Weight Loss for Patients With Gout and Concomitant Obesity: A Proof-of-Concept Randomized Trial.

OBJECTIVE: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. METHODS: We conducted a 16-week randomized nonmasked parallel-group trial in Denmark, randomly assigning (one-to-one) individuals with obesity and gout to a low-energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale-assessed pain and fatigue. RESULTS: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention-to-treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (-15.4 vs -7.7 kg; difference -7.7 kg [95% confidence interval -10.7 to -4.7], P < 0.001). Despite results being potentially in favor of a low-energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. CONCLUSION: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain.

Colchicine twice a day for hand osteoarthritis (COLOR): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Colchicine has been suggested for osteoarthritis treatment, but evidence is contradictory. We aimed to investigate colchicine's efficacy and safety compared with placebo in people with hand osteoarthritis. METHODS: In this single-centre, double-blind, randomised, placebo-controlled trial we recruited adults with symptomatic hand osteoarthritis and finger pain of at least 40 mm on a 100 mm visual analogue scale from an outpatient clinic in Denmark. The hand with the most severe finger pain at inclusion was the target hand. Participants were randomly assigned (1:1) to 0·5 mg colchicine or placebo taken orally twice a day for 12 weeks, stratified by BMI (≥30 kg/m2), sex, and age (≥75 years). Participants, outcome assessors, and data analysts were masked to treatment allocation. The primary endpoint was change from baseline to week 12 in target hand finger pain, assessed on a 100 mm visual analogue scale with a pre-specified minimal clinically important difference of 15 mm, in the intention-to-treat population. Safety was assessed at week 12 in the intention-to-treat population. The study was registered with ClinicalTrials.gov, NCT04601883, and with EudraCT, 2020-002803-20. FINDINGS: Between Jan 15, 2021, and March 3, 2022, 186 people were screened for eligibility, and 100 were randomly assigned to receive colchicine (n=50) or placebo (n=50). Participants had a mean age of 70·9 (SD 7·5) years, 69 (69%) of 100 were women and 31 (31%) were men. All participants completed the study. The mean change from baseline to week 12 in finger pain were -13·9 mm (SE 2·8) in the colchicine group and -13·5 mm (2·8) in the placebo group, with a between-group difference (colchicine vs placebo) of -0·4 mm (95% CI -7·6 to 6·7; p=0·90). In the colchicine group, there were 76 adverse events in 36 (72%) of 50 participants and one serious adverse advent (migraine attack leading to hospital admission). In the placebo group, there were 42 adverse events in 22 (44%) of 50 participants and two serious adverse events (cholecystitis and elevated alanine aminotransferase concentrations, in the same patient). INTERPRETATION: In people with painful hand osteoarthritis, treatment with 0·5 mg of colchicine twice day for 12 weeks did not effectively relieve pain, and treatment with colchicine was associated with more adverse events. FUNDING: The Oak Foundation, IMK Almene Fond, Minister Erna Hamilton's Scholarship for Science and Art, AP Moller and Wife Chastine McKinney Moller's Foundation for Medical Science Advancement, The Danish Medical Association, the Velux Foundation, Aase and Ejnar Danielsen's Foundation, and Director Emil C Hertz and Wife Inger Hertz's foundation.

Flare during tapering of biological DMARDs in patients with rheumatoid arthritis in routine care: characteristics and predictors.

OBJECTIVE: To identify predictors of flare in a 2-year follow-up study of patients with rheumatoid arthritis (RA) in sustained clinical remission tapering towards withdrawal of biological disease-modifying anti-rheumatic drugs (bDMARDs). METHODS: Sustained clinical remission was defined as Disease Activity Score for 28 joints (DAS28)-C reactive protein (CRP) ≤2.6 without radiographic progression for >1 year. bDMARDs were tapered according to a mandatory clinical guideline to two-thirds of standard dose at baseline, half of dose at week 16 and discontinuation at week 32. Prospective assessments for 2 years included clinical evaluation, conventional radiography, ultrasound and MRI for signs of inflammation and bone changes. Flare was defined as DAS28-CRP ≥2.6 with ∆DAS28-CRP ≥1.2 from baseline. Baseline predictors of flare were assessed by logistic regression analyses. RESULTS: Of 142 included patients, 121 (85%) flared during follow-up of which 86% regained remission within 24 weeks after flare. Patients that flared were more often rheumatoid factor positive, had tried more bDMARDs and had higher baseline ultrasound synovitis sum scores than those not flaring. For patients on standard dose, predictors of flare within 16 weeks after reduction to two-thirds of standard dose were baseline MRI-osteitis (OR 1.16; 95% CI 1.03 to 1.33; p=0.014), gender (female) (OR 6.71; 95% CI 1.68 to 46.12; p=0.005) and disease duration (OR 1.06; 95% CI 1.01 to 1.11; p=0.020). Baseline predictors for flare within 2 years were ultrasound grey scale synovitis sum score (OR 1.19; 95% CI 1.02 to 1.44; p=0.020) and number of previous bDMARDs (OR 4.07; 95% CI 1.35 to 24.72; p=0.007). CONCLUSION: The majority of real-world patients with RA tapering bDMARDs flared during tapering, with the majority regaining remission after stepwise dose increase. Demographic and imaging parameters (MR-osteitis/ultrasound greyscale synovitis) were independent predictors of immediate flare and flare overall and may be of importance for clinical decision-making in patients eligible for tapering.

