Therapy of rheumatoid arthritis: New developments and trends
- E. William St. Clair MD
- … show all 1 hide
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
The medical therapy of rheumatoid arthritis (RA) has been influenced strongly during the past decade by the recognition that many patients develop joint damage within the first year of disease. This observation has motivated rheumatologists to initiate disease-modifying antirheumatic drugs (DMARDs) early in the disease course. This trend has been matched by the increased use of combinatio DMARD therapy, with the aim to maximize control of the signs and symptoms of RA and limit the development of joint damage. The results from controlled clinical trials generally have supported the concept that early, aggressive treatment with DMARDs is superior to less intensive strategies. In addition, certain DMARD combinations are more effective than the individual components of these regimens, but the evidence is strong for only a few DMARD combinations such as methotrexate and cyclosporine A. Three new drugs have been recently approved for the treatment of RA. Celecoxib, a selective cyclooxygenase-2 inhibitor, has similar clinical efficacy as conventional nonsteroidal anti-inflammatory drugs, and in short-term studies causes no more gastric and duodenal ulcers and erosions than patients treated with placebo. Treatment with leflunomide, an inhibitor of pyrimidine synthesis, has been shown in controlled clinical trials to produce significant clinical improvement in 50% to 60% of patients with RA and delay radiologic progression of disease. The era of biologic therapy has dawned with the apparent success of tumor necrosis factor (TNF)-a blockade using etanercept, a recombinant TNF receptor:Fc fusion protein, and infliximab, a chimeric anti-TNF monoclonal antibody. These new agents expand our treatment options in RA and should lead to innovative and more effective treatment approaches.
- Wolfe F, Mitchell DM, Sibley JT, et al.: The mortality of rheumatoid arthritis. Arthritis Rheum 1994, 37:481–494. CrossRef
- Fuchs HA, Kaye JJ, Callahan, et al.: Evidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease. J Rheumatol 1989, 16:585–591.
- Wolfe F, Sharp JT: Radiographic outcome of recent-onset rheu-matoid arthritis. A 19-year longitudinal study of radio-graphic progression. Arthritis Rheum 1998, 41:1571–1582. CrossRef
- Mottonen T, Paimela L, Ahonen J, et al.: Outcome in patients with early rheumatoid arthritis treated according to the "sawtooth" strategy. Arthritis Rheum 1996, 39:996–1005. CrossRef
- Fries JF: Reevaluating the therapeutic approach to rheumatoid arthritis: the "sawtooth" strategy. J Rheumatol 1990, 17:12–15.
- Van Heide A, Jacobs JWG, Bijlsma JWJ, et al.: The effective-ness of early treatment with "second-line" antirheumatic drugs. Ann Intern Med 1996, 124:699–707.
- Boers M, Verhoeven AC, Markusse HM, et al.: Randomised comparison of combined step-down prednisolone, metho-trexate and sulphasalazine alone in early rheumatoid arthritis. Lancet 1997, 350:309–318. This article describes the results of a controlled clinical trial investi-gating step-down combination DMARD therapy with bridge corti-costeroid therapy in early RA. The trial is well-designed and provides an example of the potential benefits of early, aggressive therapy. CrossRef
- Haagsm CJ, van Riel PLCM, de Jong AJL, van de Putte LBA: Combination of sulfasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial. Br J Rheumatol 1997, 36:1082–1088. CrossRef
- Kirwan JR, and the Arthritis and Rheumatism Council Low Dose Glucocorticoid Study Group: The effect of glucocorti-coids on joint destruction in rheumatoid arthritis. N Engl J Med 1995, 333:142–146. CrossRef
- Hickling P, Jacoby RK, Kirwan JR, and the Arthritis and Rheu-matism Council Low Dose Glucocorticoid Study Group: Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Br J Rheumatol 1998, 37:930–936. CrossRef
- Wang BWE, Balise RR, Fries JF: Frequency of two-DMARD combinations in the treatment of rheumatoid arthritis. Arthritis Rheum 1998, 41(Suppl):S59.
- Suarez-Almazor ME: Practice patterns in the management of rheumatoid arthritis. Increased use of combination therapy. Arthritis Rheum 1998, 41(Suppl):S153.
