Reliability assessment of the OMERACT whole-body magnetic resonance imaging scoring system for juvenile idiopathic arthritis.

Inter-reader reliability of a new scoring system for evaluating joint inflammation and enthesitis in whole body MRI (WBMRI) in juvenile idiopathic arthritis was tested. The scoring system grades 732 item-region combinations of bone marrow and soft tissue changes for commonly involved joints and entheseal sites. Five radiologists rated 17 WBMRI scans through an online rating platform. Item-wise reliability was calculated for 117 items with non-zero scores in >10 % of readings. Interquartile ranges of the five-reader Kappa reliability coefficients were 0.58-0.73 (range: 0.36-0.88) for the joints, 0.65-0.81 (range: 0.39-0.95) for the entheses, and 0.62-0.75 (range: 0.60-0.76) for chronic nonbacterial osteomyelitis-like lesions.

The role of tender and swollen joints for the assessment of inflammation in PsA using ultrasound.

OBJECTIVE: To evaluate tender joints (TJ) and swollen joints (SJ) for the assessment of ultrasound (US) defined inflammation in PsA. METHODS: Eighty-three PsA patients underwent clinical and US examinations at two scheduled study visits 12 months apart. Tenderness and swelling were assessed at 68 and 66 joints, respectively, and US examinations were conducted at all 68 joints. At patient level, associations with clinical composites and US scores were performed using correlations and by analysing patients with predominantly tender (pTender) or swollen joints (pSwollen). At joint level, a Power Doppler (PD) value ≥ 1 was defined as active synovitis. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months. RESULTS: SJC showed better correlations with GS/PD scores (r = 0.37/0.47) than with TJC (PD: r = 0.33), while TJC correlated better with patient reported outcomes (PROMs) like patient global assessment (TJC: r = 0.57; SJC r = 0.39). Patients with pTender showed poorer results for PROMs and disease activity scores than patients with pSwollen, but not for laboratory or US markers of inflammation. Swollen joints showed active synovitis in 35% of cases, while only 16% of tender joints were active according to US. Swelling at baseline better predicted active synovitis at the same joint after 12 months [odds ratio (OR) 6.33, P <0.001] as compared with tenderness (OR 3.58, P <0.001). CONCLUSIONS: SJ are more closely linked with US signs of inflammation as compared with TJ in PsA. Joint swelling is a better predictor for signs of US inflammation than tenderness after one year of follow-up.

Patient Global Assessment of Disease Activity and Radiographic Progression in Early Arthritis: Three-Year Results From the ESPOIR Cohort.

OBJECTIVE: To determine whether patient global assessment of disease activity (PtGA) over the first year of disease course, as part of a Boolean-based definition of remission and considered individually, had a significant relationship with structural progression over 3 years in patients with early arthritis. METHODS: We conducted a prospective, observational study using ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) cohort data. Remission states were defined as 1) 4-variable remission, which included a tender joint count in 28 joints, a swollen joint count in 28 joints (SJC28), a C-reactive protein (CRP; mg/dl) level, and PtGA (scored 0-10, all scores of ≤1); 2) PtGA near remission, which included the same parameters as 4-variable remission with only PtGA >1 (of a maximum possible score of 10); 3) 3-variable remission (sum of the proportion of patients in 4-variable remission and the proportion of patients in PtGA near remission); or 4) nonremission. The strictest status satisfied both at 6 and 12 months was considered. Radiographic progression was determined as a change of ≥5 points in the total Sharp/van der Heijde score (ΔSHS) from baseline to 3 years. The predictive capacities for radiographic damage of different remission definitions were assessed by odds ratio (OR). The association between each individual component of remission with ΔSHS was tested through multivariate linear regression analyses. RESULTS: Among 520 patients, 7% achieved 4-variable remission and 12% achieved PtGA near remission. Radiographic progression was observed in 29% of patients who achieved 4-variable remission (OR versus nonremission; OR 0.32 [95% confidence interval (95% CI) 0.15, 0.68]) and in 45% of patients with PtGA near remission (OR 0.65 [95% CI 0.38, 1.11]); the comparison was not statistically different (OR 0.49 [95% CI 0.20, 1.18]). In 3-variable remission, radiographic progression was observed in 39%. Of the individual components, only the SJC28 and CRP level were associated with radiographic progression. CONCLUSION: All definitions of remission led to low structural degradation in early arthritis, and 4-variable remission led to less radiographic progression than PtGA near remission, but without a statistically significant difference. Both 4-variable remission and 3-variable remission appear to be useful targets when aiming for structural nonprogression.

