Subclinical joint inflammation in rheumatoid arthritis: comparing thermal and ultrasound imaging at the metacarpophalangeal joint.

BACKGROUND: While ultrasound and MRI are both superior to clinical examination in the detection of joint inflammation, there is presently a lack of data whether thermography may be similarly useful in the assessment of joint inflammation in patients with RA. Our study aims to evaluate the use of thermography in detecting subclinical joint inflammation at clinically quiescent (non-tender and non-swollen) metacarpophalangeal joints (MCPJs) in patients with rheumatoid arthritis (RA). The outcomes from thermography in our study will be compared with ultrasonography (which is a more established imaging tool used for joint inflammation assessment in RA). METHODS: The minimum (Tmin), average (Tavg) and maximum (Tmax) temperatures at the 10 MCPJs of each patient were summed to obtain the Total Tmin, Total Tavg and Total Tmax, respectively. Ultrasound grey-scale (GS) and power Doppler (PD) joint inflammation (scored semi-quantitatively, 0-3) at the 10 MCPJs were summed up to derive the respective TGS and TPD scores per patient. Pearson's correlation and simple linear regression were respectively used to assess correlation and characterize relationships between thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TGS, TPD and the number of joint(s) with PD ≥ 1 or GS ≥ 2). RESULTS: In this cross-sectional study, 420 clinically non-swollen and non-tender MCPJs from 42 RA patients were examined. All thermographic parameters (Total Tmin, Total Tavg and Total Tmax) correlated significantly (P-values ranging from 0.001 to 0.0012) with TGS score (correlation coefficient ranging from 0.421 to 0.430), TPD score (correlation coefficient ranging from 0.383 to 0.424), and the number of joint(s) with PD ≥ 1 or GS ≥ 2 (correlation coefficient ranging from 0.447 to 0.465). Similarly, simple linear regression demonstrated a statistically significant relationship (P-values ranging from 0.001 to 0.005) between all thermographic parameters (Total Tmin, Total Tavg and Total Tmax) and ultrasound imaging parameters (TPD and TGS). CONCLUSION: For the first time, thermographic temperatures were shown to correlate with ultrasound-detected joint inflammation at clinically quiescent MCPJs. The use of thermography in the detection of subclinical joint inflammation in RA appears promising and warrants further investigation.

Thermography at the Elbow Among Patients with Rheumatoid Arthritis: A Comparison with Ultrasound-Detected Joint Inflammation Findings.

INTRODUCTION: There is a lack of data on the use of thermography for elbow joint inflammation assessment among patients with rheumatoid arthritis (RA). Hence, we aimed to compare thermography with ultrasonography (a more established imaging modality for joint inflammation assessment) in the assessment of inflammation in the elbows of patients with RA. METHODS: Standardised minimum (Tmin), maximum (Tmax) and average (Tavg) temperatures at each elbow (medial, lateral, posterior and anterior aspects) were summed to obtain the thermographic parameters MIN, MAX and AVG, respectively. Ultrasound parameters of elbow joint inflammation included total greyscale (TGS) and total power Doppler (TPD) scores. Pearson's correlation coefficient was utilized for correlation analysis between parameters. The relationship between parameters was characterized using simple linear regression. RESULTS: Sixty elbows were evaluated from 30 patients with RA in this cross-sectional study. Thermographic parameters (MIN, MAX and AVG) showed significant correlation (P < 0.05) with (1) TPD scores at both elbows (correlation coefficient ranging 0.40 to 0.55) and (2) TGS scores at the right elbow (correlation coefficient ranging 0.39 to 0.42). A statistically significant relationship (P values ranging from 0.002 to 0.033) between parameters was demonstrable as follows: (1) MIN, MAX and AVG versus TPD scores (bilateral elbows) and (2) MIN, MAX and AVG versus TGS scores (right elbow). CONCLUSION: Thermographic temperatures have been demonstrated to correlate with ultrasound-detected joint inflammation at the elbow in patients with RA. The association is more consistently observed with ultrasound PD joint inflammation than its GS counterpart.

Assessment of joint inflammation at the wrist of patients with rheumatoid arthritis: thermography findings closely mirror those from ultrasonography.

