Deep Learning Enables Automatic Detection of Joint Damage Progression in Rheumatoid Arthritis-Model Development and External Validation.

OBJECTIVES: Although deep learning has demonstrated substantial potential in automatic quantification of joint damage in rheumatoid arthritis (RA), evidence for detecting longitudinal changes at an individual patient level is lacking. Here, we introduce and externally validate our automated RA scoring algorithm (AuRA), and demonstrate its utility for monitoring radiographic progression in a real-world setting. METHODS: The algorithm, originally developed during the Rheumatoid Arthritis 2-Dialogue for Reverse Engineering Assessment and Methods (RA2-DREAM) challenge, was trained to predict expert-curated Sharp-van der Heijde total scores in hand and foot radiographs from two previous clinical studies (n = 367). We externally validated AuRA against data (n = 205) from Turku University Hospital and compared the performance against two top-performing RA2-DREAM solutions. Finally, for 54 patients, we extracted additional radiograph sets from another control visit to the clinic (average time interval of 4.6 years). RESULTS: In the external validation cohort, with a root-mean-square-error (RMSE) of 23.6, AuRA outperformed both top-performing RA2-DREAM algorithms (RMSEs 35.0 and 35.6). The improved performance was explained mostly by lower errors at higher expert-assessed scores. The longitudinal changes predicted by our algorithm were significantly correlated with changes in expert-assessed scores (Pearson's R = 0.74, p< 0.001). CONCLUSION: AuRA had the best external validation performance and demonstrated potential for detecting longitudinal changes in joint damage. Available in https://hub.docker.com/r/elolab/aura, our algorithm can easily be applied for automatic detection of radiographic progression in the future, reducing the need for laborious manual scoring.

30-sit-to-stand power is a better tool than isometric knee extensor strength to detect motor impairment in people with haemophilic arthropathy.

INTRODUCTION: Regular assessment of motor impairments is crucial in people with haemophilic arthropathy (PwHA). This study aimed to determine if there are differences in 30-seconds sit-to-stand (30-STS) power and maximal voluntary isometric contraction (MVIC) of the knee extensors between PwHA and healthy control group (CG). The secondary aims were to investigate the correlation between 30-STS power and MVIC of knee extensors with clinical characteristics and to assess their effectiveness in identifying motor impairment in PwHA. METHODS: A cross-sectional study was conducted by collecting data from PwHA (n = 17) and a sedentary CG (n = 15). MVIC (torque) and 30-STS power were normalised to body mass. Correlation analysis and simple linear regression adjusted for age were used to assess the association between tests and clinical variables. Using z-scores derived from the mean and standard deviation of the CG, we compared the MVIC and the 30-STS power in PwHA. RESULTS: PwHA showed lower MVIC and 30-STS power compared to CG (p < .001; large effect size d > .8). Lower 30-STS power was associated with greater joint impairment and greater fear of movement, whereas MVIC showed no association with clinical variables. 30-STS power showed a lower z-score compared to MVIC (p < .001). In addition, 30-STS power detected 47% of PwHA with motor impairment compared to 0% for MVIC (p = .002). CONCLUSIONS: Our results suggest that 30-STS power may be more effective than knee extensors MVIC in detecting motor impairment in PwHA. Consequently, lower limb skeletal muscle power, rather than maximum knee extensor strength, appears to be more affected in PwHA.

The role of radiography in diagnosing, monitoring and prognosing juvenile idiopathic arthritis.

The current role of conventional radiography in the diagnosis, monitoring and prognosis of juvenile idiopathic arthritis (JIA) is reviewed, as its role has changed with the increasing use of ultrasound and magnetic resonance imaging, as well as with the introduction of biological drugs. Conventional radiography does not play an important role in the diagnosis of JIA, as this is based on history, clinical examination and laboratory findings. The main role of conventional radiography is in the detection and monitoring of growth disorders and chronic structural and morphological changes of the affected joints and bones, in addition to helping with the differential diagnosis of conditions that mimic JIA. Radiographic changes of the joints depend on the age of the child, the type and duration of arthritis and the specific joints affected. There are no standard protocols for arthritis monitoring and most indications for imaging are based on individual case-by-case decisions. The development of degenerative joint changes is considered a poor predictive factor, but there are no clear studies that more precisely define the predictive value of radiographic changes. Conventional radiography remains an important imaging modality in narrowing the differential diagnosis and in evaluating growth disorders and the developing destructive joint changes.

