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Osteoarthritis (OA) most commonly affects knee joints, and the next most commonly affected sites are the hands and hips. Three distinct hand OA phenotypes have been described: erosive hand OA (EHOA), nodal hand OA — also known as non-erosive hand OA (non-EHOA) — and first carpometacarpal joint OA. EHOA predominantly affects women and is the most aggressive form of hand OA, characterized by a severe clinical onset and progression, leading to joint damage, disability and reduction of quality of life. Clinical signs of inflammation associated with EHOA include the acute onset of pain, swelling and redness. Moreover, EHOA is characterized by radiographic features such as central erosion, saw-tooth and gull-wing lesions and, rarely, ankylosis. The aim of this Review is to report the latest findings on epidemiology, clinical features, pathology and aetiopathogenesis, biomarkers, imaging modalities and treatments for EHOA. The ongoing development of new hand OA classification criteria should facilitate standardization between studies.Erosive hand osteoarthritis is an aggressive condition with poor outcomes. In this Review, the authors describe the clinical features and risk factors associated with erosive hand osteoarthritis, and summarize progress in the areas of biomarkers, imaging, classification criteria and treatment.

Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1–3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4–8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence.

Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA.

Background Little evidence is available about the impact of diet on disease activity of axial spondyloarthritis (axSpA). This study evaluated the impact of a 6-month nutritional advice based on the Mediterranean diet on the disease activity of axSpA. Methods We prospectively collected the information of a group of axSpA patients who were offered nutritional advice for a 6-month period, who were compared to axSpA patients followed at the same center who were not on a specific diet. A nutritionist gave suggestions for dietary modification at baseline and thereafter every 2 months until month 6. Adherence to the Mediterranean diet was evaluated with the PREDIMED questionnaire ranging from 0 (no adherence) to 10 (optimal adherence); disease activity was evaluated with ASDAS-CRP. A multivariable regression analysis was conducted to identify independent predictors of PREDIMED and of ASDAS-CRP improvement (improvement ≥ 20% of each score). Results A total of 161 patients were included: 81 receiving nutritional advice and 80 controls; 47 in the nutritional group and 63 controls had complete information until month 6. Overall, 40 (36.4%) were females, the mean age was 51.7 ± 1.3 years, and 58 (52.7%) were affected with psoriasis. No relevant change of anthropometric or laboratory measures was observed in either group. Adherence to the Mediterranean diet was moderate (PREDIMED score 6.7 ± 1.8 at baseline; 7.6 ± 2.1 at month 6) and improved more in the nutritional group compared to controls ( p = 0.020). Predictors of a PREDIMED improvement ≥ 20% were receiving nutritional advice (OR 4.53, 1.36–15.1, p = 0.014), age (per 10-year increase OR 1.05, 1.02–1.68, p = 0.007), and BMI (OR 0.77, 0.63–0.9, p = 0.006). An ASDAS-CRP improvement ≥ 20% was more frequent in the nutritional group compared to controls ( p = 0.020). A PREDIMED improvement ≥ 20% was associated with a ASDAS-CRP improvement ≥ 20% (OR 6.75,1.8–25.3, p = 0.005). Psoriasis and disease duration were negatively but not significantly associated to the ASDAS-CRP improvement. Conclusions Improving adherence to the Mediterranean diet may have a beneficial impact on the activity of axSpA. Patients with a lower BMI and older patients are more prone to modify their diet towards the Mediterranean diet following nutritional advice. Patients with psoriasis may have a limited benefit from dietary improvement. Study registration Protocol No. 52723, Padova Hospital Medical Ethical Committee (October 11, 2010).

