Optical Spectral Transmission Research Articles

Increased predictive value of optical spectral transmission in early rheumatoid arthritis through use of patient-adjusted cut-off scores

ObjectivesThe aims of this study were to suggest patient-adjusted optical spectral transmission (OST) cut-off values for the first time and to develop clinical models that predict the probability of an early rheumatoid arthritis (RA) diagnosis based on OST findings and the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria as a reference standard.MethodsOST examinations were performed in newly diagnosed RA patients and healthy controls by the HandScan device. Moreover, RA patients underwent a full clinical [tender/swollen joint counts (TJC/SJC), disease activity score-28 (DAS28)] and laboratory evaluation. OST confounding factors were examined via logistic multivariate regression analyses and patient-adjusted OST-cut-offs were subsequently determined. Furthermore, statistical models to calculate the probability of an RA diagnosis, based on the measured OST values and the presence of OST influencing factors, were developed. Finally, correlations of OST with RA activity parameters were assessed.Results1.584 joints of 72 early RA patients were examined via OST and compared to 2.200 joints of 100 healthy controls and 1.166 joints of 53 patients with non-inflammatory arthralgia (NIA), respectively. Overall OST diagnostic performance was excellent in the whole cohort between RA- and healthy control-group [Area-Under-the-Curve (AUC): 0.810 (95%CI: 0.746–0.873); p < 0.0001], and further improved in RA-patients with ≥ 1 swollen wrist/finger joint(s) [AUC: 0.841 (95%CI: 0.773–0.908); p < 0.0001]. Comparison between RA patients and patients with non-inflammatory arthralgia showed similar results by an AUC of 0.788 (95%-CI: 0.709–0.867; p < 0.0001), and further improved in RA patients with ≥ 1 swollen wrist/finger joint(s) [AUC: 0.822 (95%CI: 0.74–0.90); p < 0.0001]. For the assessment of an adjusted RA diagnosis probability, two gender-specific statistical models were developed, based on OST values and patient age. OST cut-off values of 11.2 and 18.21 were calculated for female and male patients with active disease (sensitivity 93% and 67%; specificity 71.2% and 90%), respectively. Among RA patients, OST was associated moderately/significantly with DAS28 (r = 0.42,p < 0.001) and swollen joint count (rho = 0.355,p = 0.002).ConclusionThe development of patient-adjusted OST cut-off values and the suggested statistical models significantly enhance OST’s diagnostic performance, supporting its utility in differentiating between RA and non-inflammatory conditions. Future research should include a broader spectrum of arthritis types to validate OST’s comprehensive diagnostic utility also across various inflammatory arthritides.Trial registrationDRKS00016752 (German Registry of Clinical Trials)

Optical imaging (HandScan) can identify ultrasound remission in rheumatoid arthritis

BackgroundIdentifying remission is of high importance in rheumatoid arthritis (RA) because remission is associated with less structural progression. We investigated the efficacy of a new optical imaging device, HandScan, to identify RA remission, as defined by ultrasound (US).Methods61 RA patients were included. Disease activity was evaluated by clinical assessment and US, using gray-scale (GS) and Power Doppler (PD). HandScan determined unitary optical spectral transmission (OST) values for wrists, metacarpophalangeal and proximal interphalangeal joints. At the patient level, three composite HandScan (HS) scores were calculated: total HS score; disease activity score OST (DAS-OST) and DAS-OST without patient global assessment (PtGA). Using ROC curves, we determined HS cut-offs to identify US-defined remission.ResultsAt the joint level, unitary OST values significantly correlated with GS synovitis [odds ratio (OR) 2.43, p < 0.0001] and PD positivity (OR 3.72, p = 0.0002 ). At the patient level, total HS score and DAS-OST were significantly associated with all gray-scale US (GSUS) and power doppler US (PDUS) parameters evaluated (synovitis number and grade, synovial thickness, PD grade) (p < 0.05). The cut-off to identify US-defined remission at the joint level was of 0.92, giving an 81% sensitivity and a 96% positive predictive value (PPV). At the patient level, ROC-curves failed to identify a robust cut-off for the total HS score, but did identify a cut-off (3.68) for DAS-OST to identify US-defined remission, but with lower sensitivity (75%), specificity (56%) and PPV (67%).ConclusionsHandScan is a non-invasive optical imaging technique providing OST values that correlate with GSUS and PDUS parameters. In addition, HandScan is able to reliably identify US-defined remission in RA at the joint level, with a good sensitivity and high PPV. At the patient level, HandScan DAS-OST can also determine US remission (while total HS score failed to do so), but with lower performance.

