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Published in: Arthritis Research & Therapy 4/2003

Open Access 01-09-2003 | Research article

Serum cartilage oligomeric matrix protein (COMP) decreases in rheumatoid arthritis patients treated with infliximab or etanercept

Authors: Meliha Crnkic, Bengt Månsson, Lotta Larsson, Pierre Geborek, Dick Heinegård, Tore Saxne

Published in: Arthritis Research & Therapy | Issue 4/2003

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Abstract

Changes in serum cartilage oligomeric matrix protein (COMP) were studied during a 6-month period from initiation of treatment of rheumatoid arthritis patients with either infliximab or etanercept, to elucidate whether the favourable results of tissue protection reported in clinical trials are corroborated by changing levels of circulating COMP. Rheumatoid arthritis patients commencing treatment with infliximab (N = 32) or etanercept (N = 17) were monitored in accordance with a structured protocol. Only patients who were not receiving glucocorticoids or who were on a stable dose of oral prednisolone (<10 mg daily) were included. Serum COMP was measured by a sandwich immunoassay based on two monoclonal antibodies against human COMP in samples obtained at treatment initiation and at 3 and 6 months. Serum COMP decreased at 3 months in both infliximab- and etanercept-treated patients (P < 0.001 and <0.005, respectively) and remained low at 6 months. There was no significant correlation between changes in or concentrations of serum COMP and serum C-reactive protein at any time point. A decrease in serum COMP was seen both in ACR20 responders (patients meeting the American College of Rheumatology criteria for 20% improvement) and in nonresponders. The pattern of changes of serum COMP, a marker for cartilage turnover, in these patient groups supports the interpretation that infliximab and etanercept have a joint protective effect. Serum COMP has potential as a useful marker for evaluating tissue effects of novel treatment modalities in rheumatoid arthritis.
Literature
1.
go back to reference Welsing PM, van Gestel AM, Swinkels HL, Kiemeney LA, van Riel PL: The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis. Arthritis Rheum. 2001, 44: 2009-2017. 10.1002/1529-0131(200109)44:9<2009::AID-ART349>3.0.CO;2-L.CrossRefPubMed Welsing PM, van Gestel AM, Swinkels HL, Kiemeney LA, van Riel PL: The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis. Arthritis Rheum. 2001, 44: 2009-2017. 10.1002/1529-0131(200109)44:9<2009::AID-ART349>3.0.CO;2-L.CrossRefPubMed
2.
go back to reference van den Berg WB: Uncoupling of inflammatory and destructive mechanisms in arthritis. Semin Arthritis Rheum. 2001, 30: 7-16. 10.1053/sarh.2001.23704.CrossRefPubMed van den Berg WB: Uncoupling of inflammatory and destructive mechanisms in arthritis. Semin Arthritis Rheum. 2001, 30: 7-16. 10.1053/sarh.2001.23704.CrossRefPubMed
3.
go back to reference Feldmann M, Maini RN: Discovery of TNF-alpha as a therapeutic target in rheumatoid arthritis: preclinical and clinical studies. Joint Bone Spine. 2002, 69: 12-18. 10.1016/S1297-319X(01)00335-9.CrossRefPubMed Feldmann M, Maini RN: Discovery of TNF-alpha as a therapeutic target in rheumatoid arthritis: preclinical and clinical studies. Joint Bone Spine. 2002, 69: 12-18. 10.1016/S1297-319X(01)00335-9.CrossRefPubMed
4.
go back to reference Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Katsikis P, Brennan FM, Walker J, Bijl H, Ghrayeb J, Woody JN: Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum. 1993, 36: 1681-1690.CrossRefPubMed Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Katsikis P, Brennan FM, Walker J, Bijl H, Ghrayeb J, Woody JN: Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum. 1993, 36: 1681-1690.CrossRefPubMed
5.
go back to reference Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, Leeb B, Breedveld FC, Macfarlane JD, Bijl H, Woody JN: Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994, 344: 1105-1110. 10.1016/S0140-6736(94)90628-9.CrossRefPubMed Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, Leeb B, Breedveld FC, Macfarlane JD, Bijl H, Woody JN: Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet. 1994, 344: 1105-1110. 10.1016/S0140-6736(94)90628-9.CrossRefPubMed