Intensive treatment for the progression of joint damage in rheumatoid arthritis patients with low disease activity or remission.

OBJECTIVES: To investigate the effects of intensive treatment on joint damage in patients with rheumatoid arthritis (RA) showing progression of joint damage and low disease activity or remission. METHODS: Eighty-nine patients who had change in the van der Heijde modified total Sharp score (TSS) of >0.5 points at baseline when compared with the score 1 year ago were enrolled and categorized into two groups to receive intensive (intensive group) or current (current group) treatment. The intensive and current groups were compared for change (Δ) from baseline to 1 year of erosion score, joint space narrowing score, and TSS. RESULTS: The ΔTSS values at 1 year in the intensive and current groups were 0.67 ± 1.09 and 1.79 ± 1.70, respectively (P < 0.001). In the intensive and current groups, the ΔTSS ≤ 0.5 at 1 year were 66.7% and 32.4%, respectively (P = 0.010). CONCLUSIONS: The intensive treatment was more effective at suppressing joint damage than the current treatment. The progression of joint damage is an important target to consider for intensive treatment.

Development of prediction models to select older RA patients with comorbidities for treatment with chronic low-dose glucocorticoids.

OBJECTIVE: To develop prediction models for individual patient harm and benefit outcomes in elderly patients with RA and comorbidities treated with chronic low-dose glucocorticoid therapy or placebo. METHODS: In the Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) study, 451 RA patients ≥65 years of age were randomized to 2 years 5 mg/day prednisolone or placebo. Eight prediction models were developed from the dataset in a stepwise procedure based on prior knowledge. The first set of four models disregarded study treatment and examined general predictive factors. The second set of four models was similar but examined the additional role of low-dose prednisolone. In each set, two models focused on harm [the occurrence of one or more adverse events of special interest (AESIs) and the number of AESIs per year) and two on benefit (early clinical response/disease activity and a lack of joint damage progression). Linear and logistic multivariable regression methods with backward selection were used to develop the models. The final models were assessed and internally validated with bootstrapping techniques. RESULTS: A few variables were slightly predictive for one of the outcomes in the models, but none were of immediate clinical value. The quality of the prediction models was sufficient and the performance was low to moderate (explained variance 12-15%, area under the curve 0.67-0.69). CONCLUSION: Baseline factors are not helpful in selecting elderly RA patients for treatment with low-dose prednisolone given their low power to predict the chance of benefit or harm. TRIAL REGISTRATION: https://clinicaltrials.gov; NCT02585258.

Therapeutic Effect of Colony Stimulating Factor 1 Receptor Kinase Inhibitor, JTE-952, on Methotrexate-Refractory Pathology in a Rat Model of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and the destruction of bone and cartilage in affected joints. One of the unmet medical needs in the treatment of RA is to effectively prevent the structural destruction of joints, especially bone, which progresses because of resistance to conventional drugs that mainly have anti-inflammatory effects, and directly leads to a decline in the QOL of patients. We previously developed a novel and orally available type II kinase inhibitor of colony-stimulating factor-1 receptor (CSF1R), JTE-952. CSF1R is specifically expressed by monocytic-lineage cells, including bone-resorbing osteoclasts, and is important for promoting the differentiation and proliferation of osteoclasts. In the present study, we investigated the therapeutic effect of JTE-952 on methotrexate (MTX)-refractory joint destruction in a clinically established adjuvant-induced arthritis rat model. JTE-952 did not suppress paw swelling under inflammatory conditions, but it inhibited the destruction of joint structural components including bone and cartilage in the inflamed joints. In addition, decreased range of joint motion and mechanical hyperalgesia after disease onset were suppressed by JTE-952. These results suggest that JTE-952 is expected to prevent the progression of the structural destruction of joints and its associated effects on joint motion and pain by inhibiting CSF1/CSF1R signaling in RA pathology, which is resistant to conventional disease-modifying anti-rheumatic drugs such as MTX.

Hip Osteoarthritis: Bench to Bedside Perspective.