OBJECTIVES: To determine if thermography (in comparison with ultrasonography) may be helpful in detecting joint inflammation at the RA wrist categorised according to its clinical manifestations. METHODS: Four wrist groups were derived from the right wrist of RA subjects as follows: (1) swollen; tender (S1T1); (2) swollen; non-tender (S1T0); (3) non-swollen; tender (S0T1); (4) non-swollen; non-tender (S0T0). Thermographic parameters included the maximum (Tmax), average (Tavg) and minimum (Tmin) temperatures. Ultrasound parameters included the Total PD (TPD) and Total GS (TGS) scores. One-way ANOVA and Kruskal-Wallis test (for normally and non-normally distributed imaging parameters, respectively) and subsequent post-hoc tests were carried out for the comparative analysis of the wrist groups. RESULTS: A total of 70 wrist joints of 70 RA subjects were included in this cross-sectional study. For all imaging parameters (Tmax, Tavg, Tmin, TPD and TGS), statistically significant differences (all p<0.05) were detected (a) between the 4 wrist groups using either the one-way ANOVA or Kruskal-Wallis test and (b) for subsequent pairwise comparison of wrist group 1 (S1T1) vs. group 4 (S0T0) and group 2 (S1T0) vs. group 4 (S0T0). No significant differences (all p>0.05) were found for pairwise comparison of wrist group 3 (S0T1) vs. group 4 (S0T0) for all imaging parameters. CONCLUSIONS: Thermography at the wrist appears promising in RA with its findings closely mirroring those from ultrasonography. Swollen joints (regardless of tenderness status) have higher joint surface temperatures and greater ultrasound-detected joint inflammation, findings which were not observed for tender only (non-swollen) joints.

An update on thermal imaging in rheumatoid arthritis.

This review aims to summarise the recent literature concerning the usage of thermal imaging in the study of rheumatoid arthritis (RA). Most RA studies have applied thermal imaging as a static process alone although thermal imaging has been conducted with an additional dynamic/functional component. Algorithms to automate the analysis of thermal imaging in RA have also been described. Several RA thermal imaging studies have demonstrated differences in thermographic findings between RA patients and healthy controls and/or compared thermographic parameters with other clinical/functional/imaging parameters; while fewer studies have assessed the role of thermal imaging in discriminating disease severity in RA. Thermal imaging is a relatively low cost, non-invasive imaging technique offering an objective measurement of joint surface temperature in RA joint inflammation assessment. Although there has been an increasing literature build up on the use of thermography in RA, more validation work is still necessary to delineate the potential role(s) of its use among patients with RA. This timely review focusses on the recent literature concerning thermal imaging, and provides clinicians with an update on its recent development in RA.

Receiver operating characteristic analysis using a novel combined thermal and ultrasound imaging for assessment of disease activity in rheumatoid arthritis.

We aim to determine whether combined thermal and ultrasound (CTUS) imaging can identify rheumatoid arthritis (RA) patients with at least moderate disease activity (DAS28 > 3.2). Temperature differences of maximum (Tmax), average (Tavg) and minimum (Tmin) temperatures from a control temperature at 22 joints (bilateral hands) were summed up to derive the respective MAX, AVG and MIN per patient. MAX (PD), AVG (PD) and MIN (PD) are CTUS results derived by multiplying MAX, AVG and MIN by a factor of 2 when a patient's total ultrasound power Doppler (PD) joint inflammation score > median score, which otherwise remained unchanged. Receiver operating characteristic (ROC) analysis was used to determine whether CTUS imaging can identify patients with DAS28 > 3.2. In this cross-sectional study, 814 joints were imaged among 37 RA patients (mean disease duration, 31 months). CTUS (but not single modality) imaging parameters were all significantly greater comparing patients with DAS28 > 3.2 versus those with DAS28 ≤ 3.2 (all P < 0.01). Area under the ROC curves (AUCs) using cut-off levels of ≥ 94.5, ≥ 64.6 and ≥ 42.3 in identifying patients with DAS28 > 3.2 were 0.73 , 0.76 and 0.76 for MAX (PD), AVG (PD) and MIN (PD), respectively (with sensitivity ranging from 58 to 61% and specificity all 100%). The use of CTUS in detecting a greater severity of joint inflammation among patients with at least moderate disease activity (DAS28 > 3.2) appears promising and will require further validation in independent RA cohorts.

