SAT0634 CO-MORBIDITIES ASSOCIATED WITH DISCORDANCE BETWEEN STRUCTURAL SEVERITY AND PAIN IN OSTEOARTHRITIS: IMPLICATIONS FOR CLINICAL TRIAL DESIGN IN OA – A POST-HOC ANALYSIS OF DATA FROM TWO RANDOMIZED CONTROLLED TRIALS
Authors: Jonathan Jetsmark Bjerre-Bastos, Inger Byrjalsen, Morten Asser Karsdal, Jeppe Ragnar Andersen, Asger Bihlet
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Development of new disease-modifying drugs in OA (DMOADs) is complicated by heterogeneous study populations and insensitive endpoints of structural change and symptoms, and discordance between structural disease severity and reported symptoms. In such trials, counterintuitively, mild structural disease may be associated with severe symptoms and vice versa. Research to uncover factors distorting the perceived severity of symptoms is needed to better characterize the clinical relevance of structural improvement, if any, in DMOAD trials. Anxiety and depressive (AD) disorders are known to affect pain sensitivity and perception, and as common co-morbidities of OA, these conditions may partly explain the observed discordance between structure and symptoms. If established, exclusion of patients with AD in DMOAD trials could potentially improve the understanding of structural benefit in a clinical context. <h3>Objectives:</h3> The main objective of this analysis was to investigate the impact of AD on the association between structural features of OA and patient-reported pain. <h3>Methods:</h3> Baseline data from two phase 3 trials investigating oral salmon calcitonin in OA, NCT00486434 and NCT00704847 (total N=2206), was analyzed in a post-hoc cross-sectional analysis. Patients with self-reported current or previous depression, anxiety or post-traumatic stress syndrome (PTSD) were selected and compared to a control group, matched by sex, age, BMI and JSW. Spearman's correlation coefficient between JSW and WOMAC pain was calculated for both groups. Multiple regression analyses of both groups with WOMAC pain as the outcome variable, and age, sex, body mass index (BMI) and baseline JSW or KL-grade as explanatory variables were performed. <h3>Results:</h3> In the AD group, 149 patients had AD in medical history of which 123 reported the condition as ongoing at baseline. The study groups of AD and matched controls (MC) were comparable in terms of age, sex, BMI, JSW, KL-grade and WOMAC pain. Associations between pain and JSW In the AD group, no significant correlation between JSW and WOMAC Pain score was found, while BMI was found to be weakly associated with WOMAC pain (R= 0.19, p=0.02) in the multiple regression analysis. In the MC group, a statistically significant (p=0.004), correlation (R= -0.24) was found between JSW and pain indicating that lower JSW was associated with higher pain, with JSW accounting for approximately 6% of the total natural variation behind reported pain. In addition, a positive significant association between male sex and WOMAC pain (R=0.18, p=0.04) was found. The univariate linear relationship between JSW and pain is illustrated in Figure 1, and multivariate analyses are shown in Table 1. Associations between pain and KL-Grade In the model evaluating associations between KL-grade and symptoms, there was no correlation between KL-grade and symptoms in the AD group. Similar to the findings relating to JSW, in the MC group, a weak (R=0.16), borderline statistically significant association (p=0.07) was found between KL-grade and WOMAC pain. <h3>Conclusion:</h3> A marked structure-symptoms discordance was found in OA patients with AD, while a statistically significant correlation was seen in matched controls without AD. The results suggest that exclusion of trial patients with anxiety and depression in medical history may improve the accuracy of pain reporting in clinical OA trials. <h3>Disclosure of Interests:</h3> Jonathan Jetsmark Bjerre-Bastos Employee of: Nordic Bioscience, Inger Byrjalsen Employee of: Nordic Bioscience, Morten Asser Karsdal Shareholder of: Nordic Bioscience, Employee of: Nordic Bioscience, Jeppe Ragnar Andersen Shareholder of: Nordic Bioscience, Employee of: Nordic Bioscience, Asger Bihlet Shareholder of: Nordic Bioscience, Employee of: Nordic Bioscience