Four emerging immune cellular blood phenotypes associated with disease duration and activity established in Psoriatic Arthritis.

BACKGROUND: Psoriatic Arthritis (PsA) is an immune-mediated disease with heterogenous symptoms indicating differences in the underlying immunopathogenesis. The primary objective of the study explored the dynamic mechanisms and interplay between immune cell subtypes constituting the immune response driving PsA to evaluate possible differences in immune cellular phenotypes, and secondary examined associations between emerging immune cellular phenotypes and disease outcomes. METHODS: Peripheral blood was collected from 70 PsA patients. Frequencies of nine immune cell subtypes were determined by multicolor flow cytometry. The interplay between immune cells were examined with principal component analysis (PCA) to establish immune cellular phenotypes. Disease characteristics, Disease Activity in Psoriatic Arthritis (DAPSA) and Psoriasis Area Severity Index (PASI) were retrieved to examine associations to individual cellular phenotypes. RESULTS: Four components were identified using PCA resembling four immune cellular phenotypes. Component 1, explaining 25.6% of the variance with contribution from T-helper 17 cells (Th17), memory T regulatory cells (mTregs), dendritic cells and monocytes, was associated with longer disease duration and higher DAPSA. Component 2, driven by Th1, naïve Tregs and mTregs, was associated with shorter disease duration. Component 3 was driven by both Th1, Th17 and CD8+ T cells, while component 4 was characterized by a reverse correlation between CD8+ T cells and natural killer cells. CONCLUSION: Four immune cellular phenotypes of PsA were suggested at baseline demonstrating complex immune cellular mechanisms in PsA implying the possibility of improving PsA patient stratification based on both clinical and immune cellular phenotypes.

Multimodal imaging of the distal interphalangeal-joint synovio-entheseal complex in psoriatic arthritis (MIDAS): a cross-sectional study on the diagnostic accuracy of different imaging modalities comparing psoriatic arthritis to psoriasis and osteoarthritis.

OBJECTIVE: Can ultrasound (US), MRI and X-ray applied to the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC) discriminate between patients with psoriatic arthritis (PsA), skin psoriasis (PsO) and hand osteoarthritis (OA)? METHODS: In this prospective, cross-sectional study, patients with DIP-joint PsA and nail involvement (n=50), PsO with nail involvement (n=12); and OA (n=13); were consecutively recruited. Risk ratios (RR) were calculated for US, MRI and X-ray findings of the DIP-joint and SEC between diagnoses. RESULTS: New bone formation (NBF) in US and MRI was a hallmark of OA, reducing the risk of having PsA (RR 0.52 (95% CI 0.43 to 0.63) and 0.64 (95% CI 0.56 to 0.74). The OA group was different from PsA and PsO on all MRI and X-ray outcomes reflected in a lower RR of having PsA; RR ranging from 0.20 (95% CI 0.13 to 0.31) for MRI bone marrow oedema (BMO) to 0.85 (95% CI 0.80 to 0.90) in X-ray enthesitis. No outcome in US, MRI or X-ray was significantly associated with a higher risk of PsA versus PsO, although there was a trend to a higher degree of US erosions and NBF in PsA. 82% of PsA and 67% of PsO was treated with disease modifying antirheumatic drugs which commonly reflects the clinical setting. CONCLUSION: High grade of US, MRI and X-ray NBF reduce the RR of having PsA compared with OA. In PsA versus PsO patients, there was a trend for US to demonstrate more structural changes in PsA although this did not reach significance.