Optical spectral transmission to assess glucocorticoid therapy response in patients with arthritis: a longitudinal follow-up comparison with joint ultrasound

BackgroundOptical spectral transmission (OST) is a modern diagnostic modality, able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with arthritis. To date, there are no adequate data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes, during arthritis follow-up.Objectives of this study were therefore to examine the performance of OST in assessing response to anti-inflammatory therapy in patients with active arthritis and to explore OST associations with clinical, laboratory, and ultrasonographic (US) activity markers.Methods1173 joints of 54 patients with arthritides of the wrist and finger joints were examined by OST before and after oral administration of glucocorticoids (GC), during a disease flare. For the same time-points patients underwent clinical, laboratory, and joint US [grayscale (GSUS), power-Doppler (PDUS)] examinations. The distribution of ΔOST-values between the two time-points was compared with the respective distributions of ΔPDUS and ΔGSUS by Bayesian statistical analyses. Moreover, the diagnostic performance of OST compared to a control group (2508 joints of 114 subjects) was examined by receiver operating characteristics and associations of OST values with clinical, laboratory, and arthrosonographic parameters were evaluated by correlation analyses.ResultsOST and US performed similarly in the assessment of inflammatory changes caused by GC (same value-change tendency in 83.2% of the cases). Bayesian statistics revealed no significant differences between ΔOST and ΔPDUS for all 3 examined joint categories (accuracy: metacarpophalangeal (MCP): 68.1%; proximal interphalangeal (PIP): 60.4%; wrists: 50.4%) and between ΔOST and ΔGSUS for MCP and PIP joints (accuracy: 51.1% and 78.7%, respectively). OST diagnostic performance (patients vs. controls) was excellent in both time-points [area under the curve (AUC) before GC=0.883(95%CI=0.83–0.94) and after GC=0.811(95%CI=0.74–0.881); p<0.001]. Furthermore, OST correlated significantly with all examined sonographic activity scores (all; p<0.001) and with swollen joint counts (p<0.01).ConclusionsOST was able to assess response to therapy in a similar way to joint US and correlated significantly with arthritis activity markers. Therefore, OST has proved to be a valuable tool to assist disease activity monitoring in the examined cohort.Trial registrationGerman Registry of Clinical Trials, DRKS00016752

Clinical evaluation of optical spectral transmission imaging for detection of disease activity in rheumatoid arthritis

Objective To investigate the performance and factors of influence of optical spectral transmission (OST) imaging as a new technique for measuring joint inflammation in rheumatoid arthritis (RA). Method OST was performed in 24 RA patients and 37 controls. Mann–Whitney U-test was used to assess differences in OST score between RA patients and controls. Receiver operating characteristics (ROC), linear regression and generalized estimating equations analysis were used to assess the discriminative capability of OST and the association of OST score with clinical disease parameters, ultrasound, radiographic features and cardiovascular risk parameters. Results Median OST score was higher in RA patients than in controls [16.9 (interquartile range 12.77–19.7) vs 12.11 (10.32–14.93)]. At patient level, OST score was moderately associated with ultrasound [beta 0.38 (95% CI 0.16–0.60), p = 0.001] and clinical disease activity [28-joint Disease Activity Score–C-reactive protein beta 0.30 (95% CI 0.04– 0.57), p = 0.024] in RA patients. In controls, male sex, high body mass index, and hypertension were associated with higher OST scores, while these associations were absent in RA. At joint level, the area under the ROC curve for OST score, with ultrasound or clinical swelling as reference, ranged from 0.63 to 0.70. Joint-space narrowing and malalignment were associated with higher OST joint scores, and subchondral sclerosis with lower scores. Conclusion OST provides an objective measure of synovitis and correlates moderately with other examined disease activity assessment tools. Clinical patient characteristics must be considered when interpreting the results.

Development and Validation of Rheumatoid Arthritis Disease Activity Indices Including HandScan (Optical Spectral Transmission) Scores.

