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Objective To determine the effect of a multidisciplinary lifestyle program in patients with RA with low–moderate disease activity. Methods In the ‘Plants for Joints’ (PFJ) parallel-arm, assessor-blind randomized controlled trial, patients with RA and 28-joint DAS (DAS28) ≥2.6 and ≤5.1 were randomized to the PFJ or control group. The PFJ group followed a 16-week lifestyle program based on a whole-food plant-based diet, physical activity and stress management. The control group received usual care. Medication was kept stable 3 months before and during the trial whenever possible. We hypothesized that PFJ would lower disease activity (DAS28). Secondary outcomes included anthropometric, metabolic and patient-reported measures. An intention-to-treat analysis with a linear mixed model adjusted for baseline values was used to analyse between-group differences. Results Of the 83 people randomized, 77 completed the study. Participants were 92% female with mean (s.d.) age of 55 (12) years, BMI of 26 (4) kg/m2 and mean DAS28 of 3.8 (0.7). After 16 weeks the PFJ group had a mean 0.9-point greater improvement of DAS28 vs the control group (95% CI 0.4, 1.3; P Conclusion The 16-week PFJ multidisciplinary lifestyle program substantially decreased disease activity and improved metabolic status in people with RA with low–moderate disease activity. Trial Registration International Clinical Trials Registry Platform; https://www.who.int/clinical-trials-registry-platform; NL7800.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/., The 'MHC-I (major histocompatibility complex class I)-opathy' concept describes a family of inflammatory conditions with overlapping clinical manifestations and a strong genetic link to the MHC-I antigen presentation pathway. Classical MHC-I-opathies such as spondyloarthritis, Behçet's disease, psoriasis and birdshot uveitis are widely recognised for their strong association with certain MHC-I alleles and gene variants of the antigen processing aminopeptidases ERAP1 and ERAP2 that implicates altered MHC-I peptide presentation to CD8+T cells in the pathogenesis. Progress in understanding the cause and treatment of these disorders is hampered by patient phenotypic heterogeneity and lack of systematic investigation of the MHC-I pathway.Here, we discuss new insights into the biology of MHC-I-opathies that strongly advocate for disease-overarching and integrated molecular and clinical investigation to decipher underlying disease mechanisms. Because this requires transformative multidisciplinary collaboration, we introduce the EULAR study group on MHC-I-opathies to unite clinical expertise in rheumatology, dermatology and ophthalmology, with fundamental and translational researchers from multiple disciplines such as immunology, genomics and proteomics, alongside patient partners. We prioritise standardisation of disease phenotypes and scientific nomenclature and propose interdisciplinary genetic and translational studies to exploit emerging therapeutic strategies to understand MHC-I-mediated disease mechanisms. These collaborative efforts are required to address outstanding questions in the etiopathogenesis of MHC-I-opathies towards improving patient treatment and prognostication.

Objectives To assess whether (i) high-intensity resistance training (RT) leads to increased muscle strength compared to low-intensity RT in patients with knee osteoarthritis (OA); and (ii) RT with vitamin D supplementation leads to increased muscle strength compared to placebo in a subgroup with vitamin D deficiency. Design Randomized controlled trial Setting Outpatient rehabilitation centre Subjects Patients with knee OA Interventions 12 weeks of RT at high-intensity RT (70–80% of 1-repetition maximum (1-RM)) or low-intensity RT (40–50% of 1-RM) and 24 weeks of vitamin D (1200 International units vitamin D3 per day) or placebo supplementation. Main measures Primary outcome measure was isokinetic muscle strength. Other outcome measure for muscle strength was the estimated 1-RM. Secondary outcome measures were knee pain and physical functioning. Results 177 participants with a mean age of 67.6 ± 5.8 years were included, of whom 50 had vitamin D deficiency. Isokinetic muscle strength (in Newton metre per kilogram bodyweight) at start, end and 24 weeks after the RT was 0.98 ± 0.40, 1.11 ± 0.40, 1.09 ± 0.42 in the high-intensity group and 1.02 ± 0.41, 1.15 ± 0.42, 1.12 ± 0.40 in the low-intensity group, respectively. No differences were found between the groups, except for the estimated 1-RM in favour of the high-intensity group. In the subgroup with vitamin D deficiency, no difference on isokinetic muscle strength was found between the vitamin D and placebo group. Conclusions High-intensity RT did not result in greater improvements in isokinetic muscle strength, pain and physical functioning compared to low-intensity RT in knee OA, but was well tolerated. Therefore these results suggest that either intensity of resistance training could be utilised in exercise programmes for patients with knee osteoarthritis. No synergistic effect of vitamin D supplementation and RT was found, but this finding was based on underpowered data.

