Background/Purpose:  There is a need for successful drug development in osteoarthritis (OA) as there are currently no disease modifying drugs approved for OA. This may be due to: patient heterogeneity resulting from different disease drivers, clinical studies are complicated by unintended inclusion of patients with little or no disease activity (DA)/progression, lack of surrogate markers for DA in OA. The aim was to investigate clinical characteristics of an RA-like phenotype in OA in 2 OA phase III studies.

Methods:  Biochemical DA was assessed in serum from RA and OA patients by the acute reactant CRP and its proteolytic product CRPM¹. Association between CRPM and DA scores was investigated by spearman’s rho in the placebo group of the LITHE study (n=193, a phase III RA RCT²). OA patients were divided into 4 groups: patients with no inflammation [CRPM<9nM], local inflammation [CRPM>9nM/hsCRP<3g/L], acute inflammation [CRPM<9nM/hsCRP>3g/L], and active disease [CRPM>9nM/hsCRP>3g/L] (table). Biomarkers of soft tissue degradation (C1M, C3M), cartilage degradation (C2M, UCTX-II), bone balance (CTX/OC) and macrophage activity (VICM) were measured in the placebo groups of 2 phase III OA clinical trials (SMC1 and SMC2) including patients with radiographic knee OA³. Kellgren-Lawrence grade (KLG), joint space width (JSW) and WOMAC were recorded at baseline and 2 years

Results:  Association between DA and CRPM in RA. There was a significant correlation between DA and CRPM: HAQ (0.24. p=0.0007), VAS pain (0.16, p=0.023) and DAS28 (0.29, p<0.0001). CRP accounted for about 30% of the biological variation in CRPM, indicating CRP and CRPM reflect different biological processes, and provide independent information. Identification of OA phenotypes. The mean CRPM level was significantly high in RA than OA patients (17.1 vs. 8.5, p<0.0001); however, 31-40% of OA patients had CRPM>9nM, thus overlapping with 75% of the RA. Tissue degradation in OA. In SMC1, C1M and VICM were significantly increased in patients with high DA (p<0.0001). C2M was higher (p=0.006) in patients with local inflammation. C3M was higher in patients with local inflammation, but without acute inflammation (table). The results was replicated in SMC2. OA phenotypes and progression. There were no difference in 2-year progression of KLG, JSW, WOMAC amongst the 4 groups.

Conclusion:  This study provides a major finding: Clinical outcome measures were not different between the groups. Consequently, these data indicate that each different phenotype progress at a comparable rate; however, the underlying pathogenesis is likely to be different, thus should be targeted differently.¹Siebuhr OAC,22,44,2014.²Bay-Jensen, SAR,43,470,2014.³Karsdal OAC, 23, 532,2015.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/disease-progression-in-osteoarthritis-is-driven-by-multiple-disease-parameters-leading-to-comparable-levels-of-joint-destruction/