ObjectiveTo develop and validate a composite rheumatoid arthritis (RA) disease activity index using optical spectral transmission (OST) scores obtained with the HandScan, replacing tender and swollen joint counts.MethodsRA patients from a single center routinely undergoing HandScan measurements with at least 1 concurrent OST score and Disease Activity Score in 28 joints (DAS28) were included. Data were extracted from medical records. Linear regression analyses with the DAS28 as the outcome were performed to create a disease activity index (DAS‐OST). OST score, erythrocyte sedimentation rate (ESR), and patient global assessment (PtGA) visual analog scale (VAS), sex, age, disease duration, and rheumatoid factor status were evaluated as independent variables. Final models were derived based on the statistical significance of coefficients and model fit. Of the data, two‐thirds were used for development and one‐third for validation; external validation was performed in a cohort from another center. Agreement between DAS‐OST and DAS28 was assessed using the Bland‐Altman plot method and intraclass correlation coefficient (ICC). Diagnostic value of the DAS‐OST was determined for established definitions of remission, low disease activity (LDA), and high disease activity (HDA).ResultsData of 3,358 observations from 1,505 unique RA patients were extracted. DAS‐OST was defined as: –0.44 + OST × 0.03 + male × –0.11 + LN(ESR) × 0.77 + PtGA VAS × 0.03. The ICCs between DAS‐OST and DAS28 were 0.88 (95% confidence interval [95% CI] 0.87–0.90) and 0.82 (95% CI 0.75–0.86) and measurement errors were 0.58 and 0.87 in internal and external validation, respectively. Sensitivity for remission, LDA, and HDA was 79%, 91%, and 43%, respectively, and specificity was 92%, 80%, and 96% in external validation.ConclusionUsing the HandScan, RA disease activity can be accurately estimated if combined with ESR, PtGA VAS, and sex into a disease activity index (DAS‐OST).

Optical imaging compared to clinical examination in 484 rheumatoid arthritis patients: the Leeuwarden Handscan Registry.

The Handscan is a novel objective optical imaging device for disease follow-up and management in rheumatoid arthritis patients. We aim to examine the association between the baseline outcomes of the Handscan, disease activity levels and joint swelling. The Handscan measures differences in laser light absorption between joints of fingers and wrists and adjacent reference tissue, indicating the presence or absence of inflammation. The device gives an optical spectral transmission (OST) index per joint. The average of these indices is represented in the total optical score (TOS). Associations between TOS and DAS28 at subject level and OST and swelling at joint level were examined. 484 RA patients were included. Compared to patients with high disease activity (defined by DAS28), TOS was significantly lower in patients with moderate (estimated coefficient B: -7.09, P < 0.001), low disease activity (B: -6.99, P < 0.001) and patients in remission (B: -7.72, P < 0.001) but could not distinguish between the latter three disease states. TOS was significantly lower in females (B: -3.2, P < 0.001). OST was significantly higher in swollen than non-swollen joints (B: 0.28, P < 0.001). TOS was significantly higher in patients with high disease activity than in those in remission or with low and moderate disease activity. The difference in TOS between males and females should be accounted for in the interpretation of this outcome. The OST at joint level discriminates swollen from non-swollen joints and could be a more promising tool than the overall optical activity reflected in TOS.

Monitoring of rheumatoid arthritis: a patient survey on disease insight and possible added value of an innovative inflammation monitoring device

To enable patients with rheumatoid arthritis (RA) and their healthcare professionals to choose the optimal treatment, it is crucial to accurately assess the current state of inflammatory activity. The objectives of this study were to (1) investigate the perspective of RA patients on their insight into the current status of their disease, and to (2) investigate the patients’ perspective on the possible added value of a monitoring device based on optical spectral transmission—called the HandScan—that measures the location and severity of joint inflammation. A survey was distributed online among patients with RA in the Netherlands. Four-hundred and eight patients with RA completed the survey. Of these, 298 (73%) felt they have sufficient insight into their current disease status. Most respondents perceived either a large (n = 242; 59%) or small (n = 148; 36%) added value of the HandScan in their monitoring process, mostly because the device provides additional knowledge on the presence of inflammation. This perceived added value was higher for respondents experienced with the device (n = 46; p = .04). Respondents preferred monitoring with the device on every (n = 192; 47%) or most (n = 171; 42%) visits to the outpatient clinic, or even more often than on every visit (n = 17; 4%). Monitoring RA using an optical spectral transmission device is seen by patients as a possibly valuable addition to the monitoring process of inflammatory activity during visits to an outpatient clinic. Their main reason was that the device can increase insight into their current disease status. More insight may support patients in discussing treatment options with their rheumatologist.