6.
go back to reference Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, Ettlinger RE, Cohen S, Koopman WJ, Mohler K, Widmer MB, Blosch CM: Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med. 1997, 337: 141-147. 10.1056/NEJM199707173370301.CrossRefPubMed Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, Ettlinger RE, Cohen S, Koopman WJ, Mohler K, Widmer MB, Blosch CM: Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med. 1997, 337: 141-147. 10.1056/NEJM199707173370301.CrossRefPubMed
7.
go back to reference Bresnihan B, Alvaro-Gracia JM, Cobby M, Doherty M, Domljan Z, Emery P, Nuki G, Pavelka K, Rau R, Rozman B, Watt I, Williams B, Aitchison R, McCabe D, Musikic P: Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 1998, 41: 2196-2204. 10.1002/1529-0131(199812)41:12<2196::AID-ART15>3.3.CO;2-U.CrossRefPubMed Bresnihan B, Alvaro-Gracia JM, Cobby M, Doherty M, Domljan Z, Emery P, Nuki G, Pavelka K, Rau R, Rozman B, Watt I, Williams B, Aitchison R, McCabe D, Musikic P: Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 1998, 41: 2196-2204. 10.1002/1529-0131(199812)41:12<2196::AID-ART15>3.3.CO;2-U.CrossRefPubMed
8.
go back to reference Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Genovese MC, Wasko MC, Moreland LW, Weaver AL, Markenson J, Finck BK: A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000, 343: 1586-1593. 10.1056/NEJM200011303432201.CrossRefPubMed Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Genovese MC, Wasko MC, Moreland LW, Weaver AL, Markenson J, Finck BK: A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000, 343: 1586-1593. 10.1056/NEJM200011303432201.CrossRefPubMed
9.
go back to reference Jiang Y, Genant HK, Watt I, Cobby M, Bresnihan B, Aitchison R, McCabe D: A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum. 2000, 43: 1001-1009. 10.1002/1529-0131(200005)43:5<1001::AID-ANR7>3.0.CO;2-P.CrossRefPubMed Jiang Y, Genant HK, Watt I, Cobby M, Bresnihan B, Aitchison R, McCabe D: A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum. 2000, 43: 1001-1009. 10.1002/1529-0131(200005)43:5<1001::AID-ANR7>3.0.CO;2-P.CrossRefPubMed
10.
go back to reference Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN: Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000, 343: 1594-1602. 10.1056/NEJM200011303432202.CrossRefPubMed Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN: Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000, 343: 1594-1602. 10.1056/NEJM200011303432202.CrossRefPubMed
11.
go back to reference van der Heijde D, Simon L, Smolen J, Strand V, Sharp J, Boers M, Breedveld F, Weisman M, Weinblatt M, Rau R, Lipsky P: How to report radiographic data in randomized clinical trials in rheumatoid arthritis: guidelines from a roundtable discussion. Arthritis Rheum. 2002, 47: 215-218. 10.1002/art.10181.CrossRefPubMed van der Heijde D, Simon L, Smolen J, Strand V, Sharp J, Boers M, Breedveld F, Weisman M, Weinblatt M, Rau R, Lipsky P: How to report radiographic data in randomized clinical trials in rheumatoid arthritis: guidelines from a roundtable discussion. Arthritis Rheum. 2002, 47: 215-218. 10.1002/art.10181.CrossRefPubMed
12.
go back to reference Saxne T, Månsson B: Molecular markers for assessment of cartilage damage in rheumatoid arthritis. In Rheumatoid Arthritis: New Frontiers in Pathogenesis and Treatment. Edited by: Firestein G, Panayi GS, Wollheim FA. 2000, Oxford: Oxford University Press, 291-304. Saxne T, Månsson B: Molecular markers for assessment of cartilage damage in rheumatoid arthritis. In Rheumatoid Arthritis: New Frontiers in Pathogenesis and Treatment. Edited by: Firestein G, Panayi GS, Wollheim FA. 2000, Oxford: Oxford University Press, 291-304.
13.
go back to reference Hedbom E, Antonsson P, Hjerpe A, Aeschlimann D, Paulsson M, Rosa-Pimentel E, Sommarin Y, Wendel M, Oldberg A, Heinegård D: Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage. Biol Chem. 1992, 267: 6132-6136. Hedbom E, Antonsson P, Hjerpe A, Aeschlimann D, Paulsson M, Rosa-Pimentel E, Sommarin Y, Wendel M, Oldberg A, Heinegård D: Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage. Biol Chem. 1992, 267: 6132-6136.