Background: Pain is common in hand osteoarthritis (OA) and multiple types may occur. We investigated the prevalence, associated patient characteristics, influence on health-related quality of life (HR-QoL) and response to anti-inflammatory treatment of neuropathic-like pain in inflammatory hand OA. Methods: Data were analysed from a 6-week, randomized, double-blind, placebo-controlled trial investigating prednisolone treatment in 92 patients with painful inflammatory hand OA. Neuropathic-like pain was measured with the painDETECT questionnaire. Associations between baseline characteristics and baseline neuropathic-like pain were analysed with ordinal logistic regression, association of baseline neuropathic-like pain symptoms with baseline HR-QoL with linear regression, painDETECT and visual analogue scale (VAS) change from baseline to week 6 and interaction of painDETECT with prednisolone efficacy on VAS pain change from baseline to week 6 with generalized estimating equations (GEE). Results: Of 91 patients (79% female, mean age 64) with complete painDETECT data at baseline, 53% were unlikely to have neuropathic-like pain, 31% were indeterminate and 16% were likely to have neuropathic-like pain. Neuropathic-like pain was associated with female sex, less radiographic damage and more comorbidities. Patients with neuropathic-like pain had lower HR-QoL (PCS-6.5 [95% CI −10.4 to −2.6]) than those without. Neuropathic-like pain symptoms remained under prednisolone treatment and no interaction was seen between painDETECT and prednisolone efficacy on VAS pain. Conclusions: In this study, 16% of inflammatory hand OA patients had neuropathic-like pain. They were more often female, had more comorbidities and had lower QoL than those without. Neuropathic-like pain symptoms remained despite prednisolone treatment and did not seem to affect the outcome of prednisolone treatment. Significance: Pain is the dominant symptom in hand OA, with an unclear aetiology. In this study, we found that neuropathic-like pain may play a role in hand OA, that it showed associations with female sex, younger age and more comorbidities and that it lowered health-related quality of life in hand OA. Neuropathic-like pain in hand OA seems resistant to prednisolone therapy but did not seem to interfere with the treatment of inflammatory pain with prednisolone.

Background Several mobile apps that monitor symptoms of rheumatoid arthritis (RA) exist, but a recent systematic review indicated that high-quality apps are lacking. When patients self-monitor their own disease with patient-reported outcomes (PROs) and self-initiate care at the right moment, it may be possible to reduce the frequency of their clinic visits, which would reduce health care burden and costs. We developed an app, that is, the MijnReuma Reade app, for this purpose and performed 2 pilot tests with weekly self-monitoring. Objective The primary objective of this study was to design, develop, and evaluate the usability, satisfaction, and usage of the MijnReuma Reade app—an app that allows patients with RA to monitor their own disease. The secondary objective was to review the patients’ perspectives on app usage and its intended purpose. Methods This app was designed in collaboration with patients with RA, rheumatologists, and information technology experts. Two 1-month pilot studies were performed, after which satisfaction (0-10 scale), usability (system usability scale, 0-100), and usage (proportion of completed questionnaires) of this app were assessed. After the second pilot study, semistructured interviews were performed to determine patients’ perspectives and the promoters and barriers of app usage. Results In the first and second pilot study, 42 and 27 patients were included, respectively. Overall, the patients were satisfied (medians, 8 and 7) and found the app usable (mean system usability scores, 76 and 71) in pilot studies 1 and 2, respectively. App usage declined over time in both the pilot studies; 61% (17/28) and 37% (10/27) of the patients who disclosed their usage statistics completed the final weekly questionnaire in pilot study 1 and pilot study 2, respectively. Approximately 81% (25/31) of the patients indicated they would like to skip hospital visits if the self-monitored disease activity is low. In the semistructured interviews, technical problems, internal resistance (respondent fatigue, the app reminded them of their disease), and a lack of symptoms were identified as barriers for usage. Patients reported that “experiencing more grip on their disease” and “improved communication with their physician” were promoters for usage. Patients reported that pain positively mediated usage, that is, more pain promoted and less pain discouraged app usage. Conclusions This study illustrates the feasibility of the MijnReuma Reade app that enables self-monitoring of the disease activity in patients with RA with the overarching aim to allocate clinical consultations according to need. Satisfaction with the app and usability of the app were found to be high; however, app usage declined over time. Patients acknowledged the potential of the app to self-monitor their own disease and would like to be able to skip clinic visits if the monitored disease activity is low. To evaluate this strategy, a randomized controlled trial is underway.

Behçet's syndrome (BS) is a systemic vasculitis with heterogeneous clinical presentation and a relapsing disease course. The International Study Group (ISG) criteria are most often used for classification. A significant proportion of patients is classified as probable BS because they do not fulfil the criteria at initial presentation. The aim of this study is to explore clinical BS symptoms present at initial patient visit predictive of ISG criteria diagnosis during follow-up.Patients classified as probable BS at initial visit were included. Follow-up ISG status (defined as meeting criteria ISG+ vs. not meeting criteria ISG-) was abstracted from last visit. Univariable logistic regression was used to screen initial visit clinical features and symptoms with follow-up ISG status. All variables that passed screening at p0.10 were included in the final multivariable model, which was then used to create a probability risk score.189 patients were included (169 from New York and 20 from Amsterdam). 71 (37.6%) patients were classified as ISG+ during follow-up. In the final model, presence of morning stiffness, genital ulcers, skin lesions, and eye disease were associated with increased odds of ISG+, adjusting for age, symptom duration and family history. This was used to create a probability risk score.Over a third of patients with suspected or probable BS developed new manifestations over time that led to classification as ISG+ BS. The presence of morning stiffness, genital ulcers, skin lesions and eye disease at initial visit were independently associated with significantly higher odds for developing ISG+ Behçet's during follow-up.