Classification of rheumatoid arthritis into active or inactive with a modified Disease Activity score, for future use as a treat-to-target tool, with a HandScan score replacing joint counts.

To establish the value of a modified Disease Activity score with Optical Spectral Transmission score (DAS-OST) without joint counts but with a HandScan score, versus that of DAS28, to classify rheumatoid arthritis (RA) as active versus inactive, with as reference standard the rheumatologist's clinical classification. RA patients with at least one HandScan and DAS28 measurement performed at the same visit were included. Data was extracted from medical records, as was the clinical interpretation as active or inactive RA by the rheumatologist. Logistic regression analyses were performed to calculate areas under the receiver operating characteristics (AU-ROC) curves. The clinical interpretation was used as reference standard in all analyses, and disease activity measures were used as predictor variables. The performance of predictor variables (AU-ROCs) was compared. The data of 1505 RA patients were used for analyses. The highest AU-ROC of 0.88 (95%CI 0.85-0.90) was shown for DAS28; AU-ROC of DAS-OST was 0.78 (95%CI 0.75-0.81), difference 0.10, p<0.01. Compared to DAS28, DAS-OST classified RA statistically significantly less well as active versus inactive, when using the clinical classification as reference standard. However, a DAS-modification without joint scores might have a place in strategies limiting routine outpatients' visits to the rheumatologist.

POS1405 OPTICAL SPECTRAL TRANSMISSION (HANDSCAN) IN PATIENTS WITH PSORIATIC ARTHRITIS: FIRST DATA ON DIAGNOSTIC VALUE AND ASSOCIATIONS WITH CLINICAL AND ULTRASOUND DISEASE ACTIVITY MARKERS

Background:Valid assessment of disease activity leads to improvement of long-term outcomes in patients with inflammatory arthritis (1). Optical spectral transmission (OST) is a modern diagnostic tool able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with rheumatoid arthritis (RA) (commercial device: HandScan – Demcon/Hemics, The Netherlands) (2). Even though an increasing number of studies have evaluated diagnostic value of this new technology in RA patients (2,3), no data exist regarding psoriatic arthritis (PsA).Objectives:To examine for the first time the diagnostic value of OST in detecting inflammation in patients with PsA and to evaluate its relationship with disease activity markers and various epidemiological and anthropometric patient characteristics.Methods:OST-Measurements were performed in a group of PsA patients and a group of healthy controls. The difference between OST in the two groups was statistically examined and relationships of OST with clinical (tender / swollen joint counts, disease activity on a visual analogue scale) and serological disease activity markers were evaluated. Moreover, joint ultrasound (US) examinations were performed in a subgroup of PsA patients and OST associations with a Power Doppler- and a Grey Scale-US score were examined. Finally, relationships of OST with various anthropometric and epidemiologic parameters (BMI, hand-size, gender, age) were assessed.Results:We recruited 49 PsA patients [65.3% female; mean age 53.3 years (± 11.8 SD)] and 114 control subjects [77.2% female; mean age 46 years (± 12.8 SD)]. OST was statistically significantly higher in the patient group, compared to the control group [14.95 (12.04 - 17.18, IQR) vs. 10.31 (7.84 – 13.79, IQR); p&lt;0.001]. OST correlated moderately-strongly with both examined US scores (Power Doppler-score: r = 0.5; p = 0.026 and Grey Scale-score: r = 0.52; p = 0.028). Moreover, OST showed a moderate, statistically significant association with C-reactive protein (CRP) (r = 0,298; p = 0,037). Finally, males had significantly higher OST values than females and OST associated moderately-weakly with body mass index (BMI) in the control group (rho = 0.24; p&lt; 0.001).Conclusion:This is the first report of a possible diagnostic value of OST in patients with PsA. OST correlated with ultrasound and serological activity markers and may thus prove to be a useful tool of disease activity assessment, next to well established diagnostic modalities, such as the joint US. Correlations of OST with patient characteristics implicate the need to take also anthropometric and epidemiological patient characteristics into account when interprenting OST results in order to avoid confounding.

