Synovitis in rheumatoid arthritis detected by grey scale ultrasound predicts the development of erosions over the next three years.

OBJECTIVES: To evaluate grey scale US (GSUS) and power Doppler US synovitis (PDUS), separately or in combination (CombUS), to predict joint damage progression in RA. METHODS: In this cohort study nested in the Swiss RA register, all patients with sequential hand radiographs at their first US assessment were included. We analysed the summations of semi-quantitative GSUS, PDUS and CombUS assessments of both wrists and 16 finger joints (maximum 54 points) at their upper limit of normal, their 50th, 75th or 87.5th percentiles for the progression of joint damage (ΔXray). We adjusted for clinical disease activity measures at baseline, the use of biological DMARDs and other confounders. RESULTS: After a median of 35 months, 69 of 250 patients with CombUS (28%), 73 of 259 patients with PDUS (28%) and 75 of 287 patients with available GSUS data (26%) demonstrated joint damage progression. PDUS beyond upper limit of normal (1/54), GSUS and CombUS each at their 50th (9/54 and 10/54) and their 75th percentiles (14/54 and 15/54) were significantly associated with ΔXray in crude and adjusted models. In subgroup analyses, GSUS beyond 14/54 and CombUS higher than 15/54 remained significantly associated with ΔXray in patients on biological DMARDs, while clinical disease activity measures had no significant prognostic power in this subgroup. CONCLUSION: Higher levels of GSUS and CombUS are associated with the development of erosions. GSUS appears to be an essential component of synovitis assessment and an independent predictor of joint damage progression in patients on biological DMARDs.

[Targeted treatment in spondyloarthritis]. / Traitement ciblé des spondylarthrites.

In the absence of clearly defined prognostic markers and predictors of treatment response, the choice of therapy in spondyloarthritis is currently based on a stratification of certain clinical characteristics, which increases the probability of a good response to treatment. Consequently, the choice of DMARD (disease modifying antirheumatic drug) depends on multiple factors, such as the clinical characteristics of the disease with predominantly axial, peripheral or entheseal manifestations, the presence and severity of cutaneous psoriasis, other extra-articular manifestations and comorbidities, as well as patient preferences with regards to the mode and frequency of administration. We also lack evidence about how to best treat some sub-groups of patients excluded from most of clinical trials and thus it is difficult to truly talk about targeted treatment in spondyloarthritis.

En l'absence de marqueurs pronostiques définis et de prédicteurs de réponse, le choix du traitement dans les spondylarthrites est actuellement fondé sur une stratification selon certaines caractéristiques cliniques, ce qui permet d'augmenter la probabilité de réponse au traitement. En conséquence, le choix du DMARD (antirhumatismal modificateur de la maladie) dépend de plusieurs facteurs, comme les caractéristiques de la maladie avec une prédominance axiale, périphérique ou enthésitique, la présence et la sévérité du psoriasis cutané, d'autres manifestations extra-articulaires et comorbidités, ainsi que les préférences du patient concernant le mode et la fréquence d'administration. Cependant nous manquons de données probantes dans la gestion de certains groupes de patients exclus de la plupart des études cliniques pour pouvoir vraiment parler de traitement ciblé dans le cadre des spondylarthrites.

Safety and immunogenicity of tetanus/diphtheria vaccination in patients with rheumatic diseases-a prospective multi-centre cohort study.

OBJECTIVES: We aimed to assess the safety and immunogenicity of a diphtheria/tetanus vaccine booster dose in three different patient groups with rheumatic diseases on a variety of immunosuppressive/immunomodulatory medications compared with healthy controls (HCs). METHODS: We conducted a multi-centre prospective cohort study in Switzerland. We enrolled patients with RA, axial SpA/PsA, vasculitis (Behçet's disease, ANCA-associated vasculitis) and HCs. Diphtheria/tetanus vaccination was administered according to the Swiss vaccination recommendations. Blood samples were drawn before vaccination, and 1 month and 3 months afterwards. Antibody concentrations against vaccine antigens were measured by ELISA. Immunogenicity was compared between patient and medication groups. A mixed model was applied for multivariate analysis. Missing data were dealt with using multiple imputation. RESULTS: Between January 2014 and December 2015, we enrolled 284 patients with rheumatic diseases (131 RA, 114 SpA/PsA, 39 vasculitis) and 253 HCs. Of the patients, 89% were on immunosuppressive/immunomodulatory medication. Three months post-vaccination 100% of HCs vs 98% of patients were protected against tetanus and 84% vs 73% against diphtheria. HCs and SpA/PsA patients had significantly higher responses than RA and vasculitis patients. Assessing underlying diseases and medications in a multivariate model, rituximab was the only factor negatively influencing tetanus immunogenicity, whereas only MTX treatment had a negative influence on diphtheria antibody responses. No vaccine-related serious adverse events were recorded. CONCLUSION: Diphtheria/tetanus booster vaccination was safe. Tetanus vaccination was immunogenic; the diphtheria component was less immunogenic. Vaccine responses were blunted by rituximab and MTX. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, Identifier: NCT01947465.