BACKGROUND Several mobile apps that monitor symptoms of rheumatoid arthritis (RA) exist, but a recent systematic review indicated that high-quality apps are lacking. When patients self-monitor their own disease with patient-reported outcomes (PROs) and self-initiate care at the right moment, it may be possible to reduce the frequency of their clinic visits, which would reduce health care burden and costs. We developed an app, that is, the MijnReuma Reade app, for this purpose and performed 2 pilot tests with weekly self-monitoring. OBJECTIVE The primary objective of this study was to design, develop, and evaluate the usability, satisfaction, and usage of the MijnReuma Reade app—an app that allows patients with RA to monitor their own disease. The secondary objective was to review the patients’ perspectives on app usage and its intended purpose. METHODS This app was designed in collaboration with patients with RA, rheumatologists, and information technology experts. Two 1-month pilot studies were performed, after which satisfaction (0-10 scale), usability (system usability scale, 0-100), and usage (proportion of completed questionnaires) of this app were assessed. After the second pilot study, semistructured interviews were performed to determine patients’ perspectives and the promoters and barriers of app usage. RESULTS In the first and second pilot study, 42 and 27 patients were included, respectively. Overall, the patients were satisfied (medians, 8 and 7) and found the app usable (mean system usability scores, 76 and 71) in pilot studies 1 and 2, respectively. App usage declined over time in both the pilot studies; 61% (17/28) and 37% (10/27) of the patients who disclosed their usage statistics completed the final weekly questionnaire in pilot study 1 and pilot study 2, respectively. Approximately 81% (25/31) of the patients indicated they would like to skip hospital visits if the self-monitored disease activity is low. In the semistructured interviews, technical problems, internal resistance (respondent fatigue, the app reminded them of their disease), and a lack of symptoms were identified as barriers for usage. Patients reported that “experiencing more grip on their disease” and “improved communication with their physician” were promoters for usage. Patients reported that pain positively mediated usage, that is, more pain promoted and less pain discouraged app usage. CONCLUSIONS This study illustrates the feasibility of the MijnReuma Reade app that enables self-monitoring of the disease activity in patients with RA with the overarching aim to allocate clinical consultations according to need. Satisfaction with the app and usability of the app were found to be high; however, app usage declined over time. Patients acknowledged the potential of the app to self-monitor their own disease and would like to be able to skip clinic visits if the monitored disease activity is low. To evaluate this strategy, a randomized controlled trial is underway.

Background Telemedicine based on self-measurement of disease activity could be one of the key components to create the health care system of the future. Previous publications in various medical fields have shown that it is possible to safely telemonitor patients while reducing the number of outpatient clinic visits. For this purpose, we developed a mobile phone app for patients with rheumatoid arthritis (RA), which allows them to self-monitor their disease. Objective The objective of this study is to assess the safety and efficacy of self-initiated care assisted by a smartphone app in patients with RA. Methods This is a randomized controlled trial that will be performed for 1 year. A total of 176 patients with RA will be randomized to either self-initiated care with only one scheduled follow-up consultation assisted by our app or usual care. The coprimary outcome measures are the number of outpatient clinic consultations with a rheumatologist taking place during the trial period and the mean disease activity score as measured by the disease activity score 28 (DAS28) at 12 months. The secondary outcomes are patient satisfaction, adherence, patient empowerment, and cost evaluation of health care assisted by the app. Results Recruitment started in May 2019, and up to 18 months will be required for completion of recruitment. Thus far, 78 patients have been randomized, and thus far, experiences with the app have been positive. The study results are expected to be published by the end of 2021. Conclusions The completion of this study will provide important data regarding the following: (1) safety of self-initiated care supported by a smartphone app in terms of DAS28 and (2) efficacy of lowering health care usage with this new strategy of providing health care. Trial Registration Netherlands Trial Register NL7715; https://www.trialregister.nl/trial/7715 International Registered Report Identifier (IRRID) DERR1-10.2196/15105

Background:Pain is a common, difficult to manage symptom in hand osteoarthritis (OA). Multiple pain mechanisms may play a role in hand OA.Objectives:To investigate presence of neuropathic pain symptoms in patients with inflammatory hand OA, characteristics of those patients, their impact on health related quality of life (HR-QoL), and the influence of anti-inflammatory treatment on neuropathic pain symptoms.Methods:Data from a randomised, double-blind, placebo-controlled trial of prednisolone including 92 patients with hand OA fulfilling ACR criteria were used. At baseline patients had signs of synovial inflammation, a VAS finger pain of ≥30 mm and who flared ≥20 mm upon NSAID washout. The primary endpoint was VAS finger pain (0-100) at week 6.Neuropathic pain symptoms were measured at baseline and week 6 using the validated painDETECT questionnaire, consisting of questions on pain quality, pain intensity over time and radiating pain. Scores range -1 to 38 and patients are classified as having unlikely (18) neuropathic pain. HR-QoL was measured with physical component scale (PCS) of Short-Form 36 (SF36; 0-100), comorbidities with the Self-administered Comorbidities Questionnaire (SCQ; 0-45), radiographic severity with Kellgren-Lawrence (KL) sum score (0-120), and treatment response with OMERACT-OARSI responder criteria.Association of patient characteristics with neuropathic pain symptoms was analysed with univariate and multivariate ordinal logistic regression, with painDETECT as dependent variable. Association of neuropathic pain symptoms with HR-QoL was analysed with multivariate linear regression, adjusted for age, sex, BMI, VAS finger pain, SCQ score and KL sum score, with PCS as dependent variable. Response of neuropathic pain symptoms and VAS pain to prednisolone was analysed with generalised estimating equations. Association of neuropathic pain symptoms at baseline with response to treatment was analysed using χ2-tests and GEE.Results:91 patients had complete painDETECT data at baseline (mean painDETECT score 12.8 [SD 5.9]). Scores were 18 in 16%. Higher painDETECT score categories were associated with less radiographic damage, more comorbidities, female sex and higher VAS finger pain in multivariate analysis. (table 1)Table 1.Ordinal logistic regression with painDETECT categories as dependent variableVariablesMean (SD) N=91 (100%)Odds ratio (95% CI)Age64 (9)0.96 (0.90 to 1.02)Female sex; N (%)72 (79%)3.84 (1.19 to 12.39)*BMI; median (SD)27 (24 to 29)0.97 (0.89 to 1.06)SCQ score; median (SD)2 (1 to 5)1.04 (1.04 to 1.36)*VAS finger pain53.8 (2.1)1.02 (1.00 to 1.04)*KL sum score37 (16)0.96 (0.93 to 1.00)**pPatients with painDETECT scores >18 had a lower HR-QoL (PCS -6.5 [95%CI -10.4 to -2.6]) than those with painDETECT scores PainDETECT scores remained unchanged throughout the trial in both prednisolone-treated and placebo-treated patients, and there was no between-group difference at week 6. VAS pain improved more in the prednisolone group than in the placebo group (mean between-group difference -16.5 [95%CI -26.1 to -6.9]) (figure 1). No association between the presence of neuropathic pain symptoms at baseline and OMERACT-OARSI response to treatment was found.Conclusion:Patients with inflammatory hand OA and additional neuropathic pain symptoms are more often female and have more comorbidities, and report a lower QoL, than those without. Neuropathic pain symptoms seem unresponsive to anti-inflammatory therapy. Clinicians should be aware of neuropathic pain symptoms in their patients as they might benefit from additional, specific treatment.Acknowledgements:The authors thank all patients for their participation in the HOPE study, and participating rheumatologists for inclusion of patients in the HOPE study. We also thank research nurses B.A.M.J. van Schie-Geyer and S. Wongsodihardjo, and technicians J.C. Kwekkeboom and E.I.H. van der Voort, for their contributions.Disclosure of Interests:Coen van der Meulen: None declared, Lotte van de Stadt: None declared, Féline Kroon: None declared, Marion Kortekaas: None declared, Annelies Boonen Speakers bureau: Lecture for UCB; paid to department., Consultant of: Yes. Advisory board meetings at Galapagos, Eli Lilly and Abvvie; paid to department., Grant/research support from: Yes. Grants by Celgene and Abbvie; paid to department., Stefan Böhringer: None declared, Marieke Niesters: None declared, Monique Reijnierse: None declared, Frits Rosendaal: None declared, Naghmeh Riyazi: None declared, M. Starmans: None declared, Franktien Turkstra: None declared, Jende van Zeben: None declared, Cornelia Allaart: None declared, Margreet Kloppenburg Consultant of: For Abbvie, Pfizer, Levicept, GlaxoSmithKline, Merck-Serono, Kiniksa, Flexìon, Galapagos, Jansen, CHDR and local investigator of industry-driven trial (Abbvie). All fees were paid to the institution., Grant/research support from: Grant by the Dutch Arthritis Society

