Can tocilizumab decrease cartilage oligomeric matrix protein levels and disease activity in patients with long-standing rheumatoid arthritis?

Abstract

Serum cartilage oligomeric matrix protein (COMP) level is a new marker of joint destruction in patients with rheumatoid arthritis (RA), and a new means of identifying patients with progressive joint damage. To evaluate the effect of tocilizumab (TCZ) on serum COMP levels, and whether there is any difference in this effect between patients failing on anti-TNF treatment and those failing on disease-modifying anti-rheumatic drugs (DMARDs). Fifty-one patients with long-standing RA (42 F, 9 M; mean age 62 ± 14 years; disease duration 4.5 ± 1.2 years) unresponsive to DMARDs and anti-TNF drugs were treated with TCZ 8 mg/kg/month. Serum COMP levels were measured by means of an ELISA at baseline and after six months of TCZ treatment; the patents' DAS28 scores and levels of RF (IgM, IgG, IgA), anti-CCP autoantibodies, ESR, CRP and IL-6 were evaluated at the same times. After six months of TCZ treatment, there was a significant decrease from baseline in ESR (46.1 [28.7-68.9] vs 34.3 [4.1- 58.8] mm/h, P <0.0001), CRP (2.2 [0.8-4.4] vs 1.3 [0.7-3.8] mg/dL, P <0.0001), TNF-α (21.3 [7.6-29.8] vs 17.4 [3.4-28.6] pg/mL, P=0.0408), IL-6 (6.9 [3.5-9.6] vs 3.4 [3.0-9.6] pg/mL, p<0.0001); anti-CCP (55.1 [30.2-273.0] vs 54.7 [30.1- 269.8] IU/mL, P=0.9683), RF-IgM (142.0 [48.0-260.0] vs 138.0 [42.0-243.0] IU/mL, P=0.4828), RF-IgA (81.0 [20-140] vs 108.0 [20-175] U/mL, P=0.0003), and RF-IgG (65.2 [30-158] vs 58.3 [38.0-158.0] U/mL, P=0.2671). There was also a significant decrease in DAS28 scores (4.3 [3.2-5.9] vs 3.7 [2.3-5.4], P <0.0001), and a non-significant decrease in serum COMP levels (0.95 [0.04-2.90] vs 0.98 [0.05-2.36] μg/mL; P = 0.9856). A decrease in serum COMP levels was observed in the patients failing on anti-TNF treatment or anti-DMARDs without any difference. TCZ therapy in patients with long-standing RA is associated with a significant decrease in ESR, CRP, IL-6, TNF and DAS28 values, and a decrease in serum COMP levels, particularly in patients failing on previous anti-TNF therapy. These findings suggest that TCZ has an effect on cartilage joint destruction after only six months of treatment.

• Authors: Maurizio Benucci, Francesca Meacci, Mariangela Manfredi, Francesca Li Gobbi, Maria Infantino, Cristian Ricci, Piercarlo Sarzi-Puttini, Fabiola Atzeni
• Journal: Current rheumatology reviews (Curr Rheumatol Rev) Vol. 10 Issue 2 Pg. 131-5 ( 2014) ISSN: 1875-6360 [Electronic] United Arab Emirates
• PMID: 25599685 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Biomarkers
• Cartilage Oligomeric Matrix Protein
• Receptors, Tumor Necrosis Factor
• tocilizumab

Topics

• Aged
• Antibodies, Monoclonal, Humanized (pharmacology)
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (blood, drug therapy)
• Biomarkers (blood)
• Cartilage Oligomeric Matrix Protein (blood, drug effects)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Male
• Middle Aged
• Receptors, Tumor Necrosis Factor (therapeutic use)
• Treatment Outcome