Differences and similarities between the EULAR/ASAS-EULAR and national recommendations for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe.

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations.

Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults.

INTRODUCTION: Guselkumab is a subcutaneously administered human monoclonal antibody, selectively blocking IL-23 through binding to its p19 subunit. It was initially approved for the treatment of patients with moderate-to-severe plaque-psoriasis who are candidates for systemic therapy or phototherapy. Pubmed and Embase databases were searched for publications, using the following search terms: psoriasis, psoriatic arthritis, guselkumab, risankizumab, tildrakizumab, p19, interleukin 23, guidelines, treatment recommendations, DISCOVER, ECLIPSE, and VOYAGE. AREAS COVERED: Accumulating evidence suggests that the IL-23/Th17 pathway is important in the pathogenesis of both psoriasis and psoriatic arthritis. Following a successful development program in psoriasis, guselkumab was evaluated for its efficacy and safety in psoriatic arthritis in a comprehensive clinical trial program, comprising one phase-2 study and two phase-3 studies (DISCOVER-1 and -2). Complementary data on pharmacokinetics and safety exist from pre-clinical experiments and pooled analyses from two long-term studies in psoriasis (VOYAGE-1 and -2). Based on the DISCOVER-1 and -2 data, guselkumab was approved by the FDA for the treatment of active psoriatic arthritis in 2020. EXPERT OPINION: Guselkumab is the first selective IL-23 inhibitor approved to treat adults with active psoriatic arthritis, broadening therapeutic options in the field through a novel mode of action.

Impact of Acute Inflammation on Cytochromes P450 Activity Assessed by the Geneva Cocktail.

Cytochromes P450 (CYP) are subject to important interindividual variability in their activity due to genetic and environmental factors and some diseases. Limited human data support the idea that inflammation downregulates CYP activities. Our study aimed to evaluate the impact of orthopedic surgery (acute inflammation model) on the activity of six human CYP. This prospective observational study was conducted in 30 patients who underwent elective hip surgery at the Geneva University Hospitals in Switzerland. The Geneva phenotyping cocktail containing caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, and midazolam as probe drugs respectively assessing CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A activities was administered orally before surgery, day 1 (D1) and 3 (D3) postsurgery and at discharge. Capillary blood samples were collected 2 hours after cocktail intake to assess metabolic ratios (MRs). Serum inflammatory markers (CRP, IL-6, IL-1ß, TNF-α, and IFN-γ) were also measured in blood. CYP1A2 MRs decreased by 53% (P < 0.0001) between baseline and the nadir at D1. CYP2C19 and CYP3A activities (MRs) decreased by 57% (P = 0.0002) and 61% (P < 0.0001), respectively, with the nadir at D3. CYP2B6 and CYP2C9 MRs increased by 120% (P < 0.0001) and 79% (P = 0.018), respectively, and peaked at D1. Surgery did not have a significant impact on CYP2D6 MR. Hip surgery was a good acute inflammation model as CRP, IL-6, and TNF-α peak levels were reached between D1 and day 2 (D2). Acute inflammation modulated CYP activity in an isoform-specific manner, with different magnitudes and kinetics. Acute inflammation may thus have a clinically relevant impact on the pharmacokinetics of these CYP substrates.

Glucocorticoid injections for greater trochanteric pain syndrome: a randomised double-blind placebo-controlled (GLUTEAL) trial.

Small observational studies suggest that local glucocorticoid (GC) injection may be effective in the management of the greater trochanteric pain syndrome (GTPS). The objective was to perform the first randomised double-blind placebo-controlled trial to investigate the efficacy of local GC injection in the management of GTPS. The trial was conducted between November 2011 and May 2015. Inclusion criteria included lateral hip pain (LHP) for greater than 1 month, a LHP score of ≥ 4/10 and typical LHP reproduced by palpation of the greater trochanter. Participants were randomised in a 1:1 ratio to injection with a combination of local anaesthetic and GC (intervention) or injection with normal saline solution (placebo). The primary outcome of interest was the difference in pain intensity at 4 weeks post-injection between the two groups. Patients were followed for 6 months. A total of 46 patients were included. There were no significant differences between the two groups in terms of pain reduction at 1 month (p = 0.23). When including all measures in the first 4 weeks and using multilevel regression, there was a trend towards improvement in pain scores in favour of the intervention group (p = 0.08). There were no significant differences in pain scores between groups at 3 and 6 months. In the management of GTPS, local glucocorticoid injections are of no greater efficacy than injection of normal saline solution. Given the lack of long-term improvement and the potential for cortisone-related side effects, this intervention is of limited benefit.