HJHS 2.1 and HEAD-US assessment in the hemophilic joints: How do their findings compare?

: In hemophilic patients methods are needed to better diagnose joint damage early, so that treatments can be adjusted to slow the progression of hemophilic arthropathy. The aim of this study is to investigate the relationship between the Hemophilia Joint Health Score version 2.1 (HJHS 2.1) and hemophilia early arthropathy detection with ultrasound (HEAD-US) scales, as well as each of their individual items, to better understand the value each provides on the joint condition of patients with hemophilia. The study included data from patients with hemophilia older than 16 years of age, who attended a routine check-up. HJHS 2.1 and HEAD-US assessments were performed on the elbows, knees and ankles. We studied the correlations and agreements between the two scales and analyzed the relationship between the various items of the HJHS 2.1 (inflammation, duration, atrophy, crepitation, flexion deficit, extension deficit, pain, strength, gait) and HEAD-US (synovitis, cartilage and bone). The study included 203 joints from 66 patients with hemophilia (mean age, 34 years). We found a good correlation between the two scales (r = 0.717). However, HJHS 2.1 revealed only 54% of the cases with synovitis and 75% of the cases with osteochondral damage. HEAD-US detected several relevant physical and functional aspects in less than 53% of the cases. HJHS 2.1 and HEAD-US provide complementary data on joint disease in adults with hemophilia; both assessments should therefore, be made available. HEAD-US presented the added value of detecting early joint changes (synovitis and osteochondral damage), while HJHS 2.1 showed the added value of detecting relevant physical and functional changes.

Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment.

PURPOSE: Dapoxetine HCl (DH), a selective serotonin reuptake inhibitor, may be useful for the treatment of rheumatic arthritis (RA). The purpose of this study was to investigate the therapeutic efficacy of transdermal delivery of DH in transethosome nanovesicles (TENVs). This novel delivery of DH may overcome the drawbacks associated with orally administered DH and improve patient compliance. METHODS: DH-TENV formulations were prepared using an injection- sonication method and optimized using a 33 Box-Behnken-design with Design Expert® software. The TENV formulations were assessed for entrapment efficiency (EE-%), vesicle size, zeta potential, in vitro DH release, and skin permeation. The tolerability of the optimized DH-TENV gel was investigated using a rat skin irritation test. A pharmacokinetic analysis of the optimized DH-TENV gel was also conducted in rats. Moreover, the anti-RA activity of the optimized DH-TENV gel was assessed based on the RA-specific marker anti-cyclic cirtullinated peptide antibody (anti-CCP), the cartilage destruction marker cartilage oligomeric matrix protein (COMP) and the inflammatory marker interleukin-6 (IL-6). Level of tissue receptor activator of nuclear factor kappa-Β ligand (RANKL) were also assessed. RESULTS: The optimized DH-TENV formulation involved spherical nanovesicles that had an appropriate EE- % and skin permeation characteristic. The DH-TENV gel was well tolerated by rats. The pharmacokinetics analysis showed that the optimized DH-TENV gel boosted the bioavailability of the DH by 2.42- and 4.16-fold compared to the oral DH solution and the control DH gel, respectively. Moreover, it significantly reduced the serum anti-CCP, COMP and IL-6 levels and decreased the RANKL levels. Furthermore, the DH-TENV gel attenuated histopathological changes by almost normalizing the articular surface and synovial fluid. CONCLUSION: The results indicate that DH-TENVs can improve transdermal delivery of DH and thereby alleviate RA.

Joint microwave radiometry for inflammatory arthritis assessment.

