Optimizing drug adherence in hypertension: More than a mind game.

Poor drug adherence to prescribed drug treatments and lifestyle recommendations is a major determinant of poor blood pressure control reported around the World. Prevalence rates of antihypertensive medication nonadherence are highly variable depending on the studied population and may reach up to 40%. Remarkably, the phenomenon stays often undiagnosed and unaddressed mainly because physicians have limited tools to perform a reliable diagnosis. In this review oriented toward practicality, 5 principal aspects of nonadherence will be addressed with a special emphasis on psychological factors influencing adherence patterns, both from a patient's and physician's perspectives.

The OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (WIPE) in spondyloarthritis - reference image atlas for the knee region.

OBJECTIVE: To develop a reference image atlas for the Outcome Measures in Rheumatology whole-body MRI scoring system for inflammation in peripheral joints and entheses (OMERACT MRI-WIPE) of the knee region. METHODS: Image examples of each pathology, location and grade, were collected and discussed at web-based, interactive meetings within the OMERACT MRI in Arthritis Working Group. Subsequently, reference images were selected by consensus. RESULTS: Reference images for each grade, pathology and location are depicted, along with definitions, reader rules and recommended MRI-sequences. CONCLUSION: The atlas guides scoring whole-body MRIs for inflammation in joints and entheses of the knee region according to MRI-WIPE methodology in clinical trials and cohorts.

Hip and pelvis region MRI reference image atlas for scoring inflammation in peripheral joints and entheses according to the OMERACT-MRI WIPE scoring system in patients with spondyloarthritis.

OBJECTIVE: To develop a reference image atlas for scoring the hip/pelvis region according to the OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (MRI-WIPE). METHODS: We collected image examples of each pathology, location and grade, discussed them at web-based, interactive meetings and, finally, selected reference images by consensus. RESULTS: Reference images for each grade and location of osteitis, synovitis and soft tissue inflammation are provided, as are definitions, reader rules and recommended MRI-sequences. CONCLUSION: A reference image atlas was created to guide scoring whole-body MRIs for arthritis and enthesitis in the hip/pelvis region in spondyloarthritis/psoriatic arthritis clinical trials and cohorts.

Standardization of interstitial lung disease assessment by ultrasound: results from a Delphi process and web-reliability exercise by the OMERACT ultrasound working group.

OBJECTIVES: Over the last years ultrasound has shown to be an important tool for evaluating lung involvement, including interstitial lung disease (ILD) a potentially severe systemic involvement in many rheumatic and musculoskeletal diseases (RMD). Despite the potential sensitivity of the technique the actual use is hampered by the lack of consensual definitions of elementary lesions to be assessed and of the scanning protocol to apply. Within the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group we aimed at developing consensus-based definitions for ultrasound detected ILD findings in RMDs and assessing their reliability in dynamic images. METHODS: Based on the results from a systematic literature review, several findings were identified for defining the presence of ILD by ultrasound (i.e., Am-lines, B-lines, pleural cysts and pleural line irregularity). Therefore, a Delphi survey was conducted among 23 experts in sonography to agree on which findings should be included and on their definitions. Subsequently, a web-reliability exercise was performed to test the reliability of the agreed definitions on video-clips, by using kappa statistics. RESULTS: After three rounds of Delphi an agreement >75 % was obtained to include and define B-lines and pleural line irregularity as elementary lesions to assess. The reliability in the web-based exercise, consisting of 80 video-clips (30 for pleural line irregularity, 50 for B-lines), showed moderate inter-reader reliability for both B-lines (kappa = 0.51) and pleural line irregularity (kappa = 0.58), while intra-reader reliability was good for both B-lines (kappa = 0.72) and pleural line irregularity (kappa = 0.75). CONCLUSION: Consensus-based ultrasound definitions for B-lines and pleural line irregularity were obtained, with moderate to good reliability to detect these lesions using video-clips. The next step will be testing the reliability in patients with ILD linked to RMDs and to propose a consensual and standardized protocol to scan such patients.

Late outcomes of renal denervation are more favourable than early ones: facts or fancies?

