Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: There are two major needs in clinical DMOAD development: Identifying a population with an active and progressive disease to demonstrate significant improvements by an efficacious intervention; Phenotyping patients and linking them to a corresponding treatment mode-of-action (e.g. anti-inflammatory). CRPM is a metabolite of CRP. It is released from the inflamed tissue when CRP is degraded by proteases such as MMPs. The purpose of this study was to translate the use of the blood-based marker CRPM to OA, from rheumatoid arthritis (RA), where it has been extensively tested. Furthermore, to test whether it is predictive of radiographic progression in OA.
Methods: The placebo arms of two phase III OA trial (NCT00486434/NCT00704847), a phase III RA study (the LITHE study, N=490), which included patients with active, moderate-severe RA (NCT00106535), and in an early RA cohort (N=92) were used. Subjects with symptomatic and radiographic knee OA: WOMAC pain ≥150mm and/or WOMAC function ≥510mm, and KL grade 2 or 3. KLG were scored for both knees at baseline and year 2 (Y2). Serum CRPM and CRP were measured at baseline. The association between serum CRPM levels and disease activity score (DAS28) and CRP was investigated by Spearman’s correlations. Quartile ranges of CRPM in the early RA cohort were used to define the cut-off between inflammatory OA and non-inflammatory OA. OA knees were divided into cases and controls based on a terminology proposed by the FNIH-OAI consortium; knees with KLG≥2 at BL were excluded, and incidence OA at Y2 was defined KLG≥2. Logistic regression was used to compare cases and controls.
Results: There was a significant correlation between disease activity measures and CRPM in both RA studies. Seventy-five percent of the LITHE patients had high or very high levels of CRPM at BL, which was changed to a pattern similar to early RA after treatment (table). Mean CRPM levels were significantly lower in OA (8.5 [8.3-8.8]) compared to the RA patients (15.6 [9.5-21.6]); however, a significant subset of OA patients (41%-31% in SMC2301/02) had CRPM levels ≥9ng/mL, as 75% of patients with early RA. Patients with BL or Y2 CRPM levels ≥9ng/mL were more likely to develop knee OA than patients with low level of CRPM. Overall, moderate to very high levels of CRPM at BL and Y2 were predictive of incidence OA with odds ratio of 4.6 [1.2-17] and 2.5 [1.2-4.8].
Conclusion: CRPM is associated with disease activity and modulated in response to anti-inflammatory treatment in RA. A subset of OA patients, up to 41%, appear to have tissue inflammation comparable to that of RA, reflected by the level of CRPM. Furthermore, high CRPM levels was prognostic of incident knee OA.
To cite this abstract in AMA style:Bay-Jensen AC, Bihlet AR, Byrjalsen I, Andersen J, He Y, Siebuhr AS, Thudium CS, Riis BJ, Christiansen C, Karsdal MA. A Metabolite of C-Reactive Protein, a Marker of Disease Actvity, Is Prognostic of Radiographic Knee OA [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/a-metabolite-of-c-reactive-protein-a-marker-of-disease-actvity-is-prognostic-of-radiographic-knee-oa/. Accessed May 24, 2019.
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