Background/Purpose: Rheumatoid arthritis (RA) is partly characterized by joint destruction. Personalized health care is needed in RA to enable i) prediction of those patients that will progress most rapidly and in most need of aggressive intervention, and ii) prediction of those that will respond to a given treatment and those that will not, and thereby limiting the cases of serious side effects. Serum C1M is specific measure of connective tissue degradation, which originates from the down-stream signaling pathways of inflammatory cytokines IL-6, IL-1 and TNFα. The aims of the study were to investigate: i) whether levels of C1M could predict who would structurally progress over 1-year, ii) to which level C1M was suppressed by tocilizumab (TCZ), and iii) whether baseline levels or early changes of C1M could predict responders to TCZ either on disease activity or structural protection.

Methods: The LITHE Biomarker study (NCT00106535) was a 1-year phase III, double-blind, placebo-controlled, parallel group study of TCZ 4mg/kg+MTX (n=200), 8mg/kg+MTX (n=186) or PBO+MTX (n=199) in patients with moderate-severe active RA, but MTX-IR. All patients had radiographically confirmed joint erosion at baseline. Fasting serum was collected at baseline and week 4, 16, 24 and 52 weeks. Patients who failed to respond to treatment (≤ 20% improvement in both swollen and tender joint counts) at week 16 were designated early non-responders. Radiographs (total Genant-modified Sharp scoring system (mTSS) and joint space narrowing (JSN)) and DAS28  were obtained at baseline, week 24 and 52. The study was approved by ethical committees at each participating institution. All patients provided written informed consent. C1M was measured in samples taken at baseline and week 4. Spearman’s ranked correlation was done on baseline level and 4-week change of C1M, age, body mass index (BMI), disease duration, DAS28, JSN and mTSS weeks 24 and 52. Multiple regression analysis was performed on log-transformed data for delta structural progression (JSN and mTSS) and C1M, adjusted for age, BMI, disease duration, baseline CRP and radiography.

Results: At baseline, C1M was significantly correlated to DAS28 (ρ=0.25, P<0.0001), mTSS (ρ=0.14, P=0.0006), and JSN (ρ=0.12, P=0.0056). C1M was at correlated to change in JSN and mTSS (p<0.0001). The level of C1M was at the level of the placebo group when treated with 4mg/kg TCZ, whereas the 8mg/kg TCZ suppressed the level by 49.2% lower than at baseline, p<0.0001). The level of C1M remained at a significantly lower level in the 8 mg/kg TCZ + MTX than in PBO group throughout the study (p<0.0001). The difference in C1M between early responders and non-responders when treated with 8 mg/kg were significant (AUC 0.71, p=0.0010). C1M was not correlated to age, BMI or disease duration.

Conclusion: Baseline C1M levels correlated to worsening joint structure over one year, demonstrating this as the first structural progression marker for RA. Early changes in C1M were associated with structural efficacy. These data in combination with other technologies may be a part of the identification of those RA patients that are in most need of aggressive treatment, and the monitoring of these patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-c1m-level-predicts-disease-progression-and-early-treatment-efficacy-in-rheumatoid-arthritis/