Purpose: Exercise therapy with a focus on muscle strengthening has proven to be effective for the management of knee osteoarthritis (OA). Yet it is not known whether high-intensity resistance training (RT) is more effective in improving upper leg muscle strength and physical performance than low-intensity RT. Still, there is some controversy regarding the effectiveness of high-intensity RT and whether or not it is harmful, for instance by accelerating cartilage degeneration, osteophyte formation, or increasing synovitis. Any catabolic or anabolic response of musculoskeletal tissue to RT might first be visible on a biochemical level before changes in clinical symptoms are measurable. Serum biomarkers can objectively measure early biochemical changes and assess whether RT leads to a more anabolic or catabolic response. The aim of this study is to assess (i) whether high-intensity RT elicits a different response (e.g. catabolic) on systemic inflammation and musculoskeletal tissues in and surrounding the joint, including bone, cartilage, muscle, and synovial tissue compared to low-intensity RT; and (ii) whether there is an association between changes in serum levels of inflammatory and musculoskeletal tissue-derived biomarkers and improvements in clinical outcomes (performance-based tests and self-reported outcomes on pain and activity limitations).Methods: In a randomized controlled trial, 177 participants with knee OA conducted a high-intensity (70%-80% of the Repetition Maximum (1RM)) or low-intensity (40%-50% 1RM) RT program 3 times a week for 12 weeks. Measures of clinical outcomes and serum samples were collected at the start of RT (pre-intervention), after 3 months at the end of RT (post-intervention), and 6 months after RT (follow-up). As a reflection of systemic inflammation (CRP), synovitis (CRPM, C3M), bone turnover (OC, CTX-I), cartilage turnover (PRO-C2, C2M, huARGS), muscle turnover (PRO-C3, PRO-C6), and cell behaviour (col10neo) a total of eleven serum biomarkers were analysed. With the exception of CRP, which was determined with an immunoturbidimetric assay, ELISA assays were used to quantify serum levels of the other 10 serum biomarkers. The primary outcome measures are the changes in serum biomarker levels. Other outcome measures include upper leg muscle strength, performance-based tests, and self-reported outcomes on pain and activity limitations.Results: High-intensity RT resulted in greater improvements in muscle strength compared to low-intensity RT when measured by the estimated 1RM. No significant differences between groups were found for upper leg muscle strength (Nm/kg) when measured with an isokinetic dynamometer. Both groups showed similar improvements in pain and physical functioning. Although there is no difference between groups in clinical outcomes, except for the estimated 1RM, we expect that participants in the high-intensity RT group are more likely to have enhanced serum levels of catabolic biomarkers than participants in the low-intensity RT group. Since both the high-intensity RT group and low-intensity RT group improved over time, we expect that changes in serum biomarker levels are associated with overall improvements in clinical outcomes. Almost all participants had normal CRP values (Conclusions: The work to date on CRP serum levels suggests that RT did not influence CRP levels. This result may be explained by the high percentage of participants with normal CRP levels (

