% vs 0.202%), 20.6% for RA (0.467% vs 0.563%), 19% for SLE (0.137% vs 0.163%) and 13% for SSc (0.023% vs 0.026%). A 16.3% decrease was evident in GCA/PMR, limited to those ≥ 40 years old. In a nation-wide study we confirm that ARD prevalence increases over-time, whereas a contribution of Covid-19 pandemic to our results during 2020-2023, cannot be excluded. Additional human, medical and financial resources will be needed to cover the increased needs of ARD patients.

Outcomes of COVID-19 re-infections: a single-center cohort of 167 patients with systemic rheumatic diseases.

Data on COVID-19 re-infections in patients with systemic rheumatic diseases (SRDs) are lacking. We aimed to describe the course and outcomes of COVID-19 re-infections in these patients versus controls. In this single-center retrospective study, we included 167 consecutive SRD patients with at least one COVID-19 re-infection (mean age 47.3 years, females 70.7%). SRD patients were compared in terms of patient-perceived COVID-19 re-infection severity and hospitalizations/deaths with 167 age/sex-matched non-SRD controls. Logistic regression analysis was performed to assess potential milder re-infection versus primary infection severity, adjusting for study group, demographics (age, sex), vaccination status, body mass index, smoking, and comorbidities. 23 and 7 out of 167 re-infected SRD patients experienced two and three re-infections, respectively, which were comparable to the re-infection rates in controls (two: 32; and three: 2) who also had comparable COVID-19 vaccination history (89% and 95% vaccinated, respectively). In the initial infection, patients with SRDs were hospitalized (7.2% versus 1.8%, p = 0.017), and had received antiviral treatment (16.1% versus 4.7%, p < 0.001) more frequently than controls. However, hospitalizations (1.8% vs 0.6%) and antiviral treatment (7.8% vs 3.5%) did not differ (p > 0.05) between patients and controls at the first re-infection, as well as during the second and third re-infection; no deaths were recorded. Perceived severity of re-infections was also comparable between patients and controls (p = 0.847) and among those on biologic DMARDs or not (p = 0.482). In multivariable analysis, neither SRDs presence nor demographics or comorbidities were associated with COVID-19 re-infection severity. COVID-19 re-infection severity (patient-perceived/hospitalizations/deaths) did not differ between SRDs and controls.

Treat to target in Behcet's disease: Should we follow the paradigm of other systemic rheumatic diseases?

During the last decades the efficacy of biologic agents, mainly of anti-TNFs, in controlling the activity of serious manifestations of Behcet's Disease (BD) has been established. On the other hand, the clinical heterogeneity of BD has precluded the validation of a widely-accepted composite index for disease assessment and for target disease-state definitions, such as low disease activity and remission, and the testing of their implementation in clinical practice. Therefore, in contrast to other systemic rheumatic diseases, a treat-to-target strategy has not yet been developed in BD. There are several challenges towards this approach, including standardization of outcome measures for assessing the disease activity in each-affected organ and construction of a composite disease activity index. The challenges for the development of a treat-to-target strategy and possible solutions are discussed in this position paper, which stemmed from a round table discussion that took place in the 19th International Conference on BD.

Distinct innate and adaptive immunity phenotypic profile at the circulating single-cell level in Psoriatic Arthritis.

Mass cytometry was employed to investigate 47 circulating leukocyte subsets in patients with active psoriatic arthritis (PsA, n = 16) compared to healthy controls (n = 13), seropositive (RF and/or anti-CCP, n = 12) and seronegative (n = 9) RA patients. Comparing PsA to controls, different cell frequencies were found in both innate and adaptive immunity cell subsets, as well as in cells bridging innate and adaptive immunity. In some T cell subsets increased costimulatory molecules' expression in PsA, was also noted.No changes were observed in patients who remained disease-active after 3 months of treatment, in contrast to those who achieved remission/low-disease activity. Comparing PsA to seropositive RA, elevated frequencies of naïve and activated CD8+ T cells, B cells, MAIT/iNKT and ILCs were found, while the opposite was the case for terminal effector, senescent, and Th2-like cells. Strikingly, the composition of the leukocyte pool in PsA was comparable to seronegative RA, providing evidence for the pathogenetic similarities between these two entities.

