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

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

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

Neuropathic Pain in the IMI-APPROACH Knee Osteoarthritis Cohort: Prevalence and Phenotyping

The study is registered under clinicaltrials.gov nr: NCT03883568.[Abstract] Objectives: Osteoarthritis (OA) patients with a neuropathic pain (NP) component may represent a specific phenotype. This study compares joint damage, pain and functional disability between knee OA patients with a likely NP component, and those without a likely NP component. Methods: Baseline data from the Innovative Medicines Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway knee OA cohort study were used. Patients with a painDETECT score ≥19 (with likely NP component, n=24) were matched on a 1:2 ratio to patients with a painDETECT score ≤12 (without likely NP component), and similar knee and general pain (Knee Injury and Osteoarthritis Outcome Score pain and Short Form 36 pain). Pain, physical function and radiographic joint damage of multiple joints were determined and compared between OA patients with and without a likely NP component. Results: OA patients with painDETECT scores ≥19 had statistically significant less radiographic joint damage (p≤0.04 for Knee Images Digital Analysis parameters and Kellgren and Lawrence grade), but an impaired physical function (p<0.003 for all tests) compared with patients with a painDETECT score ≤12. In addition, more severe pain was found in joints other than the index knee (p≤0.001 for hips and hands), while joint damage throughout the body was not different. Conclusions: OA patients with a likely NP component, as determined with the painDETECT questionnaire, may represent a specific OA phenotype, where local and overall joint damage is not the main cause of pain and disability. Patients with this NP component will likely not benefit from general pain medication and/or disease-modifying OA drug (DMOAD) therapy. Reserved inclusion of these patients in DMOAD trials is advised in the quest for successful OA treatments

The effect of tumour necrosis factor inhibitors on radiographic progression in axial spondyloarthritis : A systematic literature review

The effect of TNF-α inhibitors (TNFi), with or without concomitant NSAIDs, on radiographic progression in axial SpA remains unclear. Therefore, we performed a systematic literature review up to January 2019 to determine whether longer use of standard dose TNFi is superior vs lower duration or lower dose TNFi therapy, conventional synthetic DMARDs alone, or no therapy in inhibiting radiographic progression in patients with axial SpA. Our search yielded 373 titles of which 14 full text articles and five abstracts were eligible for quantitative analysis. Studies had an overall moderate to critical risk of bias. Data could not be pooled due to clinical and methodological heterogeneity. Individual studies showed conflicting results with mainly no significant difference in radiographic progression when comparing effect of TNFi therapy to no TNFi therapy or when comparing to less TNFi therapy until 2 years of follow-up. Results that are more significant are shown after 2 years' follow-up, mainly in subgroups with baseline syndesmophytes. Data on the additional or synergistic effect of concomitant NSAID use were inconclusive

Performance of the 2012 Systemic Lupus International Collaborating Clinics classification criteria versus the 1997 American College of Rheumatology classification criteria in adult and juvenile systemic lupus erythematosus. A systematic review and meta-analysis

Objective: To evaluate the performance in classifying systemic lupus erythematosus by the 2012 Systemic Lupus International Collaborating Clinics criteria (SLICC'12), versus the revised American College of Rheumatology criteria from 1997 (ACR'97) in adult and juvenile SLE patients. Methods: A systematic literature search was conducted in PubMed and Embase for studies comparing SLICC'12 and ACR'97 with clinical diagnosis. A meta-analysis was performed to estimate the sensitivity and specificity of SLICC'12 and ACR'97. To assess classification earlier in the disease by either set, sensitivity and specificity were compared for patients with disease duration <5 years. Sensitivity and specificity of individual criteria items were also assessed. Results: In adult SLE (nine studies: 5236 patients, 1313 controls), SLICC'12 has higher sensitivity (94.6% vs. 89.6%) and similar specificity (95.5% vs. 98.1%) compared to ACR'97. For juvenile SLE (four studies: 568 patients, 339 controls), SLICC'12 demonstrates higher sensitivity (99.9% vs. 84.3%) than ACR'97, but much lower specificity (82.0% vs. 94.1%). SLICC'12 classifies juvenile SLE patients earlier in disease course. Individual items contributing to diagnostic accuracy are low complement, anti-ds DNA and acute cutaneous lupus in SLICC'12, and the immunologic and hematologic disorder in ACR'97. Conclusion: Based on sensitivity and specificity SLICC'12 is best for adult SLE. Following the view that higher specificity, i.e. avoidance of false positives, is preferable, ACR'97 is best for juvenile SLE even if associated with lower sensitivity. Our results on the contribution of the individual items of SLICC'12 and ACR´97 may be of value in future efforts to update classification criteria