BACKGROUND Rising health care costs, an increasing elderly population and shortage of (medical) personnel force us to think about alternative ways to organize our health care system. Telemedicine, based on self-measurement of disease activity, could be one of the key ingredients to create the health care system of the future. Previous publications in various fields have shown that it is possible to safely telemonitor patients whilst reducing the number of outpatient clinic visits. However, evidence for patients with RA is lacking. OBJECTIVE (1) To provide an extensive description of the development and evaluation of a smartphone application (app) for self-monitoring of rheumatoid arthritis (RA) disease activity. (2) To present the study design in order to measure the safety and efficacy of self-initiated care supported with an app. METHODS Following the Medical Research Council (MRC) guidance for developing and evaluating complex interventions, the development and evaluation of the app was carried out in three distinct phases. In the first phase design requirements were set by a team of patient representatives, health care professionals and software developers, the prototype app was developed and tested in a first pilot study. The second phase consisted of building a digital care platform, through which the app was integrated with the electronic medical record, other app-improvements and a second pilot study. The third phase comprises further improvements to achieve the set design requirements and a randomized controlled trial to evaluate the efficacy of self-management supported by the developed smartphone tool. RESULTS Two pilot studies evaluated the patient satisfaction, usability and adherence to the app. The studies were performed with 42 and 24 RA patients. In the initial pilot, the app was graded with an overall score of 8.0 (IQR 7.0-9.0). The mean system usability score was 76 (SD 15) and adherence was 60%. Consequently, improvements were made, integration to the EMR was completed and the second pilot showed similar (promising) results in terms of patient satisfaction, usability and adherence. In the planned assessor blind-pragmatic randomized controlled trial, 176 RA will be randomized to self-initiated care assisted by the app with only one scheduled follow-up consultation or to usual care. The co-primary outcome measures are the number of outpatient clinic consultations with a rheumatologist that took place during the 12 months trial period and the mean disease activity score as measured by the disease activity score 28 (DAS 28) at 12 months. Secondary outcomes include patient and physician satisfaction with care, patient empowerment, patient-physician interaction and therapeutic adherence. CONCLUSIONS We have developed an app that RA patients find satisfactory and usable for self-monitoring of disease activity. If proven safe and effective with the planned randomized controlled trial, our aim is to implement this telemonitoring strategy in the Dutch health care system. CLINICALTRIAL Trial ID: NL7715 (https://www.trialregister.nl/trial/7715)

Background Exercise therapy is the cornerstone of knee osteoarthritis (OA) management. In particular muscle strengthening exercise, targeting the characteristic loss of muscle strength present in knee OA, is a key factor for the beneficial effects reported for exercise therapy. The optimal training intensity for resistance training in patients with knee OA, however, is not known to date. Besides resistance training, vitamin D supplementation in patients with vitamin deficiency may optimize muscle strength. Objectives To assess (i) whether high-intensity resistance training leads to greater improvements in muscle strength compared to moderate-intensity resistance training in patients with knee OA; and (ii) whether vitamin D supplementation in combination with strength training leads to greater improvements in muscle strength compared to placebo in combination with strength training in patients with knee OA and vitamin D deficiency (25 (OH)D level > 15 nmol/L and Methods In a randomized controlled trial, 177 patients with a clinical diagnosis of knee OA were included. All patients were randomly allocated to a high-intensity (70-80% of the Repetition Maximum (1RM)) or a moderate-intensity (40-50% of the 1RM) resistance training program of 12 weeks. Both groups were supervised by a physical therapist twice a week and performed home exercises once a week. In addition, 50 out 177 patients had vitamin D deficiency and received supplementation of vitamin D (1200 IU vitamin D3 per day) or placebo in the 12 weeks prior to and during the resistance training program. The primary outcome measure was isokinetic (60 °/s) upper leg muscle strength (Nm/kg). In addition, the estimated 1 RM for leg press, leg curl and hip abduction were used as measures for muscle strength. Other outcome measures included severity of knee pain (NRS), self-reported and performance based activity limitations (WOMAC physical functioning (WOMAC), Get-up-and-go-test (GUG)). Measurements were performed by a blinded assessor prior to the exercise program (T0), directly after the program (T12) and at 6 months follow-up (T36). Additionally, for patients with vitamin D deficiency, measurements were also taken prior to vitamin supplementation or placebo (T-12). Results Both the high-intensity group and moderate-intensity group improved in upper leg muscle strength over time. No significant differences between groups were found for isokinetic upper leg muscle strength (p = 0.646) (see figure 1). However, when measured by the estimated 1 RM, significant differences were found between groups in favor of the high–intensity group (p = 0.001) (see figure 1). No between-group differences were found on pain (p = 0.885), or on self-reported and performance-based activity limitations (WOMAC p = 0.968; GUG p = 0.800), although both groups improved (see figure 1). An unexpected finding was that, in the (small sample of) patients with vitamin D deficiency, the placebo group showed significant greater isokinetic upper leg muscle strength over time compared to the vitamin D group (p = 0.001). Conclusion No differences between groups were found for isokinetic upper leg muscle strength. With the estimated 1 RM as a measure of muscle strength, high-intensity resistance training led to greater improvements in muscle strength compared to moderate-intensity resistance training in patients with knee OA. This did not result in greater improvements in pain and physical functioning in the high-intensity resistance group; both groups showed similar clinically important improvements. The added value of vitamin D supplementation on muscle strength in knee OA patients with vitamin D deficiency need further study. Disclosure of Interests Arjan de Zwart: None declared, Joost Dekker: None declared, Leo D. Roorda: None declared, Martin van der Esch : None declared, Paul Lips: None declared, Natasja van Schoor: None declared, Annemieke Heijboer: None declared, Franktien Turkstra: None declared, Martijn Gerritsen Grant/research support from: Grunenthal has sponsored the Reade Cohort, Arja Hakkinen: None declared, Kim Bennell: None declared, Martijn Steultjens: None declared, Willem Lems Speakers bureau: Amgen Inc., Merck, Eli Lilly and Pfizer, Marike van der Leeden : None declared