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. RESULTS: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. CONCLUSIONS: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to assess the possibility of HBV reactivation (HBVr) in patients with RA under anti-IL-6 treatment. METHODS: Using PubMed, Scopus and EMBASE, we performed a systematic literature search for articles related to HBVr in RA patients under anti-IL-6 treatment. The search was performed with no date limits and was last updated 28 January 2023. The results from all the databases were combined and duplicates were excluded, as were non-English articles, case reports, position articles, comments, and paediatric studies. RESULTS: Our initial search led to 427 articles; 28 were duplicates, 46 non-English, 169 reviews, 31 books/letters, 25 case reports, and 88 irrelevant to the meta-analysis aim; 21 were excluded due to inadequate information, leaving 19 articles, with a sum of 372 RA patients with chronic HBV (CHB) or resolved HBV infection, for further analysis. The overall risk for HBVr in RA patients with CHB was 6.7%, increasing to 37% when only RA patients with CHB and no antiviral prophylaxis were included. On the contrary, HBVr was close to 0% in RA patients with resolved HBV infection, irrespective of antiviral prophylaxis. All RA patients experiencing HBVr in these studies were successfully managed with antiviral treatment and/or drug withdrawal. CONCLUSION: Overall, anti-IL-6 treatment comes with a significant risk of HBVr in RA patients with CHB; risk is diminished when antiviral prophylaxis is used. In contrast, in RA patients with resolved HBV infection, the risk of HBVr seems to be extremely low. Large, well-designed studies (either controlled trials or multicentre/international observational studies) are warranted to further validate these results.

Different COVID-19 outcomes among systemic rheumatic diseases: a nation-wide cohort study.

OBJECTIVES: To investigate coronavirus disease 2019 (COVID-19)-associated risk of hospitalization and death in RA, AS, PsA, SLE and SSc in comparison with the general population during the first year of the pandemic, and compare their overall mortality with 2019. METHODS: Interlinking nationwide electronic registries, we recorded confirmed COVID-19-associated infections, hospitalizations and deaths, and all-cause deaths between 1 March 2020 and 28 February 2021 in all adults with RA, AS, PsA, SLE and SSc under treatment (n = 74 970, median age 67.5, 51.2, 58.1, 56.2 and 62.2 years, respectively) and in random comparators from the general population matched (1:5) on age, sex and region of domicile. Deaths from all causes during 2019 were also recorded. RESULTS: Compared with the general population, incidence rates (IR) for COVID-19-associated hospitalization were higher in RA [IR ratio (IRR) 1.71(1.50-1.95)], SLE [2.0 (1.4-2.7)] and SSc [2.28 (1.29-3.90)], while COVID-19-associated death rates were higher in RA [1.91 (1.46-2.49)]. When focusing only on severe acute respiratory syndrome coronavirus 2-infected subjects, after adjusting for age and gender, the odds ratio for COVID-19 associated death was higher in RA [1.47 (1.11-1.94)] and SSc [2.92 (1.07-7.99)] compared with the general population. The all-cause mortality rate compared with the general population increased in RA during the first year of the pandemic (IRR 0.71) with reference to 2019 (0.59), and decreased in SSc (IRR 1.94 vs 4.36). CONCLUSION: COVID-19 may have a more severe impact in patients with systemic rheumatic disease than in the general population. COVID-19-related mortality is increased in subgroups of patients with specific rheumatic diseases, underscoring the need for priority vaccination and access to targeted treatments.

Depression and anxiety in a real-world psoriatic arthritis longitudinal study: should we focus more on patients' perception?

