- Meeting abstract
- Open Access
Are DMARDs enough to prevent surgery in rheumatoid hands?
- Yeap Swan Sim1
© Sim; licensee BioMed Central Ltd. 2015
- Published: 19 May 2015
- Rheumatoid Arthritis
- Joint Damage
- Joint Space Narrowing
- Radiographic Progression
- Interphalangeal Joint
Rheumatoid arthritis (RA) is a chronic, auto-immune disorder characterised by inflammation primarily in the joints. The small joints in the hands are typically involved in RA, with both the 1987 American Rheumatism Association revised criteria for RA classification including “arthritis of hand joints” as one of the criterion  and the 2010 RA classification criteria awarding more points for small joint involvement (i.e. themetacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints and wrists) .
RA is the most common of the inflammatory arthritides; a study in the UK found the prevalence of RA to be 1.16% in women and 0.44% in men . In Asia, the prevalence of RA varies from country to country. In rural areas, the prevalence of RA is 0.12% in Thailand, 0.2% in Indonesia, 0.26% in Taiwan, 0.3% in Malaysia, 0.34% in China, 0.55% in India and 0.7% in Bangladesh .
Although a specific antigen that triggers off the immune response in RA has not been convincingly identified, cell-mediated immune responses (especially from the T cells) have been shown to be responsible for RA joint inflammation. In an susceptible host (e.g. a person with the appropriate genetic background), the T cell response results in the elaboration of T cell cytokines, with resultant recruitment of inflammatory cells, including neutrophils, macrophages, B cells and memory T cells. A target of the inflammatory cells is the synovium which becomes markedly hyperplastic and infiltrated with mononuclearcells. One feature of RA that distinguishes it from other inflammatory arthropathies is the propensity for the synovium to become locally invasive at the synovial interface with cartilage and bone. This destructive mass is called “pannus” and is responsible for the characteristic marginal erosions observed in RA . Cartilage is further destroyed in RA by the catabolic effects of cytokines such as IL-1, IL-6 and tumour necrosis factor-alpha (TNF-α) and the production of metalloproteinases, which can degrade extra-cellular matrix/cartilage, causing more joint damage.
Apart from synovitis, inflammation of the adjacent intertrabecular space (osteitis) also correlates with the development of radiographic bone erosions.Articular bone erosion represents localized bone loss (osteolysis),which results from an imbalance in which bone resorption by osteoclasts is favoured over bone formation by osteoblasts . In RA, TNF-α and receptor activated nuclear factor κ ligand (RANKL) are key cytokines mediating the activation of the osteoclasts .
Studies have shown that erosive disease develops early in the course of RA in the majority of patients. The rate of progression is fastest in the first 2 years . Longitudinal studies have shown that after 2 years approximately 36% of patients have erosions, 47% by 5 years  and 63% by 8 years . If both joint space narrowing and erosions are considered, up to 70% of patients will show radiographic damage after 3 years .
Treatment for RA must involve suppression of the immune-mediated inflammatory response, which requires the use ofdisease-modifying anti-rheumatic drugs (DMARDs). Methotrexate (MTX) is the anchor synthetic DMARD.Good control of inflammation/remission (no joint swelling or tenderness, normal ESR/CRP) will reduce the rate of progression of erosions  and hence joint damage. Compared to placebo, MTX is effective in reducing joint pain and swelling, improving function and reducing the ESR. However, its efficacy at inducing disease remission is limited (only in approximately 25% of patients) andhence less efficacious at reducing radiographic progression . Biologics are monoclonal antibodies produced against various inflammatory cytokines such as TNF-α or IL-6. Compared to MTX, biologics are very much more effective atinducing disease remission and hence reducing the progression of joint damage as assessed by radiographic change scores (e.g. [13–15]. Unfortunately, a major barrier to the widespread use of biologics is their high cost. In addition, approximately 20% of patients do not achieve adequate disease suppression with biologic treatment . So, despite the availability of treatment, many patients with RA remain undertreatedand thus have continuing joint destruction. Nonetheless, since the mid-1990s, studies have shown that the amount of hand surgery in RA patients has been slowly declining, postulated to improvements in medical therapy [17, 18].
Adequate and early treatmentof RA does reduce the rate of radiographic progression and hence joint damage. Although the drugs are available, the most effective drugs are not widely used due to cost issues. Thus, RA hand surgery will still be needed in the foreseeable future.