Ultrasonography of Inflammatory and Structural Lesions in Hand Osteoarthritis: An Outcome Measures in Rheumatology Agreement and Reliability Study.

OBJECTIVE: To standardize and assess the reliability of ultrasonographic assessment of inflammatory and structural lesions in patients with hand osteoarthritis (OA). METHODS: The Outcome Measures in Rheumatology Ultrasound Working Group selected synovial hypertrophy (SH), joint effusion (JE), and power Doppler (PD) signals as the main inflammatory lesions in hand OA, and suggested osteophytes in the scapho-trapezio-trapezoid (STT) and cartilage defects in the proximal interphalangeal (PIP) joints as novel additions to previous structural scoring systems. A complementary imaging atlas provided detailed examples of the scores. A reliability exercise of static images was performed for the inflammatory features, followed by a patient-based exercise with 6 sonographers testing inflammatory and structural features in 12 hand OA patients. We used Cohen's kappa for intrareader and Light's kappa for interreader reliability for all features except PD, in which prevalence-adjusted bias-adjusted kappa (PABAK) was applied. Percentage agreement was also assessed. RESULTS: The web-based reliability exercise demonstrated substantial intra- and interreader reliability for all inflammatory features (κ > 0.64). In the patient-based exercise, intra- and interreader reliability, respectively, varied: SH κ = 0.73 and 0.45; JE κ = 0.70 and 0.55; PD PABAK = 0.90 and 0.88; PIP joint cartilage κ = 0.56 and 0.45; and STT osteophytes κ = 0.62 and 0.36. Percentage close agreement was high for all features (>85%). CONCLUSION: With ultrasound, substantial to excellent intrareader reliability was found for inflammatory features of hand OA. Interreader reliability was moderate, but overall high close agreement between readers suggests that better reliability is achievable after further training. Assessment of osteophytes in the STT joint and cartilage in the PIP joints achieved less reliability and the latter is not endorsed.

Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial.

OBJECTIVE: To compare the efficacy of an exercise and education programme with open-label placebo given as intra-articular injections of inert saline on pain and function in individuals with knee osteoarthritis (OA). METHODS: In this open-label, randomised controlled trial, we recruited adults aged ≥50 years with symptomatic and radiographically confirmed knee OA in Denmark. Participants were randomised 1:1 to undergo an 8-week exercise and education programme or four intra-articular saline injections over 8 weeks. Primary outcome was change from baseline to week 9 in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire pain subscale (range 0 (worst)-100 (best)). Prespecified equivalence margins of ±8 KOOS pain points were chosen for the demonstration of comparable efficacy. Key secondary outcomes were the KOOS function and quality of life subscales, and patients' global assessment of disease impact. RESULTS: 206 adults were randomly assigned: 102 to exercise and education and 104 to intra-articular saline injections. For the primary outcome, the least squares mean changes in KOOS pain were 10.0 for exercise and education and 7.3 for saline injections (difference 2.7 points, 95% CI -0.6 to 6.0; test for equivalence p=0.0008). All group differences in the key secondary outcomes respected the predefined equivalence margins. Adverse events and serious adverse events were similar in the two groups. CONCLUSION: In individuals with knee OA, an 8-week exercise and education programme provided efficacy for symptomatic and functional improvements equivalent to that of four open-label intra-articular saline injections over 8 weeks. TRIAL REGISTRATION NUMBER: NCT03843931.

Novel application of optical coherence tomography and capillaroscopy in psoriatic arthritis in relationship to psoriasis and hand osteoarthritis.

OBJECTIVES: Nailfold video capillaroscopy (NVC) and angiographic optical coherence tomography (OCTA) have potential in diagnosing PsA and differentiating it from psoriasis vulgaris (PsO) and hand OA. We aimed to assess the diagnostic properties of NVC and OCTA in patients with PsA compared with patients with PsO and hand OA based on nailfold capillary patterns. METHODS: Patients with DIP joint PsA and nail involvement (n = 50), PsO with nail involvement (n = 12) and OA (n = 13) were included in this cross-sectional study. Capillaries were evaluated semi-quantitatively and qualitatively. Differences in capillary findings between groups were assessed using mixed linear models. Binary logistic regression analyses were performed to determine the probability for PsA diagnosis based on capillaroscopy findings. RESULTS: Below mean capillary density and reduced nailfold blood flow in OCTA images distinguished PsA from both PsO (P = 0.004 and P = 0.052, respectively) and OA (P = 0.024 and P < 0.001, respectively). Qualitative analysis revealed that glomerular capillaries were found in only 3% of PsA patients but in 13% of PsO patients (P = 0.003). Furthermore, crossed vessels were seen in only 55% of PsA patients and 71% of PsO patients (P = 0.043). NVC microhaemorrhage was dominant in PsA patients (13%) and significantly different from OA patients (P <0.05). No capillary pattern was associated with an increased probability of the PsA diagnosis. CONCLUSION: A pathognomonic pattern for PsA diagnosis was not identified; however, we demonstrated some characteristic capillaroscopy findings for PsA, such as decreased capillary density, reduced blood flow and fewer crossed vessels in OCTA and presence of NVC microhaemorrhages.

