OA who progressed to total knee arthroplasty (TKA) and those that did not. Methods: 50 patients with moderate medial compartment knee OA underwent gait analysis at baseline. Ground reaction forces (sampled at 1000 Hz) and segment motions (sampled at 100 Hz) were recorded during self-selected walking. Three-dimensional knee angles and moments were calculated using inverse dynamics. All waveforms were time-normalized to percent of gait cycle, and moment waveforms were amplitude-normalized to body mass. Amplitude and temporal waveform characteristics were determined using Principal Component Analysis (PCA) for each waveform separately (6 in total). During follow up phone interviews 5-8 years later, 25 patients reported undergoing TKA surgery. Unpaired Student's t-tests were used to test for differences in all baseline demographic and waveform characteristics (PC scores) between the group that had TKA and the group that did not (a¼0.05). Results: There were no between-group differences in age (59 years in TKA group vs. 57 years in no-TKA group), mass (93.5 kg vs. 93.8 kg), body mass index (30.6 kg/m2 vs. 30.8 kg/m2), and gait speed (1.23 m/s vs. 1.27 m/s), with similar radiographic disease severity (Kellgren-Lawrence score) distribution at baseline. The mean time between baseline and follow up was 7.8 yrs for each group. The group that progressed to TKA had a significantly higher overall magnitude of the KAM (Fig 1, PC1, p < 0.05), less of a difference between the first peak KAM and the mid-stance KAM (Fig 1, PC2, p < 0.05), more tibial external rotation during mid-stance (PC4, p<0.05), and a trend toward reduced early stance knee flexion and late stance knee extension moments (PC2, p¼0.073) than the no-TKA group at baseline. Conclusions: The KAM findings suggest that the group that went on to TKA had higher overall medial compartment loading throughout the gait cycle at baseline (PC1), and a reduced ability to unload the medial compartment during mid-stance (PC2). These results support a cumulative rather than an impulse loading mechanism for progression. Furthermore, increased tibial external rotation (PC4) and a trend toward altered sagittal plane moment characteristics (PC2) were found in those that progressed. Together these findings indicate that dynamic frontal, transverse, and sagittal plane mechanical features are related to knee OA progression and should be considered in future prediction models of progression.

Background First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) have a fourfold increased risk of developing RA. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire was developed to document symptoms in persons at risk of RA. The aims of this study were (1) to describe symptoms in a cohort of FDRs of patients with RA overall and stratified by seropositivity and elevated CRP and (2) to determine if patient characteristics were associated with symptoms suggestive of RA. Methods A cross-sectional study of FDRs of patients with RA, in the PREVeNT-RA study, who completed a study questionnaire, provided a blood sample measured for rheumatoid factor, anti-CCP and CRP and completed the SPARRA questionnaire. Moderate/severe symptoms and symmetrical, small and large joint pain were identified and described. Symptoms associated with both seropositivity and elevated CRP were considered suggestive of RA. Logistic regression was used to determine if symptoms suggestive of RA were associated with patient characteristics. Results Eight hundred seventy participants provided all data, 43 (5%) were seropositive and 122 (14%) had elevated CRP. The most frequently reported symptoms were sleep disturbances (20.3%) and joint pain (17.9%). Symmetrical and small joint pain were 11.3% and 12.8% higher, respectively, in those who were seropositive and 11.5% and 10.7% higher in those with elevated CRP. In the logistic regression model, seropositivity, older age and feeling depressed were associated with increased odds of small and symmetrical joint pain. Conclusions This is the first time the SPARRA questionnaire has been applied in FDRs of patients with RA and has demonstrated that the presence of symmetrical and small joint pain in this group may be useful in identifying people at higher risk of developing RA.

ObjectivesTo identify predictors of remission and disease activity patterns in patients with rheumatoid arthritis (RA) using individual participant data (IPD) from clinical trials.MethodsPhase II and III clinical trials completed between 2002 and 2012 were identified by systematic literature review and contact with UK market authorisation holders. Anonymised baseline and follow-up IPD from non-biological arms were amalgamated. Multiple imputation was used to handle missing outcome and covariate information. Random effects logistic regression was used to identify predictors of remission, measured by the Disease Activity Score 28 (DAS28) at 6 months. Novel latent class mixed models characterised DAS28 over time.ResultsIPD of 3290 participants from 18 trials were included. Of these participants, 92% received methotrexate (MTX). Remission rates were estimated at 8.4%(95%CI 7.4%to9.5%) overall, 17%(95%CI 14.8%to19.4%) for MTX-naïve patients with early RA and 3.2% (95% CI 2.4% to 4.3%) for those with prior MTX exposure at entry. In prior MTX-exposed patients, lower baseline DAS28 and MTX reinitiation were associated with remission. In MTX-naïve patients, being young, white, male, with better functional and mental health, lower baseline DAS28 and receiving concomitant glucocorticoids were associated with remission. Three DAS28 trajectory subpopulations were identified in MTX-naïve and MTX-exposed patients. A number of variables were associated with subpopulation membership and DAS28 levels within subpopulations.Conclusions Predictors of remission differed between MTX-naïve and prior MTX-exposed patients at entry. Latent class mixed models supported differential non-biological therapy response, with three distinct trajectories observed in both MTX-naïve and MTX-exposed patients. Findings should be useful when designing future RA trials and interpreting results of biomarker studies.