A Sex Difference in HandScan Scores in Rheumatoid Arthritis Patients and Controls? An Ongoing Analysis of the Sex Difference and Other Potential Confounders

To the Editor: A recent paper by Triantafyllias, et al described that optical spectral transmission (OST) scores, obtained by the HandScan, were significantly higher in male compared to female patients with rheumatoid arthritis (RA) and controls, and an association between OST score and age, BMI, and hand surface area was found.1 The difference in sex that Triantafyllias, et al showed is in line with results of studies performed at our department. We developed and validated a new disease activity index, Disease Activity Score (DAS)-OST, in which tender and swollen joint counts are replaced by the OST score. In the construction of the DAS-OST formula, sex had to be taken into account, because in this study, OST scores were higher in males than in females.2 In addition, by comparing single OST scores to the rheumatologist’s clinical classification into active or inactive RA as reference, different optimal cutoffs for males and females were calculated, again indicating a sex difference. Based on these findings, we investigated whether this difference in sex was also … Address correspondence to Dr. M.M. Verhoeven, Department of Rheumatology & Clinical Immunology G02.228, P.O. Box 85500, 3508GA Utrecht, the Netherlands. Email: m.m.a.verhoeven-15{at}umcutrecht.nl.

Dr. Triantafyllias, et al reply.

We have read with great interest the letter of Verhoeven, et al,1 referring to our recent publication on the diagnostic value of optical spectral transmission (OST) in rheumatoid arthritis (RA).2 In our work we had described for the first time, to our knowledge, that OST values could be influenced not only by disease-associated factors (i.e., inflammatory activity) but also by patient-associated characteristics, such as sex, BMI, and age.2.

Utility of the HandScan in monitoring disease activity and prediction of clinical response in rheumatoid arthritis patients: an explorative study.

ObjectivesThe aims were to determine the ability of the HandScan [assessing inflammation in hand and wrist joints using optical spectral transmission (OST)] to measure RA disease activity longitudinally, compared with DAS28, and to determine whether short-term (i.e. 1 month) changes in the OST score can predict treatment response at 3 or 6 months.MethodsParticipants visited the outpatient clinic before the start of (additional) RA medication and 1, 3 and 6 months thereafter. Disease activity was monitored at each visit with the HandScan and DAS28 in parallel. A mixed effects model with DAS28 as the outcome variable with a random intercept at patient level, visit month and DAS28 one visit earlier was used to evaluate whether changes in the OST score are related to changes in DAS28. Binary logistic regression was used to test the predictive value of short-term changes in the OST score together with the baseline OST score for achievement of treatment response (EULAR or ACR criteria). All models were adjusted for RA stage (early or established).ResultsIn total, 64 RA patients were included. One unit change in OST score was found to be related to an average DAS28 change of 0.03 (95% CI: 0.01, 0.06, P = 0.03). When adding OST score as a variable in the longitudinal model, the ability of the model to estimate DAS28 (i.e. explained variance) increased by 2%, to 59%. Neither baseline OST score nor short-term change in OST score was predictive for treatment response at 3 or 6 months.ConclusionA longitudinal association of OST score with DAS28 exists, although explained variance is low. The predictive ability of short-term changes in HandScan for treatment response is limited.

SAT0571 OPTICAL SPECTRAL TRANSMISSION TO ASSESS THERAPY RESPONSE IN PATIENTS WITH ARTHRITIS: A COMPARATIVE STUDY WITH CLINICAL, LABORATORY AND ULTRASONOGRAPHIC ACTIVITY MARKERS.