Joint damage in rheumatoid arthritis: Lessons learned from an extended 36-joint ultrasonography and 28-joint Disease Activity Score assessments.

AIM: To study joint damage severity in rheumatoid arthritis (RA) patients classified using ultrasound power Doppler (PD) and gray-scale (GS) joint inflammation outcomes and the 28-joint Disease Activity Score (DAS28). METHOD: Ultrasound erosion scores were compared between (a) patients in group 1 (PD positive and GS ≥ median score), group 2 (PD negative and GS ≥ median score) and group 3 (PD positive and GS < median score) vs group 4 (PD negative and GS < median score) and (b) patients with high, moderate and low DAS28 scores vs those in DAS28 remission. Comparative analyses were performed using the 2-sample Student's t test. RESULTS: There were 1080 joints and 1800 joint recesses from 36 joints scanned in 30 RA adult patients (mean DAS28, 3.58; mean disease duration, 70.3 months) in this cross-sectional study. The mean and 95% CI ultrasound erosion scores were significantly higher (P = .026) for groups 1 (9.75, 6.69-12.81) vs 4 (3.4, 1.11-5.69) with a difference (95% CI) of 6.35 (0.78-11.83), but not significantly different (P values all > .05) for (a) groups 2 and 3 vs 4 and (b) patients with high, moderate and low DAS28 scores vs those in DAS28 remission. CONCLUSION: Severity of ultrasound-detected bone erosions was significantly greater when both positive PD and a greater degree of GS joint inflammation were present in RA. This association was not observed when either component was absent. Single time point ultrasound joint inflammation assessment - and not DAS28 - is reflective of joint damage severity in RA patients.

A novel use of combined thermal and ultrasound imaging in detecting joint inflammation in rheumatoid arthritis.

PURPOSE: To evaluate the use of combined thermal and ultrasound imaging to assess joint inflammation in rheumatoid arthritis (RA). METHOD: 22-joint (bilateral hands) thermography and ultrasonography were performed. For each patient, the MAX, MIN and AVG represent the sum of the temperature differences with a control temperature, for the respective maximum (Tmax), minimum (Tmin) and average (Tavg) temperatures at the joints. MAX (PD), MIN (PD) and AVG (PD) represent the results of combined thermal imaging with a patient's total ultrasound power Doppler (PD) joint inflammation score (Total PD) (when Total PD > median score, MAX, MIN and AVG was multiplied by a factor of 2, otherwise MAX (PD), MIN (PD) and AVG (PD) remained the same as the MAX, MIN and AVG). Pearson correlation and linear regression were used to assess correlation and characterize relationships of imaging parameters with the 28-joint disease activity score (DAS28). RESULTS: In this cross-sectional study, 814 joints were examined in 37 adult RA patients (75.7 % female, 75.7 % Chinese; mean DAS28, 4.43). Among the imaging parameters, only MAX (PD) and AVG (PD) correlated significantly with DAS28 (correlation coefficient (95 % CI): MAX (PD), 0.393 (0.079, 0.636), P = 0.016; AVG (PD): 0.376 (0.060, 0.624), P = 0.022). Similarly, only MAX (PD) and AVG (PD) demonstrated a statistically significant relationship with DAS28 (regression coefficient (95 % CI): MAX (PD), 0.009 (0.002, 0.015), P = 0.016; AVG (PD), 0.011 (0.002, 0.020), P = 0.022). CONCLUSIONS: Novel use of combined thermal and ultrasound imaging in RA shows superiority to either imaging alone in terms of correlation with DAS28.

The Role of Musculoskeletal Ultrasound Imaging in Rheumatoid Arthritis.

Musculoskeletal ultrasound (MSUS) is gaining popularity among rheumatologists, especially in the context of rheumatoid arthritis (RA) joint assessment, as it is a non-invasive, radiation-free imaging modality that is relatively easy to set up in a clinic setting. Although ultrasonography (US) is often regarded as being operator dependent with associated reproducibility issues, the use of consensus-based scoring system along with standardized definition of joint inflammation in RA has been shown to improve its performance/reliability as an outcome measurement tool. Through this review article, we have (i) gone through the principle US findings in RA joint assessment, (ii) discussed various scoring systems for evaluation of US joint pathologies, (iii) described the literature in the use of US in areas of RA diagnosis and disease prognostication and (iv) examined the findings of recent major randomized controlled trials incorporating US as monitoring tools to help target treatment in RA. By doing so, we hope to provide clinicians with an insight into the role of musculoskeletal US imaging in areas of RA diagnosis, prognosis and disease monitoring.