Following second-generation randomized trials, there is evidence that renal denervation (RDN) decreases blood pressure (BP), although to a lesser extent than suggested in the initial controlled and observational studies. The recent publication of the 36-month follow-up of the Symplicity HTN-3 trial has raised expectations, suggesting increasing, late benefits of the procedure, despite initially negative results. These findings come after those obtained at 36 months in the sham-controlled trial SPYRAL HTN-ON MED and in the Global Symplicity Registry. However, they are susceptible to biases inherent in observational studies (after unblinding for sham-control) and non-random, substantial attrition of treatment groups at 36 months, and used interpolation of missing BPs. More importantly, in SPYRAL HTN-ON MED and Symplicity HTN-3, long-term BP changes in patients from the initial RDN group were compared with those in a heterogeneous control group, including both control patients who did not benefit from RDN and patients who eventually crossed over to RDN. In crossover patients, the last BP before RDN was imputed to subsequent follow-up. In Symplicity HTN-3, this particular approach led to the claim of increasing long-term benefits of RDN. However, comparison of BP changes in patients from the RDN group and control patients who did not undergo RDN, without imputation of BPs from crossover patients, does not support this view. The good news is that despite the suggestion of sympathetic nerve regrowth after RDN in some animal models, there is no strong signal in favour of a decreasing effect of RDN over time, up to 24 or even 36 months. Still, current data do not support a long-term increase in the effect of RDN and the durability of RDN-related BP reduction remains to be formally demonstrated.

Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52-week clinical and ultrasound results from the randomised, double-blind ULTIMATE trial with open label extension.

OBJECTIVES: In the ULTIMATE study with an open label extension, we assessed the long-term effect of secukinumab at tissue level on synovitis and enthesitis, and across all psoriatic arthritis (PsA) manifestations, using both clinical evaluations and power Doppler ultrasonography (PDUS). METHODS: This randomised, placebo-controlled, Phase 3 study (ULTIMATE) included biologic-naïve patients with PsA with active PDUS synovitis and clinical enthesitis, and inadequate response to conventional synthetic disease-modifying antirheumatic drugs. The study consisted of 3 treatment periods; in the first period (baseline to week 12) patients were randomised to receive subcutaneous secukinumab (150 mg or 300 mg according to severity of skin psoriasis) or placebo every week until week 4 and once every 4 weeks up to week 12. In the second period (weeks 12-24) all patients received open-label secukinumab with placebo patients switching to secukinumab (150 mg or 300 mg). The third period (weeks 24-52) was an extended open-label treatment period. The long-term responsiveness of the Global EULAR-OMERACT Synovitis Score (GLOESS), clinical enthesitis and global PDUS-detected enthesitis score (using two candidate definitions of activity) at patient level, together with clinical efficacy across key manifestations of PsA and safety were assessed. RESULTS: Of the 166 patients enrolled, 144 completed week 52. A significant reduction in GLOESS was demonstrated in the secukinumab group vs placebo at week 12, followed by a stable reduction of synovitis until week 52 in the secukinumab group while placebo switchers from week 12 reached a similar level of reduction at week 24 with stability thereafter. Likewise, a significant reduction in the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index was shown in the secukinumab group vs placebo at week 12 with sustained improvement to week 52. Global OMERACT PDUS enthesitis scores were numerically lower in secukinumab vs placebo switchers in the first two treatment periods, with some stability in the third period in both groups. Improvements in clinical responses were also observed across all key domains of PsA up to week 52 in both treatment groups with no new or unexpected safety signals. CONCLUSIONS: ULTIMATE showed consistent improvements in clinically and ultrasound-assessed synovitis and enthesitis and sustained clinical efficacy through week 52 in patients with PsA treated with secukinumab and placebo switched to secukinumab.

From Fibromuscular Dysplasia to Arterial Dissection and Back.