Osteoarthritis is a major source of pain, disability, and economic cost worldwide. For nearly a century, there has been a debate about the causes of hip osteoarthritis and the role that structural abnormalities may play as a causative factor. Recent advances in open and minimally invasive techniques such as the periacetabular osteotomy, surgical hip dislocation and arthroscopic approaches have allowed us safe access into the joint to not only improve the abnormal bony structure and repair damaged tissue but also to gain clinical insights into the cause of joint damage. At present, structural abnormalities such as acetabular dysplasia and CAM deformities of the proximal femur are thought to be a major factor causing premature hip OA. Over the past 30 years, our understanding of the function and biology of articular cartilage has evolved from a relatively acellular lubricating cushion to a metabolically active tissue that can modulate its tissue composition in response to mechanical loading. Using advanced biochemical MR imaging technique called delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC), it has been shown that alteration in the mechanical environment of the hip with a pelvic osteotomy in acetabular dysplasia can alter the articular cartilage composition. This further demonstrates the importance of mechanics in development of joint damage and the potential for surgical correction to prevent or slow down the progression of OA.

A novel magnetic resonance imaging scoring system for active and chronic changes in children and adolescents with juvenile idiopathic arthritis of the hip.

BACKGROUND: Hip involvement predicts severe disease in juvenile idiopathic arthritis (JIA) and is accurately assessed by MRI. However, a child-specific hip MRI scoring system has not been validated. OBJECTIVE: To test the intra- and interobserver agreement of several MRI markers for active and chronic hip changes in children and young adults with JIA and to examine the precision of measurements commonly used for the assessment of growth abnormalities. MATERIALS AND METHODS: Hip MRIs from 60 consecutive children, adolescents and young adults with JIA were scored independently by two sets of radiologists. One set scored the same MRIs twice. Features of active and chronic changes, growth abnormalities and secondary post-inflammatory changes were scored. We used kappa statistics to analyze inter- and intraobserver agreement for categorical variables and a Bland-Altman approach to test the precision of continuous variables. RESULTS: Among active changes, there was good intra- and interobserver agreement for grading overall inflammation (kappa 0.6-0.7). Synovial enhancement showed a good intraobserver agreement (kappa 0.7-0.8), while the interobserver agreement was moderate (kappa 0.4-0.5). Regarding acetabular erosions on a 0-3 scale, the intraobserver agreement was 0.6 for the right hip and 0.7 for the left hip, while the interobserver agreement was 0.6 for both hips. Measurements of joint space width, caput-collum-diaphyseal angle, femoral neck-head length, femoral width and trochanteric distance were imprecise. CONCLUSION: We identified a set of MRI markers for active and chronic changes in JIA and suggest that the more robust markers be included in future studies addressing clinical validity and long-term patient outcomes.

Altered neural control of gait and its association with pain and joint impairment in adults with haemophilic arthropathy: Clinical and methodological implications.

INTRODUCTION: It is unknown whether altered neural control is associated with clinical outcomes in people with haemophilic arthropathy (PWHA). The dynamic motor control index during walking (Walk-DMC) is a summary metric of neural control. AIMS: The primary aim of this study was to apply the Walk-DMC to assess if people diagnosed with haemophilic arthropathy have impaired neural control of gait and investigate the association of Walk-DMC with pain and joint impairment. METHOD: The Walk-DMC was assessed using surface electromyography in 11 leg muscles. Twenty-two PWHA and 15 healthy subjects walked on a 30-m walkway at 1 m/s. In addition, pain (visual analogue scale), knee flexion contracture (degrees) and joint impairment (Haemophilia Joint Health Score, HJHS) were assessed. The clinical outcomes were correlated with the Walk-DMC. Multiple regression analysis was performed to predict the Walk-DMC using the clinical outcomes. RESULTS: In 13 PWHA the Walk-DMC was beyond the normal range (80-120 pts). PWHA with an altered Walk-DMC showed more years with arthropathy, more pain, higher knee flexion contracture and a higher HJHS score (P < .05, effect size > .8). Significant negative moderate associations between Walk-DMC and pain, knee flexion contracture and HJHS were found (P < .05). The model that best predicted the Walk-DMC was the pain with knee flexion contracture (R2  = .44; P = .004). CONCLUSIONS: PWHA with abnormal neural control of gait also has more years with arthropathy, more pain, and more impaired joints. Our results indicate an association between the Walk-DMC index and joint damage, specifically with pain in combination with knee flexion contracture.

Application of Spectral Entropy in Haul Truck Joint Damage Detection.

