Combination Therapy for Rheumatoid Arthritis in the Era of Biologicals


Early, aggressive disease management is critical for halting disease progression and joint destruction in patients with rheumatoid arthritis. Combination therapy with at least two disease-modifying antirheumatic drugs, such as methotrexate (MTX), sulfasalazine, or hydroxychloroquine, is often more effective than monotherapy in reducing disease activity. Biologic therapies represent more effective and tolerable treatment options that, when combined with MTX, have been shown to dramatically reduce inflammation, inhibit radiographic progression, and induce remission. Although several types of treatment strategies are used in clinical practice, the most aggressive approaches that target early disease have shown the most promise in reversing disease progression and reducing disease-related costs.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

    SE Gabriel (2001) ArticleTitleThe epidemiology of rheumatoid arthritis Rheum Dis Clin North Am 27 269–281 Occurrence Handle10.1016/S0889-857X(05)70201-5 Occurrence Handle1:STN:280:DC%2BD3MzivVKguw%3D%3D Occurrence Handle11396092

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    DM Lee ME Weinblatt (2001) ArticleTitleRheumatoid arthritis Lancet 358 903–911 Occurrence Handle10.1016/S0140-6736(01)06075-5 Occurrence Handle1:CAS:528:DC%2BD3MXmvVKmtr8%3D Occurrence Handle11567728

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    FM McQueen N Stewart J Crabbe et al. (1998) ArticleTitleMagnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset Ann Rheum Dis 57 350–356 Occurrence Handle1:STN:280:DyaK1cvksVWnug%3D%3D Occurrence Handle9771209

    CAS  PubMed  Google Scholar 

  4. 4.

    HA Fuchs JJ Kaye LF Callahan et al. (1989) ArticleTitleEvidence of significant radiographic damage in rheumatoid arthritis within the first 2 years of disease J Rheumatol 16 585–591 Occurrence Handle1:STN:280:BiaA38fptVY%3D Occurrence Handle2754663

    CAS  PubMed  Google Scholar 

  5. 5.

    W Felts E Yelin (1989) ArticleTitleThe economic impact of the rheumatic diseases in the United States J Rheumatol 16 867–884 Occurrence Handle1:STN:280:BiaA283ivVQ%3D Occurrence Handle2527991

    CAS  PubMed  Google Scholar 

  6. 6.

    ME Weinblatt (2004) ArticleTitleRheumatoid arthritis: more aggressive approach improves outlook Clevel Clin J Med 71 409–413

    Google Scholar 

  7. 7.

    DM Heijde Particlevan der (1995) ArticleTitleJoint erosions and patients with early rheumatoid arthritis Br J Rheumatol 34 IssueIDSuppl 2 74–78 Occurrence Handle8535653

    PubMed  Google Scholar 

  8. 8.

    DM Heijde Particlevan der MA Leeuwen Particlevan PL Riel Particlevan et al. (1995) ArticleTitleRadiographic 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 22 1792–1796 Occurrence Handle8523365

    PubMed  Google Scholar 

  9. 9.

    AA Stenger MA Leeuwen ParticleVan PM Houtman et al. (1998) ArticleTitleEarly effective suppression of inflammation in rheumatoid arthritis reduces radiographic progression Br J Rheumatol 37 1157–1163 Occurrence Handle10.1093/rheumatology/37.11.1157 Occurrence Handle1:CAS:528:DyaK1MXkslGi Occurrence Handle9851262

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    LR Lard H Visser I Speyer et al. (2001) ArticleTitleEarly versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies Am J Med 111 446–451 Occurrence Handle10.1016/S0002-9343(01)00872-5 Occurrence Handle1:CAS:528:DC%2BD3MXnvFCqsrk%3D Occurrence Handle11690569

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    M Boers AC Verhoeven HM Markusse et al. (1997) ArticleTitleRandomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis Lancet 350 309–318 Occurrence Handle10.1016/S0140-6736(97)01300-7 Occurrence Handle1:CAS:528:DyaK2sXls1emtbc%3D Occurrence Handle9251634

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    M Korpela L Laasonen P Hannonen et al. (2004) ArticleTitleRetardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumatic drugs: five-year experience from the FIN-RACo study Arthritis Rheum 50 2072–2081 Occurrence Handle10.1002/art.20351 Occurrence Handle1:CAS:528:DC%2BD2cXmsVansL0%3D Occurrence Handle15248204

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    JM Kremer MC Genovese GW Cannon et al. (2002) ArticleTitleConcomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial Ann Intern Med 137 726–733 Occurrence Handle1:CAS:528:DC%2BD38XovFylurc%3D Occurrence Handle12416946

    CAS  PubMed  Google Scholar 

  14. 14.

