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Objective: To investigate the prevalence of poly‐refractory rheumatoid arthritis (RA) defined as failure of all biological (b)/targeted synthetic (ts)‐disease‐modifying drugs (DMARDs). To further investigate whether patients with persistent inflammatory refractory RA (PIRRA) and noninflammatory refractory RA (NIRRA), determined by objective ultrasound (US) synovitis, have distinct clinical phenotypes in both EULAR difficult‐to‐treat RA (D2T‐RA) and poly‐refractory RA groups. Methods: A cross‐sectional study of 1,591 patients with RA on b/tsDMARDs that evaluated D2T‐RA criteria and subclassified as poly‐refractory if inefficacy/toxicity to at least one drug of all classes. PIRRA was defined if US synovitis in one or more swollen joint and NIRRA if absent. Univariate tests and multivariate logistic regression were conducted to investigate factors associated with poly‐refractory, PIRRA, and NIRRA phenotypes. Results: 122 of 1,591 were excluded due to missing data. 247 of 1,469 (16.8%) had D2T‐RA and only 40 of 1,469 (2.7%) poly‐refractory RA. This latter group had higher disease activity score 28 C‐reactive protein (CRP) (median 5.4 vs 5.02, P < 0.05), CRP levels (median 13 vs 5 mg/l, P < 0.01), and smoking (ever) rates (20% vs 4%, P < 0.01) compared with other D2T patients. Smoking was associated with poly‐refractory RA (odds ratio 5.067, 95% CI 1.774–14.472, P = 0.002). Of 107 patients with D2T‐RA with recent US, 61 (57%) were PIRRA and 46 (43%), NIRRA. Patients with NIRRA had elevated body mass index (median 30 vs 26, P < 0.001) and higher fibromyalgia prevalence (15% vs 3%, P < 0.05), lower swollen joint count (median: 2 vs 5, P < 0.001), and lower CRP levels (5 vs 10, P < 0.01). Conclusion: Only 2.7% of D2T‐RA failed all classes of b/tsDMARDs. Among D2T‐RA, less than 60% had objective signs of inflammation, representing a target for innovative strategies. [ABSTRACT FROM AUTHOR]

Objective. We previously reported the coexistence, within cultured mesenchymal stem cells (MSCs) from human synovial membrane, of single-cell-derived clonal cell populations with distinct differentiation potency. The aim of this study was to investigate marker sets for prospective purification of functionally distinct MSC subsets.Methods. Cells were enzymatically released from human synovium and culture expanded. Phenotype analysis was performed by flow cytometry using combinations of MSC markers. Sorting was carried out using the FACS DiVA cell sorter. Sorted cell populations were assessed for clonogenicity, kinetics of growth, cell senescence and chondro-osteogenic potency.Results. During culture expansion, the co-localization of CD39 within the CD73+ cell population identified a small cell subset that was maintained from passage 1 (P1) up to at least P12 in all donors tested. The CD73+CD39+ cell subset displayed higher expression levels of Sox9 and Runx2 and a significantly greater chondro-osteogenic potency than the CD73+CD39− cell subset. In contrast, it was less clonogenic and proliferative. There was no difference in cell senescence between the sorted MSC subsets and the parental MSCs. Notably, there were no detectable differences in chondro-osteogenic potency between the CD73+CD39− and CD73+CD39+ cell subsets purified from fresh synovial cell populations.Conclusion. Our findings indicate that the combination of CD73 and CD39 allows the prospective purification from culture-expanded heterogeneous synovial MSC populations of a distinct MSC subset with greater chondro-osteogenic potency. We anticipate that such an approach will enhance the consistency of cell-based therapeutic protocols for the repair of osteochondral defects. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain. Methods/design: HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to -treat basis. Discussion: The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting. Trial registration: ISRCTN91859104. [ABSTRACT FROM AUTHOR]

Objective. MTX is widely used to treat synovitis in PsA without supporting trial evidence. The aim of our study was to test the value of MTX in the first large randomized placebo-controlled trial (RCT) in PsA.Methods. A 6-month double-blind RCT compared MTX (15 mg/week) with placebo in active PsA. The primary outcome was PsA response criteria (PsARC). Other outcomes included ACR20, DAS-28 and their individual components. Missing data were imputed using multiple imputation methods. Treatments were compared using logistic regression analysis (adjusted for age, sex, disease duration and, where appropriate, individual baseline scores).Results. Four hundred and sixty-two patients were screened and 221 recruited. One hundred and nine patients received MTX and 112 received placebo. Forty-four patients were lost to follow-up (21 MTX, 23 placebo). Twenty-six patients discontinued treatment (14 MTX, 12 placebo). Comparing MTX with placebo in all randomized patients at 6 months showed no significant effect on PsARC [odds ratio (OR) 1.77, 95% CI 0.97, 3.23], ACR20 (OR 2.00, 95% CI 0.65, 6.22) or DAS-28 (OR 1.70, 95% CI 0.90, 3.17). There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ and pain. The only benefits of MTX were reductions in patient and assessor global scores and skin scores at 6 months (P = 0.03, P < 0.001 and P = 0.02, respectively). There were no unexpected adverse events.Conclusions. This trial of active PsA found no evidence for MTX improving synovitis and consequently raises questions about its classification as a disease-modifying drug in PsA.Trial registration. Current Controlled Trials, www.controlled-trials.com, ISRCTN:54376151. [ABSTRACT FROM AUTHOR]