Doppler ultrasound predicts successful discontinuation of biological DMARDs in rheumatoid arthritis patients in clinical remission.

OBJECTIVE: To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. METHODS: Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0-3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. RESULTS: Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10-0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. CONCLUSION: Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up-the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.

Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE: To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS: The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS: In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS: In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.

Exercise therapy and patient education versus intra-articular saline injections in the treatment of knee osteoarthritis: an evidence-based protocol for an open-label randomised controlled trial (the DISCO trial).

BACKGROUND: Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the 'active' ingredients are unknown. Designing and executing an adequate and 'blindable placebo' version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used 'state-of-art' exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA. METHODS: In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients' global assessment of disease impact, physical performance tests, and presence of knee joint swelling. DISCUSSION: This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019.

Patients with Rheumatoid Arthritis Acquire Sustainable Skills for Home Monitoring: A Prospective Dual-country Cohort Study (ELECTOR Clinical Trial I).

OBJECTIVE: In an eHealth setting, to investigate intra- and interrater reliability and agreement of joint assessments and Disease Activity Score using C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA) and test the effect of repeated joint assessment training. METHODS: Patients with DAS28-CRP ≤ 5.1 were included in a prospective cohort study (clinicaltrials.gov: NCT02317939). Intrarater reliability and agreement of patient-performed joint counts were assessed through completion of 5 joint assessments over a 2-month period. All patients received training on joint assessment at baseline; only half of the patients received repeated training. A subset of patients was included in an appraisal of interrater reliability and agreement comparing joint assessments completed by patients, healthcare professionals (HCP), and ultrasonography. Cohen's κ coefficients and intraclass correlation coefficients (ICC) were used for quantifying of reliability of joint assessments and DAS28-CRP. Agreement was assessed using Bland-Altman plots. RESULTS: Intrarater reliability was excellent with ICC of 0.87 (95% CI 0.83-0.90) and minimal detectable change of 1.13. ICC for interrater reliability ranged between 0.69 and 0.90 (good to excellent). Patients tended to rate DAS28-CRP slightly higher than HCP. In patients receiving repeated training, a mean difference in DAS28-CRP of -0.08 was observed (limits of agreements of -1.06 and 0.90). After 2 months, reliability between patients and HCP was similar between groups receiving single or repeated training. CONCLUSION: Patient-performed assessments of joints and DAS28-CRP in an eHealth home-monitoring solution were reliable and comparable with HCP. Patients can acquire the necessary skills to conduct a correct joint assessment after initial and thorough training. [clinicaltrials.gov (NCT02317939)].

Reliability of the Copenhagen Achilles length measure (CALM) on patients with an Achilles tendon rupture.

PURPOSE: The primary objective was to examine the reliability of the Copenhagen Achilles length measure (CALM) in patients with an Achilles tendon rupture and secondary to examine the reliability of Achilles tendon resting angle (ATRA) and Achilles tendon length measure (ATLM). METHOD: The study was executed as a cross-sectional study on two different groups: one focused on CALM and the other on ATRA/ATLM. CALM was performed on 56 patients at four timepoints during the first year after injury, whereas ATRA/ATLM were carried out on 28 patients. Intra- and inter-rater reliabilities were determined using the intra-class correlation coefficient (ICC), the standard error of the measurement (SEM), and the minimal detectable change (MDC). RESULTS: For CALM, all measurements, both for injured and non-injured sides as well as for elongation, indicated excellent relative reliability (ICC ≥ 0.75). During the four timepoints, the inter-rater absolute reliability had an SEM that ranged between 0.3 and 0.8 cm (1-4 SEM%) for injured and non-injured sides and 0.3-0.6 cm (18-29 SEM%) for elongation. On an individual level, the inter-rater absolute reliability had an MDC ranging between 0.8 and 2.2 cm (4-11 MDC%) for injured and non-injured sides and 0.8-1.7 cm (47-81 MDC%) for elongation. In the case of ATRA, relative reliability was excellent (ICC ≥ 0.75), and for ATLM, it was fair to excellent (ICC 0.58-0.79). ATRA presented a lower measurement error than ATLM. CONCLUSION: Copenhagen Achilles length measure showed excellent relative reliability, but had a significant measurement error at four timepoints the first year following an Achilles tendon rupture. LEVEL OF EVIDENCE: II.

