Disease characteristics,pathogenesis, and treatment controversies of axial psoriatic arthritis

Axial psoriatic arthritis (axPsA) has considerable overlap with axial spondyloarthritis (axSpA) but has some unique features that sometimes preclude classification into axSpA. It has some clinical and radiographic differences compared to axSpA. Imaging typically shows asymmetric syndesmophytes, mainly in the cervical spine, with less frequent sacroiliitis. It more commonly presents later in life and is associated with less severe inflammatory back pain than axSpA. The interleukin (IL) IL-23/IL-17 axis is central to the pathogenesis of both diseases. However, the response to therapies targeting these cytokines has been different. IL-23 inhibitors are ineffective in axSpA but may be effective in psoriatic arthritis (PsA). Recent post hoc analyses of clinical trial data with IL-23 inhibitors in PsA have raised the possibility of their efficacy in axPsA and need evaluation in future clinical trials. Moreover, there is a need for classification criteria for axPsA and better tools to assess therapeutic response.     

Involvement of foot in patients with spondyloarthritis: Prevalence and clinical features

Background

The purpose of this study was to evaluate the foot involvement in a group of patients with spondyloarthritis in regard to symptoms, type and frequency of deformities, location and radiological changes.

Cardiovascular risk profile in patients with spondyloarthritis

ObjectivesThe spondyloarthritides (SpA) are associated with an increased cardiovascular risk. We studied cardiovascular risk factors in patients with SpA.MethodsThe following risk factors were assessed in SpA patients and healthy controls: smoking, family history of premature ischemic heart disease, obesity, serum lipids, apolipoproteins, urate and carotid intima media thickness (IMT).ResultsOverall 150 patients (73 with ankylosing spondylitis [AS], 71 with psoriatic arthritis [PsA] and six with other SpA types) were included. Generally SpA patients were significantly more often smokers, while PsA patients had greater values of abdominal obesity. AS patients had significantly lower levels of triglyceride, HDL, ApoB, ApoE and Lp(a) and a higher atherogenic index (total cholesterol/HDL). PsA patients had significantly lower levels of HDL, ApoAI and ApoE, an elevated atherogenic index and higher serum urate. In multivariate analysis the atherogenic index was positively associated with SpA across all patient groups independently of smoking and other lipid parameters. Carotid IMT in SpA patients (0.71 mm) was higher than controls (0.63 mm, P = 0.017), although after adjusting for smoking this ceased to be significant. Treatment of patients with previously untreated disease resulted in a small but significant decline in ApoB levels at 6 months (P = 0.045), which, however, was no longer evident at 12 months.ConclusionSpondyloarthritis patients are at a greater cardiovascular risk owing to the higher prevalence of smoking and a higher atherogenic index. PsA patients have more abdominal fat and higher urate levels. Immunosuppressive treatment of SpA produces minor and temporary effects on the lipid profile.     

2022 French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis,including psoriatic arthritis

ObjectiveUpdate the French Society for Rheumatology (SFR) recommendations on the everyday management of patients with spondyloarthritis, including psoriatic arthritis.MethodsFollowing standardized procedures, a systematic literature review was done by four supervised rheumatology residents based on questions defined by a task force of 16 attending rheumatologists. The findings were reviewed during three working meetings that culminated in each recommendation receiving a grade and the level of agreement among experts being determined.ResultsFive general principles and 15 recommendations were developed. They take into account pharmacological and non-pharmacological measures along with treatment methods based on the dominant phenotype present (axial, articular, enthesitis/dactylitis) and the extra-articular manifestations (psoriasis, inflammatory bowel disease, uveitis). NSAIDs are the first-line pharmacological treatment in the various presentations. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are not indicated in the axial and isolated entheseal forms. If the response to conventional treatment is not adequate, targeted therapies (biologics, synthetics) should be considered; the indications depend on the clinical phenotype and presence of extra-articular manifestations.ConclusionThis update incorporates recent data (published since the prior update in 2018) and the predominant clinical phenotype concept. It aims to help physicians with the everyday management of patients affected by spondyloarthritis, including psoriatic arthritis.     