Early detection of machine failures is often beneficial, both financially and in terms of worker safety. The article presents the problem of frequently damaged joints in haul trucks, which are a real threat to the health and life of drivers. It was decided to investigate the problem in terms of dynamic overloads using two NGIMU inertial sensors and placing them in two places on the machine in close proximity to a joint. The data were captured during the standard operation of various machines in several mining departments, which allowed for the detection of a variety of factors influencing vibration. A hypothesis was developed that any changes in the joint would cause a change in the characteristics of vibrations, which were measured using the spectral entropy of vertical vibrations. Analyses have shown that there is a relationship between the change in spectral entropy difference (between the front and back of the vehicle) and joint events: nut tightening, nut replacement, and even joint fracture and replacement. The presented results offer the potential to create a tool for joint diagnostics and the early detection of damage or backlash.

Anti-Inflammatory and Analgesic Properties of the Cannabis Terpene Myrcene in Rat Adjuvant Monoarthritis.

Cannabis-based terpenes are believed to modulate physiological responses to disease and alter the efficacy of cannabinoids in the so-called "entourage effect". The monoterpene myrcene can reduce nociception produced by noxious thermal and mechanical stimuli as well as reducing acute inflammation. The current study examined the role of myrcene and cannabidiol (CBD) in controlling chronic joint inflammation and pain. Chronic arthritis was induced in male Wistar rats by intra-articular injection of Freund's complete adjuvant into the right knee. On days 7 and 21 after arthritis induction, joint pain (von Frey hair algesiometry), inflammation (intravital microscopy, laser speckle contrast analysis) and joint histopathology were assessed. Local application of myrcene (1 and 5 mg/kg s.c.) reduced joint pain and inflammation via a cannabinoid receptor mechanism. The combination of myrcene and CBD (200 µg) was not significantly different from myrcene alone. Repeated myrcene treatment had no effect on joint damage or inflammatory cytokine production. These data suggest that topical myrcene has the potential to reduce chronic arthritis pain and inflammation; however, it has no synergistic effect with CBD.

Predictors of joint damage progression and stringent remission in patients with established rheumatoid arthritis in clinical remission.

OBJECTIVES: To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy. METHODS: RA patients (DAS28-CRP <3.2, no swollen joints) receiving conventional synthetic DMARDs were randomized to conventional or MRI-targeted treat-to-target strategies with predefined algorithmic treatment escalations. Potentially predictive baseline variables were tested in multivariate logistic regression analyses. RESULTS: In the 171 patients included, baseline MRI osteitis independently predicted progression in MRI erosion [odds ratio (OR) 1.13 (95% CI 1.06, 1.22)], joint space narrowing [OR 1.15 (95% CI 1.07, 1.24)] and combined damage [OR 1.23 (95% CI 1.13, 1.37)], while tenosynovitis independently predicted MRI erosion progression [OR 1.13 (95% CI 1.03, 1.25)]. A predictor of radiographic erosion progression was age, while gender predicted progression in joint space narrowing. Following an MRI treat-to-target strategy predicted stringent remission across all remission definitions: Clinical Disease Activity Index remission OR 2.94 (95% CI 1.25, 7.52), Simplified Disease Activity Index remission OR 2.50 (95% CI 1.01, 6.66), ACR/EULAR Boolean remission OR 5.47 (95% CI 2.33, 14.13). Similarly, low tender joint count and low patient visual analogue scale pain and global independently predicted achievement of more stringent remission. CONCLUSION: Baseline MRI osteitis and tenosynovitis were independent predictors of 2 year MRI damage progression in RA patients in clinical remission, while independent predictors of radiographic damage progression were age and gender. Following an MRI treat-to-target strategy, low scores of patient-reported outcomes and low tender joint count predicted achievement of stringent remission. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01656278.

Expression of mBD4, mBD3 and CRAMP during type II collagen-induced arthritis/CIA and their association with inflammation and bone-remodeling markers.