Hand exercise for women with rheumatoid arthritis and decreased hand function: an exploratory randomized controlled trial.

BACKGROUND: People with hand-related rheumatoid arthritis (RA) experience problems performing activities of daily living (ADL). Compensatory strategies to improve ADL ability have shown effective. Similarly, hand exercise has shown effect on pain, grip strength, and self-reported ability. A combination has shown positive effects based on self-report, but self-report and observation provide distinct information about ADL. The purpose of this study was to examine whether hand exercise as add on to compensatory intervention (CIP) will improve observed ADL ability in RA. METHODS: Women (n = 55) with hand-related RA were randomized to CIPEXERCISE (intervention) or CIP only (control). CIP is focused on joint protection, assistive devices, and alternative ways of performing AD. The hand-exercise program addressed range of motion and muscle strength. Primary outcome was change in observed ADL motor ability measured by the Assessment of Motor and Process Skills (AMPS). Baseline measures were repeated after 8 weeks. RESULTS: Improvements in ADL motor ability in CIPEXERCISE (mean change = 0.24 logits; 95% CI = 0.09 to 0.39) and CIPCONTROL (mean change =0.20 logits; 95% CI = 0.05 to 0.35) were statistically significant, with no differences between groups (mean difference = 0.04 logits; 95% CI = - 0.16 to 0.25). Thirteen (46.4%) participants in the CIPEXERCISE and 12 (44.4%) in the CIPCONTROL obtained clinically relevant improvements (≥ 0.30 logits) in ADL motor ability; this group difference was not significant (z = 0.15; p = 0.88). CONCLUSION: Adding hand exercise to a compensatory intervention did not yield additional benefits in women with hand-related RA. The study was approved by the ethics committee 14th of April 2014 (H-3-2014-025) and registered at ClinicalTrials.gov 16th of May 2014 (NCT02140866).

Effect of liraglutide on body weight and pain in patients with overweight and knee osteoarthritis: protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial.

INTRODUCTION: With an increasing prevalence of citizens of older age and with overweight, the health issues related to knee osteoarthritis (OA) will intensify. Weight loss is considered a primary management strategy in patients with concomitant overweight and knee OA. However, there are no widely available and feasible methods to sustain weight loss in patients with overweight and knee OA. The present protocol describes a randomised controlled trial evaluating the efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide in a 3 mg/day dosing in patients with overweight and knee OA. METHODS AND ANALYSIS: 150 volunteer adult patients with overweight or obesity and knee OA will participate in a randomised, double-blind, placebo-controlled, parallel-group and single-centre trial. The participants will partake in a run-in diet intervention phase (week -8 to 0) including a low calorie diet and dietetic counselling. At week 0, patients will be randomised to either liraglutide 3 mg/day or liraglutide placebo 3 mg/day for 52 weeks as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle. The co-primary outcomes are changes in body weight and the Knee Injury and Osteoarthritis Outcome Score pain subscale from week 0 to week 52. ETHICS AND DISSEMINATION: The trial has been approved by the regional ethics committee in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. An external monitoring committee (The Good Clinical Practice Unit at Copenhagen University Hospitals) will oversee the trial. The results will be presented at international scientific meetings and through publications in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: 2015-005163-16, NCT02905864, U1111-1171-4970 BASED ON PROTOCOL VERSION: V.6; 30 January 2017, 15:30 hours.

Ultrasound pathology of the entheses in an age and gender stratified sample of healthy adult subjects: a prospective cross-sectional frequency study.