Background:Valid assessment of disease activity leads to outcome improvement in patients with rheumatoid arthritis (RA) (1). Optical spectral transmission (OST) is a modern diagnostic tool able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of RA patients (commercial device: HandScan - Hemics, The Netherlands) (2).Objectives:To our knowledge, there are no data regarding the diagnostic value of OST in the evaluation of inflammatory activity changes during arthitis follow up.Thus, aims of this study were to examine the ability of OST to detect response to anti-inflammatory therapy in patients with arthritis and to explore OST associations with clinical, laboratory and ultrasonographic (US) activity markers.Methods:OST measurements were performed in patients with active arthritides of the wrist and finger joints before and after administration of glucocorticoids (GC), during a disease flare. For the same points in time (a and b) patients and healthy controls underwent clinical, laboratory and joint US [Grey Scale (GSUS) - Power Doppler (PDUS)] examinations. OST-values before and after therapy were subsequently compared with their corresponding DAS28- and US-values. The distributions of Delta-PDUS und OST-values between the two time points were compared by Bayesian statistics. Moreover, OST diagnostic performance was tested by Receiver Operating Characteristics (ROC).Results:We recruited 54 patients with active inflammatory arthritis: 39 RA, 4 gout, 7 peripheral spondylarthritides and 4 other miscellaneous arthritides (66.7% females) and 114 controls.Previous to therapy with GC, median OST was [OST(a):8.75(5.38-16.25, IQR)] and after therapy [OST(b):4.75(2.38-8.63, IQR)] (p&lt;0.05). Similarly, DAS28 dropped significantly after GC therapy [DAS28(a):5.12(4.33-6.10, IQR) vs. DAS28(b):3.85(3.40-4.82),p&lt;0.05)]. OST correlated moderately with PDUS at both time points: (a)rho=0.449and (b)rho=0.414, respectively (both;p&lt;0.01). Moreover, OST correlated significantly with swollen joint count at both time points (a)rho=0.379and (b)rho=0.382,p&lt;0.01respectively.OST and US performed similarly in the assessment of inflammatory changes caused by the administration of GC (same tendency in the change of OST values in83.2%of the cases). Furthermore, Bayesian statistic revealed no significant differences between OST and US for all 3 examined joint categories (MCP:p=0.81; PIP:p=0.74; wrists:p=0.60).In addition, ROC revealed that OST is a very good tool to distinguish patients with arthritis from healthy controls at both examination points [AUC(a):0.883(95% CI=0.83-0.94) and AUC(b):0.811(95% CI=0.74-0.881)].Conclusion:OST was able to assess response to therapy in arthritis patients comparable to US. Moreover, OST correlated with disease activity markers and could effectively differentiate between arthritis patients and controls. Therefore, OST could prove to be a valuable non-interventional time- and resource-saving diagnostic tool to assist arthritis monitoring.

THU0110 DIAGNOSTIC ISSUES IN DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: PRELIMINARY RESULTS OF A SYSTEMATIC LITERATURE REVIEW INFORMING THE 2020 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) patients treated according to European League Against Rheumatism (EULAR) recommendations failing ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) with a different mode of action who still have complaints which may be suggestive of active disease may be defined as suffering from ‘difficult-to-treat RA’. Before switching to another DMARD in these patients, the diagnosis of RA and the presence of inflammatory activity should be verified to prevent possible over- and under treatment.Objectives:To systematically summarise evidence in the literature on diagnostic issues regarding (mis-)diagnosis of RA and mimicking diseases, and assessment of inflammatory disease activity in difficult-to-treat RA patients, informing the 2020 EULAR recommendations for the management of difficult-to-treat RA.Methods:A systematic literature search was performed: PubMed and Embase databases were searched up to December 2018. Relevant papers were selected and appraised (Figure 1).Results:Regarding (mis-)diagnosis of RA and its differential diagnoses, four studies were selected (Figure 1a): one assessed the diagnosis of RA and three focused on coexisting mimicking diseases (fibromyalgia and bacterial infection). No diagnostic tests were replicated. For evaluation of inflammatory activity in RA, and specifically the effect of comorbidities on assessing inflammatory activity, 63 and five studies, respectively, were included (Figure 1b). At patient level, ultrasonography (US) scores were related to composite indices (range of correlations (r): 0.25-0.70) and swollen joint counts (range r: 0.33-0.78). A multi-biomarker disease activity score (range r with composite indices: 0.41-0.52) and optical spectral transmission measures (range r with US: 0.54-0.64) were promising measures, but cut-offs are preliminary. At joint level, US was related to MRI (range of sensitivity 64-91% and specificity 60-94% for synovitis) and histology (range r: 0.52-0.65 for inflammation). Concomitant obesity and fibromyalgia may lead to overestimation of disease activity according to composite indices, US may be used to assess inflammatory activity in these patients.Conclusion:This SLR highlights the gap of knowledge in the optimal confirmation of a (mis-)diagnosis of RA or diagnosis of mimicking diseases in difficult-to-treat RA patients. Current evidence for optimal assessment of inflammatory activity when there is doubt based on clinical assessment and composite indices is limited. Most studies reported correlations which are not directly useful in clinical practice to determine presence or absence of inflammatory activity. The evidence will be updated up to December 2019. Currently, US seems the most accurate measure to evaluate the presence of inflammation in difficult-to-treat RA patients, including those with concomitant obesity or fibromyalgia.Disclosure of Interests:Nadia M. T. Roodenrijs: None declared, Melinda Kedves: None declared, Attila Hamar: None declared, György Nagy: None declared, Jacob M. van Laar Grant/research support from: MSD, Genentech, Consultant of: MSD, Roche, Pfizer, Eli Lilly, BMS, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Paco Welsing: None declared

Diagnostic Value of Optical Spectral Transmission in Rheumatoid Arthritis: Associations with Clinical Characteristics and Comparison with Joint Ultrasonography.

