Purpose: One common conservative treatment in medial knee osteoarthritis (OA) are lateral wedge insoles which can be worn long-term and have been shown to reduce the medial knee loading. Studies assessing the external knee adduction moment (EKAM) have demonstrated reductions of around 5–6%. However, it has been shown that there are inconsistent reductions in EKAM in individuals with medial knee OA whereby around 30% of individuals have an increase in their moment. These are classed as non-responders to the biomechanical treatment. To date, there have been no reports on what happens to the individual over time and if an individual who is classed as a non-responder at a baseline visit still remains a non-responder at a follow-up visit. We hypothesized that individuals who are biomechanical non-responders remain biomechanical non-responders after an eight-week intervention period. Methods: This ancillary study is part of a larger randomised controlled cross-over trial of persons with painful medial knee OA (In-Respond trial). The inclusion criteria were global knee pain in last week >=4 [0–10 scale]) age 40–85 years who had knee x-rays showing Kellgren and Lawrence grade 2–4 OA and definite medial without lateral narrowing. On examination by an experienced physiotherapist, they had to have medial tenderness but were excluded if they had pain at the lateral patellar facet or a positive patellar compression test. Subjects underwent three-dimensional motion analysis screening in both their own shoes and an off-the-shelf lateral wedge insole (Salford Lateral Wedge, 5 degree and 70 Shore A density). The individuals were classified into biomechanical responders (ones who's EKAM was reduced over 2% compared to their own shoe and a neutral insole) and biomechanical non-responders (those who's EKAM did not reach those reductions). The biomechanical non-responders were given a lateral wedge insole and were followed for eight weeks to determine any changes in EKAM. The analysis tested whether individuals who were biomechanical non-responders were still classified as this after 8 weeks. We calculated the percentage difference in EKAM when the lateral wedge was worn in the patients' compared to no insole, and also against a neutral insole. Percentage differences were calculated at both the baseline and 8 weeks visits. Excluding patients who had reductions in EKAM naturally leads to a non-normally distributed sample, hence we summarized the data at both time points using a five number summary (median, minimum, maximum, and interquartile range). In addition, we used Wilcoxon signed-rank tests for to test formally whether distributions of percentage changes differed between visits. Results: 192 potential subjects were screened for the study, where 109 were excluded who didn't meet inclusion criteria (60 did not meet x-ray criteria; 28 were ineligible based mostly on patellofemoral findings on physical examination, the remainder for other reasons). Out of these 83 remaining individuals 21 were classed as non-responders (mean increase 1.5%; range 18% increase –1% decrease in EKAM). Of these 21, 16 returned for the second gait analysis with 5 withdrawing from the study (3 due to problems with increased pain and 2 were not contactable). There was no difference when comparing the median reduction in EKAM between the baseline and the follow-up visit (Table 1). However, 12 of the individuals still remained as a biomechanical non-responder but 4 individuals demonstrated a change into a biomechanical responder which would have resulted in them being eligible for this trial.Table 1Percentage Differences in EKAM in Lateral Wedge Condition, Relative to Control ConditionsGait conditionStudy visitPercentage differencesWilcoxon signed-rank test for equality of distributions between visitsMedianLower quartileUpper quartileMinimumMaximumz, POwn shoe vs Lateral wedge insoleBaseline0.61−1.222.34−1.7017.561.75, 0.088 week follow-up−0.62−6.071.82−10.2314.24Neutral insole vs Lateral wedge insoleBaseline0.43−0.752.99−4.2716.591.34, 0.188 week follow-up−0.63−3.952.07−6.827.70 Open table in a new tab Conclusions: As in previous studies, there were individuals who did not biomechanically respond to the lateral wedge insoles. When using this as stratification for inclusion in a trial, it showed that the majority of these individuals remained classed as this non-responder. However, four individuals did change. Understanding why these individuals changed classification is a future research direction.