The aim of this study was to analyze the expression of mBD4, mBD3 and CRAMP in joint of mice with type II collagen-induced arthritis/CIA and to explore its possible association with IL-10, IL-4, IFN-γ, IL-17, MMP3, RANK/RANKL/OPG and histological parameters. METHODS: CIA was induced in 44 DBA/1 J mice. The joints from mice were classified into the onset, peak and remission phase of CIA. Histological sections were stained with hematoxylin-eosin and safranin O. The expression of CRAMP, mBD-3, mBD-4, and MMP-3 was evaluated using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. The expression of IL-10, IL-4, IFN-γ, IL-17, RANK/RANKL/OPG was analyzed by RT-PCR. RESULTS: We observed that inflammation and immunostained cells for CRAMP increased in the peak and remission phases compared to the control group. In addition, increments in relative expressions of CRAMP were detected for the remission phase and in IL-4 and IL-17 in the peak phase compared to the control and onset phase. In addition, an increase in IL-10 in a peak phase compared to the control, as well as the relative expression of IFN-γ in remission phase was higher than in the onset phase. This was accompanied by an increase in cartilage damage in the peak phase compared to the control. Cells immunostained to MMP3 increased in the peak phase compared to the onset and control group, and relative expression of MMP3 was detected in the peak phase compared to the onset, remission, and control group. We observed that the relative expression of RANK and RANKL in the peak phase was higher than in control and onset phase. Finally, the relative expression of OPG in the peak phase compared to the onset, remission, and control group was detected. Regarding CRAMP behavior in the different phases studied, it was positively correlated with IL-4 and RANK, and showed a negative correlation with IFN-γ, IL-17, IL-10, RANKL, OPG and RANKL/OPG ratio in the control group. Also was positively correlated with IFN-γ, IL-17, IL-4, IL-10, as well as with RANK, RANKL, and OPG in the onset and peak phases of the CIA. In the peak phase, CRAMP showed a positive association with MMP3, and we observed a direct correlation between CRAMP and IFN-γ and RANKL/OPG ratio in remission phase. mBD3 correlates positively with IFN-γ, IL-17, IL-10, RANKL, OPG and RANKL/OPG ratio, and showed a negative correlation with CRAMP, MMP3, and RANK in the control group. Also, it was directly associated with IFN-γ, IL-17, IL-4, IL-10 and RANKL in the onset phase while it was inversely associated with CRAMP, MMP-3, RANK, RANKL, and OPG in the peak phase. Finally, mBD3 was inversely correlated with MMP3 in the remission phase and was directly associated with CRAMP, IFN-γ and RANKL/OPG ratio in this phase. mBD4 was directly associated with CRAMP, IFN-γ, IL-17, IL-4, IL-10, RANKL / OPG in the onset phase, and with CRAMP, IFN-γ, IL-17, IL-4, IL-10, MMP3, RANK, RANKL and OPG in the peak phase. Finally, mBD4 was positively associated with mBD3, IFN-γ, IL-17, IL-10, RANK, RANKL OPG and RANKL/OPG in the CIA remission phase. CONCLUSIONS: Our results demonstrate that CRAMP plays an important role in CIA progress and suggest that its abundance is associated with local pro- and anti-inflammatory status. This makes us propose CRAMP as a possible contributor of bone reconstruction in the last stage of CIA.

Quality of life and its predictors among adult patients with haemophilic arthropathy. An observational study.

BACKGROUND: Recurrent hemarthrosis that begin in childhood lead to progressive joint deterioration. Patients with haemophilia have chronic pain, functional disability and a reduced perception of health-related quality of life. PURPOSE: To analyse the perceived quality of life of adult patients with haemophilic arthropathy and its relationship with pain, joint condition, kinesiophobia and catastrophism. METHODS: Eighty-three adult patients with haemophilia were included in this multicentre, cross-sectional, descriptive study. Perceived quality of life (36-Item Short Form Health Survey), perceived usual and maximum pain (visual analogue scale), joint condition (Haemophilia Joint Health Score), kinesiophobia (Tampa Scale of Kinesiophobia) and catastrophism (Pain Catastrophizing Scale) were assessed. Sociodemographic, clinical and therapeutic variables and drug consumption for pain control were collected. Descriptive statistics used means and standard deviations. The correlation of quality of life with the dependent variables was calculated with the Pearson correlation test. The differences in quality of life as a function of the binomial variables were calculated with Student's t-test for independent samples. RESULTS: Physical component of quality of life perceived by patients with hemophilia is lower than Spanish population (30.51 VS 48.85). Regarding the mental component, patients with hemophilia showed higher values (56.07 VS 49.97). Catastrophism correlated (p < .05) with all items of quality of life questionnaire. Kinesiophobia correlated (p < .05) with all items of quality of life except to role-emotional (r = -.18; p > .05). Habitual and maximal joint pain correlated with all items except to role-emotional (r = - .19 and r = - .09, respectively) and mental component score (r = - .16 and r = - .07, respectively). Catastrophism and weekly drug intake were inversely correlated with quality of life. Age was positively correlated with perceived quality of life. There were differences in quality of life as a function of the severity of haemophilia and the intake of drugs for pain control. CONCLUSIONS: The perceived quality of life of adult patients with haemophilia is worse than that of the Spanish population. Pain, kinesiophobia, catastrophism, haemophilia severity and the intake of pain-control medication influence the quality of life of these patients.