OBJECTIVES: Increased in-depth joint temperature measured by the rapid, easy-to-perform microwave radiometry (MWR) method may reflect inflammation, even in the absence of clinical signs. We hypothesized that MWR is useful for RA and spondyloarthritis patients' assessment. METHODS: Clinical examination, joint ultrasound and/or MRI and MWR were performed in two independent patient-control cohorts (n = 243). RESULTS: Among single RA joints MWR performed best in the knee using ultrasound as reference, with 75% sensitivity-73% specificity for grey-scale synovitis score ⩾2, and 80% sensitivity-82% specificity for power Doppler positivity. A stronger agreement was evident between increased knee relative temperature (Δt) and power Doppler positivity (82%) than with clinical examination (76%). In a different patient cohort with painful knees, a knee Δt ⩽0.2 predicted power Doppler positivity with 100% positive and negative predictive values. A thermo-score summing 10 Δt values of three large and seven small RA joints (elbow, knee, ankle, wrist, four hand and two foot joints of the clinically dominant arm or hand and leg or foot) correlated with ultrasound scores of synovitis/tenosynovitis (all P < 0.001) and the 28-joint Disease Activity Score (DAS28) (P = 0.004). The agreement of the thermo-score with ultrasound-defined joint inflammation (82%) was stronger than with DAS28 (64%). The thermo-score improved significantly after 90 days of treatment in patients with active RA at baseline (P = 0.004). Using MRI as reference, Δt of sacroiliac joints could discriminate between spondyloarthritis patients with or without sacroiliitis with 78% sensitivity-74% specificity. CONCLUSION: In-depth increased MWR-derived joint temperature reflects both subclinical and clinically overt inflammation and may serve as a biomarker in arthritis.

Ultrasound in the assessment of musculoskeletal involvement in systemic lupus erythematosus: state of the art and perspectives.

Musculoskeletal manifestations are extremely common in patients with systemic lupus erythematosus. Transient and migratory arthralgia is frequently reported even without clinical signs of joint or tendon inflammation. In less than 15% of patients, joints may be more severely affected by deforming (Jaccoud's arthropathy) and/or erosive arthropathy (Rhupus syndrome). In recent years, ultrasound has emerged as a promising imaging technique for the assessment of musculoskeletal involvement in systemic lupus erythematosus, having demonstrated the ability to detect inflammation and structural damage both at articular and periarticular level. Recent ultrasound studies have also revealed new insights into musculoskeletal involvement in patients with systemic lupus erythematosus, some of them questioning the traditional concepts of systemic lupus erythematosus arthropathy, with potential clinical, prognostic and therapeutic implications. In daily clinical practice, the use of ultrasound in the assessment of joint and tendon involvement in patients with systemic lupus erythematosus is still limited. Several methodological issues encountered in ultrasound studies evaluating musculoskeletal involvement in systemic lupus erythematosus patients need to be addressed in order to improve both the reliability and clinical usefulness of ultrasound findings. This paper reviews ultrasound studies assessing musculoskeletal involvement in patients with systemic lupus erythematosus, highlighting certainty, limits, potential applications and future perspectives of ultrasound use in systemic lupus erythematosus patients.

Perceptions of Doppler ultrasound for rheumatoid arthritis disease activity assessment and education.

AIM: The aim of this qualitative study was to report the findings of the Defining rheumatoid arthritis progression using Doppler Ultrasound in Clinical practice (DEDUCE) Medical Practice Activity, which was developed to facilitate the utilization of Doppler ultrasound (DUS) by Australian rheumatologists in the treatment of patients with rheumatoid arthritis (RA). METHOD: Twenty-one rheumatologists recruited a total of 80 patients with RA in Disease Activity Score of 28 joints (DAS28) remission for DUS assessment and completed a pre- and post-activity questionnaire assessing their experience with DUS, as well as a 6-month follow-up questionnaire. Rheumatologists discussed DUS results with patients using visual aids. Patients completed a pre- and post-DUS assessment questionnaire. Data were summarized using descriptive statistics. RESULTS: Following completion of the activity, 95% of rheumatologists (20/21) believed DUS was a useful assessment tool for patients with RA. The majority found the DUS results useful and more than half thought the DUS assessment fit well into their consultation. A majority of rheumatologists indicated they would use DUS imaging in patients with low disease activity and remission, and for disease activity assessment to inform in therapeutic decision-making. All patients who responded found the visual aids useful and most felt that discussing DUS results improved understanding of their disease and would help with medication adherence. CONCLUSION: Incorporation of DUS imaging into routine clinical practice is feasible, encourages rheumatologists to utilize and expand their clinical application of DUS imaging in patients with RA, and may improve patient understanding of their disease and adherence to medication.