The Initial Validation of a Markov Model for the Economic Evaluation of (New) Treatments for Rheumatoid Arthritis

Objective: Markov models are increasingly used in economic evaluations of (new) treatments for chronic diseases. In this study we propose a Markov model with health states defined by the disease activity score (DAS) to be used to extrapolate efficacy data from short-term clinical trials in rheumatoid arthritis to longer term cost-effectiveness results. Moreover, we perform an initial validation of this model. Methods: To test the validity of the model, the expected disease course (according to the model) was first compared with the observed disease course in an inception cohort of newly diagnosed rheumatoid arthritis patients. Then the relationship of the health states with utility and costs was investigated. Finally, costs and QALYs were calculated for usual care of patients in the first 5 years of their disease using the model and compared with the literature. Results: The model seemed to be able to extrapolate 1-year efficacy data as seen by a comparable distribution over the Markov states between the model results and the observational data. The health states had a significant relationship with costs and utility, and population characteristics had only a moderate effect on the cost and utility values of the Markov states. The distribution over the Markov states resulted in 3.266 expected QALYs per patient over 5 years. The expected medical and total costs per patient over 5 years were _6754 (1997 values) and _12_641, respectively, for standard rheumatoid arthritis care in The Netherlands. Conclusion: The developed Markov model seems a valid model for use in economic evaluations in rheumatoid arthritis. The model produced similar utilities, but lower total costs, to those in previously published studies. Although the steps to develop and validate this Markov model were applied in the context of rheumatoid arthritis, they can be generalised to other chronic diseases.Markov-model, Rheumatoid-arthritis

Radiographic joint damage in early rheumatoid arthritis patients : Comparing tocilizumab- and methotrexate-based treat-to-target strategies

Objective. To evaluate the progression of erosions and joint space narrowing (JSN) in feet and hands in the U-Act-Early trial. Methods. In this trial, 317 newly diagnosed DMARD-naive RA patients initiated randomly tocilizumab, or step-up MTX or a combination of the two. Radiographs were scored at baseline and after 52 and 104weeks using the Sharp-van der Heijde erosion and JSN score. Between the strategy arms, changes from baseline and the proportions of patients without radiographic progression (change from baseline ≤0) were compared. Results. Mean changes from baseline in erosion and JSN scores for the whole study population were after 52 weeks 0.59 and 0.18 and after 104 weeks 0.70 and 0.50, respectively. For JSN, at both time points no differences in progression were found between strategies (P≥0.09). For erosions, the progression was significantly lower at week 104 in both tocilizumab arms when compared with the MTX arm ((p≤0.023). Less progression of erosions in the feet was found after 104 weeks in both tocilizumab arms (P≤0.046); this was not significant for the hands (P≥0.11). The proportion of patients without progression in erosions was higher in the tocilizumab arms at week 52 (tocilizumab plus MTX: 87%, P = 0.038; tocilizumab: 81%, P = 0.29) and 104 (tocilizumab plus MTX: 85%, P = 0.001; tocilizumab: 77%, P = 0.028), compared with the MTX arm (74 and 60%, respectively). Conclusion. In DMARD-naive early RA patients, initiating a tocilizumab-based treat-to-target strategy inhibits the progression of erosions, especially in the feet, more compared with initiation of a step-up MTX strategy