Matrix-induced chondrogenesis is a valid and safe cartilage repair option for small- to medium-sized cartilage defects of the knee: a systematic review.

PURPOSE: The purpose of this study was to perform a systematic review of randomized controlled trials comparing the results of matrix-induced chondrogenesis with other therapies for local chondral lesions of the knee. METHODS: A systematic search for randomized controlled trials (RCT) about matrix-induced chondrogenesis for focal chondral lesions in the knee was performed according to the PRISMA guidelines. Data source was PubMed central, EMBASE and Google scholar. RESULTS: Five articles could be included, whereas two originated from the same study group. Three studies compared matrix-induced chondrogenesis to microfracture (MFx) only. One trial compared AMIC® to collagen-covered autologous chondrocyte implantation (ACI-C). One study assessed the improvements given by the combination of AMIC® with bone marrow aspirate concentrate (BMAC). In three studies, clinical improvements compared to baseline were seen at 2-year postoperation, irrespective of the technique used. After 5 years, one trial showed better results for the AMIC® group compared to MFx, including MRI defect filling. One study showed also good results after AMIC® with faster recovery for patients with AMIC® + BMAC 12 months postoperatively. CONCLUSION: Results of RCTs comparing matrix-induced chondrogenesis with other treatment options showed that matrix-induced chondrogenesis is a valid and safe cartilage repair option for small- to medium-sized cartilage defects of the knee. This one-stage surgical technique presents a good alternative for patients. LEVEL OF EVIDENCE: I.

Protease Activated Receptors and Arthritis.

The catabolic and destructive activity of serine proteases in arthritic joints is well known; however, these enzymes can also signal pain and inflammation in joints. For example, thrombin, trypsin, tryptase, and neutrophil elastase cleave the extracellular N-terminus of a family of G protein-coupled receptors and the remaining tethered ligand sequence then binds to the same receptor to initiate a series of molecular signalling processes. These protease activated receptors (PARs) pervade multiple tissues and cells throughout joints where they have the potential to regulate joint homeostasis. Overall, joint PARs contribute to pain, inflammation, and structural integrity by altering vascular reactivity, nociceptor sensitivity, and tissue remodelling. This review highlights the therapeutic potential of targeting PARs to alleviate the pain and destructive nature of elevated proteases in various arthritic conditions.

Prognostic value of comorbidity indices and lung diseases in early rheumatoid arthritis: a UK population-based study.

OBJECTIVES: We assessed comorbidity burden in people with RA at diagnosis and early disease (3 years) and its association with early mortality and joint destruction. The association between lung disease and mortality in RA is not well studied; we also explored this relationship. METHODS: From a contemporary UK-based population (n = 1, 475 762) we identified a cohort with incident RA (n = 6591). The prevalence of comorbidities at diagnosis of RA and at 3 years was compared with age- and gender-matched controls (n = 6591). In individuals with RA we assessed the prognostic value of the Charlson Comorbidity Index and Rheumatic Disease Comorbidity Index calculated at diagnosis for all-cause mortality and joint destruction (with joint surgery as a surrogate marker). We separately evaluated the association between individual lung diseases [chronic obstructive pulmonary disease (COPD), asthma and interstitial lung disease] and mortality. RESULTS: Respiratory disease, cardiovascular disease, stroke, diabetes, previous fracture and depression were more common (P < 0.05) in patients with RA at diagnosis than controls. Comorbidity (assessed using RDCI) was associated with all-cause mortality in RA [adjusted hazard ratio (HR) 1.26, 95% CI 1.00-1.60]. There was no association with joint destruction. COPD, but not asthma, was associated with mortality (COPD HR 2.84, 95% CI 1.13-7.12). CONCLUSION: There is an excess burden of comorbidity at diagnosis of RA including COPD, asthma and interstitial lung disease. COPD is a major predictor of early mortality in early RA. Early assessment of comorbidity including lung disease should form part of the routine management of RA patients.

The role of IL-23 receptor signaling in inflammation-mediated erosive autoimmune arthritis and bone remodeling.

