title: 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.forename: Maurizio
authors.initials: M
authors.lastname: Benucci
authors.forename: Francesca
authors.initials: F
authors.lastname: Meacci
authors.forename: Mariangela
authors.initials: M
authors.lastname: Manfredi
authors.forename: Francesca Li
authors.initials: FL
authors.lastname: Gobbi
authors.forename: Maria
authors.initials: M
authors.lastname: Infantino
authors.forename: Cristian
authors.initials: C
authors.lastname: Ricci
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Sarzi-Puttini
authors.affiliation: Rheumatology Unit, Azienda Sanitaria di Firenze, Hospital S. Giovanni di Dio, Via Torregalli 3, 50143 Firenze FI, Italy. maubenucci@tiscali.it.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Atzeni
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D064236:Cartilage Oligomeric Matrix Protein / Q000097:blood / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D018124:Receptors, Tumor Necrosis Factor; C502936:tocilizumab