Fibromuscular dysplasia (FMD) is an idiopathic and systemic non-inflammatory and non-atherosclerotic arterial disease. Fifteen to 25% of patients with FMD present with arterial dissection in at least one arterial bed. Conversely, a substantial number of patients with renal, carotid, and visceral dissection have underlying FMD. Also, while few patients with FMD develop coronary artery dissection, lesions suggestive of multifocal FMD have been reported in 30-80% of patients with spontaneous coronary artery dissection (SCAD), and the relation between these two entities remains controversial. The frequent association of FMD with arterial dissection, both in coronary and extra-coronary arteries raises a number of practical and theoretical questions: (i) Are FMD and arterial dissections two different facets of the same disease or distinct though related entities? (ii) Is SCAD just a manifestation of coronary FMD or a different disease? (iii) What is the risk and which are predictive factors of developing arterial dissection in a patient with FMD? (iv) What proportion of patients who experienced an arterial dissection have underlying FMD, and does this finding influence the risk of subsequent arterial complications? In this review we will address these different questions using fragmentary, mostly cross-sectional evidence derived from large registries and studies from Europe and the United States, as well as arguments derived from demographics, clinical presentation, imaging, and when available histology and genetics. From there we will derive practical consequences for nosology, screening and follow-up.

Management of Enthesitis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Enthesitis is a key pathological and clinical feature of psoriatic arthritis (PsA) in children and adults. Enthesitis is typically assessed clinically using several validated enthesitis scoring systems that have been used in clinical trials. Enthesitis treatment response has been reported as change in the total enthesitis score or the proportion of patients who achieved complete resolution. The majority of trials in PsA did not require patients to have enthesitis at study entry since enthesitis was evaluated only as a secondary outcome. Despite the inherent limitations of the clinical assessment of enthesitis, imaging of the entheses using ultrasound or magnetic resonance imaging has rarely been used in clinical trials to assess response to treatment of enthesitis. This systematic review summarizes existing evidence regarding pharmaceutical and nonpharmaceutical interventions for enthesitis in patients with PsA to facilitate an evidence-based update of the Group for Research and Assessment in Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for PsA. METHODS: We performed a systematic literature review to identify 41 randomized clinical trials that reported enthesitis treatment response in patients with PsA. For each intervention, the response effect size was summarized and the quality of evidence was graded. Recommendations were then formulated for the various pharmacological and nonpharmacological therapies. RESULTS: We included 41 randomized clinical trials in our review and graded each intervention. CONCLUSION: Several classes of systemic conventional and advanced therapies and local measures were recommended for active enthesitis in patients with PsA.

Very low prevalence of ultrasound-detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study.

OBJECTIVES: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. METHODS: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. RESULTS: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. CONCLUSIONS: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Arthritis and enthesitis in the hip and pelvis region in spondyloarthritis - OMERACT validation of two whole-body MRI methods.

OBJECTIVE: To validate reliability, correlation and responsiveness of two whole-body MRI scores for the hip/pelvis region in spondyloarthritis. METHODS: Assessment of hip/pelvis inflammation in 4 multi-reader exercises using the OMERACT MRI Whole-body score for Inflammation in Peripheral joints and Entheses (MRI-WIPE) and Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS). RESULTS: In exercises 3-4 (11/20 cases, respectively; 9 readers) reliability was mostly good for the 3 best calibrated readers. Median pairwise single-measure ICC for status were 0.58-0.65 (WIPE-osteitis), 0.10-0.88 (HIMRISS-osteitis) and for status/change 0.38-0.72/0.52-0.60 (WIPE-synovitis/effusion) and 0.68-0.89/0.78-0.85 (HIMRISS-synovitis/effusion). SRM was 1.23 for WIPE-osteitis, while lower for WIPE-synovitis/effusion and HIMRISS. CONCLUSION: MRI-WIPE and HIMRISS may after further validation be useful in future spondyloarthritis trials.

Joint and entheseal inflammation in the knee region in spondyloarthritis - reliability and responsiveness of two OMERACT whole-body MRI scores.

OBJECTIVE: To perform region-based development of whole-body MRI through validation of knee region scoring systems in spondyloarthritis (SpA). METHODS: Assessment of knee inflammatory pathologies using 2 systems, OMERACT MRI Whole-body score for Inflammation in Peripheral joints and Entheses (MRI-WIPE) and Knee Inflammation MRI Scoring System (KIMRISS), in 4 iterative multi-reader exercises. RESULTS: In the final exercise, reliability was mostly good for readers with highest agreement in previous exercise. Median pairwise single-measure ICCs for osteitis and synovitis/effusion status/change were 0.71/0.48 (WIPE-osteitis), 0.48/0.77 (WIPE-synovitis/effusion), 0.59/0.91 (KIMRISS-osteitis) and 0.92/0.97 (KIMRISS-synovitis/effusion). SRMs were 0.74 (WIPE-synovitis/effusion) and 0.78 (KIMRISS-synovitis/effusion). CONCLUSION: MRI-WIPE and KIMRISS may both be useful in SpA whole-body evaluation studies.