Anti-cyclic citrullinated peptide but not rheumatoid factor is associated with ultrasound-detected bone erosion among rheumatoid arthritis patients with at least moderate disease activity.

AIM: To investigate anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) in relation to ultrasound-detected joint inflammation and bone erosion in patients with rheumatoid arthritis (RA) as previous studies have mainly utilized radiographic damage as imaging outcomes. METHOD: In this cross-sectional study, patients were grouped based on their Disease Activity Score at 28 joints (DAS28 < 3.2, DAS28 ≥ 3.2). Ultrasound variables (power Doppler and gray scale joint inflammation graded 0-3 semi-quantitatively; bone erosion graded Yes = 1/No = 0 dichotomously) were correlated with antibodies levels using Pearson correlation. Simple linear regression was used to characterize relationships between variables. Receiver operating characteristic (ROC) analysis was performed to determine statistically optimal cut-off values for identifying patient subgroups with ultrasound erosion scores >25th, >50th and >75th percentiles. RESULTS: One thousand and eighty joints and 1800 joint recesses from 36 peripheral joint sites were scanned in 30 adult RA patients (mean disease duration, 70.3 months; 93.3% female; 93.3% anti-CCP positive; 93.3% RF positive). In the DAS28 < 3.2 group, no significant correlations were found between antibody levels and ultrasound variables. In the DAS28 ≥ 3.2 group, anti-CCP levels correlated significantly (r = 0.46, P = .048) and were predictive (P = .048) of ultrasound erosion scores. Area under the ROC curve based on cut-off anti-CCP level of ≥95.2 to identify patients with ultrasound erosion scores >7 (75th percentile) was 0.72 (sensitivity = 83.3%, specificity = 53.8%). CONCLUSION: The association of anti-CCP and RF with joint damage appears to differ in RA. Among patients with at least moderate disease activity (DAS28 ≥ 3.2), anti-CCP-but not RF-is associated with joint damage, being moderately correlated with ultrasound-detected bone erosion.

Extended 36-joint sonographic examination: What it reveals about bone erosions in patients with rheumatoid arthritis.

PURPOSE: To identify joints commonly exhibiting bone erosions using an extended 36-joint sonographic (US) examination in patients with rheumatoid arthritis (RA) and to study bone erosion in relation to US-detected joint inflammation. METHODS: In this cross-sectional study, power Doppler (PD) and gray-scale (GS) joint inflammation scores (semi-quantitative [0-3] grading) at each joint recess were summed to obtain a combined US score (CUS). Bone erosion was scored as present/absent. Generalized Estimating Equations were used to compare mean US scores between joint recesses with and without bone erosion. RESULTS: Bone erosion was found in 144/1080 (13.3%) joints and 189/1800 (10.5%) joint recesses in 30 RA patients. The five joints most frequently associated with bone erosion were: wrist, n = 49/144 (34.0%); first MTPJ, n = 19/144 (13.2%); thumb IPJ, n = 13/144 (9.0%); second MCPJ, n = 11/144 (7.6%); and third MCPJ, n = 11/144 (7.6%). Mean (95% CI) US scores for joint recesses with and without bone erosion were PD: 0.36 (0.21, 0.50) vs 0.01 (0.00, 0.02); GS: 1.77 (1.54, 2.00) vs 0.47 (0.40, 0.55); and CUS: 2.13 (1.78, 2.47) vs 0.49 (0.41, 0.57) (all differences significant at P < .001). CONCLUSION: The five joints most frequently showing bone erosion were identified. Joint recesses with bone erosion are more likely to exhibit greater PD and GS joint inflammation severity.

Detecting joints with erosion(s) in rheumatoid arthritis: a novel individualized-ultrasound method performs better than existing methods.