The IL-23/Th17 axis has been implicated in the development of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). RA and PsA are heterogeneous diseases with substantial burden on patients. Increasing evidence suggests that the IL-23 signaling pathway may be involved in the development of autoimmunity and erosive joint damage. IL-23 can act either directly or indirectly on bone forming osteoblasts as well as on bone resorbing osteoclasts. As IL-23 regulates the activity of cells of the bone, it is conceivable that in addition to inflammation-mediated joint erosion, IL-23 may play a role in physiological bone remodeling. In this review, we focus on the role of IL-23 in autoimmune arthritis in patients and murine models, and provide an overview of IL-23 producing and responding cells in autoimmune arthritic joints. In addition, we discuss the role of IL-23 on bone forming osteoblasts and bone resorbing osteoclasts regarding inflammation-mediated joint damage and bone remodeling. At last, we briefly discuss the clinical implications of targeting this pathway for joint damage and systemic bone loss in autoimmune arthritis.

Radiographic joint damage in early rheumatoid arthritis patients: comparing tocilizumab- and methotrexate-based treat-to-target strategies.

OBJECTIVE: To evaluate the progression of erosions and joint space narrowing (JSN) in feet and hands in the U-Act-Early trial. METHODS: In this trial, 317 newly diagnosed DMARD-naïve RA patients initiated randomly tocilizumab, or step-up MTX or a combination of the two. Radiographs were scored at baseline and after 52 and 104 weeks using the Sharp-van der Heijde erosion and JSN score. Between the strategy arms, changes from baseline and the proportions of patients without radiographic progression (change from baseline ≤0) were compared. RESULTS: Mean changes from baseline in erosion and JSN scores for the whole study population were after 52 weeks 0.59 and 0.18 and after 104 weeks 0.70 and 0.50, respectively. For JSN, at both time points no differences in progression were found between strategies (P ⩾ 0.09). For erosions, the progression was significantly lower at week 104 in both tocilizumab arms when compared with the MTX arm ((p≤0.023). Less progression of erosions in the feet was found after 104 weeks in both tocilizumab arms (P ⩽ 0.046); this was not significant for the hands (P ⩾ 0.11). The proportion of patients without progression in erosions was higher in the tocilizumab arms at week 52 (tocilizumab plus MTX: 87%, P = 0.038; tocilizumab: 81%, P = 0.29) and 104 (tocilizumab plus MTX: 85%, P = 0.001; tocilizumab: 77%, P = 0.028), compared with the MTX arm (74 and 60%, respectively). CONCLUSION: In DMARD-naïve early RA patients, initiating a tocilizumab-based treat-to-target strategy inhibits the progression of erosions, especially in the feet, more compared with initiation of a step-up MTX strategy. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01034137.

Manual therapy in the treatment of patients with hemophilia B and inhibitor.

BACKGROUND: The main clinical manifestations of hemophilia are muscle and joint bleeding. Recurrent bleeding leads to a degenerative process known as hemophilic arthropathy. The development of inhibitors (antibodies against FVIII/FIX concentrates) is the main complication in the treatment of hemophilia. The objective was to assess the safety and efficacy of manual therapy treatment in a patient with hemophilia and inhibitor. CASE PRESENTATION: A 26-year-old patient with hemophilia B and inhibitor received physiotherapy treatment based on manual therapy for 3 months, with a frequency of 2 sessions per week. The joint status was evaluated using the Hemophilia Joint Health Score; pain was assessed with the Visual Analog Scale; and the range of movement was evaluated using a universal goniometer. The patient developed no joint bleeding in the knees or ankles as a result of the physiotherapy treatment. Following treatment, improvements were noted in the range of movement of knees and ankles, the perception of pain in both knees, and ankle functionality. CONCLUSIONS: Until now, manual therapy using joint traction was contraindicated in patients with hemophilia and inhibitor, as it was feared to cause possible joint bleeding. This is the first case study to address the safety and efficacy of manual therapy in a patient with hemophilia and an inhibitor. The results of this study may help to establish which manual therapy treatments are indicated in patients with hemophilic arthropathy and inhibitors. Thus, a physiotherapy program based on manual therapy may be safe in patients with hemophilia and inhibitor and such therapy may improve joint condition, pain, and joint range of motion in patients with hemophilia and inhibitor. Randomized clinical trials are needed to confirm the results of this case study.