slowly in plasma (median T max 24 to 72 hours) and had systemic exposure 56% to 89% lower than that of the parent drug across all doses. The T ½ for GRC 27884 was similar to that for GRC 27864 and appeared independent of dose. No notable pharmacokinetic differ- ences or any biochemical or liver enzyme markers were observed in elderly subjects. Pharmacodynamics: Dose-dependent inhibition of ex-vivo LPS-induced whole-blood PGE2 release was seen from 10 mg to 1000 mg. The maximum inhibition was significantly different from placebo at single doses of GRC 27864 from 100 mg upwards. Upon single dosing, with both GRC 27864 (1000 mg) and Celecoxib (400 mg), a significant difference was observed in LPS-induced whole-blood PGE2 in EAUC 0-336h (P < 0.001), but no significant dif- ference in EAUC 0-24h or Epeak; however, the response appeared to be maintained for longer duration with GRC 27864 than with celecoxib. A trend of urinary PGEM reduction was seen with both GRC 27864 and celecoxib; however, Celecoxib showed non-selective inhibition with a trend (median) towards urinary PGIM and TXAM inhibition Conclusions: GRC 27864 was found to be safe and well tolerated as single doses up to 1000 mg in healthy adult subjects. GRC 27864 showed marked inhibition of ex vivo LPS induced PGE2 release in a dose-dependent manner from 10 mg to 1000 mg and showed com- parable inhibition to celecoxib (400 mg) at 1000 mg dose. This was accompanied by reduction of urinary PGEM by both GRC 27864 and celecoxib; however only celecoxib showed a trend of inhibition of uri- nary PGIM and TXAM. The study supports the novel mechanism of action of GRC 27864 that spares PGI2 with highly selective PGE2 inhibition 659 COMPARING OBSERVED WITH EXPECTED ASSESSMENTS OF OSTEOARTHRITIC PAIN OVER TIME: APPLICATION OF SUCCESSIVE PREDICTION TO DATA FROM THE OSTEOARTHRITIS INITIATIVE S. Mongin, N. Onizuka, L. Langsetmo, A. Shmagel. UMN, Minneapolis, MN, USA Purpose: High variability in patient-reported outcome scores presents a major challenge in the design and interpretation of clinical studies in osteoarthritis (OA). We present a novel successive prediction algorithm that forecasts individual WOMAC scores based on known clinical parameters and identifies risk factors for deviations between observed and predicted scores. Methods: Participants from the Osteoarthritis Initiative progression cohort with a baseline Kellgren-Lawrence grade 2 for either knee were selected for analysis (N ¼ 1,122). Demographic data, history of pain and depression, BMI, and physical activity parameters at baseline and eight subsequent annual observation times were processed to maximize the number of complete records. WOMAC scores were predicted for study years four through eight, using a mixed effects regression model applied to data up to, but not including, each study year. The predictive model adjusted for continuous time trends for individual subjects as well as the overall cohort, yielding an expected WOMAC score for each participant. To identify subgroups with excessive residual WOMAC scores, subject-specific residuals were analyzed by a separate multi- variable regression at each time point. Results: We were able to accurately model WOMAC scores and to use the fitted models to predict individual scores for each successive year. The predictive model for each visit showed significant overall fit (P < 0.0001 at all targeted study years). The succession of fitted models adapted to new information gained over time, and adjusted predictions to minimize residuals (Figure 1). Factors associated with lower than expected WOMAC scores on more than one successive visit (Figure 2) were long-standing history of knee pain and history of hip pain, with mean residual WOMAC (95% confidence interval) ranging from 3.3 (5.5, 1.7) to 7.7 (13.2, e2.3). The factor associated with higher than expected WOMAC scores was high performance on the 20-m walk test, with mean residual WOMAC ranging from þ3.3 (þ0.5, þ6.0) to þ4.5 (þ1.7, þ7.2). Conclusions: A successive prediction model closely predicted WOMAC scores based on traditional OA risk factors and prior clinical assessments. Subjects with long-standing histories of knee pain and associated hip pain, as well as subjects with good physical performance displayed unexpected WOMAC scores over time. Figure 1. Figure 2. 660 DISABILITY IN UNDERWEIGHT PERSONS WITH OR AT HIGHER RISK FOR KNEE OSTEOARTHRITIS N. Ghosh, J.S. Chmiel, O. Almagor, K.W. Hayes, K.C. Moisio, A.H. Chang, J. Szymaszek, L. Sharma. Northwestern Univ., Chicago, IL, USA Purpose: Several studies of the general population have revealed a U- shaped relationship between BMI and poor outcomes, such that both Abstracts / Osteoarthritis and Cartilage 26 (2018) S60eS474 S352