Whole-body MRI for the investigation of joint involvement in inflammatory arthritis.

OBJECTIVES: This study aimed to develop a novel whole-body MRI protocol capable of assessing inflammatory arthritis at an early stage in multiple joints in one examination. MATERIALS AND METHODS: Forty-six patients with inflammatory joint symptoms and 9 healthy volunteers underwent whole-body MR imaging on a 3.0 T MRI scanner in this prospective study. Image quality and pathology in each joint, bursae, entheses and tendons were scored by two of three radiologists and compared to clinical joint scores. Participants were divided into three groups based on diagnosis at 1-year follow-up (healthy volunteers, rheumatoid arthritis and all other types of arthritis). Radiology scores were compared between the three groups using a Kruskal-Wallis test. The clinical utility of radiology scoring was compared to clinical scoring using ROC analysis. RESULTS: A protocol capable of whole-body MR imaging of the joints with an image acquisition time under 20 min was developed with excellent image quality. Synovitis scores were significantly higher in patients who were diagnosed with rheumatoid arthritis at 12 months (p < 0.05). Radiology scoring of bursitis showed statistically significant differences between each of the three groups-healthy control, rheumatoid arthritis and non-rheumatoid arthritis (p < 0.05). There was no statistically significant difference in ROC analysis between MRI and clinical scores. CONCLUSION: This study has developed a whole-body MRI joint imaging protocol that is clinically feasible and shows good differentiation of joint pathology between healthy controls, patients with rheumatoid arthritis and patients with other forms of arthritis.

Regulation of entheseal IL-23 expression by IL-4 and IL-13 as an explanation for arthropathy development under dupilumab therapy.

OBJECTIVES: Dupilumab blocks the IL-4 receptor (IL-4R) and thus signalling of the 'Th2' cytokines IL-4 and IL-13. It has a license to treat atopic eczema and was recently linked to emergent enthesitis and psoriasis. We investigated the cellular and functional basis for how IL-4/IL-13 regulates the IL-23-IL-17 axis in entheseal stromal, myeloid and lymphocyte cells. METHODS: Immunohistochemistry was performed on healthy enthesis samples from patients undergoing elective spinal surgery to investigate entheseal tissue IL-4R expression and cytokine expression by intracellular flow cytometry for IL-4 and IL-13. Digested human enthesis samples were stimulated with lipopolysaccharide (LPS) for IL-23 induction, either alone or with IL-4 or IL-13. Enthesis fibroblasts were stimulated with TNF and IL-17 with and without IL-4 or IL-13 to assess the effect on CCL20 secretion. Synovial fluid samples from PsA patients were also analysed by ELISA for levels of IL-4 and IL-13. RESULTS: The IL-4/IL-13 receptor was present in both the peri-entheseal bone and enthesis soft tissue, and entheseal-derived T cells produced basal levels of IL-4, but not IL-13. Both IL-4 and IL-13 attenuated LPS-induced entheseal IL-23 production. IL-4 also downregulated secretion of TNF/IL-17A-induced CCL20 from entheseal fibroblasts. Both IL-13 and IL-4 were also detectable in the synovial fluid of PsA patients. We also noted a seronegative inflammatory oligoarthritis whilst under dupilumab therapy. CONCLUSION: Our findings suggest a previously unknown protective role for IL-4/IL-13 in entheseal induction of the IL-23-IL-17 axis. These findings point towards a novel explanation for IL-13 pathway single nucleotide polymorphisms in PsA and also a molecular explanation for why anti-IL-4/IL-13 therapy may induce musculoskeletal entheseal pathology as recently reported.

Receptor activator of nuclear factor kappa-Β ligand (RANKL) serum levels are associated with progression to seropositive/negative rheumatoid arthritis.

OBJECTIVES: The aim of this study was to establish whether serum RANKL levels in early inflammatory arthritis (IA) were associated with rheumatoid arthritis (RA) diagnosis at follow-up, and to evaluate the added value of RANKL for RA diagnosis. METHODS: Serum from 298 patients was collected. Demographic and clinical (swollen/tender joint counts, CRP, DAS28-CRP, RF, ACPA and shared-epitope data were recorded. Baseline ultrasound of 26 joints was performed, including total power Doppler (PD). An ELISA was used to measure RANKL. Predictors of progression were identified using multivariable logistic regression analysis. Area under the receiver operating characteristics (AUROC) was used to assess the performance of the prediction models and quantify the added value of RANKL in RA diagnosis. RESULTS: 151 patients developed RA and 147 were non-RA (undifferentiated IA, other inflammatory diagnoses or non-persistent inflammation). RANKL levels were significantly higher in RA (median [IQR]: 474.1 [270.8-1430.6]) than in non-RA (median [IQR]: 301.0 [174.1-477.5]. Three clinical factors (age, SJC and PD) were identified by multivariable logistic regression with model performance AUROC of 77.9% (95% CI 72.1-83.8%). Adding RANKL resulted in a relative increase of 6.5% in the model classification performance of an AUROC of 83.0% (95% CI 77.9-88.1%). In ACPA-negative patients, the model performance increased from 77.6% (95% CI 69.5-85.7%) with clinical data only to 81.9% (95% CI 73.7-89.8%) with added value of RANKL and imaging. CONCLUSIONS: RANKL levels can predict RA diagnosis over clinical biomarkers alone, both seropositive and particularly in seronegative IA patients.