- Verhoeven AC, Boers M, Tugwell P: Combination therapy in rheumatoid arthritis: updated systematic review. Br J Rheumatol 1998, 37:612–619. An excellent up-to-date critical review of combination DMARD therapy in RA. The authors use criteria for selecting only high quality studies that provide strong evidence for the observed results. CrossRef
- Tugwell P, Pincus T, Yocum D, et al.: Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthri-tis. N Engl J Med 1995, 333:137–141. CrossRef
- O’Dell JR, Haire CE, Erikson N, et al.: Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxy-chloroquine, or a combination of all three medications. N Engl J Med 1996, 334:1287–1291. CrossRef
- Trnavsky K, Gatterová J, Lindusková M, et al.: Combination therapy with hydroxychloroquine and methotrexate in rheumatoid arthritis. J Rheumatol 1993, 52:292–296.
- Scott DL, Dawes PT, Tunn E, et al.: Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: a pro-spective, randomized, placebo-controlled study. Br J Rheuma-tol 1989, 28:128–133. CrossRef
- Ferraz MB, Pinheiro GRC, Helfenstein M, et sal.:Combination therapy with methotrexate and chloroquine in rheumatoid arthritis. A multicenter randomized placebo-controlled trial. Scand J Rheumatol 1994, 23:231–236.
- Bendix G, Bjelle A: Adding low-dose cyclosporine A to a parenteral gold therapy in rheumatoid arthritis: a double-blind placebo-controlled study. Br J Rheumatol 1996, 35 1142–1149. CrossRef
- Faarvang KL, Egsmose C, Kryger P, et al.: Hydroxychloroquine and sulphasalazine alone and in combination in rheumatoid arthritis: a randomised double blind trial. Ann Rheum Dis 1993, 2:711–715. CrossRef
- Gibson T, Emery P, Armstrong RD, et al.: Combined D-penicil-lamine and chloroquine treatment of rheumatoid arthritis—a comparative study. Br J Rheumatol 1987, 27:279–284. CrossRef
- Haar D, Sølvkjaer M, Unger B, et al.: A double-blind com-parative study of hydroxychloroquine and dapsone, alone and in combination, in rheumatoid arthritis. Scand J Rheumatol 1993, 22:113–118.
- Williams HJ, Ward JR, Reading JC, et al.: Comparison of auranofin, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 1992, 35:259–269. CrossRef
- Willkens RF, Urowitz MB, Stablein DM, et al.: Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 1992, 35:849–856. CrossRef
- Felson DT, Anderson JJ, Meenan RF: The efficacy and toxicity of combination therapy in rheumatoid arthritis. A meta-analysis. Arthritis Rheum 1994, 37:1487–1491. CrossRef
- Hawkey CJ: COX-2 inhibitors. Lancet 1999, 353:307–314. An outstanding contemporary overview of specific COX-2 inhibitors. The authors explain the structural basis for specific COX-2 inhibition, the concept of COX-1 and COX-2 selectivity, and the therapeutic ration-ale for selective COX-2 inhibition in RA as well as other diseases. CrossRef
- Crofford LJ, Wilder RL, Ristimäki AP, et al.: Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues: effects of interleukin-1b, phorbol ester, and corticosteroids. J Clin Invest 1994, 93:1095–1101.
- Simon LS, Lanza FL, Lipsky PE, et al.: Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibi-tor. Efficacy and safety in two placebo-controlled trials in osteoar-thritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998, 41:1591–1602. CrossRef
- Geis GS, Hubbard R, Callison D, et al.: Safety and efficacy of celecoxib, a specific COX-2 inhibitor, in patients with rheumatoid arthritis. Arthritis Rheum 1998, 41(Suppl):S364.
- Geis GS, Stead H, Morant S, et al.: Efficacy and safety of celecoxib, a specific COX-2 inhibitor, in patients with rheumatoid arthritis. Arthritis Rheum 1998, 41(Suppl):S316.
- Fox RI: Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol 1998, 25(Suppl 53):20–26.
- Rozman B: Clinical experience with leflunomide in rheuma-toid arthritis. J Rheumatol 1998, 25(Suppl 53):27–32.
- Mladenovic V, Domljan Z, Rozman B, et al.: Safety and effectivene of leflunomide in the treatment of patients with active rheuma-toid arthritis. Arthritis Rheum 1995, 38:1595 1603. CrossRef
- Smolen JS, Kalden JR, Scott DL, et al.: Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. Lancet 1999, 353:259–256. This article describes a pivotal 24-week controlled trial showing that leflunomide was superior to placebo for the treatment of RA. Lefluno-mide was comparable in efficacy to sulfasalazine. Leflunomide as well as sulfasalazine was shown to retard the progression of radiographic joint damage even though the study only lasted 24 weeks. CrossRef
- Weaver A, Caldwell J, Olsen N, et al.: Treatment of active rheumatoid arthritis with leflunomide compared to placebo or methotrexate. Arthritis Rheum 1998, 41(Suppl):S131.