Validity of 7-Joint Versus Simplified 12-Joint Ultrasonography Scoring Systems in Assessment of Rheumatoid Arthritis Activity.

INTRODUCTION: Musculoskeletal ultrasonography (US) is an objective tool for the evaluation of disease activity in rheumatoid arthritis (RA) patients. There is no consensus on the exact number of joints that should be examined. Examination of reduced joint count is more practical than the comprehensive one. OBJECTIVES: This is a cross-sectional study investigated the validity of a 7-joint US score (US7) in assessment of joint inflammation in RA patients compared with a simplified 12-joint US score (US12) and correlated both to composite disease activity indices. METHODS: The activity status of 50 RA patients was assessed clinically and ultrasonographically. The disease activity was calculated using 3 composite indices. Ultrasonography was performed by 1 blinded rheumatologist, using power Doppler (PD) and gray-scale (GS) US examination. The US7 and simplified US12 were performed as originally described. However, the GS synovitis and PD synovitis of US12 were computed in 2 separate scores instead of 1. Two sum US7 scores were added, sum (GS) US7 and sum (PD) US7 after summating synovitis and tenosynovitis scores. Ultrasonography interobserver/intraobserver reliability was evaluated on 40 stored images. RESULTS: Correlation coefficient between the different ultrasonographic scores showed no difference. The GS scores showed no correlation with disease activity parameters; however, the PD scores did. The sum (PD) US7 was the only score that showed significant correlation with the 3 different composite disease indices. CONCLUSIONS: All studied US scores proved valid in assessment of disease activity status in RA. This is in favor of using the less-time-consuming US7 scores. The strongest correlation found with sum (PD) US7 confirmed the importance of incorporating the tendon in the disease activity assessment.

Overweight and obesity affect clinical assessment of synovitis in rheumatoid arthritis: comparison of ultrasonography and clinical exam.

OBJECTIVES: Body mass index (BMI) might affect rheumatoid arthritis (RA) outcomes. Clinical assessment of swollen joint count (SJC) might also be affected by obesity in terms of obesity-related excess adipose tissue. In this study, we compared ultrasonography (US) and clinical examination in assessing the effect of BMI on RA disease activity assessment. METHODS: This was a single-centre study including RA (ACR/EULAR criteria) patients. US assessment was performed by one trained rheumatologist blinded to clinical data. US synovitis was defined as grey-scale score ≥2 and/or power Doppler score ≥1. The primary outcome measure was difference in SJC (ΔSJC) between clinical and US assessment (US-clinical examination). The secondary outcome was to evaluate the difference between clinical and US assessment of the Disease Activity Score in 28 joints (ΔDAS28) in the 3 BMI subgroups according to the WHO classification. RESULTS: We included 76 RA patients (mean age 53.8 ± 11.8 years; 67% female). Overall, 28 (36.8%), 33 (43.4%) and 15 (19.7%) were normal weight, overweight and obese, respectively. Baseline characteristics did not differ between the 3 BMI subgroups. US-determined SJC was significantly higher than clinical-determined SJC for overweight and obese RA patients: p=0.001 and p=0.049, respectively. The DAS28 was higher with US than clinical examination within the overweight group only (p=0.002). One-way analysis of variance (ANOVA) revealed a significant difference between ΔDAS28 among the 3 BMI subgroups (p=0.046). CONCLUSIONS: In high BMI RA patients both SJC and DAS28 seem to be undervalued by clinical assessment when compared to US.

Performance of routine assessment of patient index data 3 (RAPID3) in monitoring disease activity of Chinese rheumatoid arthritis patients.