PURPOSE: To determine if a novel individualized-ultrasound (IUS) method can detect more joints with erosion(s) in rheumatoid arthritis (RA) patients versus existing methods. MATERIALS AND METHODS: The IUS method selects up to 7 or 14 ultrasonographically most inflamed joints whereas existing methods pre-fix 7 or 14 joints for ultrasonography. Using ultrasonography, the mean total inflammatory score (TIS), mean number of affected joints and mean number of joints with erosion(s) were compared between novel and existing methods among 30 RA patients using the paired Student t test. RESULTS: Using 7-joint approach, comparing IUS versus existing methods, the mean (95% CI) for TIS, number of affected joints, and number of joints with erosion(s) were: 2.18 (1.88, 2.48) versus 0.95 (0.78, 1.11); 7 (7, 7) versus 4.43 (3.93, 4.94); 3.20 (2.44, 3.96) versus 1.33 (0.94, 1.72), respectively. Using 14-joint approach, comparing IUS versus existing methods, the mean (95% CI) for TIS, number of affected joints, and number of joints with erosion(s) were: 3.17 (2.75, 3.6) versus 1.71 (1.38, 2.04); 13.5 (13.05, 13.95) versus 8.13 (7.24, 9.02); 4.23 (3.13, 5.34) versus 2.77 (2.03, 3.50), respectively. p values all < 0.0001. CONCLUSIONS: A novel IUS method detects substantially more joints with erosion(s) in RA patients versus existing methods.

Ultrasound power Doppler and gray scale joint inflammation: What they reveal in rheumatoid arthritis.

AIM: Power Doppler (PD) and gray scale (GS) imaging are commonly employed during ultrasonography in rheumatoid arthritis (RA). While PD vascularity is often regarded as an ultrasound feature of more active joint inflammation, the true clinical significance of GS joint inflammation is less understood. We aimed to gain further insight into ultrasound PD and GS joint inflammation by studying their association with Disease Activity Score of 28 joints (DAS28) (a disease activity measure) and ultrasound-detected bone erosion (a structural damage measure). METHOD: In this cross-sectional study, ultrasound PD and GS joint inflammation were graded 0-3 (semi-quantitatively) and bone erosion was graded as yes = 1/no = 0 at each joint recess. Linear regression and Pearson correlation were used to characterize relationships and assess correlation of PD and GS scores with DAS28 and ultrasound erosion scores. RESULTS: One thousand and eighty joints and 1800 joint recesses from 36 peripheral joint sites (bilateral metacarpophalangeal joints, thumb interphalangeal joints, proximal interphalangeal joints, metatarsophalangeal joints, elbow, wrist and ankle) were scanned in 30 adult RA patients. PD scores correlated with DAS28 (r = 0.46, P = 0.0104) but not with ultrasound erosion scores; GS scores correlated with ultrasound erosion (r = 0.64, P = 0.0001) but not with DAS28 scores. Simple linear regression revealed PD as predictive of DAS28 (P = 0.0104) and GS as predictive of ultrasound-detected bone erosion (P = 0.0001). CONCLUSION: Ultrasound PD joint inflammation is associated with disease activity and is correlated with DAS28. In contrast, GS joint inflammation is associated with structural damage and is correlated with ultrasound-detected bone erosion.

Receiver operating characteristic analysis of ultrasound joint inflammation in relation to structural damage and disease activity in rheumatoid arthritis.