Objective To isolate recombinant antibodies with specificity for human arthritic synovium and to develop targeting reagents with joint-specific delivery capacity for therapeutic and/or diagnostic applications. Methods In vivo single-chain Fv (scFv) antibody phage display screening using a human synovial xenograft model was used to isolate antibodies specific to the microvasculature of human arthritic synovium. Single-chain Fv antibody tissue-specific reactivity was assessed by immunostaining of synovial tissues from normal controls and from patients with rheumatoid arthritis and osteoarthritis, normal human tissue arrays, and tissues from other patients with inflammatory diseases displaying neovasculogenesis. In vivo scFv antibody tissue-specific targeting capacity was examined in the human synovial xenograft model using both 125I-labeled and biotinylated antibody. Results We isolated a novel recombinant human antibody, scFv A7, with specificity for the microvasculature of human arthritic synovium. We showed that in vivo, this antibody could efficiently target human synovial microvasculature in SCID mice transplanted with human arthritic synovial xenografts. Our results demonstrated that scFv A7 antibody had no reactivity with the microvasculature or with other cellular components found in a comprehensive range of normal human tissues including normal human synovium. Further, we showed that the reactivity of the scFv A7 antibody was not a common feature of neovasculogenesis associated with chronic inflammatory conditions. Conclusion Here we report for the first time the identification of an scFv antibody, A7, that specifically recognizes an epitope expressed in the microvasculature of human arthritic synovium and that has the potential to be developed as a joint-specific pharmaceutical. [ABSTRACT FROM AUTHOR]