OBJECTIVES: Longitudinal studies using validated tools to evaluate depression and anxiety in psoriatic arthritis (PsA) are lacking. We aimed to estimate their course in PsA and to examine possible associations with disease-related parameters and patient-reported outcomes (PROs). METHODS: PsA patients attending two outpatient rheumatology clinics were consecutively enrolled (January 2019-June 2021, n=128). The hospital anxiety and depression scale (HADS) was used at two sequential visits (mean±SD: 10±6 months) to prospectively assess depression (HADS-Depression) and anxiety (HADS-Anxiety) (cut-off scores ≥11). Associations with demographic, clinical, laboratory features and PROs for quality of life (QoL) (EQ-5D), functional status (HAQ-DI) and nocebo-behaviour (Q-No) were examined. 'Change' was the difference between values at the first and second visit. RESULTS: Prevalence of depression and anxiety at the first visit was 19.5% and 21.1%, respectively. Depression was associated with EQ-5D [OR (95% CI): 1.70 (1.02-2.59), p=0.019] and anxiety with EQ-5D [1.81 (1.20 to 2.72), p=0.005], nocebo-behaviour [1.19 (1.01-1.40), p=0.04] and current corticosteroid use [6.95 (1.75-27.59), p=0.006]. At the second visit, HADS-Depression and HADS-Anxiety scores were improved in 40.9% and 41.9% of patients, respectively. While no associations were found for HADS-Anxiety score change, changes in HADS-Depression score correlated with changes in subjective (tender joint count, r= 0.204, p=0.049; PtG, r= 0.236, p=0.023; patient pain assessment, r= 0.266, p=0.01) but not objective (swollen joint count, ESR, CRP) parameters of disease activity. CONCLUSIONS: In PsA, depression and anxiety are associated with worse PROs, including QoL. Subjective parameters of disease activity parallel course of depression.

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.

Higher frequency but similar recurrence rate of uveitis episodes in axial spondylarthritis compared to psoriatic arthritis. A multicentre retrospective study.

BACKGROUND/OBJECTIVE: Data on risk factors predicting uveitis development in spondyloarthritis (SpA) is scarce. Our aim was to examine associations between demographic, clinical and/or laboratory characteristics of SpA with the occurrence and the course of uveitis, including ocular damage and recurrence rate. METHODS: Characteristics (at disease diagnosis and ever-present) from axSpA and Psoriatic arthritis (PsA) patients followed in 3 tertiary rheumatology-clinics were retrospectively recorded. Comparisons were made between patients with and without uveitis, as well as between those with uveitis-rate [episodes/year] above the median uveitis-rate in the whole cohort ("recurrent"-uveitis) and the remaining uveitis patients ("non-recurrent uveitis"). In multivariable models, age, gender and variables significantly different in univariate analyses were included. RESULTS: 264 axSpA and 369 PsA patients were enrolled. In axSpA, uveitis occurred in 11.7% and was associated with HLA-B27 (OR = 4.15, 95%CI 1.16-14.80, p = 0.028) and ever-present peripheral arthritis (OR = 3.05 (1.10-8.41, p = 0.031). In contrast, uveitis in PsA occurred only in 2.7% of patients and was associated with SpA family-history (OR = 6.35 (1.29-31.27), p = 0.023) axial disease at diagnosis (OR = 5.61 [1.01-28.69], p = 0.038) and disease duration (OR = 1.12 [1.04-1.21], p = 0.004). Median uveitis recurrence rate was comparable between axSpA and PsA (0.205 and 0.285 episodes/year, respectively). No associations were found between recurrent uveitis and demographic/clinical/laboratory characteristics. Ocular damage (e.g. synechiae) was seen in 16.1% of axSpA and 30% of PsA patients, all of them with recurrent uveitis. CONCLUSION: Uveitis occurred more commonly in axSpA than in PsA patients, while uveitis recurrence rate was similar. Permanent ocular damage may occur more often in PsA than axSpA.

Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases.

OBJECTIVE: Τo report outcomes of breakthrough COVID-19 in comparison with COVID-19 in unvaccinated patients with systemic rheumatic diseases (SRDs). METHODS: Patients with SRD with COVID-19 (vaccinated and unvaccinated) were included by their rheumatologists in a registry operated by the Greek Rheumatology Society in a voluntarily basis. Type, date and doses of SARS-CoV-2 vaccines were recorded, and demographics, type of SRD, concurrent treatment, comorbidities and COVID-19 outcomes (hospitalisation, need for oxygen supplementation and death) were compared between vaccinated and unvaccinated patients. RESULTS: Between 1 March 2020 and 31 August 2021, 195 patients with SRD with COVID-19 were included; 147 unvaccinated and 48 vaccinated with at least one dose of a SARS-CoV-2 vaccine (Pfizer n=38 or AstraZeneca n=10). Among vaccinated patients, 29 developed breakthrough COVID-19 >14 days after the second vaccine dose (fully vaccinated), while 19 between the first and <14 days after the second vaccine dose (partially vaccinated). Despite no differences in demographics, SRD type, treatment or comorbidities between unvaccinated and vaccinated patients, hospitalisation and mortality rates were higher in unvaccinated (29.3% and 4.1%, respectively) compared with partially vaccinated (21% and 0%) or fully vaccinated (10.3% and 0%) patients. CONCLUSIONS: Vaccinated patients with SRD with breakthrough COVID-19 have better outcomes compared with unvaccinated counterparts with similar disease/treatment characteristics.

Axial psoriatic arthritis and ankylosing spondylitis: same or different? A real-world study with emphasis on comorbidities.

OBJECTIVES: Axial involvement affects 25-70% of psoriatic arthritis (PsA) patients, depending on the criteria used for its definition. Efforts are underway to clarify the similarities and differences between axial-PsA and ankylosing spondylitis (AS). We aimed to compare, in a real-world setting, axial-PsA and AS, in terms of demographic, radiologic and clinical (musculoskeletal and extra-articular) characteristics, with a focus on comorbidities. METHODS: All AS (New York criteria, n=128) and PsA patients (CASPAR criteria, n=78) with axial involvement who were regularly followed-up in the outpatients' rheumatology clinics from two tertiary hospitals (December 2018-July 2020) were included. Demographic, radiologic and clinical characteristics were recorded and compared between the two groups. For comorbidities (coronary disease, cerebrovascular accidents, hypertension, diabetes mellitus, dyslipidaemia, depression, osteoporosis, and malignancies), adjustments were made for relevant confounders. RESULTS: AS patients were younger (p=0.05) and were diagnosed at a younger age (p=0.002), more frequently of male gender (p=0.04), had lower BMI (p=0.006) and they were more frequently HLA-B27-positive (p=0.006). In AS patients, peripheral arthritis, dactylitis and nail involvement were less common (p=0.001 for all), in contrast to eye (p=0.001) and bowel involvement (p=0.004). Frequency of radiologic abnormalities in the spine was similar between the two groups while sacroiliitis was more often bilateral in AS and unilateral in axial-PsA. Comorbidities, including cardiovascular-related ones, were comparable between AS and axial-PsA, apart from depression which was more frequent in axial-PsA (p=0.07 in logistic regression). CONCLUSIONS: AS and axial-PsA have certain clinical and radiologic differences. Comorbidities were comparable, while depression was more common in axial-PsA.

COVID-19 vaccine safety and nocebo-prone associated hesitancy in patients with systemic rheumatic diseases: a cross-sectional study.