OBJECTIVE: To investigate whether ultrasound greyscale (GS) and power Doppler (PD) joint inflammation may be useful in identifying rheumatoid arthritis (RA) patients in different states of structural damage and disease activity. METHODS: In this cross-sectional study utilizing 36-joint ultrasonography, bone erosion was scored dichotomously (1 = yes/0 = no) while GS and PD joint inflammations were graded semi-quantitatively (0-3) at each joint recess. Sensitivity, specificity and receiver operating characteristic (ROC) curve analysis was applied to study ultrasound joint inflammation as a clinical marker for identifying patients with erosion score > 4.5 (median) and DAS28 > 2.6, > 3.2 and > 5.1, respectively. RESULTS: 1080 joints and 1800 joint recesses were scanned in 30 RA patients (mean disease duration, 70.3 months). Patients with GS score > 35.5 (median) had significantly higher ultrasound erosion scores when compared to those with GS score ≤ 35.5 (mean (95% CI) ultrasound erosion scores, 9.27 (6.12-12.4) versus 3.33 (2.31-4.36), respectively. p = 0.0027). Patients with PD positivity had significantly higher DAS28 scores compared to those with PD negativity (mean (95% CI) DAS28, 3.84 (3.35, 4.34) versus 2.86 (2.18, 3.54), respectively. p = 0.0457). Area under the ROC curve (AUC) based on cut-off GS scores ≥ 38 to identify patients with ultrasound erosion score >4.5 was 0.82 (sensitivity = 73.3%, specificity = 86.7%, accuracy = 80%). AUC based on cut-off PD scores ≥ 2.5 for identifying patients with DAS28 > 5.1 was 0.88 (sensitivity = 100%, specificity = 69.2%, accuracy = 73.3%). CONCLUSIONS: Ultrasound GS and PD joint inflammation scores can be useful in identifying RA patients with high bone erosion burden (ultrasound erosion score > 4.5) and high disease activity (DAS28 > 5.1), respectively.

Back to the basics: Understanding joint swelling and tenderness at the wrist in rheumatoid arthritis through the use of ultrasonography.

AIM: To compare ultrasound-detected inflammation with clinical manifestations at the wrist in rheumatoid arthritis (RA). METHOD: Wrists assessed serially by assessors blinded to ultrasound findings were categorized into 4 groups: 1 = S0T0 (not swollen; not tender); 2 = S0T1 (not swollen; tender); 3 = S1T0 (swollen; not tender); 4 = S1T1 (swollen; tender). Ultrasound synovitis and tenosynovitis were graded semi-quantitatively (0-3) and dichotomously (0 or 1), respectively. The (a) power Doppler (PD), gray-scale (GS) and combined (PD + GS) ultrasound (CUS) scores and (b) their positivity (score > 0) were analyzed using a general linear repeated measures mixed model (a) assuming Gaussian errors and (b) with binary distribution and logit link, respectively. Pairwise comparisons among wrist groups were performed within context of the models. RESULTS: In 122 wrist assessments (baseline = 64; 3 months = 58) from 32 treated RA patients (87.5% female; mean disease duration 42.8 months), significant differences among groups for (a) scores were: 4 vs 1 (PD, P = 0.0031; GS, P = 0.0159; CUS, P = 0.0045), 4 vs 2 (PD, P = 0.0176; GS, P = 0.0160; CUS, P = 0.0074), and 4 vs 3 (CUS, P = 0.0374); and (b) positivity were: 4 vs 1 (PD, P = 0.0007), 4 vs 2 (PD, P = 0.0234), and 3 vs 1 (PD, P = 0.0202). No significant differences in results were found for groups 2 vs 1. No significant effects were attributable to differences in wrist side or follow-up visit. CONCLUSION: Ultrasound detected substantial inflammation when wrist joint swelling and tenderness are both present. Joint swelling without tenderness is associated with significantly more frequent PD detection. Without swelling, joint tenderness is not associated with a significantly greater degree of ultrasound-detected inflammation.

Greater rheumatoid arthritis joint improvement with more subjects achieving response across improvement categories using novel versus existing ultrasound methods.

We compared the change in joint inflammation and the proportion of subjects achieving threshold levels of improvement using the existing methods employing ultrasonography on pre-determined joint sites versus novel methods. These novel methods select the most affected joints based on (i) ultrasonography-the Individualized-Ultrasound (IUS) method, or (ii) ultrasonography and clinical joint assessment-the individualized-Composite-Ultrasound (ICUS) method. Mean 3-month change in total inflammation score (ΔTIS) and 95% CI was computed for each method on 24 RA subjects initiated or escalated on treatment. Individual improvement in TIS per subject, calculated as the 3-month ΔTIS divided by the maximum possible TIS score expressed as a percentage, was used to obtain the proportion of subjects achieving response across improvement categories. Mean 3-month ΔTIS was significantly greater (p values ranging from 0.0003 to 0.0026) for novel versus existing methods using 12- and 7-joint approaches. Using 12-joint approach, percentages of subjects in improvement categories ≥5%, ≥10%, ≥15% and ≥20% were, respectively, 50, 37.5, 12.5 and 8.3% for IUS; 58.3, 37.5, 12.5 and 8.3% for ICUS; and 16.7, 0, 0 and 0% for the existing method. Using 7-joint approach, the respective category percentages were 62.5, 37.5, 25 and 12.5% for IUS; 62.5, 41.7, 16.7 and 8.3% for ICUS; and 12.5, 4.2, 4.2 and 0% for the existing method. Novel ultrasound methods are more likely to detect improvement in joint inflammation, with more subjects achieving response across improvement categories, thereby representing a substantial advantage over the existing methods. However, this requires confirmation in larger RA cohorts.