Long-term follow-up of patients in the TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) trial.

OBJECTIVES: The TIght COntrol of inflammation in early Psoriatic Arthritis (TICOPA) study was the first strategy trial in psoriatic arthritis using an early treat-to-target strategy to improve clinical outcomes. The current study aimed to review a cohort of patients who had completed TICOPA to judge if the clinical advantage gained by participants in the tight control (TC) arm was sustained, and to explore subsequent therapy. METHODS: A case note review was conducted for a cohort of patients who had participated in TICOPA. Current drug use and clinical status were obtained, with low disease activity judged as no tender or swollen joints, no dactylitis and enthesitis, and no change in treatment required. RESULTS: Approximately five years after completion of the TICOPA study, notes were reviewed for 110 patients [TC, n = 54; standard care (StdC), n = 56]. Disease activity was found to be similar in both groups (current low disease activity: TC 69%, StdC 76%). Biologic use at the end of the study was higher in the TC arm (TC 33%, StdC 9%), but at review a similar percentage in both groups were taking biologic drugs (TC 54%, StdC 52%), whereas MTX use diminished. CONCLUSION: After several years, clinical outcomes and therapeutic drug use were similarly good for patients in both arms of the TICOPA study, with no obvious clinical advantage after TC ended. Notably, TC did not result in greater biological use long term, and MTX use decreased in both arms of the study.

MRI inflammation of the hand interosseous tendons occurs in anti-CCP-positive at-risk individuals and may precede the development of clinical synovitis.

Interosseous tendon inflammation (ITI) has been described in rheumatoid arthritis (RA). Whether ITI occurs in at-risk individuals before the onset of clinical synovitis is unknown. OBJECTIVES: To investigate, by MRI, ITI in anti-cyclic citrullinated peptide (CCP)-positive at-risk individuals (CCP +at risk) and to describe the anatomy, prevalence and clinical associations across the RA continuum. METHODS: Hand MRI was performed in 93 CCP + at risk, 47 early RA (ERA), 28 established 'late' RA (LRA) and 20 healthy controls (HC) and scored for ITI, flexor tenosynovitis (TSV) and RA MRI scoring at the metacarpophalangeal joints (MCPJs). Cadaveric and histological studies were performed to explore the anatomical basis for MRI ITI. RESULTS: The proportion of subjects with ITI and the number of inflamed interosseous tendons (ITs) increased along the disease continuum (p<0.001): 19% of CCP +at risk, 49% of ERA and 57% of LRA had ≥1 IT inflamed . ITI was not found in any HC. ITI was more frequently identified in tender MCPJs compared with nontender MCPJs (28% vs 12%, respectively). No IT tenosynovial sheath was identified in cadavers on dissection or histological studies suggesting MRI findings represent peritendonitis. Dye studies indicated no communication between the IT and the joint. CONCLUSIONS: ITI occurs in CCP + at-risk individuals and can precede the onset of clinical synovitis. The ITs may be important nonsynovial extracapsular targets in the development and progression of RA.

Validity of a two-component imaging-derived disease activity score for improved assessment of synovitis in early rheumatoid arthritis.

OBJECTIVES: Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis. METHODS: Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients). RESULTS: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood <-2.6, P < 0.01), Larsen score and presence of erosions. CONCLUSION: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10-7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.

Abatacept reduces disease activity and ultrasound power Doppler in ACPA-negative undifferentiated arthritis: a proof-of-concept clinical and imaging study.