- Arend WP, Dayer J-M: Inhibition of the production and effects of interleukin-1 and tumor necrosis factor a in rheumatoid arthritis. Arthritis Rheum 1995, 38:151–160. CrossRef
- Firestein GS, Alvaro-Gracia JM, Maki R: Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immu-nol 1990, 144:3347–3353.
- Bresnihan B, Alvaro-Gracia JM, Cobb M, et al.: Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum 1998, 41:2196–2204. CrossRef
- Bazzoni F, Beutler B: The tumor necrosis factor ligand and receptor families. N Engl J Med 1996, 334:1717–1725. CrossRef
- Deleuran BW, Chu C-Q, Field M, et al.: Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis. Impli-cations for local actions of tumor necrosis factor a. Arthritis Rheum 1992, 35:1170–1178. CrossRef
- Cope AP, Aderka D, Doherty M, et al.: Increased levels o soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum 1992, 35:1160–1169. CrossRef
- Moreland LW, Baumgartner SW, Schiff MH, et al.: Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997, 337:141–147. This paper describes the results of a controlled clinical trial using a TNF receptor:Fc fusion protein (etanercept) in RA. This landmark study in RA represents the first trial of a biologic agent where the results pro-vided strong evidence for significant clinical efficacy. It paved the way for subsequent studies and the approval of etanercept for this indication CrossRef
- Weinblatt M, Moreland LW, Schiff MH, et al.: Longterm and phase III treatment of DMARD failing rheumatoid arthritis with TNF receptor p75 Fc fusion protein (TNFR:Fc, Enbrel). Arthritis Rheum 1998, 41(Suppl):S126.
- Weinblatt ME, Kremer JM, Bankhurst AD, et al.: A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiv-ing methotrexate. N Engl J Med 1999, 340:253–259. Methotrexate often serves as the anchor drug in combination regimens because of its well-established efficacy and tolerability. This trial provides data to show that patients with active RA who are receiv-ing methotrexate significantly benefit from the addition of etanercept. It is anticipated that in routine clinical practice biologics such as etanercept will be used frequently in combination with MTX and other DMARDs. CrossRef
- Moreland LW, Baumgartner SW, Tindall EA, et al.: Longterm safety and efficacy of TNF receptor (p75) Fc fusion protein (TNFR:Fc, Enbrel) in DMARD refractory rheumatoid arthritis (RA). Arthritis Rheum 1998, 41(Suppl):S364. CrossRef
- Elliott MJ, Maini RN, Feldmann M, et al.:Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor a (cA2) versus placebo in rheumatoid arthritis. Lancet 1994, 344:1105–1110. CrossRef
- Elliott MJ, Maini RN, Feldmann M, et al.: Repeated therapy with monoclonal antibody to tumour necrosis factor a (cA2) in patients with rheumatoid arthritis. Lancet 1994, 344:1125–1127. CrossRef
- Maini RN, Breedveld FC, Kalden JR, et al.: Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor a monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998, 41:1552–1563. This controlled trial shows the ability of repeated infusions of a chimeric anti-TNF monoclonal antibody (infliximab) to produce a sustained clin-ical response. Combining the therapeutic antibody with methotrexat reduced the incidence of human anti-chimeric antibody responses. CrossRef
- Lipsky P, St. Clair EW, Kavanaug A, et al.: Long-term control of signs and symptoms of rheumatoid arthritis with chimeric mon-oclonal anti-TNFa antibody (infliximab) in patients with active disease on methotrexate. Arthritis Rheum 1998, 1(Suppl):S364.
- Porter DR, Capell HA, Hunter J: Combination therapy in rheu-matoid arthritis—no benefit of addition of hydroxychloro-quine to patients with a suboptimal response to intramuscular gold therapy. J Rheumatol 1993, 20:645–649.
- Salaffi F, Carotti M, Cervini C: Combination therapy of cyclospo-rine A with methotrexate or hydroxychloroquine in refractory rheumatoid arthritis. Scand J Rheumatol 1996, 25 16–23.
- Therapy of rheumatoid arthritis: New developments and trends
Current Rheumatology Reports
Volume 1, Issue 2 , pp 149-156
- Cover Date
- Print ISSN
- Online ISSN
- Current Medicine Group
- Additional Links
- Author Affiliations
- 1. Division of Rheumatology, Allergy, and Clinical Immunology, Duke University Medical Center, Box 3874, 27710, Durham, NC, USA