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Published in: BMC Musculoskeletal Disorders 1/2011

Open Access 01-12-2011 | Research article

Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: Subanalysis of the PREMIER study

Authors: Mari Hoff, Tore K Kvien, Johan Kälvesten, Aake Elden, Arthur Kavanaugh, Glenn Haugeberg

Published in: BMC Musculoskeletal Disorders | Issue 1/2011

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Abstract

Background

Anti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response. This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA.
The objective of this study was to examine if treatment with the TNF-α inhibitor adalimumab also could reduce periarticular bone loss in RA patients independent of disease activity.

Methods

RA patients were recruited from the PREMIER study and included 214 patients treated with methotrexate (MTX) plus adalimumab and 188 patients treated with MTX monotherapy. Periarticular bone loss was assessed by digital X-ray radiogrammetry metacarpal cortical index (DXR-MCI). Change in DXR-MCI was evaluated in patients with different levels of clinical response, as assessed by changes in DAS28 score at 52 weeks and in mean C-reactive protein (CRP) levels during follow-up.

Results

In the MTX group, there was a greater median DXR-MCI loss among patients with moderate and high disease activity compared to those in remission or with low disease activity (-3.3% vs. -2.2%, p = 0.01). In contrast, periarticular bone loss was independent of disease activity (-1.9% vs. -2.4%, p = 0.99) in the combination group. In the MTX group patients with a mean CRP of ≥ 10 mg/l lost significantly more DXR-MCI than patients with low CRP (-3.1% vs. -1.9%, p <0.01) whereas in the combination group no significant differences between the two CRP groups was seen (-2.4% vs. -2.0%, p = 0.48).

Conclusion

Adalimumab in combination with MTX reduces periarticular bone loss independently of clinical response. These results support the hypothesis that TNF-α stimulates the osteoclast not only by the inflammatory pathway but do also have a direct effect on the osteoclast.