OBJECTIVE: To describe the rate and type of adverse effects (AEs) and the frequency of disease flares after COVID-19 vaccination and to assess the reasons for vaccination hesitancy (non-vaccination) in SRD patients. METHODS: Telephone interviews were conducted of SRD patients consecutively enrolled (15/06/2021-1/7/2021). Participants were asked about the type of AEs and disease flare after vaccination. Reasons for vaccination hesitancy were recorded. Univariate and mutivariable analyses examined associations of demographic, clinical and other features, with occurrence of AEs, disease flare and non-vaccination. For the latter, association with negative vaccination behaviour (not influenza vaccinated for the last 2 years) and nocebo-prone behaviour (denoting AEs attributed to negative expectations [Q-No questionnaire]) was also tested. RESULTS: 561 out of 580 contacted patients were included in the study. 441/561 (78.6%) patients were vaccinated [90% (Pfizer, Moderna), 10% (Astra-Zeneca)]. AEs were reported by 148/441 (33.6%), with rates being comparable between the three vaccines. AEs were more common in females and those with chronic obstructive pulmonary disease [OR, 95% CI; females: 2.23 (1.30-3.83); COPD: 3.31 (1.24-8.83)]. Disease flare was reported in 9/441 (2%) patients. For those unvaccinated, fear that the vaccine would be harmful (53.3%), could cause disease flare (24.2%) and/or could cause thrombosis (21.7%) were the main reasons to do so. Multivariable analysis identified as independent variables for non-vaccination: nocebo-prone behaviour (OR; 95% CI, 3.88; 1.76-8.55), negative vaccination behaviour (6.56; 3.21-13.42) and previous COVID-19 infection (2.83; 1.13-7.05). Higher educational status was protective (0.49; 0.26-0.92). CONCLUSION: No new safety signals for COVID-19 vaccination were observed. Vaccination campaign should target SRD patients with nocebo-prone and negative influenza vaccination behaviour.

The role for JAK inhibitors in the treatment of immune-mediated rheumatic and related conditions.

JAK inhibitors (JAKIs) are a new class of targeted therapy that have entered clinical practice for the treatment of immune-mediated rheumatic conditions. JAKIs can block the signaling activity of a variety of proinflammatory cytokines and therefore have the potential to mediate therapeutic benefits across a wide range of immune-mediated conditions. Several JAKIs are licensed, and many more are undergoing clinical trials. Here we provide a narrative review of the current and upcoming JAKIs for adult immune-mediated rheumatic and related conditions, with a specific focus on efficacy in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, psoriasis, and inflammatory bowel disease. The overall safety profile of JAKIs appears largely comparable to that of existing biologic cytokine-targeting agents, particularly, TNF inhibitors, apart from risk of herpes zoster, which is increased for JAKIs. Importantly however, unresolved safety concerns remain, particularly relating to increased venous thromboembolism.

2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis.

BACKGROUND: An important but often insufficient aspect of care in people with inflammatory arthritis (IA) is empowering patients to acquire a good understanding of their disease and building their ability to deal effectively with the practical, physical and psychological impacts of it. Self-management skills can be helpful in this regard. OBJECTIVES: To develop recommendations for the implementation of self-management strategies in IA. METHODS: A multidisciplinary taskforce of 18 members from 11 European countries was convened. A systematic review and other supportive information (survey of healthcare professionals (HCPs) and patient organisations) were used to formulate the recommendations. RESULTS: Three overarching principles and nine recommendations were formulated. These focused on empowering patients to become active partners of the team and to take a more proactive role. The importance of patient education and key self-management interventions such as problem solving, goal setting and cognitive behavioural therapy were highlighted. Role of patient organisations and HCPs in promoting and signposting patients to available resources has been highlighted through the promotion of physical activity, lifestyle advice, support with mental health aspects and ability to remain at work. Digital healthcare is essential in supporting and optimising self-management and the HCPs need to be aware of available resources to signpost patients. CONCLUSION: These recommendations support the inclusion of self-management advice and resources in the routine management of people with IA and aim to empower and support patients and encourage a more holistic, patient-centred approach to care which could result in improved patient experience of care and outcomes.