Background Hand osteoarthritis (OA) is a prevalent joint disease with high disease-burden in need for effective therapeutic options. Studies have shown that synovial inflammation is often present in hand OA and a main determinant of pain and radiographic disease progression. Objectives To investigate the efficacy and safety of short-term low-dose prednisolone in patients with painful hand OA. Methods This randomised, double-blind, placebo-controlled trial enrolled patients with painful hand OA, fulfilling American College of Rheumatology criteria, and signs of synovial inflammation. Patients with ≥4 interphalangeal joints (IPJ) with osteoarthritic nodes, ≥1 IPJ with soft swelling or erythema and ≥1 IPJ with positive power Doppler signal (PDS) or synovitis grade ≥2 on ultrasound, were eligible. Key exclusion criteria were chronic inflammatory rheumatic diseases, psoriasis, using immune modulating drugs within 90 days before baseline, and predominant thumb base pain. Eligible patients with visual analogue scale (VAS) finger pain ≥30 mm, flaring ≥20 mm upon non-steroidal anti-inflammatory drug washout, were randomised to receive prednisolone 10 mg daily for 6 weeks or placebo, followed by a two-week tapering scheme and 6 weeks without study medication. Outcomes were assessed at 2, 4, 6, 8 and 14 weeks. Primary endpoint was VAS finger pain at week 6 in intention-to-treat analysis. Secondary clinical endpoints included fulfilment of OMERACT-OARSI responder criteria, Australian/Canadian Hand OA Index (AUSCAN) pain/function, Functional Index for Hand OA (FIHOA), VAS patient global assessment, Short-Form 36 and grip strength. Imaging endpoints included ultrasound synovitis and PDS. Results Of 92 patients (mean (SD) age 63.9 (8.8), 79% women) randomised to prednisolone (n=46) or placebo (n=46), 42 patients in each group completed the study. Baseline characteristics were well-balanced between the groups. The mean (SD) change from baseline to week 6 in VAS finger pain was -21.5 (21.7) in the prednisolone and -5.2 (24.3) in the placebo group, with a mean between-group difference of -16.5 (95% confidence interval (CI) -26.1 to -6.9; figure). At week 6, 33 (72%) patients in the prednisolone versus 15 (33%) in the placebo group fulfilled OARSI responder criteria (odds ratio 5.3, 95% CI 2.0 to 13.6, p=0.001). In analogy with the primary endpoint, prednisolone was superior to placebo in most other secondary clinical endpoints (table). Ultrasound synovitis significantly improved at week 6 in the prednisolone compared to the placebo group, while no difference was observed in PDS (table). After tapering, between-group differences disappeared. Adverse events were mostly mild and comparable between groups. Conclusion Six-week treatment with low-dose oral prednisolone led to a substantial improvement of symptoms in patients with painful hand OA and signs of inflammation. This trial provides evidence that local inflammation is a suitable target for drug-treatment in hand OA. Acknowledgement The HOPE study was supported by a grant from the Dutch arthritis foundation (ReumaNederland). Disclosure of Interests Feline Kroon: None declared, Marion Kortekaas: None declared, Annelies Boonen: None declared, Stefan Bohringer: None declared, Monique Reijnierse Grant/research support from: Funding from the Dutch Arthritis Foundation. The funding source had no role in the design and conduct of the study., Frits Rosendaal: None declared, Naghmeh Riyazi: None declared, Mirian Starmans: None declared, Franktien Turkstra: None declared, Jende van Zeben: None declared, Cornelia Allaart: None declared, Margreet Kloppenburg Grant/research support from: Pfizer, IMI-APPROACH (Grant Agreement n° 115770), Consultant for: GlaxoSmithKline, Merck-Serono, Abbvie, Levicept, Pfizer

Background: Several mobile applications (apps) exist to monitor symptoms of rheumatoid arthritis (RA), but high-quality apps are lacking.1 We developed an app with patients, following the Medical Research Council guidance for developing and evaluating complex interventions.2 The app facilitates telemonitoring through a weekly MDHAQ/RAPID33 questionnaire and has been integrated with the local electronic medical record. Objectives: To evaluate the users’ satisfaction, usability and engagement of the application, as a first and preparatory step toward the ultimate goal of telemonitoring and self-initiated care. Methods: In a first, one month, pilot study 42 RA patients used the app. User’s satisfaction was measured using an 11-point Likert scale. Usability was measured using the three concepts of the Technology Acceptance Model (TAM).4 According to TAM, perceived usefulness (PU), perceived ease of use (PEOU), (behavioral) intention to use (ITU) predict how and when a product will be used. The PU and PEOU were measured using the system usability scale (0-100). A score of 68, or higher, indicates sufficient system usability.5 The ITU was measured on a 11-point Likert scale. Engagement was measured by the percentage of patients completing all weekly questionnaires. General feedback was collected and implemented. In a second, one month, pilot study, the improved app was evaluated in 24 RA patients using 5 themes derived from the Mobile App Rating Score6: “engagement”, “functionality”, “aesthetics”, “information” and “subjective quality.” Participants rated the questions on a 5 - point Likert scale. All responses were categorized into three categories: negative (1-2), neutral (3) and positive (4-5). Afterwards, nine participants (three users, three dropout users, and three non-users) agreed to participate in a semi-structured interview to get feedback on the App. Results: In the first study, the ReumaMeter scored an overall median score of 8.0 (interquartile range (IQR) 7.0-9.0), a mean system usability score of 76 (SD 14.8) and participants intended to keep using the ReumaMeter in the future (median 7.0, IQR 5.0-9.0). Engagement decreased to 61% in week 4. During the second study, the number of positive responses for each category was at least twice as high as the number of negative responses (Figure 1). Feedback that emerged during the interviews matched these responses. In addition, several participants stated that app usage declined due to low disease activity. Conclusion: The participants’ overall feedback was positive in terms of users’ satisfaction and usability. Engagement dropped, which may be due to lack of internal triggers to measure disease activity when patients are in remission. To assess the overall impact of the app on RA patient care, a randomized controlled trial is planned. References [1] Grainger R, et al. JMIR Mhealth Uhealth. 2017. 2:e7. [2] Craig P., et al. BMJ. 2008. doi:10.1136/bmj.a1655 [3] Pincus, T.et.al. The Journal of Rheumatology. 2008. 35,2136-37. [4] Davis, F.D. MIS Quarterly. 1989. 13(3):319-339. [5] Bangor, A. International Journal of Human-Computer Intervction. 2008. 24(6) 574-594. [6] Stoyanov, S.R., et al. JMIR Mhealth Uhealth, 2015. 3(1): p.e27. Disclosure of Interests: Bart Seppen: None declared, Merel J. l’Ami: None declared, Sharon Rico: None declared, Marieke ter Wee Grant/research support from: Nonrestricted grant from Lilly Netherlands BV, Speakers bureau: ARC Preceptorship program, Franktien Turkstra: None declared, Leo D. Roorda: None declared, Fabio Catarinella: None declared, Dirkjan van Schaardenburg: None declared, Michael Nurmohamed Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Maarten Boers: None declared, W.H. Bos Grant/research support from: Abbvie, Sanofi, Novartis, UCB, Celgene, Roche, Speakers bureau: Abbvie, Sanofi, Eli Lilly