OBJECTIVES: No proven treatment exists for ACPA-negative undifferentiated arthritis (UA). The aim of this study was to evaluate whether abatacept is effective in treating poor prognosis, ACPA-negative UA, including its effect on power Doppler on US (PDUS). METHODS: A proof-of-concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA-negative UA (⩾2 joint synovitis) and PDUS ⩾ 1 with clinical and 20-joint US (grey scale/PDUS) assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). The primary end point was a composite of the proportion of patients that at 6 months achieved DAS44 remission, a maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (over 0-12 months). RESULTS: Twenty of the 23 patients screened were enrolled [14 female; mean (sd) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary end point. A reduction in the mean (sd) DAS44 was observed from a baseline value of 2.66 (0.77) to 2.01 (0.81) at 6 months and to 1.78 (0.95) at 12 months. The DAS44 remission rates were 6/20 (30%; 95% CI: 15, 51%) at 6 months and 8/20 (40%; 95% CI: 22, 62%) at 12 months. A striking decrease in the median (interquartile range; IQR) total PDUS score was noted from 10 (4-23) at baseline to 3 (2-12) and 3 (0-5) at 6 and 12 months, respectively. CONCLUSION: This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor-prognosis, ACPA-negative UA, supported by a clear reduction in PDUS. These data justify evaluation in a controlled study.

Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: implications for the use of ultrasound within a treatment-to-target strategy.

OBJECTIVE: To assess the prevalence, relationship between and predictors of clinical and imaging remission in early RA, achieved with treat-to-target management in clinical practice. METHODS: A prospective observational study was conducted in patients with new-onset RA. The treatment target was remission by DAS28-CRP < 2.6. Twelve-month outcomes included DAS28-CRP remission, DAS44-CRP remission, ACR/EULAR Boolean remission (BR) and absent or absent/minimal power Doppler activity (PDA) on US of 26 joints (total PDA score = 0 or ⩽1, respectively). Logistic regression was conducted to identify baseline predictors of these outcomes. RESULTS: Of 105 patients with complete 12-month data, the rate of DAS28-CRP remission was 43%, DAS44-CRP remission was 39%, BR was 14%, absent PDA was 40% and absent/minimal PDA was 57%. Among patients achieving clinical remission defined by DAS28-CRP, DAS44-CRP or BR, absence of PDA was observed in 42, 44 and 40%, respectively; absent/minimal PDA was detected in 62, 66 and 67%, respectively. On multivariable analysis, shorter symptom duration, male gender, fewer tender joints and lower disability were associated with the clinical remission definitions. Lack of OA predicted absence of PDA, and lower total baseline PDA predicted absent/minimal PDA. CONCLUSION: DAS28-CRP remission and absence of PDA were observed in almost half of the patients, but less than a quarter achieved both. Achievement of BR was rare. The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis, with implications for treat-to-target management. Long-term follow-up should determine the most appropriate target.

The prevalence of tenosynovitis of the interosseous tendons of the hand in patients with rheumatoid arthritis.

AIM: The aim of this study was to establish the prevalence of tenosynovitis affecting the interosseous tendons of the hand in a rheumatoid arthritis (RA) population and to assess for association with metacarpophalangeal (MCP) joint synovitis, flexor tendon tenosynovitis or ulnar drift. METHODS: Forty-four patients with RA underwent hand MRI along with 20 normal controls. Coronal 3D T1 VIBE sequences pre- and post-contrast were performed and reconstructed. The presence of interosseous tendon tenosynovitis was recorded alongside MCP joint synovitis, flexor tendon tenosynovitis and ulnar drift. RESULTS: Twenty-one (47.7%) patients with RA showed interosseous tendon tenosynovitis. Fifty-two (14.8%) interosseous tendons showed tenosynovitis amongst the RA patients. Interosseous tendon tenosynovitis was more commonly seen in association with adjacent MCP joint synovitis (p < 0.001), but nine MCP joints (5.1%) showed adjacent interosseous tenosynovitis in the absence of joint synovitis. Interosseous tendon tenosynovitis was more frequently seen in fingers which also showed flexor tendon tenosynovitis (p < 0.001) and in patients with ulnar drift of the fingers (p = 0.01). CONCLUSION: Tenosynovitis of the hand interosseous tendons was found in 47.7% of patients with RA. In the majority of cases this was adjacent to MCP joint synovitis; however, interosseous tendon tenosynovitis was also seen in isolation. KEY POINTS: • Tenosynovitis of the interosseous tendons of the hand occurs in rheumatoid arthritis. • Interosseous tendon tenosynovitis has a prevalence of 47.7% in patients with RA. • Interosseous tendon tenosynovitis is related to MCP joint synovitis in the adjacent joints.

Whole-body MRI of patients with polymyalgia rheumatica identifies a distinct subset with complete patient-reported response to glucocorticoids.