Background Very little literature exists in supporting the assessment and management of cystic fibrosis related arthritis (CFA) particularly in paediatric and adolescent cases. Methods A 12 year-old male with cystic fibrosis (CF) was admitted via A&E with severe joint pain that was thought to be associated with a respiratory infection and was treated accordingly. Repeated exacerbations of joint disease occurred every 1-2 months, lasting approximately 1 week with significant joint pain, stiffness, and reduced function. The patient did not feel his exacerbations of CFA were related to his respiratory symptoms, admitting he under reported arthritis symptoms to avoid being admitted for IV antibiotics. Initial rheumatology review resulted in treatment with IV antibiotics and piroxicam. Flares continued, prompting his CF physiotherapist and multidisciplinary team to seek further specialist review for his now longstanding symptoms. He scored 16 out of 50 on the McGill Pain Questionnaire (MPQ) with a visual analogue score (VAS) of 46 out of 100. At 16 years old he was seen by an MSK physiotherapy and rheumatology team working within a wider CF team. He had a 4 year history of symmetrical joint pain affecting knees, wrists and hands, on a background of bronchiectasis with previous non-tuberculous mycobacteria infection, cystic fibrosis related diabetes, and poor nutrition. He reported some episodes being so bad he was unable to get out of bed, and struggling with the stairs at college. He had 6 swollen and 8 tender joints including wrists, MCPs and knees. Ultrasound imaging of the wrists and hands showed confirmed active synovitis with grade 3 greyscale changes and grade 2 power Doppler. Hydroxychloroquine was commenced with naproxen as required, and wrist splints were provided. Results At follow-up he reported significant symptomatic improvement with occasional minor stiffness in wrists and knees which responded quickly to naproxen and was no longer limiting his activities. Repeat ultrasound confirmed improvement with no active power Doppler, but some ongoing grade 1 greyscale changes and a small wrist effusion. He has returned to previous function with an MPQ score of 0, and VAS of 10 out of 100. He reported improved quality of life due to reduced pain and fewer, shorter, and more manageable exacerbations. Conclusion Specialist review and commencement on disease modifying anti-rheumatic medication helped to manage CFA in this case. All cases of suspected CFA should be referred for specialist rheumatology opinion. CF physiotherapists are in an excellent position to identify cases and empowering the multidisciplinary team has been vital in this case. Further trials are required to investigate optimal management of CFA, but it seems likely that directly addressing the arthritis with disease modifying therapy may play an important role. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Poster presentation Tuesday 8 October Background The ankle is one of the most commonly affected joints in juvenile idiopathic arthritis (JIA) and ankle joint damage is a known complication. The frequency of ankle damage in modern JIA cohorts is unknown and optimal management pathways are unclear. Magnetic resonance imaging (MRI) is the most sensitive imaging modality for the assessment of joint damage. The aim of this analysis was to investigate the demographics, disease features and management of JIA patients with MRI changes consistent with ankle damage. Methods A single-centre, retrospective study over a four year period was conducted. JIA cases with damage based on MRI features were included in the study. MRI was reviewed by an experienced musculoskeletal radiologist and joint damage was defined as radiological evidence of cartilage loss or joint space narrowing. A standardised electronic pro forma was used to record demographics, disease features and treatments received. Results Fifty one JIA cases had an MRI scan during the study period and 16/51 (31%) had radiological evidence of ankle damage at a median interquartile range (IQR) follow-up of 7.6 (6.9 – 11.0) years; 7/16 (44%) had developed bilateral ankle damage. The median (IQR) duration of symptoms at diagnosis was 2(1.0-10.5) months. The mean age at diagnosis and at detection of ankle damage was 5.2 years and 12.1 years respectively. The most frequent JIA subtype was oligo-articular extended (50%), and 50% were ANA positive. The median (IQR) duration between detection of ankle damage and first episode of ankle synovitis was 5.4 (4.6 – 6.4) years. Ankle synovitis was present at diagnosis in 10/16 (62%). Median (IQR) number of ankle corticosteroid injections before the ankle damage was detected was 3 (2-3), one patient had evidence of damage at diagnosis. Median (IQR) number of any type of ankle imaging done before the ankle damage was detected was 1 (1-3). The median (IQR) time to start methotrexate from diagnosis was 6 (0 - 29.5) months and median (IQR) number of biologic and synthetic DMARDs used at follow-up were 3.5 (2.2 – 4.0). 7/16 (44%) patients had undergone an orthopaedic surgical procedure for their ankle damage. Conclusion Ankle synovitis at presentation and an extended oligo-articular disease course were common in this cohort of children and young people (CYP) with JIA and ankle damage. Ankle damage is an important challenge in JIA; a substantial number of this cohort ultimately required surgical intervention. There is an urgent need to develop a care pathway designed to improve early recognition and management of evolving ankle joint damage in JIA. Our analysis suggests that attention may need to focus on CYP presenting with ankle synovitis, particularly those who develop a poly-articular disease course, may merit high levels of vigilance with be at particularly high risk. Conflicts of Interest The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: Data from a recent clinical trial of vitamin D therapy in knee OA suggests that, compared to placebo, vitamin D therapy may be associated with a reduction in effusion-synovitis. Our aim was, using contrast-enhanced (CE) magnetic resonance imaging (MRI), to examine the effect of vitamin D therapy on synovial tissue volume (STV) and also subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA.Methods: Data was acquired from participants who took part in a randomised placebo-controlled trial (UK VIDEO) investigating the effect of vitamin D therapy (800 IU cholecalciferol daily) on radiographic joint space narrowing. A subsample had serial CE MRI scans acquired during the trial. Subjects with serial images were assessed (N = 50) for STV and subchondral BML volume. The difference in the mean change from baseline in these structural outcomes between intervention and placebo groups was assessed using random-effects modelling.Results: The mean age of the 50 subjects (24 active group, 26 placebo group) who contributed data to the analysis was 63.3 years (SD 6.5) and 74% were female. There was no significant difference at 2 years follow-up between the vitamin D and placebo groups in the mean change from baseline for STV (93.9 mm3, 95% CI -1605.0 to 1792.7) and subchondral BML volume (- 313.5 mm3, 95% CI -4244.7 to 3617.7).Conclusions: Vitamin D supplementation does not appear to have an effect on synovitis or BML volume in patients with symptomatic knee OA.Trial Registration: VIDEO was registered with EudraCT: ref. 2004-000169-37. The protocol for the trial can be accessed at https://www.ctu.mrc.ac.uk/studies/all-studies/v/video/. [ABSTRACT FROM AUTHOR]

The article offers news about diseases in pigs in Great Britain. Postweaning multisystemic wasting syndrome was diagnosed in 12-week-old grower pigs from a unit where poor growth rates and diarrhea were reported. Acute enteritis related to Clostridium perfringens type A was confirmed in a two-day old piglet. Acute synovitis linked to Mycoplasma hyosynoviae was detected in two finishing pigs.