- Arnett : 1988Google Scholar
- Aletaha D, Neogi T, Silman AJ, et al: Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010, 69: 1580-1588. 10.1136/ard.2010.138461.PubMedView ArticleGoogle Scholar
- Symmons D, Turner G, Webb R, et al: The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century. Rheumatology. 2002, 41: 793-800. 10.1093/rheumatology/41.7.793.PubMedView ArticleGoogle Scholar
- Chopra A, Abdel-Nasser A: Epidemiology of rheumatic musculoskeletal disorders in the developing world. Best Pract Res Clin Rheumatol. 2008, 22 (4): 583-604. 10.1016/j.berh.2008.07.001.PubMedView ArticleGoogle Scholar
- Firestein GS: Rheumatoid synovitis and pannus. Rheumatology. Edited by: Hochberg M, Silman AJ, Smolen JS, et al. 2003, Mosby, ThirdGoogle Scholar
- Schett G, Gravallese E: Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol. 2012, 8: 656-664. 10.1038/nrrheum.2012.153.PubMedPubMed CentralView ArticleGoogle Scholar
- McQueen F, Naredo E: The ‘disconnect’ between synovitis and erosion in rheumatoid arthritis: a result of treatment or intrinsic to the disease process itself?. Ann Rheum Dis. 2011, 70: 241-244. 10.1136/ard.2010.139535.PubMedView ArticleGoogle Scholar
- Fex E, Jonsson K, Johnson U, Eberhardt K: Development of radiographic damage during the first 5-6 yr of rheumatoid arthritis. A prospective follow-up study of a Swedish cohort. Br J Rheumatol. 1996, 35 (11): 1106-15. 10.1093/rheumatology/35.11.1106.PubMedView ArticleGoogle Scholar
- Bukhari M, Harrison B, Lunt M, et al: Time to first occurrence of erosions in inflammatory polyarthritis: results from a prospective community-based study. Arthritis Rheum. 2001, 44 (6): 1248-53. 10.1002/1529-0131(200106)44:6<1248::AID-ART215>3.0.CO;2-8.PubMedView ArticleGoogle Scholar
- Plant MJ, Jones PW, Saklatvala J, et al: Patterns of radiological progression in early rheumatoid arthritis: results of an 8 year prospective study. J Rheumatol. 1998, 25 (3): 417-26.PubMedGoogle Scholar
- van der Heijde DM, van Leeuwen MA, van Riel PL, van de Putte LB: Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp's method (van der Heijde modification). J Rheumatol. 1995, 22 (9): 1792-6.PubMedGoogle Scholar
- Welsing PMJ, Landewe´ RBM, van Riel PLCM, et al: The Relationship Between Disease Activity andRadiologic Progression in Patients With Rheumatoid Arthritis. A Longitudinal Analysis. Arthritis Rheum. 2004, 50: 2082-93. 10.1002/art.20350.PubMedView ArticleGoogle Scholar
- Breedveld FC, Weisman MH, Kavanaugh AF, et al: 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 (1): 26-37. 10.1002/art.21519.PubMedView ArticleGoogle Scholar
- Lipsky PE, van der Heijde DM, St Clair EW, et al: nfliximab 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. 10.1056/NEJM200011303432202.PubMedView ArticleGoogle Scholar
- Klareskog L, van der Heijde D, de Jager JP, et al: Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004, 363 (9410): 675-81. 10.1016/S0140-6736(04)15640-7.PubMedView ArticleGoogle Scholar
- Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al: Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial. Arthritis Rheum. 2008, 58 (2 Suppl): S126-35.PubMedGoogle Scholar
- Weiss RJ, Ehlin A, Montgomery SM, et al: Decrease of RA-related orthopaedic surgery of the upper limbs between 1998 and 2004: data from 54 579 Swedish RA inpatients. Rheumatology. 2008, 47: 491-494.PubMedView ArticleGoogle Scholar
- Dafydd M, Whitaker IS, Murison MS, Boyce DE: Change in operative workload for rheumatoid disease of the hand: 1,109 procedures over 13 years. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2012, 65: 800-803. 10.1016/j.bjps.2011.11.050.View ArticleGoogle Scholar
- Firestein GS: Etiology and pathogenesis of rheumatoid arthritis. Kelley’s Textbook of Rheumatology. Edited by: Firestein GS, Budd RC, Harris ED Jr et al. 2009, Saunders Elsevier, EighthGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.