To examine the value of optical spectral transmission (OST) in detecting joint inflammation in patients with rheumatoid arthritis (RA) and to evaluate whether OST correlates with certain patient characteristics. OST measurements were performed in the metacarpophalangeal, proximal intraphalangeal, and wrist joints of 168 patients with RA and 114 controls. OST difference between the 2 groups was statistically examined and subsequently controlled for the effect of possible confounding factors. Diagnostic OST performance was tested by receiver-operating characteristics. Moreover, associations of OST with clinical and serological activity markers (patient group), joint ultrasound (US; patient subgroup) and various anthropometric and epidemiologic parameters (patient and control group) were evaluated by Spearman correlation coefficient and a generalized linear statistical adjustment model. OST was significantly higher in the RA group than in the control group, even after adjustment for confounding factors (1.89; 95% CI 0.709-3.070, padj = 0.002). Taking US as a reference, area under the curve for all 1251 joints simultaneously was 0.67 (95% CI 0.631-0.709). In the patient group, correlation and adjustment analyses showed associations of OST with various disease activity markers [28-joint count Disease Activity Score (rho 0.313), swollen joint counts (rho 0.361), C-reactive protein (rho 0.389); all, padj = 0.001], age (rho 0.276, p < 0.001), and osteoarthritis (p = 0.022). Moreover, OST associated with a power Doppler US score (rho 0.442; p = 0.001) and a greyscale US score (rho 0.591; p < 0.001). In both groups males had significantly higher OST values than females and OST associated moderately weakly with body mass index (rho patients 0.316, rho controls 0.24; all, p < 0.001). Patients with RA showed higher OST values in comparison to controls. Moreover, OST associated with clinical, US, and laboratory disease activity markers.

Novel optical spectral transmission (OST)-guided versus conventionally disease activity-guided treatment: study protocol of a randomized clinical trial on guidance of a treat-to-target strategy for early rheumatoid arthritis

BackgroundAssessment of disease activity is a critical component of tight-control, treat-to-target treatment strategies of rheumatoid arthritis (RA). Recently, the HandScan has been validated as a novel method for objectively assessing RA disease activity in only 1.5 min, using optical spectral transmission (OST) in hands and wrists. We describe the protocol of a randomized controlled clinical trial (RCT) to investigate whether HandScan-guided treatment aimed at ‘HandScan remission’ (HandScan arm) is at least as effective as and more cost-effective than clinically guided treatment aimed at ACR/EULAR 2011 Boolean remission (DAS arm).Methods/designThe study is a multi-center, double-blind, non-inferiority RCT of 18 months duration. Patients ≥ 18 years with newly diagnosed, disease-modifying antirheumatic drug (DMARD)-naïve RA according to the ACR 2010 classification criteria, will be randomized to the DAS arm or the HandScan arm. The efficacy of the arms will be compared by evaluating Health Assessment Questionnaire (HAQ) scores (primary outcome) after 18 months of DMARD therapy, aimed at remission. The equivalence margin in HAQ scores between study arms is 0.2. Secondary outcomes are differences in cost-effectiveness and radiographic joint damage between treatment arms. The non-inferiority sample size calculation to obtain a power of 80% at a one-sided p value of 0.05, with 10% dropouts, resulted in 61 patients per arm. In both arms, DMARD strategy will be intensified monthly according to predefined steps until remission is achieved; in both arms DMARDs and treatment steps are identical. If sustained remission, defined as remission that persists consistently over three consecutive months, is achieved, DMARD therapy will be tapered.DiscussionThe study protocol and the specifically designed decision-making software application allow for implementation of this RCT. To test a novel method of assessing disease activity and comparing (cost-)effectiveness with the contemporary method in treat-to-target DMARD strategies in early RA patients.Trial registrationDutch Trial Register, NTR6388. Registered on 6 April 2017 (NL50026.041.14). Protocol version 3.0, 19-01-2017.

Can optical spectral transmission assess ultrasound-detected synovitis in hand osteoarthritis?

