Current concepts in the management of rheumatoid arthritis
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Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate, a synthetic disease-modifying antirheumatic drug (DMARD), and biologic DMARD has revolutionized treatment of RA. Clinical remission is now realistic targets, achieved by a large proportion of RA patients, and rapid and appropriate induction of remission by intensive treatment with biological DMARD and methotrexate is prerequisite to halt joint damage and functional disabilities. However, biological DMARD is limited to intravenous or subcutaneous uses and orally available small but strong molecules have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active patients with methotrexatenaïve, inadequately responsive to methotrexate or tumor necrosis factor (TNF)- inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. Meanwhile, association of tofacitinib on carcinogenicity and malignancy is under debate and further investigation on post-marketing survey would be warranted. On the other hand, discontinuation of a biological DMARD without disease flare is our next goal and desirable from the standpoint of risk reduction and cost effectiveness, especially for patients with clinical remission. Recent reports indicate that more than half of early RA patients could discontinue TNF-targeted biological DMARD without clinical flare and functional impairment after obtaining clinical remission. Contrarily, for established RA, fewer patients sustained remission after the discontinuation of biological DMARD and “deep remission” at the discontinuation was a key factor to keep the treatment holiday of biological DMARD.
Abstract
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction that causes significant morbidity and mortality. However, the combined use of methotrexate, a synthetic disease-modifying antirheumatic drug (DMARD), and biologic DMARD has revolutionized treatment of RA. Clinical remission is now realistic targets, achieved by a large proportion of RA patients, and rapid and appropriate induction of remission by intensive treatment with biological DMARD and methotrexate is prerequisite to halt joint damage and functional disabilities. However, biological DMARD is limited to intravenous or subcutaneous uses and orally available small but strong molecules have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active patients with methotrexatenaïve, inadequately responsive to methotrexate or tumor necrosis factor (TNF)- inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. Meanwhile, association of tofacitinib on carcinogenicity and malignancy is under debate and further investigation on post-marketing survey would be warranted. On the other hand, discontinuation of a biological DMARD without disease flare is our next goal and desirable from the standpoint of risk reduction and cost effectiveness, especially for patients with clinical remission. Recent reports indicate that more than half of early RA patients could discontinue TNF-targeted biological DMARD without clinical flare and functional impairment after obtaining clinical remission. Contrarily, for established RA, fewer patients sustained remission after the discontinuation of biological DMARD and “deep remission” at the discontinuation was a key factor to keep the treatment holiday of biological DMARD.
참고문헌 (35)
- Burmester GR, "Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial", Ann Rheum Dis, 74, pp.1037~1044 (2015)
- Furst DE, "Rheumatoid arthritis pathophysiology:update on emerging cytokine and cytokine-associated cell targets", Rheumatology, 53, pp.1560~1569 (2014)
- McInnes IB, "The pathogenesis of rheumatoid arthritis", N Engl J Med, 365, pp.2205~2219 (2011)
- Aletaha D, "Rheumatoid arthritis classification criteria: an American College of Rheumatology", European League Against Rheumatism collaborative initiative, 2010, pp.62, 2569~2581
- Smolen JS, "Treating rheumatoid arthritis to target: recommendations of an international task force", Ann Rheum Dis, 69, pp.631~637 (2010)
- Smolen JS, "Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial", Lancet, 383, pp.321~332 (2014)
- Takeuchi T, "Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study", Ann Rheum Dis, 73, pp.536~543 (2014)
- Felson DT, "American College of Rheumatology", European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials, 2011, pp.70, 404~413
- Weinblatt ME, "Safety and efficacy of etanercept beyond 10 years of therapy in North American patients with early and longstanding rheumatoid arthritis", Arthritis Care Res, 63, pp.373~382 (2011)
- D’Aura Swanson C, "Tyrosine kinases as targets for the treatment of rheumatoid arthritis", Nat Rev Rheumatol, 5, pp.317~324 (2009)
- Macchi P, "Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency(SCID)", Nature, 377, pp.65~68 (1995)
- Pesu M, "Therapeutic targeting of Janus kinases", Immunol Rev, 223, pp.132~142 (2008)
- Tanaka Y, "JAK inhibitor tofacitinib for treating rheumatoid arthritis: from basic to clinical", Mod Rheumatol, 23, pp.415~424 (2013)
- O’Shea JJ, "Janus kinase inhibitors in autoimmune diseases", Ann Rheum Dis, 72(Suppl 2), pp.ii111~ii115 (2013)
- Changelian PS, "Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor", Science, 302, pp.875~878 (2003)
- Flanagan ME, "Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection", J Med Chem, 53, pp.8468~8484 (2010)
- Tanaka Y, "Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate", Arthritis Care Res, 63, pp.1150~1158 (2011)
- Fleischmann R, "Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs", Arthritis Rheum, 64, pp.617~629 (2012)
- Fleischmann R, "Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis", N Engl J Med, 367, pp.495~507 (2012)
- Kremer J, "Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial", Ann Intern Med, 159, pp.253~261 (2013)
- Lee EB, "Tofacitinib versus methotrexate in rheumatoid arthritis", N Engl J Med, 370, pp.2377~2386 (2014)
- van Vollenhoven RF, "Tofacitinib or adalimumab versus placebo in rheumatoid arthritis", N Engl J Med, 367, pp.508~519 (2012)
- van der Heijde D, "Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study", Arthritis Rheum, 65, pp.559~570 (2013)
- Sonomoto K, "Effects of tofacitinib on lymphocytes in rheumatoid arthritis: relation to efficacy and infectious adverse events", Rheumatology, 53, pp.914~918 (2014)
- Ghoreschi K, "Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550)", J Immunol, 186, pp.4234~4243 (2011)
- Ghoreschi K, "Janus kinases in immune cell signaling", Immunol Rev, 228, pp.273~287 (2009)
- Maeshima K, "The JAK inhibitor tofacitinib regulates synovitis through inhibition of interferon-gamma and interleukin-17 production by human CD4+ T cells", Arthritis Rheum, 64, pp.1790~1798 (2012)
- Wang SP, "Amplification of IL-21 signalling pathway through Bruton’s tyrosine kinase in human B cell activation", Rheumatology, 54, pp.1488~1497 (2015)
- Kubo S, "The JAK inhibitor, tofacitinib, reduces the T cell stimulatory capacity of human monocyte-derived dendritic cells", Ann Rheum Dis, 73, pp.2192~2198 (2014)
- Tanaka Y, "Discontinuation of biologics in patients with rheumatoid arthritis", Clin Exp Rheumatol, 31(4 Suppl 78), pp.S22~S27 (2013)
- Tanaka Y, "Intensive treatment and treatment holiday of TNF-inhibitors in rheumatoid arthritis", Curr Opin Rheumatol, 24, pp.319~326 (2012)
- Tanaka Y, "Next stage of RA treatment: is TNF inhibitor-free remission a possible treatment goal?", Ann Rheum Dis, 72(Suppl 2), pp.ii124~ii127 (2013)
- Saleem B, "Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped?", Ann Rheum Dis, 69, pp.1636~1642 (2010)
- Tanaka Y, "Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study", Ann Rheum Dis, 74, pp.389~395 (2015)
- Tanaka Y, "Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study", Ann Rheum Dis, 69, pp.1286~1291 (2010)