Patient-defined flares and disease activity worsening in 222 patients with psoriatic arthritis from 14 countries

ObjectivesTo explore patient-defined flares in psoriatic arthritis (PsA), compared to an increase in disease activity in psoriatic arthritis (DAPSA) and to analyze the validity of a patient-reported flare question.MethodsReFlap (NCT03119805) was a longitudinal study in 14 countries of consecutive patients with definite PsA. Patients were seen twice in the context of usual care, 4.5 ± 2.2 months apart. Flares were reported by patients and physicians at the second visit using a single question. DAPSA worsening was defined as a change to a higher DAPSA category. Agreement between the definitions of worsening was calculated by prevalence adjusted bias adjusted kappa (PABAK). Validity of patient-reported flare was assessed by comparing patients with versus without flare and transition to flares.ResultsIn 222 patients, mean disease duration 10.8 ± 8.3 years, 127 (58.8%) males: disease activity was low (mean DAPSA 11.5 ± 14.0); 63.3% received a bDMARD. Patient-reported flares between the 2 visits were seen in 27% patients (for these patients, mean 2.2 ± 3.7 flares per patient, mean duration 12.6 ± 21.0 days per flare). Physician- reported flares were seen in 17.6% and worsening in DAPSA in 40.1% of patients. Agreement between definitions was moderate (PABAK = 0.32-0.59). Patients in flare had significantly more active disease than patients not in flare for all outcomes (all P < 0.001). At the patient-level, transition to flare state was associated to a worsening in disease activity and impact outcomes.ConclusionsPatient flares were frequent and were associated with active and symptomatic disease. These findings provide preliminary validation for patient-reported flares in PsA.     

Effect of biologics on fatigue in psoriatic arthritis: A systematic literature review with meta-analysis

Objectives

Fatigue is a significant issue in psoriatic arthritis. The objective was to assess the effect of biological disease modifying antirheumatic drugs and apremilast on fatigue in psoriatic arthritis randomised controlled trials and to compare this effect with the effect in the same trials, on pain, through a systematic literature review and meta-analysis.

SARS-CoV-2 neutralizing antibodies after first vaccination dose in breast cancer patients receiving CDK4/6 inhibitors

Undoubtedly, the development of COVID-19 vaccines displays a critical step towards ending this devastating pandemic, considering their protective benefits in the general population. Yet, data regarding their efficacy and safety in cancer patients are limited. Herein we provide the initial analysis of immune responses after the first dose of vaccination in 21 breast cancer patients receiving cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. The levels of neutralizing antibodies post vaccination were similar to the matched healthy controls, whereas no safety issues have been raised. Further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.     

2018 update of French Society for Rheumatology (SFR) recommendations about the everyday management of patients with spondyloarthritis

Objective

To update French Society for Rheumatology recommendations about the management in clinical practice of patients with spondyloarthritis (SpA). SpA is considered across the range of clinical phenotypes (axial, peripheral, and entheseal) and concomitant manifestations. Psoriatic arthritis is included among the SpA phenotypes.

Determinants of sleep impairment in psoriatic arthritis: An observational study with 396 patients from 14 countries

ObjectiveSleep quality is diminished in patients with psoriatic arthritis (PsA) and close to 40% of PsA patients consider sleep difficulties a priority domain. This work analyzes determinants of impaired sleep in patients with PsA.MethodsThis was a cross-sectional analysis of an observational study (ReFlap, NCT NCT03119805), which included adult patients with definite PsA with ≥ 2 years disease duration from 14 countries. Sleep was assessed using the patient self-reported evaluation of sleep on a 0-10 numerical scale, included in the Psoriatic Arthritis Impact of Disease questionnaire (PSAID-12). A score ≥ 4 was considered as sleep impairment. Demographic and clinical variables associated to sleep impairment were assessed through univariate analysis and Poisson regression modeling leading to prevalence ratio (PR) [95% confidence interval].ResultsA total of 396 patients were analyzed: mean age 51.9 ± 12.6 years, 51% were females, 59.7% were receiving biologic therapy, 53.3% had 1–5% of body surface area affected by psoriasis; 23.7% were in remission and 36.9% in low disease activity according to the Disease Activity in Psoriatic Arthritis (DAPSA) score. Median (25th–75th) patient's self-evaluation of sleep difficulties was 2 (0–6), 157 (39.6%) had sleep impairment. In the Poisson regression model, self-reported levels of anxiety (PR: 1.05 [1.02–1.08], P = 0.003) and pain (PR: 1.06 [1.04–1.09], P < 0.001) were independently associated to sleep impairment.ConclusionsIn this multicentric study, sleep impairment was present in 40% of PsA patients; pain and anxiety were associated to sleep impairment whereas inflammation was not. Impact on sleep appears multifactorial in PsA.     