ObjectiveTo determine whether optical spectral transmission (OST) can be used to assess synovitis in hand and wrist joints of patients with hand osteoarthritis (OA).DesignHand and wrist joints of 47 primary hand OA patients with at least one clinically inflamed hand or wrist joint were assessed for synovitis by OST and ultrasound (US). Associations between standardized OST and US synovitis were studied in linear mixed effects models, across all joint types together and individually for wrist, proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints, and were adjusted for OA features that showed associations with US synovitis. Diagnostic performance was determined using receiver operator characteristic (ROC) curves analysis, with US as reference standard.ResultsAltogether, 6.7% of joints showed US synovitis. Statistically significant associations between OST scores and US synovitis were found for all joints combined (Δ0.37SD, p<0.001) and PIP joints (Δ0.81SD, p<0.001), but not for DIP (Δ0.14SD, p = 0.484) or wrist joints (Δ0.37SD, p = 0.178). All associations were independent of other OA features, i.e. osteophytes and dorsal vascularity. Analysis of diagnostic performance of OST, revealed an area under the ROC curve (AUC-ROC) of 0.74 for all joints together (p<0.001), 0.69 for PIP joints (p<0.001), 0.54 for DIP joints (p = 0.486), and 0.61 for wrist joints (p = 0.234).ConclusionsOST scores and US synovitis are statistically significantly associated, independent of osteophytes and dorsal vascularity. At this stage, OST performs fair in the assessment of synovitis in PIP joints of hand OA patients.

Optical spectral transmission to assess inflammation in hand and wrist joints of rheumatoid arthritis patients.

To develop an optical spectral transmission (OST) model to measure joint inflammation, and thus disease activity, as well as to evaluate (patho-)physiological findings that could lead to misclassification of inflammation. Forty-six RA patients were included in this cross-sectional study, where US scores, duplicate OST measurements and 28-joint DAS (DAS28) were acquired. With US as a reference standard, the diagnostic performance of OST in detecting inflammation at the joint level was evaluated using receiver operating characteristic (ROC) curve analyses. At the patient level, correlations with US were analysed for DAS28 and OST, and at joint level for OST and tender and swollen joint counts (TJC and SJC, respectively). Joint pathology potentially influencing misclassification by OST [erosions, osteophytes, tendon (sheath) inflammation (ab)normal vasculature and chondrocalcinosis] was evaluated for significance in a multivariate nominal logistic regression model. Diagnostic performance of OST was good for MCP [area under the ROC curve (AUC-ROC) 0.88], PIP (AUC-ROC 0.83) and wrist (AUC-ROC 0.74) joints and for all joints together (AUC-ROC 0.85). At the patient level, DAS28 correlated very poorly (ρ = 0.06) and OST moderately (ρ = 0.54) with US. At the joint level, US correlation with OST was strong (ρ = 0.64), with SJC it was weak (ρ = 0.30) and with TJC it was very weak (ρ = -0.02). Misclassification of inflammation by OST was relatively rare (17%). Dorsal erosions [odds ratio (OR) 4.0], osteophytes (OR 2.1) and extensor tendinitis (OR 4.6) increased the risk of underestimating inflammation of MCP and PIP joints and osteophytes (OR 3.0) also increased the risk of overestimating inflammation. OST is a sensitive, specific and objective technique to assess joints inflammation of the hands and wrists of RA patients, even though bone and tendon pathology increases the risk of misclassification.

OPTICAL BISTABILITY IN ALL-PASS MOBIUS CONFIGURATION MICRORING RESONATOR

A novel design of microring resonator called all-pass Mobius ring resonator is used to study optical bistability effect and spectral transmission for all-optical switching application with clockwise hysteresis loop operation. The bright soliton pulse is applied as the input source of the system. The propagation of the pulses within the system is simulated using the transfer matrix analysis. The all-pass Mobius ring resonator is able to operate under high nonlinearity as it has longer propagation length per roundtrip. The all-pass Mobius provides low transmission peak power of 3.65 mW as compared to the conventional all-pass configuration. The output-to-input relation of both design shows that the Mobius configuration is able to generate a higher hysteresis loop width of the bistable signal from 15.79 mW to 18.10 mW input power. The switching power of the optical bistability in Mobius configuration is 3.67 mW for threshold power of 16.95mW. This work shows the Mobius configuration is more suitable to be used for all-optical switching application as compared to the conventional all-pass ring resonator configuration.

Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique

ObjectivesIn rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive...