Imaging modalities in hand osteoarthritis - status and perspectives of conventional radiography, magnetic resonance imaging, and ultrasonography

Hand osteoarthritis (OA) is very frequent in middle-aged and older women and men in the general population. Currently, owing to high feasibility and low costs, conventional radiography (CR) is the method of choice for evaluation of hand OA. CR provides a two-dimensional picture of bony changes, such as osteophytes, erosions, cysts, and sclerosis, and joint space narrowing as an indirect measure of cartilage loss. There are several standardized scoring methods for evaluation of radiographic hand OA. The scales have shown similar reliability, validity, and sensitivity to change, and no conclusion about the preferred instrument has been drawn. Patients with hand OA may experience pain, stiffness, and physical disability, but the associations between radiographic findings and clinical symptoms are weak to moderate and vary across studies. OA is, indeed, recognized to involve the whole joint, and modern imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI) could be valuable tools for better evaluation of hand OA. Standardized scoring methods have been proposed for both modalities. Several studies have examined the validity of US features in hand OA, whereas knowledge of the validity of MRI is more limited. However, both synovitis (detected by either US or MRI) and MRI-defined bone marrow lesions have been associated with pain, indicating that treatment of inflammation is important for pain management in hand OA. Both US and MRI have shown better sensitivity than CR in detection of erosions, and this may indicate that erosive hand OA may be more common than previously thought

Development of radiographic classification criteria for hand osteoarthritis: a methodological report (Phase 2)

ObjectivesIn Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic findings could better discriminate patients with hand OA and controls than clinical examination findings. The objective of Phase 2 was to achieve consensus on the features and their weights to be included in three radiographic criteria sets of overall hand OA, interphalangeal OA and thumb base OA.MethodsMultidisciplinary, international expert panels were convened. Patient vignettes were used to identify important features consistent with hand OA. A consensus-based decision analysis approach implemented using 1000minds software was applied to identify the most important features and their relative importance influencing the likelihood of symptoms being due to hand OA. Analyses were repeated for interphalangeal and thumb base OA. The reliability and validity of the proposed criteria sets were tested.ResultsThe experts agreed that the criteria sets should be applied in a population with pain, aching or stiffness in hand joint(s) not explained by another disease or acute injury. In this setting, five additional criteria were considered important: age, morning stiffness, radiographic osteophytes, radiographic joint space narrowing and concordance between symptoms and radiographic findings. The reliability and validity were very good.ConclusionRadiographic features were considered critical when determining whether a patient had symptoms due to hand OA. The consensus-based decision analysis approach in Phase 2 complemented the data-driven results from Phase 1, which will form the basis of the final classification criteria set

GaitSmart motion analysis compared to commonly used function outcome measures in the IMI-APPROACH knee osteoarthritis cohort

[Abstract] Background: There are multiple measures for assessment of physical function in knee osteoarthritis (OA), but each has its strengths and limitations. The GaitSmart® system, which uses inertial measurement units (IMUs), might be a user-friendly and objective method to assess function. This study evaluates the validity and responsiveness of GaitSmart® motion analysis as a function measurement in knee OA and compares this to Knee Injury and Osteoarthritis Outcome Score (KOOS), Short Form 36 Health Survey (SF-36), 30s chair stand test, and 40m self-paced walk test. Methods: The 2-year Innovative Medicines Initiative-Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) knee OA cohort was conducted between January 2018 and April 2021. For this study, available baseline and 6 months follow-up data (n = 262) was used. Principal component analysis was used to investigate whether above mentioned function instruments could represent one or more function domains. Subsequently, linear regression was used to explore the association between GaitSmart® parameters and those function domains. In addition, standardized response means, effect sizes and t-tests were calculated to evaluate the ability of GaitSmart® to differentiate between good and poor general health (based on SF-36). Lastly, the responsiveness of GaitSmart® to detect changes in function was determined. Results: KOOS, SF-36, 30s chair test and 40m self-paced walk test were first combined into one function domain (total function). Thereafter, two function domains were substracted related to either performance based (objective function) or self-reported (subjective function) function. Linear regression resulted in the highest R2 for the total function domain: 0.314 (R2 for objective and subjective function were 0.252 and 0.142, respectively.). Furthermore, GaitSmart® was able to distinguish a difference in general health status, and is responsive to changes in the different aspects of objective function (Standardized response mean (SRMs) up to 0.74). Conclusion: GaitSmart® analysis can reflect performance based and self-reported function and may be of value in the evaluation of function in knee OA. Future studies are warranted to validate whether GaitSmart® can be used as clinical outcome measure in OA research and clinical practice

Baseline clinical characteristics of predicted structural and pain progressors in the IMI-APPROACH knee OA cohort

[Abstract] Objectives: To describe the relations between baseline clinical characteristics of the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) participants and their predicted probabilities for knee osteoarthritis (OA) structural (S) progression and/or pain (P) progression. Methods: Baseline clinical characteristics of the IMI-APPROACH participants were used for this study. Radiographs were evaluated according to Kellgren and Lawrence (K&L grade) and Knee Image Digital Analysis. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Numeric Rating Scale (NRS) were used to evaluate pain. Predicted progression scores for each individual were determined using machine learning models. Pearson correlation coefficients were used to evaluate correlations between scores for predicted progression and baseline characteristics. T-tests and χ2 tests were used to evaluate differences between participants with high versus low progression scores. Results: Participants with high S progressions score were found to have statistically significantly less structural damage compared with participants with low S progression scores (minimum Joint Space Width, minJSW 3.56 mm vs 1.63 mm; p<0.001, K&L grade; p=0.028). Participants with high P progression scores had statistically significantly more pain compared with participants with low P progression scores (KOOS pain 51.71 vs 82.11; p<0.001, NRS pain 6.7 vs 2.4; p<0.001). Conclusions: The baseline minJSW of the IMI-APPROACH participants contradicts the idea that the (predicted) course of knee OA follows a pattern of inertia, where patients who have progressed previously are more likely to display further progression. In contrast, for pain progressors the pattern of inertia seems valid, since participants with high P score already have more pain at baseline compared with participants with a low P score

a protocol for developing a patient-reported outcome measurement instrument

Introduction: There is no consensus about what constitutes the most appropriate patient-reported outcome measurement (PROM) instrument for measuring physical function in patients with rheumatic hand conditions. Existing instruments lack psychometric testing and vary in feasibility and their psychometric qualities. We aim to develop a PROM instrument to assess hand-related physical function in rheumatic hand conditions. Methods and analysis: We will perform a systematic search to identify existing PROMs to rheumatic hand conditions, and select items relevant for hand-related physical function as well as those items from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank that are relevant to patients with rheumatic hand conditions. Selection will be based on consensus among reviewers. Content validity of selected items will be established through the use of focus groups. If patients deem necessary, we will develop new items based on the patients' input. We will examine whether it is valid to score all selected and developed items on the same scale as the original items from the PROMIS PF item bank. Our analyses will follow the methods used for calibrating the original PROMIS PF item bank in US samples, which were largely based on the general PROMIS approach. Ethics and dissemination: This study will be carried out in accordance with the Helsinki Declaration. Ethics approvals will be obtained where necessary, and signed informed consent will be obtained from all participants. We aim to disseminate the results of the study through publication in international peer-reviewed journals and at international conferences

Relationship Between Motion, Using the GaitSmartTM System, and Radiographic Knee Osteoarthritis: An Explorative Analysis in the IMI-APPROACH Cohort

Multicenter study[Abstract] Objectives: To assess underlying domains measured by GaitSmartTMparameters and whether these are additional to established OA markers including patient reported outcome measures (PROMs) and radiographic parameters, and to evaluate if GaitSmart analysis is related to the presence and severity of radiographic knee OA. Methods: GaitSmart analysis was performed during baseline visits of participants of the APPROACH cohort (n = 297). Principal component analyses (PCA) were performed to explore structure in relationships between GaitSmart parameters alone and in addition to radiographic parameters and PROMs. Logistic and linear regression analyses were performed to analyse the relationship of GaitSmart with the presence (Kellgren and Lawrence grade ≥2 in at least one knee) and severity of radiographic OA (ROA). Results: Two hundred and eighty-four successful GaitSmart analyses were performed. The PCA identified five underlying GaitSmart domains. Radiographic parameters and PROMs formed additional domains indicating that GaitSmart largely measures separate concepts. Several GaitSmart domains were related to the presence of ROA as well as the severity of joint damage in addition to demographics and PROMs with an area under the receiver operating characteristic curve of 0.724 and explained variances (adjusted R2) of 0.107, 0.132 and 0.147 for minimum joint space width, osteophyte area and mean subchondral bone density, respectively. Conclusions: GaitSmart analysis provides additional information over established OA outcomes. GaitSmart parameters are also associated with the presence of ROA and extent of radiographic severity over demographics and PROMS. These results indicate that GaitsmartTM may be an additional outcome measure for the evaluation of OA

Report from the Hand Osteoarthritis Working Group at OMERACT 2018: Update on Core Instrument Set Development

Objective: To evaluate hand osteoarthritis tools for core instrument set development. Methods: For OMERACT 2018, a systematic literature review and advances in instrument validation were presented. Results: Visual analog and numerical rating scales were considered valuable for pain and patient’s global assessment, despite heterogeneous phrasing and missing psychometric evidence for some aspects. The Modified Intermittent and Constant Osteoarthritis Pain scale was lacking evidence. The Michigan Hand Outcomes Questionnaire had advantages above other pain/function questionnaires. The Hand Mobility in Scleroderma scale was valid, although responsiveness was questioned. Potential joint activity instruments were evaluated. Conclusion: The development of the core instrument set is progressing, and a research agenda was also developed

Hand-related physical function in rheumatic hand conditions:a protocol for developing a patient-reported outcome measurement instrument

Introduction: There is no consensus about what constitutes the most appropriate patient-reported outcome measurement (PROM) instrument for measuring physical function in patients with rheumatic hand conditions. Existing instruments lack psychometric testing and vary in feasibility and their psychometric qualities. We aim to develop a PROM instrument to assess hand-related physical function in rheumatic hand conditions. Methods and analysis: We will perform a systematic search to identify existing PROMs to rheumatic hand conditions, and select items relevant for hand-related physical function as well as those items from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank that are relevant to patients with rheumatic hand conditions. Selection will be based on consensus among reviewers. Content validity of selected items will be established through the use of focus groups. If patients deem necessary, we will develop new items based on the patients' input. We will examine whether it is valid to score all selected and developed items on the same scale as the original items from the PROMIS PF item bank. Our analyses will follow the methods used for calibrating the original PROMIS PF item bank in US samples, which were largely based on the general PROMIS approach. Ethics and dissemination: This study will be carried out in accordance with the Helsinki Declaration. Ethics approvals will be obtained where necessary, and signed informed consent will be obtained from all participants. We aim to disseminate the results of the study through publication in international peer-reviewed journals and at international conferences

Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis

Objective: To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1 alpha/beta dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA). Methods: Patients with >= 1 erosive and >= 3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200 mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks. At baseline and week 26, subjects had bilateral hand radiographs and MRI of the hand with the greatest number of baseline tender and/or swollen joints. Continuous endpoints were assessed using analysis of covariance models, with treatment and country as main factors and baseline measurements as covariates. Results: Of 132 randomised subjects, 1 received no study drug and 110 completed the study (placebo, 61/67 (91%); lutikizumab, 49/64 (77%)). AUSCAN pain was not different among subjects treated with lutikizumab versus placebo at week 16 (least squares mean difference, 1.5 (95% CI -1.9 to 5.0)). Other clinical and imaging endpoints were not different between lutikizumab and placebo. Lutikizumab significantly decreased serum high-sensitivity C reactive protein levels, IL-1 alpha and IL-1 beta levels, and blood neutrophils. Lutikizumab pharmacokinetics were consistent with phase I studies and not affected by antidrug antibodies. Injection site reactions and neutropaenia were more common in the lutikizumab group; discontinuations because of adverse events occurred more frequently with lutikizumab (4/64) versus placebo (1/67). Conclusion: Despite adequate blockade of IL-1, lutikizumab did not improve pain or imaging outcomes in erosive HOA compared with placebo

Predicted and actual 2-year structural and pain progression in the IMI-APPROACH knee osteoarthritis cohort

ClinicalTrials.gov, https://clinicaltrials.gov, NCT03883568[Abstract] Objectives: The IMI-APPROACH knee osteoarthritis study used machine learning (ML) to predict structural and/or pain progression, expressed by a structural (S) and pain (P) predicted-progression score, to select patients from existing cohorts. This study evaluates the actual 2-year progression within the IMI-APPROACH, in relation to the predicted-progression scores. Methods: Actual structural progression was measured using minimum joint space width (minJSW). Actual pain (progression) was evaluated using the Knee injury and Osteoarthritis Outcomes Score (KOOS) pain questionnaire. Progression was presented as actual change (Δ) after 2 years, and as progression over 2 years based on a per patient fitted regression line using 0, 0.5, 1 and 2-year values. Differences in predicted-progression scores between actual progressors and non-progressors were evaluated. Receiver operating characteristic (ROC) curves were constructed and corresponding area under the curve (AUC) reported. Using Youden's index, optimal cut-offs were chosen to enable evaluation of both predicted-progression scores to identify actual progressors. Results: Actual structural progressors were initially assigned higher S predicted-progression scores compared with structural non-progressors. Likewise, actual pain progressors were assigned higher P predicted-progression scores compared with pain non-progressors. The AUC-ROC for the S predicted-progression score to identify actual structural progressors was poor (0.612 and 0.599 for Δ and regression minJSW, respectively). The AUC-ROC for the P predicted-progression score to identify actual pain progressors were good (0.817 and 0.830 for Δ and regression KOOS pain, respectively). Conclusion: The S and P predicted-progression scores as provided by the ML models developed and used for the selection of IMI-APPROACH patients were to some degree able to distinguish between actual progressors and non-progressors