Novel joint selection methods can reduce sample size for rheumatoid arthritis clinical trials with ultrasound endpoints.

OBJECTIVES: To determine whether novel methods of selecting joints through (i) ultrasonography (individualized-ultrasound [IUS] method), or (ii) ultrasonography and clinical examination (individualized-composite-ultrasound [ICUS] method) translate into smaller rheumatoid arthritis (RA) clinical trial sample sizes when compared to existing methods utilizing predetermined joint sites for ultrasonography. METHODS: Cohen's effect size (ES) was estimated (ES^) and a 95% CI (ES^L, ES^U) calculated on a mean change in 3-month total inflammatory score for each method. Corresponding 95% CIs [nL(ES^U), nU(ES^L)] were obtained on a post hoc sample size reflecting the uncertainty in ES^. Sample size calculations were based on a one-sample t-test as the patient numbers needed to provide 80% power at α = 0.05 to reject a null hypothesis H0 : ES = 0 versus alternative hypotheses H1 : ES = ES^, ES = ES^L and ES = ES^U. We aimed to provide point and interval estimates on projected sample sizes for future studies reflecting the uncertainty in our study ES^S. RESULTS: Twenty-four treated RA patients were followed up for 3 months. Utilizing the 12-joint approach and existing methods, the post hoc sample size (95% CI) was 22 (10-245). Corresponding sample sizes using ICUS and IUS were 11 (7-40) and 11 (6-38), respectively. Utilizing a seven-joint approach, the corresponding sample sizes using ICUS and IUS methods were nine (6-24) and 11 (6-35), respectively. CONCLUSIONS: Our pilot study suggests that sample size for RA clinical trials with ultrasound endpoints may be reduced using the novel methods, providing justification for larger studies to confirm these observations.

Utility of ultrasonography in guiding modification of disease modifying anti-rheumatic drugs and steroid therapy for inflammatory arthritis in routine clinical practice.

OBJECTIVE: To determine the utility of ultrasonography in guiding modification of disease-modifying anti-rheumatic drug (DMARD) and steroid therapy for inflammatory arthritis (IA) in routine clinical practice. METHODS: In this retrospective study, we analyzed DMARD and steroid use in IA patients referred to a rheumatologist-led ultrasound clinic. Power Doppler (PD) vascularity and greyscale (GS) synovial hypertrophy joint findings were categorized as positive/negative for each patient. The erythrocyte sedimentation rate (ESR) was used as a measure of disease activity. RESULTS: We assessed single visit data for 46 adult IA patients: 67.4% (n = 31) rheumatoid arthritis (RA), 15.2% (n = 7) psoriatic arthritis, 10.9% (n = 5) spondyloarthritis, and 6.5% (n = 3) undifferentiated IA. The mean ESR was 28.8 mm/h. Thirty-seven patients with both GS and PD ultrasound results were subsequently analyzed. All patients (n = 10) escalated and/or initiated on DMARD and 9/10 patients escalated or initiated on steroids were PD and GS positive. Six of seven patients with dose reduction and/or cessation of DMARDs and five of seven patients with dose reduction or cessation of steroids were PD negative. Of six patients who were GS positive and PD negative, three had dose reduction and/or cessation of DMARDs, while four had dose reduction of steroids; none of the six patients had DMARD/steroid escalation. CONCLUSION: By clarifying joint inflammation in an IA cohort with overall low ESR, ultrasonography of physician-selected joints can improve clinical assessment, resulting in treatment modification. Positive PD findings were particularly influential, while the clinical significance of GS positivity alone requires further investigation.