14.
go back to reference Saxne T, Heinegård D: Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Br J Rheumatol. 1992, 31: 583-591.CrossRefPubMed Saxne T, Heinegård D: Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in synovial fluid and blood. Br J Rheumatol. 1992, 31: 583-591.CrossRefPubMed
15.
go back to reference Geborek P, Crnkic M, Petersson IF, Saxne T: Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden. Ann Rheum Dis. 2002, 61: 793-798. 10.1136/ard.61.9.793.PubMedCentralCrossRefPubMed Geborek P, Crnkic M, Petersson IF, Saxne T: Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden. Ann Rheum Dis. 2002, 61: 793-798. 10.1136/ard.61.9.793.PubMedCentralCrossRefPubMed
16.
go back to reference Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324.CrossRefPubMed Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324.CrossRefPubMed
17.
go back to reference DiCesare P, Hauser N, Lehman D, Pasumarti S, Paulsson M: Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon. FEBS Lett. 1994, 354: 237-240. 10.1016/0014-5793(94)01134-6.CrossRefPubMed DiCesare P, Hauser N, Lehman D, Pasumarti S, Paulsson M: Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon. FEBS Lett. 1994, 354: 237-240. 10.1016/0014-5793(94)01134-6.CrossRefPubMed
18.
go back to reference Smith RK, Zunino L, Webbon PM, Heinegård D: The distribution of cartilage oligomeric matrix protein (COMP) in tendon and its variation with tendon site, age and load. Matrix Biol. 1997, 16: 255-271. 10.1016/S0945-053X(97)90014-7.CrossRefPubMed Smith RK, Zunino L, Webbon PM, Heinegård D: The distribution of cartilage oligomeric matrix protein (COMP) in tendon and its variation with tendon site, age and load. Matrix Biol. 1997, 16: 255-271. 10.1016/S0945-053X(97)90014-7.CrossRefPubMed
19.
go back to reference Recklies AD, Baillargeon L, White C: Regulation of cartilage oligomeric matrix protein synthesis in human synovial cells and articular chondrocytes. Arthritis Rheum. 1998, 41: 997-1006. 10.1002/1529-0131(199806)41:6<997::AID-ART6>3.0.CO;2-G.CrossRefPubMed Recklies AD, Baillargeon L, White C: Regulation of cartilage oligomeric matrix protein synthesis in human synovial cells and articular chondrocytes. Arthritis Rheum. 1998, 41: 997-1006. 10.1002/1529-0131(199806)41:6<997::AID-ART6>3.0.CO;2-G.CrossRefPubMed
20.
go back to reference den Broeder AA, Joosten LA, Saxne T, Heinegård D, Fenner H, Miltenburg AM, Frasa WL, van Tits LJ, Buurman WA, van Riel PL, van de Putte LB, Barrera P: Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Ann Rheum Dis. 2002, 61: 311-318. 10.1136/ard.61.4.311.PubMedCentralCrossRefPubMed den Broeder AA, Joosten LA, Saxne T, Heinegård D, Fenner H, Miltenburg AM, Frasa WL, van Tits LJ, Buurman WA, van Riel PL, van de Putte LB, Barrera P: Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Ann Rheum Dis. 2002, 61: 311-318. 10.1136/ard.61.4.311.PubMedCentralCrossRefPubMed
21.
go back to reference Kirwan JR: The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med. 1995, 333: 142-146. 10.1056/NEJM199507203330302.CrossRefPubMed Kirwan JR: The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med. 1995, 333: 142-146. 10.1056/NEJM199507203330302.CrossRefPubMed
22.
go back to reference van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW: Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med. 2002, 136: 1-12.CrossRefPubMed van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW: Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med. 2002, 136: 1-12.CrossRefPubMed
Metadata
Title
Serum cartilage oligomeric matrix protein (COMP) decreases in rheumatoid arthritis patients treated with infliximab or etanercept
Authors
Meliha Crnkic
Bengt Månsson
Lotta Larsson
Pierre Geborek
Dick Heinegård
Tore Saxne
Publication date
01-09-2003
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2003
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar760

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