AIM: To explore the performance of routine assessment of patient index data 3 (RAPID3) in reflecting disease activity in Chinese rheumatoid arthritis (RA) patients. METHOD: The clinical data of 189 consecutive RA patients, including RAPID3 questionnaire, Disease Activity Score based on 28-joint count (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI), and ultrasonography of hand and wrist joints were collected. The consistency between RAPID3 and DAS28, CDAI, SDAI in RA patients with different disease activities was performed by Spearman's correlations, kappa and/or weighted kappa coefficients. RESULT: RAPID3 score was significantly associated with DAS28 and erythrocyte sedimentation rate (ESR), DAS28 with C-reactive protein (CRP), CDAI, SDAI (r = 0.797, 0.786, 0.784, and 0.760 respectively, P < 0.001 for all). RAPID3 was also significantly correlated with tender joint count, swollen joint count, ESR and CRP. The agreement of RAPID3 with DAS28 scoring systems was better in patients with moderate/high disease activity than those in remission/low disease activity. Ultrasonographic subclinical synovitis was presented in 42.3%-48.6% of patients in remission/low disease activity defined by various scoring criteria including RAPID3 with no significant difference observed (P = 0.22, >0.05). CONCLUSION: RAPID3 showed good correlation with DAS28 scoring systems, especially in patients with moderate/high disease activity. RAPID3 is a reliable and convenient tool to monitor disease activity.

Musculoskeletal ultrasonography for arthropathy assessment in patients with hemophilia: A single-center cross-sectional study from Shanxi Province, China.

Magnetic resonance imaging (MRI) is currently considered the gold standard for assessing hemophilic arthropathy (HA) severity; however, MRI is often costly, time-consuming, and difficult to perform in children. In the present study, we evaluated the joint status of hemophilic patients from Shanxi Province, China, using musculoskeletal ultrasonography (MSKUS) and identified the factors that most strongly correlated with disease severity.The study included 104 patients with hemophilia, who underwent MSKUS examination. A total of 1248 joints (including the shoulder, elbow, wrist, hip, knee, and ankle joints on both sides) from these patients were evaluated. Effusion, hypertrophy, cartilage modification, and bone erosion were assessed. The chi-square test was used to analyze categorical variables, and multivariate logistic regression was used to analyze the relationship between joint disease and risk factors.MSKUS allowed clear visualization of synovial lesions, effusion, cartilage modification, and bone surface damage; however, it was unable to identify changes deep within bones. The distribution of damaged joints was as follows: shoulder, 2 (1.0%); elbow, 80 (38.5%); wrist, 4 (1.9%); hip, 4 (1.9%); knee, 126 (60.6%); and ankle, 90 (43.3%). Damage was more common in the knee, elbow, and ankle joints than in the shoulder, wrist, and hip joints (P < .001). Among the 1248 joints, 306 showed lesions, which included effusion in 102 (8.2%) joints, synovium hypertrophy in 176 (14.1%), cartilage modification in 193 (15.5%), and bone damage in 176 (14.1%). Many joints had multiple lesions at the same time. The chi-square test and multivariate logistic analysis showed that age and hemophilia severity were significantly associated with joint disease, while type of hemophilia and treatment categories were not associated with joint disease.MSKUS is a convenient and cost-effective examination that can play an important role in the diagnosis and long-term monitoring of HA.

Additively manufactured implant components for imaging validation studies.

Radiographic imaging is the current standard for evaluating postoperative joint replacements. Prior to application, such imaging methods need to be validated to determine the lower limits of performance under ideal conditions, using either a phantom or cadaver setup. Conventionally manufactured orthopedic implants for use in such studies are not always accessible and may be cost-prohibitive to purchase. We propose the use of additively manufactured implants as a cheaper, more accessible alternative for use in radiographic imaging validation studies. Bias and repeatability were compared between conventionally manufactured and additively manufactured reverse total shoulder implant sets under a standard model-based radiostereometric analysis phantom study environment. Measurements were compared using the humeral stem or glenosphere model relative to reference bone beads, and the humeral stem relative to the glenosphere model to measure implant relative displacement. Compared to the conventionally manufactured implants, the additively manufactured implants had less bias along the internal-external rotation axis (p < 0.001), but greater bias along the abduction-adduction and flexion-extension rotation axes (p = 0.005, 0.011). Additively manufactured implants had greater repeatability along the internal-external rotation axis (p < 0.001), but worse repeatability along the medial-lateral translation axis (p = 0.001) and the abduction-adduction rotation axis (p < 0.001). Differences were on the orders of 0.01 mm and 0.5°. For the purpose of validating two-dimensional-three-dimensional radiographic imaging techniques of orthopedic implants, additively manufactured implants can be used in place of conventionally manufactured implants, assuming they are fabricated to the manufacturer's specifications. Observed differences were within the errors of the measurement technique and not clinically meaningful.

Paraprosthetic Complications After Endoprosthesis Replacement of Pelvis Joint with Implants.

PURPOSE: The purpose of the paper is shaping of ideas about possible ways of decreasing complications of the analyzed types of operations and identification of opportunities of the impact on the socio-economic environment among the Afro-American population of USA. The paper demonstrates that the issue of coxofemoral prosthesis is not only a purely medical but also a social problem. In particular, availability of timely aid, as well as insurance in the form of surgery, refer to relevance of the range of problems. METHODOLOGY: The experimental method was used in the study. Patients were implanted different types of endoprostheses. 90 patients were implanted customized endoprostheses, 27 patients were implanted foreign module endoprostheses. The research subject is prediction of complications after endoprosthesis replacement surgeries depending on methods, types and forms. RESULTS: As a result, we can see that available health insurance is more acceptable understanding of the need for endoprosthesis replacement. Post-operative care issues fall into the range of social policy problems. A comparative aspect of a country with general insurance and differentiated coverage among the Afro-America population appears innovative. CONCLUSIONS: In the context of the current situation it can be concluded that surgery is the last stage for already established support system of the population. For this reason, it's worth mentioning that state bodies of the U.S. should put a greater emphasis on the health care of the Afro-American population.

Ultrasonographic assessment of joint pathology in type 2 diabetes and hyperuricemia: The Fremantle Diabetes Study Phase II.

AIMS: The prevalence and consequences (articular and extra-articular) of hyperuricemia in type 2 diabetes, especially when asymptomatic (ASH), are incompletely understood. The aim of this study was to use ultrasonography to assess pathology associated with monosodium urate deposition in the joints of well-characterized hyperuricemic patients with type 2 diabetes. METHODS: A subset of 101 participants (mean age 70.4 years, 59.8% males, median diabetes duration 14.6 years) with hyperuricemia (fasting serum uric acid ≥0.42 mmol/L) from the community-based observational Fremantle Diabetes Study Phase II were assessed by ultrasound for signs of intra-articular urate deposition and inflammation in 14 joints at increased risk of involvement in patients with gout. RESULTS: Most participants had evidence of crystal deposition comprising aggregates (59.4%), tophi (19.8%) or a double contour sign (27.7%), and 37% had a power Doppler signal indicative of inflammation in at least one joint. There was no difference between the prevalence of these abnormalities in those with ASH (n = 60) versus participants with a history of gout (n = 41; P ≥ 0.15). There was no association between a history of ischemic heart disease (reported by 17.8% of participants) and either any abnormality on joint ultrasound or inflammatory changes assessed by power Doppler (P ≥ 0.41). CONCLUSIONS: Joint inflammation and/or urate deposition were present in the majority of community-based patients with type 2 diabetes and hyperuricemia regardless of whether there was a history of gout. Given the potential consequences of chronic inflammation for joint damage and extra-articular complications such as cardiovascular disease, these data have potential clinical implications.

MRI assessment of erosion repair in patients with long-standing rheumatoid arthritis receiving double-filtration plasmapheresis in addition to leflunomide and methotrexate: a randomized controlled trial.

The objective of this study is to investigate whether the addition of double-filtration plasmapheresis (DFPP) to leflunomide and methotrexate repairs MRI bone erosion in patients with long-standing rheumatoid arthritis (RA). Seventy-two patients with highly active RA of > 3 years' duration were randomized to receive DFPP in addition to DMARDs (leflunomide and methotrexate) or DMARDs. Contrast-enhanced MRI of the right wrist was performed at months 0, 6, and 12. MRI bone erosion, synovitis, and bone edema were scored with validated methods. The primary endpoint was the change in MRI bone erosion over 12 months. Patients treated with DFPP in addition to DMARDs demonstrated significantly greater decrease in MRI erosion score compared with those treated with DMARDs, being 11.3 ± 9.6 at month 12, compared with 16.9 ± 8.3 in patients with DMARDs (P < 0.001), and compared with 14.4 ± 9.6 at baseline (P < 0.001). 84.2% of patients treated with DFPP in addition to DMARDs demonstrated a decrease in MRI erosion score. Synovitis and bone edema improved significantly with DFPP in addition to DMARDs compared with DMARDs at months 6 and 12. (1.05 ± 1.7 and 2.0 ± 3.9 compared with 8.0 ± 1.4 and 12.6 ± 7.9 at month 12). Patients without synovitis and bone edema reached in 55.3% among patients with DFPP in addition to DMARDs. This study demonstrated that DFPP combination therapy significantly decreased bone erosion and received the primary goal of repair of erosions through abrogating MRI inflammation (synovitis and bone edema) in long-standing RA patients with high disease activity. The findings suggest that addition of DFPP is associated with repair of erosions and further suppression of inflammation.

Matrix metalloproteinase-3 and the 7-joint ultrasound score in the assessment of disease activity and therapeutic efficacy in patients with moderate to severe rheumatoid arthritis.

BACKGROUND: This study aimed to investigate the reliability and validity of serum matrix metalloproteinase-3 (MMP-3) levels and articular ultrasound (US) scores in assessing disease activity and therapeutic response in rheumatoid arthritis (RA) patients. METHODS: A total of 151 RA patients were enrolled, of whom 22 were treated with certolizumab pegol (Cimzia, CZP). The RA patients were divided into the following four subgroups according to their disease activity score in 28 joints (DAS28): stable, mild activity, moderate activity, and high activity. Forty-three healthy controls were simultaneously studied. The serum MMP-3 levels and 7-joint US (US7) scores of all subjects were determined. The patients who were treated with CZP were subsequently followed for 6 months. RESULTS: The serum MMP-3 levels of all the RA patients were significantly higher than those of healthy controls, and those of patients with moderate and severe RA were significantly higher than those of patients with stable RA. The US7 scores of patients with severe RA were significantly higher than those of patients in other groups. Using the DAS28 as a reference standard, the corresponding cutoff value of MMP-3 was 70.5 ng/ml. After CZP treatment, the MMP-3 levels and US7 scores were significantly decreased at week 2, and the mean changes in US7 scores at weeks 12 and 24 were significantly higher in both groups with American College of Rheumatology 50% positive response (ACR50) and ACR 70% positive response (ACR70) than in the negative groups. CONCLUSION: Serum MMP-3 and the US7 scores could both effectively reflect disease activity and therapeutic responses in patients with moderate to severe RA. TRIAL REGISTRATION: CTR20140405 (RA0044), CTR20140405: A phase 3, Multicenter, Double-blind, Placebo Controlled, Parallel Group, Randomized, 24-Week Study to Evaluate the Safety and Efficacy of Certolizumab Pegol as Additional Medication to Methotrexate in Chinese Subjects With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate, Registered on 13 June 2014. CTR20140412 (RA0078), CTR20140412: A phase 3, Multicenter, Open-label Extension Study to Assess the Safety and Efficacy of Certolizumab Pegol as Additional Medication to Methotrexate in Chinese Subjects With Active Rheumatoid Arthritis Who Participated in RA0044, Registered on 02 July 2014.

Effect of late prophylaxis in hemophilia on joint status: a randomized trial.

Essentials High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropathy. SUMMARY: Background Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives To describe 3-year bleeding, joint health and structure, health-related quality-of-life (HRQoL) and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods Males aged 12-50 years with severe hemophilia A, ≥ 150 factor VIII exposure days, no inhibitors and no prophylaxis for > 12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results Following 3 years of prophylaxis, adults maintained excellent adherence, with a 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had fewer than two BEs per year, respectively. As compared with OD, prophylaxis was associated with improved CAJAS scores (least squares [LS] mean, - 0.31 [n = 42] versus + 0.63 [n = 42]) and HAEMO-QoL-A scores (LS mean, + 3.98 [n = 41] versus - 6.00 [n = 42]), less chronic pain (50% decrease), and approximately two-fold less HRU; activity, Euro QoL-5D-3L (EQ-5D-3L) scores and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, + 0.79 [n = 41] versus + 0.96 [n = 38]). Conclusions Over a period of 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting that pre-existing joint arthropathy may be irreversible.