Trial Registration

ClinicalTrials (NCT): NCT001195663
Appendix
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Literature
1.
go back to reference Schett G, Teitelbaum SL: Osteoclasts and arthritis. J Bone Miner Res. 2009, 24: 1142-1146. 10.1359/jbmr.090533.CrossRef Schett G, Teitelbaum SL: Osteoclasts and arthritis. J Bone Miner Res. 2009, 24: 1142-1146. 10.1359/jbmr.090533.CrossRef
2.
go back to reference Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR: 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: 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
3.
go back to reference Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS: Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004, 50: 1400-1411. 10.1002/art.20217.CrossRefPubMed Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS: Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004, 50: 1400-1411. 10.1002/art.20217.CrossRefPubMed
4.
go back to reference St Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P: Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004, 50: 3432-3443. 10.1002/art.20568.CrossRefPubMed St Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P: Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004, 50: 3432-3443. 10.1002/art.20568.CrossRefPubMed
5.
go back to reference Guler-Yuksel M, Allaart CF, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Groenendael JH, Mallee C: Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis. 2009, 68: 330-336. 10.1136/ard.2007.086348.CrossRefPubMed Guler-Yuksel M, Allaart CF, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Groenendael JH, Mallee C: Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis. 2009, 68: 330-336. 10.1136/ard.2007.086348.CrossRefPubMed
6.
go back to reference Hoff M, Kvien TK, Kalvesten J, Elden A, Haugeberg G: Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study. Ann Rheum Dis. 2009, 68: 1171-1176. 10.1136/ard.2008.091264.CrossRefPubMed Hoff M, Kvien TK, Kalvesten J, Elden A, Haugeberg G: Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study. Ann Rheum Dis. 2009, 68: 1171-1176. 10.1136/ard.2008.091264.CrossRefPubMed
7.
go back to reference Emery P, Genovese MC, van Vollenhoven R, Sharp JT, Patra K, Sasso EH: Less radiographic progression with adalimumab plus methotrexate versus methotrexate monotherapy across the spectrum of clinical response in early rheumatoid arthritis. J Rheumatol. 2009, 36: 1429-1441. 10.3899/jrheum.081018.CrossRefPubMed Emery P, Genovese MC, van Vollenhoven R, Sharp JT, Patra K, Sasso EH: Less radiographic progression with adalimumab plus methotrexate versus methotrexate monotherapy across the spectrum of clinical response in early rheumatoid arthritis. J Rheumatol. 2009, 36: 1429-1441. 10.3899/jrheum.081018.CrossRefPubMed
8.
go back to reference Smolen JS, Han C, van der Heijde DM, Emery P, Bathon JM, Keystone E: Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade. Ann Rheum Dis. 2009, 68: 823-827. 10.1136/ard.2008.090019.CrossRefPubMed Smolen JS, Han C, van der Heijde DM, Emery P, Bathon JM, Keystone E: Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade. Ann Rheum Dis. 2009, 68: 823-827. 10.1136/ard.2008.090019.CrossRefPubMed
9.
go back to reference Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R: The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006, 54: 26-37. 10.1002/art.21519.CrossRefPubMed Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R: The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006, 54: 26-37. 10.1002/art.21519.CrossRefPubMed
10.
go back to reference Hyldstrup L, Nielsen SP: Metacarpal index by digital X-ray radiogrammetry: normative reference values and comparison with dual X-ray absorptiometry. J Clin Densitom. 2001, 4: 299-306. 10.1385/JCD:4:4:299.CrossRefPubMed Hyldstrup L, Nielsen SP: Metacarpal index by digital X-ray radiogrammetry: normative reference values and comparison with dual X-ray absorptiometry. J Clin Densitom. 2001, 4: 299-306. 10.1385/JCD:4:4:299.CrossRefPubMed
11.
go back to reference Nielsen SP: The metacarpal index revisited: a brief overview. J Clin Densitom. 2001, 4: 199-207. 10.1385/JCD:4:3:199.CrossRefPubMed Nielsen SP: The metacarpal index revisited: a brief overview. J Clin Densitom. 2001, 4: 199-207. 10.1385/JCD:4:3:199.CrossRefPubMed
12.
go back to reference Rosholm A, Hyldstrup L, Backsgaard L, Grunkin M, Thodberg HH: Estimation of bone mineral density by digital X-ray radiogrammetry: theoretical background and clinical testing. Osteoporos Int. 2001, 12: 961-969. 10.1007/s001980170026.CrossRefPubMed Rosholm A, Hyldstrup L, Backsgaard L, Grunkin M, Thodberg HH: Estimation of bone mineral density by digital X-ray radiogrammetry: theoretical background and clinical testing. Osteoporos Int. 2001, 12: 961-969. 10.1007/s001980170026.CrossRefPubMed
13.
go back to reference Hoff M, Dhainaut A, Kvien TK, Haugeberg G: Short time precision assessed with digital X-ray radiogrammetry in healthy individuals and rheumatoid arthritis patients. Annals of the rheumatic diseases. 2008, 67 (suppl 2): 563-Abstract Hoff M, Dhainaut A, Kvien TK, Haugeberg G: Short time precision assessed with digital X-ray radiogrammetry in healthy individuals and rheumatoid arthritis patients. Annals of the rheumatic diseases. 2008, 67 (suppl 2): 563-Abstract
14.
go back to reference Hoff M, Haugeberg G, Kvien TK: Hand bone loss as an outcome measure in established rheumatoid arthritis: 2-year observational study comparing cortical and total bone loss. Arthritis Res Ther. 2007, 9: R81-10.1186/ar2280.CrossRefPubMedPubMedCentral Hoff M, Haugeberg G, Kvien TK: Hand bone loss as an outcome measure in established rheumatoid arthritis: 2-year observational study comparing cortical and total bone loss. Arthritis Res Ther. 2007, 9: R81-10.1186/ar2280.CrossRefPubMedPubMedCentral
15.
go back to reference Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL: Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995, 38: 44-48. 10.1002/art.1780380107.CrossRefPubMed Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL: Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995, 38: 44-48. 10.1002/art.1780380107.CrossRefPubMed
16.
go back to reference van Gestel AM, Anderson JJ, van Riel PL, Boers M, Haagsma CJ, Rich B: ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. American College of Rheumatology European League of Associations for Rheumatology. J Rheumatol. 1999, 26: 705-711.PubMed van Gestel AM, Anderson JJ, van Riel PL, Boers M, Haagsma CJ, Rich B: ACR and EULAR improvement criteria have comparable validity in rheumatoid arthritis trials. American College of Rheumatology European League of Associations for Rheumatology. J Rheumatol. 1999, 26: 705-711.PubMed
17.
go back to reference Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL: TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest. 2000, 106: 1481-1488. 10.1172/JCI11176.CrossRefPubMedPubMedCentral Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL: TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest. 2000, 106: 1481-1488. 10.1172/JCI11176.CrossRefPubMedPubMedCentral
18.
go back to reference Emery P: The Dunlop-Dottridge Lecture: prognosis in inflammatory arthritis: the value of HLA genotyping and the oncological analogy. J Rheumatol. 1997, 24: 1436-1442.PubMed Emery P: The Dunlop-Dottridge Lecture: prognosis in inflammatory arthritis: the value of HLA genotyping and the oncological analogy. J Rheumatol. 1997, 24: 1436-1442.PubMed
19.
go back to reference Hyldstrup L, Jorgensen JT, Sorensen TK, Baeksgaard L: Response of cortical bone to antiresorptive treatment. Calcif Tissue Int. 2001, 68: 135-139. 10.1007/s002230001204.CrossRefPubMed Hyldstrup L, Jorgensen JT, Sorensen TK, Baeksgaard L: Response of cortical bone to antiresorptive treatment. Calcif Tissue Int. 2001, 68: 135-139. 10.1007/s002230001204.CrossRefPubMed
Metadata
Title
Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: Subanalysis of the PREMIER study
Authors
Mari Hoff
Tore K Kvien
Johan Kälvesten
Aake Elden
Arthur Kavanaugh
Glenn Haugeberg
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2011
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-12-54

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