OBJECTIVES: To determine whether whole-body MRI defines clinically relevant subgroups within polymyalgia rheumatica (PMR) including glucocorticoid responsiveness. METHODS: 22 patients with PMR and 16 with rheumatoid arthritis (RA), untreated and diagnosed by consultant rheumatologists, underwent whole-body, multiple-joint MRI, scored by two experts. Patients with PMR reported whether they felt 'back to normal' on glucocorticoid therapy and were followed for a median of 2 years. RESULTS: All patients with PMR were deemed to respond to glucocorticoids clinically. A characteristic pattern of symmetrical, extracapsular inflammation, adjacent to greater trochanter, acetabulum, ischial tuberosity and/or symphysis pubis, was observed in 14/22 of the PMR cases. In PMR, this pattern was associated with complete glucocorticoid response (p=0.01), higher pretreatment C-reactive protein (CRP) and serum interleukin-6 (IL-6), and better post-treatment fatigue and function. Only 1/14 in the extracapsular group could stop glucocorticoids within 1 year, compared with 4/7 of the others. A score derived from the five sites discriminating best between PMR and RA correlated with IL-6 (p<0.002). IL-6 levels ≥16.8 pg/mL had 86% sensitivity and 86% specificity for the extracapsular MRI pattern. CONCLUSIONS: A subset of patients with rheumatologist-diagnosed PMR had a characteristic, extracapsular pattern of MRI inflammation, associated with elevated IL-6/CRP and with complete patient-reported glucocorticoid responsiveness.

The specificity of ultrasound-detected bone erosions for rheumatoid arthritis.

BACKGROUND: Bone erosion is one of the hallmarks of rheumatoid arthritis (RA), but also seen in other rheumatic diseases. The objective of this study was to determine the specificity of ultrasound (US)-detected bone erosions (including their size) in the classical 'target' joints for RA. METHODS: Patients fulfilling the diagnostic criteria for RA, psoriatic arthritis, osteoarthritis or gout in addition to healthy volunteers were included. The following areas were examined by US: distal radius and ulna, 2nd, 3rd and 5th metacarpophalangeal (MCP), 2nd and 3rd proximal interphalangeal (PIP) and 1st and 5th metatarsophalangeal (MTP) joints. All joints were scanned in four quadrants using both semiquantitative (0-3) and quantitative (erosion diameter) scoring systems. RESULTS: 310 subjects were recruited. The inter-reader and intrareader agreements were good to excellent. US-detected bone erosions were more frequent but not specific for RA (specificity 32.9% and sensitivity 91.4%). The presence of erosions with semiquantitative score ≥2 in four target joints (2nd, 5rd MCP, 5th MTP joints and distal ulna) was highly specific for RA (specificity 97.9% and sensitivity 41.4%). Size of erosion was found to be associated with RA. Erosions of any size in the 5th MTP joint were both specific and sensitive for RA (specificity 85.4% and sensitivity 68.6%). CONCLUSIONS: The presence of US-detected erosions is not specific for RA. However, larger erosions in selected joints, especially 2nd and 5rd MCP, 5th MTP joints and distal ulna, were highly specific for and predictive of RA.

Real-world experience of IL-17Ai drug survival in a large cohort of axial spondyloarthritis and psoriatic arthritis.

Objective: The aim was to assess the use and drug survival of IL-17Ai in a real-world cohort of axial SpA (axSpA) and PsA patients. Methods: Patients ever commenced on an IL-17Ai (secukinumab or ixekizumab) for axSpA or PsA at the Leeds Specialist Spondyloarthritis Service were identified. Demographics, IL-17Ai treatment length and reason for cessation were collected. Drug survival data were plotted as a Kaplan-Meier curve, with log rank test of median survival compared between axSpA and PsA. Cox regression analysis was performed to investigate the relationship between diagnosis and length of drug survival. Results: In total, 228 patients (91 axSpA and 137 PsA) were exposed to IL-17Ai. Drug survival for all patients at 12 months was 69% (95% Confidence Interval (CI) 63, 75%) and at 24 months 60% (95% CI 54, 67%). In axSpA and PsA, drug survival at 12 months was 63% (CI 54, 74%) and 73% (CI 66, 81%), respectively, and at 24 months it was 53% (CI 44, 65%) and 65% (CI 57, 75%), respectively. Median survival did not differ significantly between both diseases (log rank test 0.65). There was no association between diagnosis and survival (hazard ratio 0.92, 95% CI 0.63, 1.33), including when adjusting for age, previous biologic DMARD usage and sex (hazard ratio 0.89, 95% CI 0.61, 1.13). Conclusion: This is the first study, to our knowledge, to analyse and compare real-world IL-17Ai drug survival in patients with axSpA and PsA from a single centre. We demonstrate that there is no difference in IL-17Ai survival rates and no relationship between diagnosis and drug survival. These results contribute to the body of real-world evidence confirming the role of IL-17Ai in the management of axSpA and PsA.