Targeted resequencing of the 13q13 spondyloarthritis-linked locus identifies a rare variant in FREM2 possibly associated with familial spondyloarthritis

ObjectivesThe strong heritability of spondyloarthritis remains poorly explained, despite several large-scale association studies. A recent linkage analysis identified a new region linked to SpA on 13q13. Here we searched for variants potentially explaining this linkage signal by deep-sequencing of the region.MethodsRe-sequencing of the 1.4 Mb target interval was performed in 92 subjects from the 43 best-linked multicases families (71 spondyloarthritis and 21 unaffected relatives), using hybridization capture-based protocol (Illumina Nextera®). Variants of interest were then genotyped by TaqMan and high resolution melting to check their co-segregation with disease in the same families and to test their association with spondyloarthritis in an independent cohort of 1,091 unrelated cases and 399 controls. Expression of FREM2 was assessed by immunostaining.ResultsOf the 7,563 variants identified, 24 were non-synonymous coding single-nucleotide variants. Two of them were located in the FREM2 gene on a haplotype co-segregating with the disease, including one common variant (R1840 W, minor allele frequency = 0.11) and one rare variant (R727H, minor allele frequency = 0.0001). In the case-control analysis, there was no significant association between R1840 W and spondyloarthritis (P-value = 0.21), whereas R727H was not detected in any of the genotyped individuals. Immunostaining experiments revealed that FREM2 is expressed in synovial membrane, cartilage and colon.ConclusionsTargeted re-sequencing of a spondyloarthritis-linked region allowed us to identify a rare non-synonymous coding variant in FREM2, co-segregating with spondyloarthritis in a large family. This gene is expressed in several tissues relevant to spondyloarthritis pathogenesis, supporting its putative implication in spondyloarthritis.     

COVID-19 in patients with juvenile idiopathic arthritis: frequency and severity

The aim of the study was to determine the frequency and the course of COVID-19 infection in children with juvenile idiopathic arthritis (JIA). The study involved 51 patients with JIA aged 2 to 18 years. Evidence of COVID-19 was found in 10 (19.6%) patients with JIA. COVID-19 infection occurred more often in patients with systemic arthritis (OR = 6.1667, 95% CI: 1.2053–31.5511, p = 0.0289). The course of COVID-19 infection in patients with JIA was generally similar to the course in the pediatric population, despite immunosuppressive therapy. In 3 out of 10 patients the infection caused an exacerbation of JIA, which required therapy escalation.     

A cross-sectional study of immune seroconversion to SARS-CoV-2 in frontline maternity health professionals

COVID-19, the respiratory disease caused by SARS-CoV-2, is thought to cause a milder illness in pregnancy with a greater proportion of asymptomatic carriers. This has important implications for the risk of patient-to-staff, staff-to-staff and staff-to-patient transmission among health professionals in maternity units. The aim of this study was to investigate the prevalence of previously undiagnosed SARS-CoV-2 infection in health professionals from two tertiary-level maternity units in London, UK, and to determine associations between healthcare workers’ characteristics, reported symptoms and serological evidence of prior SARS-CoV-2 infection. In total, 200 anaesthetists, midwives and obstetricians, with no previously confirmed diagnosis of COVID-19, were tested for immune seroconversion using laboratory IgG assays. Comprehensive symptom and medical histories were also collected. Five out of 40 (12.5%; 95%CI 4.2–26.8%) anaesthetists, 7/52 (13.5%; 95%CI 5.6–25.8%) obstetricians and 17/108 (15.7%; 95%CI 9.5–24.0%) midwives were seropositive, with an overall total of 29/200 (14.5%; 95%CI 9.9–20.1%) of maternity healthcare workers testing positive for IgG antibodies against SARS-CoV-2. Of those who had seroconverted, 10/29 (35.5%) were completely asymptomatic. Fever or cough were only present in 6/29 (21%) and 10/29 (35%) respectively. Anosmia was the most common symptom occurring in 15/29 (52%) seropositive participants and was the only symptom that was predictive of positive seroconversion (OR 18; 95%CI 6–55). Of those who were seropositive, 59% had not self-isolated at any point and continued to provide patient care in the hospital setting. This is the largest study of baseline immune seroconversion in maternity healthcare workers conducted to date and reveals that one out of six were seropositive, of whom one out of three were asymptomatic. This has significant implications for the risk of occupational transmission of SARS-CoV-2 for both staff and patients in maternity units. Regular testing of staff, including asymptomatic staff should be considered to reduce transmission risk.