Background Treatment of rheumatoid arthritis (RA) frequently requires Janus kinase inhibitors (JAKi) and biologic DMARDs (bDMARDs) with other mechanisms of action (OMA) after tumour necrosis factor inhibitors (TNFi) failure. Comparative safety data between JAKis and OMA in TNFi-inadequate responders (TNFi-IR) remain limited. Objectives To evaluate and compare safety profiles of JAKis versus OMA in TNFi-IR RA patients. Methods A retrospective cohort study followed 305 RA patients (163 JAKis; 142 OMA) previously treated with TNFi for up to 24 months. Incidence rates (IR) of adverse events (AEs) per 100 patient-years (PY) and incidence rate ratios (IRR) adjusted for disease activity and previous bDMARD exposure were calculated using Poisson regression. Results At baseline, OMA patients had higher disease activity (DAS28-CRP = 4.5 vs. 3.8), whereas comorbidities and other baseline characteristics were similar. Overall, AE incidence was higher with OMA (IR 111.6/100 PY) compared to JAKis (IR 65.3/100 PY; adjusted IRR 1.67, 95% CI 1.22–2.31). Serious AEs occurred more frequently with OMA (IR 11.7/100 PY) versus JAKis (IR 7.9/100 PY; adjusted IRR 0.41, 95% CI 0.18–0.95). Infection rates were comparable; herpes zoster occurred exclusively in the JAKi group during the initial year. Venous thromboembolism, cardiovascular events, and malignancies were rare and similar between groups. Conclusion In RA patients with inadequate response to TNFis, JAKis and OMA showed comparable safety profiles over 24 months. Serious AEs were numerically higher with OMA; herpes zoster was more frequent with JAKis. No new significant safety signals emerged. Key messages What is already known on this topic • Janus kinase inhibitors (JAKis) and non-TNF biologic DMARDs (OMA) are increasingly prescribed for RA patients who have an inadequate response to TNF inhibitors, though comparative safety data between these drug classes are limited. What this study adds • This study provides direct comparative evidence on the safety profiles of JAKis versus OMA in RA patients with inadequate response to TNFi, demonstrating similar overall safety outcomes, albeit highlighting differences in the timing and frequency of specific adverse events, such as herpes zoster infections with JAKis and serious adverse events with OMA. How this study might affect research, practice, or policy • These results reinforce existing guidelines advocating for individualised therapeutic choices based on patient-specific risk factors and suggest the continued need for careful patient monitoring, particularly for infections and serious adverse events, guiding clinicians in selecting appropriate therapies after TNFi failure.

ObjectivesWe aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of multiple therapies in psoriatic arthritis (PsA).Materials and methodsWe enrolled consecutive PsA patients attending our unit and undergoing bDMARDs during 2004–2020. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were recorded. Disease activity and functional and clinimetric scores were recorded at baseline and yearly and were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Effectiveness was evaluated over time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of response and failure of multiple bDMARDs. Kaplan–Meier curves were used to assess differences in time-to-first bDMARD discontinuation. Infections and adverse events were recorded.ResultsTwo hundred sixty-four patients were included (117 (44.32%) females, mean age 56 years, mean PsA duration 15 years); 117 (44.32%) switched bDMARDs at least once. Switchers were mostly females, with higher Psoriasis Area and Severity Index and worse Health Assessment Questionnaire at baseline. Mean time-to-first bDMARD discontinuation was 72 months; 2-year and 5-year retention rates were 75% and 60%, respectively. Survival curves for anti-TNFα/anti-IL12/23/anti-IL17 were similar (p = 0.66). Main reasons for switching were inefficacy (67.52%) and adverse events (25.7%). Female sex was associated with a higher risk of first bDMARD discontinuation (HR = 2.39; 95% CI: 1.50–3.81) and failure of multiple bDMARDs (OR = 1.99; 95% CI: 1.07–3.69); initiating therapy before 2015 was protective (HR = 0.40; 95% CI: 0.22–0.73).ConclusionsSurvival rate was good for anti-TNFα and other bDMARDs. Female sex was a predictor of first bDMARD discontinuation, unlike mechanism of action, comorbidities, and BMI. Key Points• Drug survival in PsA patients was confirmed be greater for the first bDMARD administered.• In case of failure of the first bDMARD, switching/swapping proved a good treatment option, as reflected by a persistent satisfactory effectiveness with second-line bDMARDs and so subsequent switches.• Female sex may constitute a predisposing risk factor for flare and therapeutic switches.• Discontinuation or switching of biologics due to mechanism of action, comorbidities tolerability and BMI did not seem to impact first bDMARD withdrawal.

Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.