OBJECTIVES: Ultrasound (US) examination of the entheses is increasingly used. However, little is known about US findings in the entheses in asymptomatic persons. The aim of this study was to investigate the appearance of US signs in the enthuses of the lower limb in asymptomatic subjects. METHODS: We recruited 64 subjects, eight women and eight men whose ages covered four decades, from 20 to 60 years. None had tendon or joint disease in the lower limbs. Participants were examined by a rheumatologist and blood samples were collected to rule out enthesis pathology. The enthesis of the dominant leg were examined with grey-scale and Doppler US to evaluate increased thickness, changed structure, enthesophytes/calcifications, erosions, and colour Doppler signal. RESULTS: Ultrasound examination of 320 entheses was made. At enthesis level, elementary lesions were seen at 73 (22.8%) sites, at subject-level 47 (73.4%) persons showed elementary lesions, in 27 (57%) only one enthesis was affected. Doppler activity was seen in four sites, three at the quadriceps insertion. Most common US elementary lesion was enthesophytes at the Achilles and quadriceps tendon insertion. A tendency towards more elementary lesions was seen in men, and a slight increase was seen with increasing age, however, not statistically significance. CONCLUSIONS: Our findings suggest that US can be used to diagnose/examine subjects in adulthood for pathological changes in the entheses; however, caution should be taken regarding enthesophytes of the quadriceps and Achilles tendon.

Pain Mechanisms and Ultrasonic Inflammatory Activity as Prognostic Factors in Patients With Psoriatic Arthritis: A Prospective Cohort Study.

OBJECTIVE: To study the prognostic value of widespread pain and of musculoskeletal ultrasound (US) examination for subsequent treatment outcomes in patients with psoriatic arthritis (PsA). METHODS: An exploratory prospective cohort study enrolled patients with PsA initiating biologic or conventional synthetic disease-modifying antirheumatic drugs in routine care. Clinical, US, and patient-reported measures were collected at baseline and after 4 months. Widespread nonarthritic pain (WP) was defined as a Widespread Pain Index score of ≥4 with pain in ≥4 of 5 regions. PsA activity by US was defined as color Doppler (yes/no) in selected entheses, joints, or tendons. The main response criteria included the American College of Rheumatology 20% improvement, the Disease Activity in Psoriatic Arthritis 50% improvement, and minimal disease activity. The primary analyses were age- and sex-adjusted logistic regression. RESULTS: WP was present in 24 of 69 included patients (35%) and was associated with worse patient-reported and composite baseline measures, while US and other objective findings were similar to those in patients without WP. The odds of reaching minimal disease activity after 4 months were significantly greater for patients enrolled without WP (odds ratio 18.43 [95% confidence interval 1.51, 224.41]; P = 0.022), while WP did not impair other response measures. Patients with baseline color Doppler activity (n = 42 [61%]) had a worse objective PsA burden, but their chance of treatment response was comparable to those without color Doppler. CONCLUSION: More than one-third of patients with PsA presented with WP, which was associated with worse patient-reported scores and failure to achieve minimal disease activity following conventional synthetic or biologic disease-modifying antirheumatic drug therapy. PsA activity by color Doppler US had no influence on subsequent treatment response in this PsA cohort.

Association between IL-6 production in synovial explants from rheumatoid arthritis patients and clinical and imaging response to biologic treatment: A pilot study.

INTRODUCTION: The need for biomarkers which can predict disease course and treatment response in rheumatoid arthritis (RA) is evident. We explored whether clinical and imaging responses to biologic disease modifying anti-rheumatic drug treatment (bDMARD) were associated with the individual's mediator production in explants obtained at baseline. METHODS: RA Patients were evaluated by disease activity score 28 joint C-reactive protein (DAS 28-)), colour Doppler ultrasound (CDUS) and 3 Tesla RA magnetic resonance imaging scores (RAMRIS). Explants were established from synovectomies from a needle arthroscopic procedure prior to initiation of bDMARD. Explants were incubated with the bDMARD in question, and the productions of interleukin-6 (IL-6), monocyte chemo-attractive protein-1 (MCP-1) and macrophage inflammatory protein-1-beta (MIP-1b) were measured by multiplex immunoassays. The changes in clinical and imaging variables following a minimum of 3 months bDMARD treatment were compared to the baseline explant results. Mixed models and Spearman's rank correlations were performed. P-values below 0.05 were considered statistically significant. RESULTS: 16 patients were included. IL-6 production in bDMARD-treated explants was significantly higher among clinical non-responders compared to responders (P = 0.04), and a lack of suppression of IL-6 by the bDMARDS correlated to a high DAS-28 (ρ = 0.57, P = 0.03), CDUS (ρ = 0.53, P = 0.04) and bone marrow oedema (ρ = 0.56, P = 0.03) at follow-up. No clinical association was found with explant MCP-1 production. MIP-1b could not be assessed due to a large number of samples below the detection limit. CONCLUSIONS: Synovial explants appear to deliver a disease-relevant output testing which when carried out in advance of bDMARD treatment can potentially pave the road for a more patient tailored treatment approach with better treatment effects.