Adalimumab Reduces Hand Bone Loss in Rheumatoid Arthritis Independent of Clinical Response: Subanalysis of the PREMIER Study

Overview

Journal BMC Musculoskelet Disord

Publisher Biomed Central

Specialties Orthopedics
Physiology

Date 2011 Mar 1

PMID 21352592

Citations 25

Authors

Mari Hoff

Tore K Kvien

Johan Kalvesten

Aake Elden

Arthur Kavanaugh

Glenn Haugeberg

Affiliations

Soon will be listed here.

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.

Citing Articles

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn's disease.

Zhou S, Huang Z, Hou W, Lin Y, Yu J Inflamm Res. 2024; 73(2):199-209.

PMID: 38168701 PMC: 10824800. DOI: 10.1007/s00011-023-01828-7.

Effects of Biological/Targeted Therapies on Bone Mineral Density in Inflammatory Arthritis.

Chen T, Chang K, Su K Int J Mol Sci. 2022; 23(8).

PMID: 35456929 PMC: 9029148. DOI: 10.3390/ijms23084111.

Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis.

Kondo N, Kuroda T, Kobayashi D Int J Mol Sci. 2021; 22(20).

PMID: 34681582 PMC: 8539723. DOI: 10.3390/ijms222010922.

Bone Metabolism and RANKL/OPG Ratio in Rheumatoid Arthritis Women Treated with TNF-α Inhibitors.

Jura-Poltorak A, Szeremeta A, Olczyk K, Zon-Giebel A, Komosinska-Vassev K J Clin Med. 2021; 10(13).

PMID: 34209821 PMC: 8267676. DOI: 10.3390/jcm10132905.

Effect of disease-modifying anti-rheumatic drugs on bone structure and strength in psoriatic arthritis patients.

Simon D, Kleyer A, Bayat S, Tascilar K, Kampylafka E, Meinderink T Arthritis Res Ther. 2019; 21(1):162.

PMID: 31269973 PMC: 6607518. DOI: 10.1186/s13075-019-1938-3.

References

Keystone E, Kavanaugh A, Sharp J, Tannenbaum H, Hua Y, Teoh L . 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,.... Arthritis Rheum. 2004; 50(5):1400-11. DOI: 10.1002/art.20217. View

Hyldstrup L, Jorgensen J, Sorensen T, Baeksgaard L . Response of cortical bone to antiresorptive treatment. Calcif Tissue Int. 2001; 68(3):135-9. DOI: 10.1007/s002230001204. View

Hyldstrup L, Nielsen S . Metacarpal index by digital X-ray radiogrammetry: normative reference values and comparison with dual X-ray absorptiometry. J Clin Densitom. 2001; 4(4):299-306. DOI: 10.1385/jcd:4:4:299. View

Emery P . The Dunlop-Dottridge Lecture: prognosis in inflammatory arthritis: the value of HLA genotyping and the oncological analogy. J Rheumatol. 1997; 24(7):1436-42. View

St Clair E, van der Heijde D, Smolen J, Maini R, Bathon J, Emery P . Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004; 50(11):3432-43. DOI: 10.1002/art.20568. View

Breedveld F, Weisman M, Kavanaugh A, Cohen S, 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.... Arthritis Rheum. 2005; 54(1):26-37. DOI: 10.1002/art.21519. View

Hoff M, Haugeberg G, Kvien T . 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(4):R81. PMC: 2206380. DOI: 10.1186/ar2280. View

Lipsky P, van der Heijde D, St Clair E, Furst D, Breedveld F, Kalden J . 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(22):1594-602. DOI: 10.1056/NEJM200011303432202. View

Rosholm A, Hyldstrup L, Backsgaard L, Grunkin M, Thodberg H . Estimation of bone mineral density by digital X-ray radiogrammetry: theoretical background and clinical testing. Osteoporos Int. 2002; 12(11):961-9. DOI: 10.1007/s001980170026. View

10.

Emery P, Genovese M, van Vollenhoven R, Sharp J, Patra K, Sasso E . Less radiographic progression with adalimumab plus methotrexate versus methotrexate monotherapy across the spectrum of clinical response in early rheumatoid arthritis. J Rheumatol. 2009; 36(7):1429-41. DOI: 10.3899/jrheum.081018. View

11.

Hoff M, Kvien T, 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. 2008; 68(7):1171-6. PMC: 2689520. DOI: 10.1136/ard.2008.091264. View

12.

Guler-Yuksel M, Allaart C, Goekoop-Ruiterman Y, de Vries-Bouwstra J, van Groenendael J, Mallee C . Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis. 2008; 68(3):330-6. DOI: 10.1136/ard.2007.086348. View

13.

Smolen J, Han C, van der Heijde D, Emery P, Bathon J, 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. 2008; 68(6):823-7. DOI: 10.1136/ard.2008.090019. View

14.

van Gestel A, Anderson J, van Riel P, Boers M, Haagsma C, 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(3):705-11. View

15.

Lam J, Takeshita S, Barker J, Kanagawa O, Ross F, Teitelbaum S . TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest. 2000; 106(12):1481-8. PMC: 387259. DOI: 10.1172/JCI11176. View

16.

Schett G, Teitelbaum S . Osteoclasts and arthritis. J Bone Miner Res. 2009; 24(7):1142-6. DOI: 10.1359/jbmr.090533. View

17.

Prevoo M, van t Hof M, Kuper H, van Leeuwen M, van de Putte L, van Riel P . 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(1):44-8. DOI: 10.1002/art.1780380107. View

18.

Nielsen S . The metacarpal index revisited: a brief overview. J Clin Densitom. 2001; 4(3):199-207. DOI: 10.1385/jcd:4:3:199. View