Musculoskeletal Ultrasound in Systemic Lupus Erythematosus: Systematic Literature Review by the Lupus Task Force of the OMERACT Ultrasound Working Group.

OBJECTIVE: To identify and synthesize the best available evidence on the application of musculoskeletal (MSK) ultrasound (US) in patients with systemic lupus erythematosus (SLE) and to present the measurement properties of US in different elementary lesions and pathologies. METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library was performed. Original articles were included that were published in English between August 1, 2014, and December 31, 2018, reporting US, Doppler, synovitis, joint effusion, bone erosion, tenosynovitis, and enthesitis in patients with SLE. Data extraction focused on the definition and quantification of US-detected synovitis, joint effusion, bone erosion, tenosynovitis, enthesitis, and the measurement properties of US according to the OMERACT Filter 2.1 instruments selection. RESULTS: Of the 143 identified articles, 15 were included. Most articles were cross-sectional studies (14/15, 93%). The majority of the studies used the OMERACT definitions for ultrasonographic pathology. Regarding the measurement properties of US in different elementary lesions and pathologies, all studies dealt with face validity, content validity, and feasibility. Most studies achieved construct validity. Concerning the reliability of image reading, 1 study (1/15, 7%) assessed both intraobserver and interobserver reliability. For image acquisition, 4 studies (4/15, 27%) evaluated interobserver reliability and none had evaluated intraobserver reliability. Criterion validity was assessed in 1 study (1/15, 7%). Responsiveness was not considered in any of the studies. CONCLUSION: This literature review demonstrates the need for further research and validation work to define the involvement of US as an outcome measurement instrument for the MSK manifestations in patients with SLE.

Development and Validation of an OMERACT MRI Whole-Body Score for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE).

OBJECTIVE: To develop a whole-body magnetic resonance imaging (MRI) scoring system for peripheral arthritis and enthesitis. METHODS: After consensus on definitions/locations of MRI pathologies, 4 multireader exercises were performed. Eighty-three joints were scored 0-3 separately for synovitis and osteitis, and 33 entheses 0-3 separately for soft tissue inflammation and osteitis. RESULTS: In the last exercise, reliability was moderate-good for musculoskeletal radiologists and rheumatologists with previously demonstrated good scoring proficiency. Median pairwise single-measure/average-measure ICC were 0.67/0.80 for status scores and 0.69/0.82 for change scores; κ ranged 0.35-0.77. CONCLUSION: Whole-body MRI scoring of peripheral arthritis and enthesitis is reliable, which encourages further testing and refinement in clinical trials.

The OMERACT MRI in Enthesitis Initiative: Definitions of Key Pathologies, Suggested MRI Sequences, and a Novel Heel Enthesitis Scoring System.

OBJECTIVE: To develop and validate an enthesitis magnetic resonance imaging (MRI) scoring system for spondyloarthritis/psoriatic arthritis, using the heel as model. METHODS: Consensus definitions of key pathologies and 3 heel enthesitis multireader scoring exercises were done, separated by discussion, training, and calibration. RESULTS: Definitions for bone and soft tissue pathologies were agreed. In the final exercise, median pairwise single-measures intraclass correlation coefficients (ICC; patient-level) for entheseal inflammation status/change scores were 0.83/0.82 for all readers. For radiologists and selected rheumatologists, ICC were 0.91/0.84 and quadratic-weighted κ (lesion-level) 0.57-0.91/0.45-0.81. CONCLUSION: The proposed definitions and Heel Enthesitis Scoring System (HEMRIS) are reliable among trained readers and promising for clinical trials.

Overexpression of ubiquitin-specific peptidase 15 in systemic sclerosis fibroblasts increases response to transforming growth factor ß.

