Efficacy and safety of leflunomide in DMARD-naïve patients with early rheumatoid arthritis: Comparison of a loading and a fixed-dose regimen

Rheumatology (United Kingdom)

Volumn 52, Issue 6, 2013, Pages 1132-1140

  Cutolo, Maurizio ^a   Boloşiu, Horatiu ^b   Perdriset, Gilles ^c  

^a UNIVERSITY OF GENOA   (Italy)

^b IULIU HATIEGANU UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^c SANOFI   (France)

Author keywords

Early rheumatoid arthritis; Efficacy; Leflunomide; Loading dose; Safety

Indexed keywords

LEFLUNOMIDE;

ADULT; AGED; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; DIARRHEA; DISEASE DURATION; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG SAFETY; FEMALE; HUMAN; HYPERTRANSAMINASEMIA; INTENTION TO TREAT ANALYSIS; LOADING DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MORNING STIFFNESS; MULTICENTER STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; THROMBOCYTOPENIA; TREATMENT RESPONSE;

EARLY RHEUMATOID ARTHRITIS; EFFICACY; LEFLUNOMIDE; LOADING DOSE; SAFETY;

ADULT; AGED; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; ISOXAZOLES; MALE; MIDDLE AGED; TREATMENT OUTCOME;

EID: 84878135791     PISSN: 14620324     EISSN: 14620332     Source Type: Journal    
DOI: 10.1093/rheumatology/kes321     Document Type: Article

References (37)

1. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum 2002;46:328-46.
2. Saag KG, Teng GG, Patkar NM et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008;59: 762-84.
3. Smolen JS, Landewe R, Breedveld FC et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010;69:964-75.
4. Osiri M, Shea B, Robinson V et al. Leflunomide for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. J Rheumatol 2003;30:1182-90.
5. Gaujoux-Viala C, Smolen JS, Landewe R et al. Current evidence for the management of rheumatoid arthritis with synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010;69:1004-9.
6. Cutolo M, Capellino S, Montagna P, Sulli A, Seriolo B, Villaggio B. Anti-inflammatory effects of leflunomide in combination with methotrexate on co-culture of T lymphocytes and synovial macrophages from rheumatoid arthritis patients. Ann Rheum Dis 2006;65:728-35.
7. Cutolo M, Sulli A, Ghiorzo P, Pizzorni C, Craviotto C, Villaggio B. Anti-inflammatory effects of leflunomide on cultured synovial macrophages from patients with rheumatoid arthritis. Ann Rheum Dis 2003;62: 297-302.
8. Cutolo M, Villaggio B, Brizzolara R et al. Identification and quantification of selected inflammatory genes modulated by leflunomide and prednisone treatment in early rheumatoid arthritis patients. Clin Exp Rheumatol 2011;29: 72-9.
9. Cutolo M, Villaggio B, Pizzorni C et al. Inflammatory gene profile in early rheumatoid arthritis and modulation by leflunomide and prednisone treatment. Ann N Y Acad Sci 2010;1193:15-21.
10. Fox RI. Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl 1998;53:20-6.
11. Montagna P, Brizzolara R, Soldano S, Pizzorni C, Sulli A, Cutolo M. Sex hormones and leflunomide treatment of human macrophage cultures: effects on apoptosis. Int J Clin Exp Med 2009;2:221-32.
12. Rückemann K, Fairbanks LD, Carrey EA et al. Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans. J Biol Chem 1998;273:21682-91.
13. Dayer JM, Cutolo M. Is there a rationale to using leflunomide in early rheumatoid arthritis? Clin Exp Rheumatol 2005;23:404-12.
14. Smolen JS, Breedveld F, Strand V et al. Efficacy of leflunomide in DMARD-naive patients with early RA. Ann Rheum Dis 2002;61:166.
15. Kellner H, Bornholdt K, Hein G. Leflunomide in the treatment of patients with early rheumatoid arthritis-results of a prospective non-interventional study. Clin Rheumatol 2010;29:913-20.
16. Combe B, Landewe R, Lukas C et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007;66:34-45.
17. Erra A, Tomas C, Barcelo P, Vilardell M, Marsal S. Is the recommended dose of leflunomide the best regimen to treat rheumatoid arthritis patients? Rheumatology 2003; 42:1123-4.
18. Siva C, Eisen SA, Shepherd R et al. Leflunomide use during the first 33 months after food and drug administration approval: experience with a national cohort of 3,325 patients. Arthritis Rheum 2003;49:745-51.
19. Maddison P, Kiely P, Kirkham B et al. Leflunomide in rheumatoid arthritis: recommendations through a process of consensus. Rheumatology 2005;44:280-6.
20. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31:315-24.
21. Strand V, Cohen S, Schiff M et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med 1999;159: 2542-50.
22. Bathon JM, Martin RW, Fleischmann RM et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343: 1586-93.
23. European Medicines Agency. Points to consider on clinical investigation of medicinal products other than NSAIDS for treatment of rheumatoid arthritis. London: EMA, 2003.
24. European Medicines Agency. Draft guideline on clinical investigation of medicinal products other than non-steroidal anti-inflammatory drugs for treatment of rheumatoid arthritis. London: EMA, 2011.
25. Prevoo ML, van't Hof MA, Kuper HH et al. 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;38:44-8.
26. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-83.
27. St Clair EW, van der Heijde DM, Smolen JS et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004;50:3432-43.
28. 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;54:26-37.
29. Emery P, Breedveld FC, Hall S et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet 2008;372: 375-82.
30. 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. European Leflunomide Study Group. Lancet 1999;353:259-66.
31. Emery P, Breedveld FC, Lemmel EM et al. A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology 2000;39:655-65.
32. Nell VP, Machold KP, Eberl G et al. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology 2004;43:906-14.
33. Lard LR, Visser H, Speyer I et al. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 2001;111:446-51.
34. Emery P. Evidence supporting the benefit of early intervention in rheumatoid arthritis. J Rheumatol Suppl 2002; 66:3-8.
35. Alcorn N, Saunders S, Madhok R. Benefit-risk assessment of leflunomide: an appraisal of leflunomide in rheumatoid arthritis 10 years after licensing. Drug Saf 2009;32: 1123-34.
36. Svensson B, Hafstrom I. Effects on joint destruction and remission, bone turnover and lack of influence on atherogenesis: a review of the BARFOT low-dose prednisolone studies on patients with early RA. Clin Exp Rheumatol 2011;29:S63-7.
37. 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 2005;52:3381-90.