Background Seropositive arthralgia patients are at risk of developing rheumatoid arthritis (RA). Ultrasound (US) might be used to further predict which seropositive individuals will progress to RA. However, the value of US in the prediction of RA is still a point of debate, mainly due to the use of different scoring systems and compositions of joints in US protocols in literature. Objectives To investigate which joints are most discriminative in predicting arthritis development in seropositive arthralgia patients. Methods We included 174 seropositive patients with arthralgia, but without clinical arthritis. US was performed at baseline in 16 joints: bilateral metacarpal phalangeal (MCP) 2 and 3, proximal interphalangeal (PIP) 2 and 3, wrist and metatarsal phalangeal (MTP) joints 2, 3 and 5. Images were scored for grey-scale (GS) synovitis and Power Doppler (PD) on a scale of 0–3. Grades≥2 for GS synovitis and grades≥1 for PD were regarded as abnormal. Clinical arthritis development was assessed in any of 44 joints during yearly follow-up or during an unscheduled visit in case of progression of symptoms. Patients were followed until clinical arthritis development or for a maximum of 5 years. Results In a total of 2784 joints that were imaged, 112 showed GS synovitis and 14 PD. The majority of GS synovitis was present in MTP2 and MTP3 joints (56 (50%) and 32 (29%), respectively), followed by wrists (15 (13%)), MCP3 (4 (4%)), MTP5 (3 (3%)), MCP2 (2 (2%)) and none in PIPs. Out of 14 joints with PD, 7 were wrists, 3 MTP5, 2 MCP2 and 2 PIP3. Fifty-one (29%) of the patients developed clinical arthritis in at least one joint after a median follow-up of 12 (interquartile range 6–23) months. For GS synovitis, the wrist, MCP2 and MTP5 were most discriminative in predicting clinical arthritis development (12/15 (80%) of patients with GS synovitis in wrist developed clinical arthritis, 3/3 (100%) in MTP5 and 2/2 (100%) in MCP2). MTP2 and 3 were least discriminative ( Conclusions Wrist, MCP2 and MTP5 joints (although numbers were small) showed the highest predictive value for development of clinical arthritis in any of 44 joints. Although most GS synovitis was observed in MTP2 and 3, predictive value of MTP2 and 3 joints for development of clinical arthritis was low. These results indicate that the choice of joints in the US protocol may influence the predictive value of ultrasound in predicting clinical arthritis development in seropositive arthralgia patients. Disclosure of Interest None declared

Table S2. Association of ultrasound abnormalities with clinical arthritis development, only ACPA-positive versus ACPA-positive and RF-positive patients (patient level). (DOCX 15 kb)

Background The value of joint ultrasonography (US) in the prediction of clinical arthritis in individuals at risk of developing rheumatoid arthritis (RA) is still a point of debate, due to varying scanning protocols and different populations. We investigated whether US abnormalities assessed with a standard joint protocol can predict development of arthritis in seropositive patients with arthralgia. Methods Anti-citrullinated protein antibodies and/or rheumatoid factor positive patients with arthralgia, but without clinical arthritis were included. US was performed at baseline in 16 joints: bilateral metacarpophalangeal 2–3, proximal interphalangeal 2–3, wrist and metatarsophalangeal (MTP) joints 2–3 and 5. Images were scored semi-quantitatively for synovial thickening and for positive signs on power Doppler (PD). Association between US abnormalities and arthritis development at the joint and at the patient level was evaluated. Also, we investigated the added value of US over clinical parameters. Results Out of 163 patients who underwent US examination, 51 (31%) developed clinical arthritis after a median follow-up time of 12 (interquartile range 5–24) months, of which 44 (86%) satisfied the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA. US revealed synovial thickening and PD in at least one joint in 49 patients (30%) and 7 patients (4%), respectively. Synovial thickening was associated with both development and timing of clinical arthritis in any joint (patient level) when MTP joints were excluded from the US assessment (odds ratio 6.6, confidence interval (CI) 1.9–22), and hazard ratio 3.4, CI 1.6–6.8, respectively, with a mean time to arthritis of 23 versus 45 months when synovial thickening was present versus not present). There was no association between US and arthritis development at the joint level. Predictive capacity was highest in the groups with an intermediate and high risk of developing arthritis based on a prediction rule with clinical parameters. Conclusions Synovial thickening on US predicted clinical arthritis development at the patient level in seropositive patients with arthralgia when MTPs were excluded from the US assessment. Positive PD signs were infrequently seen in these at-risk individuals and was not predictive. In patients at intermediate risk of RA, US may help to identify those at higher risk of developing arthritis. Electronic supplementary material The online version of this article (10.1186/s13075-018-1767-9) contains supplementary material, which is available to authorized users.