OBJECTIVE: Ubiquitination of proteins leads to their degradation by the proteasome, and is regulated by ubiquitin ligases and substrate-specific ubiquitin-specific peptidases (USPs). The ubiquitination process also plays important roles in the regulation of cell metabolism and cell cycle. Here, we found that the expression of several USPs is increased in SSc tenosynovial and skin biopsies, and we demonstrated that USP inhibition decreases TGF-ß signalling in primary fibroblast cell lines. METHODS: High-density transcriptomic studies were performed using total RNA obtained from SSc tenosynovial samples. Confirmatory immunostaining experiments were performed on tenosynovial and skin samples. In vitro experiments were conducted in order to study the influence of USP modulation on responses to TGF-ß stimulation. RESULTS: Tenosynovial biopsies from SSc patients overexpressed known disease-associated gene pathways: fibrosis, cytokines and chemokines, and Wnt/TGF-ß signalling, but also several USPs. Immunohistochemistry experiments confirmed the detection of USPs in the same samples, and in SSc skin biopsies. Exposure of primary fibroblast cell lines to TGF-ß induced USP gene expression. The use of a pan-USP inhibitor decreased SMAD3 phosphorylation, and expression of COL1A1, COL3A1 and fibronectin gene expression in TGF-ß-stimulated fibroblasts. The effect of the USP inhibitor resulted in increased SMAD3 ubiquitination, and was blocked by a proteasome inhibitor, thereby confirming the specificity of its action. CONCLUSION: Overexpression of several USPs, including USP15, amplifies fibrotic responses induced by TGF-ß, and is a potential therapeutic target in SSc.

Ultrasound of Subtalar Joint Synovitis in Patients with Rheumatoid Arthritis: Results of an OMERACT Reliability Exercise Using Consensual Definitions.

OBJECTIVE: To evaluate the intraobserver and interobserver reliability of the ultrasonographic (US) assessment of subtalar joint (STJ) synovitis in patients with rheumatoid arthritis (RA). METHODS: Following a Delphi process, 12 sonographers conducted an US reliability exercise on 10 RA patients with hindfoot pain. The anteromedial, posteromedial, and posterolateral STJ was assessed using B-mode and power Doppler (PD) techniques according to an agreed US protocol and using a 4-grade semiquantitative grading score for synovitis [synovial hypertrophy (SH) and signal] and a dichotomous score for the presence of joint effusion (JE). Intraobserver and interobserver reliability were computed by Cohen's and Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. RESULTS: Mean weighted Cohen's κ for SH, PD, and JE were 0.80 (95% CI 0.62-0.98), 0.61 (95% CI 0.48-0.73), and 0.52 (95% CI 0.36-0.67), respectively. Weighted Cohen's κ for SH, PD, and JE in the anteromedial, posteromedial, and posterolateral STJ were -0.04 to 0.79, 0.42-0.95, and 0.28-0.77; 0.31-1, -0.05 to 0.65, and -0.2 to 0.69; 0.66-1, 0.52-1, and 0.42-0.88, respectively. Weighted Light's κ for SH was 0.67 (95% CI 0.58-0.74), 0.46 (95% CI 0.35-0.59) for PD, and 0.16 (95% CI 0.08-0.27) for JE. Weighted Light's κ for SH, PD, and JE were 0.63 (95% CI 0.45-0.82), 0.33 (95% CI 0.19-0.42), and 0.09 (95% CI -0.01 to 0.19), for the anteromedial; 0.49 (95% CI 0.27-0.64), 0.35 (95% CI 0.27-0.4), and 0.04 (95% CI -0.06 to 0.1) for posteromedial; and 0.82 (95% CI 0.75-0.89), 0.66 (95% CI 0.56-0.8), and 0.18 (95% CI 0.04-0.34) for posterolateral STJ, respectively. CONCLUSION: Using a multisite assessment, US appears to be a reliable tool for assessing synovitis of STJ in RA.

The OMERACT Ultrasound Group: A Report from the OMERACT 2016 Meeting and Perspectives.