Does joint position affect US findings in inflammatory arthritis?

OBJECTIVE: Musculoskeletal US is being increasingly used for the assessment of synovitis, although questions remain about its reliability. One potential factor affecting reliability is the lack of consensus of image acquisition methods such as using different joint positions. This may have an implication on the reproducibility of studies that use US as an outcome measure. The aim of this study was to determine whether a change in joint position might significantly alter the quantification of US-detected synovitis in patients with inflammatory arthritis (IA). METHODS: IA patients with clinically swollen wrists, MCP and/or knee joints were recruited. These joints were assessed quantitatively for the presence of synovitis when they were placed in different positions. RESULTS: Seventy-five patients with IA were assessed. The greatest grey scale (GS) and power Doppler (PD) scores for the MCP joints were found in the flat (0°) position (91 and 100% of cases, respectively) compared with other positions (P < 0.001). Similar results were found in the wrist joints. The greatest GS and PD scores for the knee joint were found in 30° flexion [100 and 95.6% of cases, respectively, compared with other positions (P < 0.001)]. The inter- and intra-reader reliability was good to excellent. CONCLUSION: The position in which a joint is scanned for synovitis appears to significantly influence the US assessment of synovitis. Our study suggests that the standardized scanning of the hand joints in a flat position and the knees in a 30° position are associated with the highest GS and PD scores.

An ultrasonographic study of metatarsophalangeal joint pain: synovitis, structural pathology and their relationship to symptoms and function.

BACKGROUND: Pain in the first metatarsophalangeal joint (MTPJ) is common, though the link between pathology and symptoms is poorly understood. OBJECTIVES: To examine the relationship between pain, function and ultrasound (US)-detected pathology in the first MTPJ. METHODS: 33 subjects with first MTPJ pain and 20 asymptomatic controls completed questionnaires about pain and function, then underwent clinical examination, US examination and objective assessment of function using a motion tracking system. RESULTS: Low-level grey scale synovitis and osteophytes were common in patients and controls. Osteophytes were more prevalent in symptomatic first MTPJ [24/33 (73%) vs. 7/20 (35%), p=0.007], and greater osteophyte numbers were weakly associated with higher levels of pain [increase in pain VAS per osteophyte (95% CI)=13.78mm (0.12mm-27.43mm), p=0.048]. A power Doppler (PD) signal was present in a fifth of painful first MTPJs and absent in controls. A PD signal was associated with osteophytes and joint space narrowing but was not independently related to target joint pain. For all first MTPJs, osteophytes and the presence of a PD signal was associated with worse patient-reported function. US features did not predict objective function. CONCLUSION: Osteophytes, representing subchondral bone remodelling, were associated with the presence of first MTPJ pain and, together with more severe (PD) synovitis, also contributed to poorer function. Detailed imaging of bone may provide more information on peripheral pain associations.

Do non-steroidal anti-inflammatory drugs have a significant effect on detection and grading of ultrasound-detected synovitis in patients with rheumatoid arthritis? Results from a randomised study.

OBJECTIVES: To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) have a significant effect on ultrasonographic (US) grey scale (GS) and power Doppler (PD) assessment of synovitis in rheumatoid arthritis (RA). METHODS: Patients with RA taking NSAIDs were randomised to either stopping (for a minimum of 5 drug half-lives) or continuing the drug. All patients had a clinical assessment and US examination of both hands and wrists before and after stopping/continuing the NSAID. Changes at follow-up were compared between groups using Mann-Whitney U tests. RESULTS: A total of 58 patients with RA were recruited. All the clinical assessment parameters (including disease activity, pain, general state of health and physician global visual analogue score and tender and swollen joints count) showed an increase in the group who stopped their NSAID treatment. The total GS and PD score showed median (first to third quartiles) increase of 9.5 (5.75 to 19.0) and 4.0 (2.0 to 6.0) per patient, respectively, in the patients who stopped their NSAID in comparison with 1.0 (-1.0 to 2.25) and 0.0 (-2.0 to 3.0), respectively, in the patients who continued their NSAID (p<0.001). There was an increase in the number of joints scoring >0 for GS and PD in the patients who stopped the NSAID. The inter- and intrareader agreement was good to excellent for the US examination. CONCLUSION: NSAID usage may mask the GS and PD signal and result in lower scoring despite continuing disease activity. Consideration should be given to the NSAID effect in designing clinical studies which use US to assess response to therapeutic.