Axial spondyloarthritis (axSpA) is a group of debilitating, chronic, rheumatic conditions characterized by inflammation and new bone formation, mainly involving the spine and the sacroiliac joints. The lack of biomarkers in axSpA is well known. Despite significant treatment advances in recent years thanks to the introduction of drugs with a new mode of action, such as new biologic and targeted synthetic disease-modifying antirheumatic drugs, no relevant improvement in the identification of disease biomarkers has been achieved. Common parameters, such as erythrocyte sedimentation rate and C-reactive protein, which are routinely used to measure systemic inflammation, are the sole markers available to date and are not adequate to assess disease activity in all patients. The aim of this study is to review the most promising serum biomarkers that may help treatment decision in axSpA via a proper assessment of disease activity and identification of negative prognostic factors.

Very low-calorie ketogenic diet (VLCKD) is a low-carbohydrate, low-calorie regimen that leads to rapid weight loss and may reduce inflammation. This study assessed the impact of VLCKD on anthropometric measurements, inflammatory biomarkers, metabolic health, and cardiovascular risk in psoriatic arthritis (PsA) patients moderately overweight or in class I obesity. A proof-of-concept single-arm monocentric study involved PsA patients undergoing a 9-week VLCKD treatment. Patients with Body Mass Index (BMI) ≥27 and <35, in stable (≥6 months) remission or low disease activity, as defined by Disease Activity in PSoriatic Arthritis (DAPSA) score, were included and underwent nutritional evaluations every 3 weeks. The study analyzed changes after the VLCKD intervention and the association between changes of anthropometric parameters and clinical and laboratory variables. Twenty patients were enrolled since April 2022 and completed the study in May 2023. Median baseline BMI was 30.9 (interquartile range 29.1-33) kg/m². All participants exhibited low baseline disease activity, which correlated with BMI (Spearman's correlation coefficient (rs)=0.59,p=0.007). Following VLCKD, significant improvements were observed in all anthropometric measures (BMI -3.5[-4;-2.6]), PsA activity (DAPSA -6.1[-16.8;3.7]), cardiovascular parameters (SCORE2 index -0.2[-0.7;0.1]), insulin resistance (Homeostatic Model Assessment-Insuline Resistance -2.1[-1.1;-3.0]), and lipid profile. Most inflammatory biomarkers remained within normal limits. BMI reduction correlated with changes in DAPSA scores (rs=0.52,p=0.020). Patients with higher baseline weight or clinical activity experienced more pronounced improvements. VLCKD significantly improved PsA activity and metabolic health. Patients with a higher BMI and less controlled disease are particularly motivated and could benefit more from VLCKD compared to those with lower BMI or better disease control.

Background and aimJuvenile idiopathic arthritis-associated uveitis (JIAU) is a potentially blinding condition beginning in childhood. Flare-ups may occur throughout life, leading to cumulative ocular damage. This systematic review aimed to summarise the latest evidence on long-term ocular damage in adults with JIAU, focusing on studies published in the past 20 years.MethodsThe review protocol was registered in PROSPERO (ID 1033522). We included human studies on JIAU with at least 5 years of follow-up and/or young people ≥18 years old, published after 2000. Study quality was assessed using the Newcastle-Ottawa Scale. We extracted the cumulative incidence of complications and performed a meta-analysis to obtain pooled estimates (PE), assess heterogeneity, sensitivity, robustness and reporting bias using R packages.Results22 retrospective or cohort studies were eligible, encompassing 2208 long-term JIAU cases. Study quality was rated as good in 10, fair in 7 and poor in 5. Despite high heterogeneity (p<0.01), sensitivity analyses supported robustness. Evidence of reporting bias was found for severe visual impairment and cataract. The pooled incidence of severe visual impairment was 16.6% (95% CI 9.9% to 22.6%) at approximately 18 years. Cataract was the most frequent complication (PE 44.3% (95% CI 27.5% to 61.7%)), followed by glaucoma, synechiae, band keratopathy and hypotony. In cohorts with >50% biologic exposure, PE were numerically lower.ConclusionLong-term prevalence and cumulative incidence of JIAU complications may persist in adulthood, with >10% developing severe visual impairment despite biologic therapy.