OBJECTIVE: To provide an update from the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group on the progress for defining ultrasound (US) minimal disease activity threshold at joint level in rheumatoid arthritis (RA) and for standardization of US application in juvenile idiopathic arthritis (JIA). METHODS: For minimal disease activity, healthy controls (HC) and patients with early arthritis (EA) who were naive to disease-modifying antirheumatic drugs were recruited from 2 centers. US was performed of the hands and feet, and scored semiquantitatively (0-3) for synovial hypertrophy (SH) and power Doppler (PD). Synovial effusion (SE) was scored a binary variable. For JIA, a Delphi approach and subsequent validation in static images and patient-based exercises were used to developed preliminary definitions for synovitis and a scoring system. RESULTS: For minimal disease activity, 7% HC had at least 1 joint abnormality versus 30% in the EA group. In HC, the findings of SH and PD were predominantly grade 1 whereas all grades were seen in the EA cohort, but SE was rare. In JIA, synovitis can be diagnosed based on B-mode findings alone because of the presence of physiological vascularization. A semiquantitative scoring system (0-3) for synovitis for both B-mode and Doppler were developed in which the cutoff between Doppler grade 2 and grade 3 was 30%. CONCLUSION: The first step has been taken to define the threshold for minimal disease activity in RA by US and to define and develop a scoring system for synovitis in JIA. Further steps are planned for the continuous validation of US in these areas.

Tendon friction rubs in systemic sclerosis: a possible explanation--an ultrasound and magnetic resonance imaging study.

OBJECTIVE: To assess the tendon and joint involvement at wrists and ankles of patients suffering from diffuse SSc and to identify the morphological substrate of tendon friction rubs (TFRs). METHODS: Fifteen consecutive patients suffering from diffuse SSc were included. All patients had two musculoskeletal US (MSUS) examinations of the wrists and ankles. MRI was performed at the most affected joints as detected by MSUS and in all sites in which TFRs were present. RESULTS: No clinically overt arthritis or tenosynovitis was detected in the wrists and/or ankles prior to MSUS. Synovitis, tenosynovitis and tendon tear were identified in 8, 4 and 2 of 15 patients, respectively, by both MSUS and MRI. At entry, 5 patients had palpable TFRs (4 bilateral and 1 unilateral) and 10 patients did not. Tenosynovitis was more frequently found in ankles with TFRs (3/9) than in those without TFRs (3/21), although the difference was not statistically different (P = 0.3). Using MRI, deep connective tissue infiltrates surrounding tendons were present in all sites with TFRs but in only one patient without TFRs. CONCLUSION: Both MSUS and MRI are effective in detecting synovitis and tenosynovitis in diffuse SSc patients. Tenosynovitis, synovitis and thickened retinacula are not infrequently seen in these patients. Our data suggest that juxta-tendinous connective tissue infiltrates might be the morphological substrate of tendon friction rubs, which may thus be a misnomer for tissue friction rubs.

Repeat kidney biopsies fail to detect differences between azathioprine and mycophenolate mofetil maintenance therapy for lupus nephritis: data from the MAINTAIN Nephritis Trial.

BACKGROUND: In the MAINTAIN Nephritis Trial, azathioprine (AZA) and mycophenolate mofetil (MMF) were compared as maintenance immunosuppressive treatment of proliferative lupus nephritis (LN) after a short-course of intravenous cyclophosphamide. Here, we compare the pathological findings on repeat kidney biopsies between the two groups. METHODS: Per protocol, repeat renal biopsies were obtained in 30 patients (16 AZA and 14 MMF) at 2 years (±6 months). Baseline and follow-up biopsies were graded according to the International Society of Nephrology/Renal Pathological Society (ISN/RPS) classification. The activity and chronicity indices (AI, CI) were calculated using two different semiquantitative scoring systems (Morel-Maroger and National Institutes of Health). Statistics were performed by non-parametric tests. RESULTS: The clinical characteristics of the 30 re-biopsied patients only marginally differ from the entire MAINTAIN cohort (105 patients). Clinical baseline and follow-up characteristics of AZA- and MMF-treated re-biopsied patients did not differ. Time (SD) to repeat renal biopsy was 25.0 (2.0) and 26.5 (3.3) months in AZA and MMF patients, respectively. More patients had normal renal biopsies or Classes I/II/V LN at follow-up compared to baseline and conversely, less patients had Class IV LN at follow-up. In both groups, the AI statistically decreased at follow-up compared to baseline, while the CI slightly, but significantly, increased. No differences could be detected between the groups. CONCLUSION: Centralized pathological analyses, including ISN/RPS classification and comparisons of AI/CI, failed to find differences between MMF and AZA at 2 years, a result well in line with the absence of difference in long-term clinical outcome reported elsewhere.