Table S1. Association of ultrasound abnormalities with clinical arthritis development, ACPA-positive versus ACPA-negative patients (patient level). (DOCX 14 kb)

To assess adherence to published guidelines for the treatment of Behçet's syndrome (BS) in two geographic areas.We extracted guideline statements from the 2008 EULAR recommendations. Adherence to these statements was evaluated retrospectively in both New York (USA) and Amsterdam (The Netherlands), by reviewing records from patients fulfilling the ISG criteria. We analysed data per statement and event, and divided data according to the year in which an event occurred. We compared events prior to 2009 to those after publication of the EULAR recommendations (2009 and later).474 patients were evaluated, 24 of whom were from Amsterdam. Treatment adherence varied substantially across various Behçet's manifestations, ranging from 21% vs. 31% in posterior uveitis, 50% vs. 25% in arterial disease, 29% vs. 29% in arthritis and 38% vs. 55% in erythema nodosum to 65% vs. 67% in deep venous thrombosis (DVT), before and after publication of the guidelines respectively. Topical treatment of mucocutaneous disease was only 2% vs. 8%, whereas adherence in neuro-Behçet was ≥ 94% and 100% in gastrointestinal disease.Adherence to treatment guidelines varies substantially by Behçet's manifestation. Lack of adherence in manifestations such as eye disease and arthritis suggests that current recommendations are not sufficient or other concurrent manifestations require more aggressive treatment. The extensive use of anti-TNF agents might indicate a shift towards more aggressive treatment. Thus, our results suggest the 2008 guidelines were not in line with treatment in clinical practice over the past years and the recent revision of the recommendations was indeed needed.

Objective.To determine whether macrophage targeting by (R)-11C-PK11195 positron emission tomography (PET) can visualize subclinical joint inflammation in patients with rheumatoid arthritis (RA) without clinical arthritis during or after treatment, with flare as clinical outcome measure.Methods.(R)-11C-PK11195 PET and contrast-enhanced magnetic resonance imaging (MRI) of hands/wrists were performed in 29 patients with RA without clinical arthritis. (R)-11C-PK11195 PET uptake (semiquantitative score 0–3) in metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22 joints per patient) was scored and summed to obtain a cumulative PET score (range 0–66). Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) was performed on similar joints. Synovitis and bone marrow edema scores (> 1) were summed to obtain a cumulative MRI score (range 0–288). Occurrence of flare was determined during 3-year followup.Results.Flare was observed in 17/29 patients (59%). (R)-11C-PK11195 PET showed enhanced tracer uptake in 16/29 patients (55%), of which 11 (69%) developed a flare. Highest cumulative PET scores (> 6, n = 3) corresponded with highest cumulative MRI scores (> 39) and were related to development of flare in hands/wrists within 6 months. Cumulative PET scores of patients developing a flare were higher than those of patients without a flare [median (interquartile range) 2 (0–4.5) vs 0 (0–1), p < 0.05]. In contrast, no significant differences were found between cumulative MRI scores of patients with and without a flare.Conclusion.(R)-11C-PK11195 PET showed enhanced uptake, pointing to presence of subclinical synovitis in over half of patients without clinical arthritis. (R)-11C-PK11195 PET may be of value for prediction of exacerbation of RA, since cumulative PET scores > 1 were associated with development of flare within 3 years.

Introduction: Ultrasonography (US) has better sensitivity than clinical evaluation for the detection of synovitis in early rheumatoid arthritis (RA). Patients presenting with arthralgia and a positive anti-citrullinated protein antibodies (ACPA) and/or Rheumatoid Factor (IgM-RF) status are at risk for developing RA. In the present study, US utility and predictive properties in arthralgia patients at risk for the development of arthritis were studied. Methods: 192 arthralgia patients with ACPA and/or IgM-RF were included. Absence of clinical arthritis was confirmed by two physicians. US was performed by one of two trained radiologists of any painful joint, and of adjacent and contralateral joints. Joint effusion, synovitis and power Doppler (PD) signal in the synovial membrane of the joints and tenosynovitis adjacent to the joint were evaluated and classified on a 4-grade semi-quantitative scale. Grade 2-3 joint effusion, synovitis, tenosynovitis and grade 1-3 Power Doppler signal were classified as abnormal. Results: Forty-five patients (23%) developed arthritis after a mean of 11 months. Inter-observer reliability for synovitis and PD was moderate (kappa 0.46, and 0.56, respectively) and for joint effusion low (kappa 0.23). The prevalence of tenosynovitis was too low to calculate representative kappa values. At joint level, a significant association was found between US abnormalities and arthritis development in that joint for joint effusion, synovitis and PD. At patient level, a trend was seen towards more arthritis development in patients who had US abnormalities for joint effusion, synovitis, PD and tenosynovitis. Conclusions: US abnormalities were associated with arthritis development at joint level, although this association did not reach statistical significance at patient level. US could potentially be used as a diagnostic tool for subclinical arthritis in seropositive arthralgia patients. However, further research is necessary to improve test characteristics.

In this case report, we describe a patient with longstanding rheumatoid arthritis who developed tracheobronchomalacia with fatal outcome. Despite negative antemortem biopsies of abdominal fat and tongue, amyloid was found postmortem in the trachea and appeared to be associated with tracheobronchomalacia.