    RB Landewe M Boers AC Verhoeven et al. (2002) ArticleTitleCOBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention Arthritis Rheum 46 347–356 Occurrence Handle1:CAS:528:DC%2BD38XhvF2ru7s%3D Occurrence Handle11840436

    CAS  PubMed  Google Scholar 

  15. 15.

    JR O'Dell CE Haire N Erikson et al. (1996) ArticleTitleTreatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications N Engl J Med 334 1287–1291 Occurrence Handle10.1056/NEJM199605163342002 Occurrence Handle8609945

    Article  PubMed  Google Scholar 

  16. 16.

    JR O'Dell R Leff G Paulsen et al. (2002) ArticleTitleTreatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial Arthritis Rheum 46 1164–1170 Occurrence Handle12115219

    PubMed  Google Scholar 

  17. 17.

    P Tugwell T Pincus D Yocum et al. (1995) ArticleTitleCombination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate–Cyclosporine Combination Study Group N Engl J Med 333 137–141 Occurrence Handle10.1056/NEJM199507203330301 Occurrence Handle1:STN:280:ByqA3M3gtVw%3D Occurrence Handle7791814

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    M Dougados B Combe A Cantagrel et al. (1999) ArticleTitleCombination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components Ann Rheum Dis 58 220–225 Occurrence Handle1:CAS:528:DyaK1MXjtVCru74%3D Occurrence Handle10364900 Occurrence Handle10.1136/ard.58.4.220

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    CJ Haagsma PL Riel Particlevan AJ Jong Particlede et al. (1997) ArticleTitleCombination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial Br J Rheumatol 36 1082–1088 Occurrence Handle10.1093/rheumatology/36.10.1082 Occurrence Handle1:CAS:528:DyaK2sXnslWqurk%3D Occurrence Handle9374925

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    SM Proudman PG Conaghan C Richardson et al. (2000) ArticleTitleTreatment of poor-prognosis early rheumatoid arthritis. A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone Arthritis Rheum 43 1809–1819 Occurrence Handle10.1002/1529-0131(200008)43:8<1809::AID-ANR17>3.0.CO;2-D Occurrence Handle1:CAS:528:DC%2BD3cXmtFKju74%3D Occurrence Handle10943871

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    BE Borne Particlevan den RB Landewe HS Goei The et al. (1998) ArticleTitleCombination therapy in recent onset rheumatoid arthritis: a randomized double blind trial of the addition of low dose cyclosporine to patients treated with low dose chloroquine J Rheumatol 25 1493–1498 Occurrence Handle9712089

    PubMed  Google Scholar 

  22. 22.

    Enbrel® (etanercept) [package insert] (2004) Thousand Oaks, CA: Amgen Inc. and Wyeth-Ayerst Pharmaceuticals

  23. 23.

    Remicade® (infliximab) [package insert] (2003) Malvern, PA: Centacor Inc.

  24. 24.

    Humira® (adalimumab) [package insert] (2003) North Chicago, IL: Abbott Laboratories

  25. 25.

    Kineret® (anakinra) [package insert] (2002) Thousand Oaks, CA; Amgen Inc.

  26. 26.

    S Cohen E Hurd J Cush et al. (2002) ArticleTitleTreatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial Arthritis Rheum 46 614–624 Occurrence Handle1:CAS:528:DC%2BD38XisFOmt7w%3D Occurrence Handle11920396

    CAS  PubMed  Google Scholar 

  27. 27.

    DE Furst MH Schiff RM Fleischmann et al. (2003) ArticleTitleAdalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: Results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis) J Rheumatol 30 2563–2571 Occurrence Handle1:CAS:528:DC%2BD2cXktVCgtbw%3D Occurrence Handle14719195

    CAS  PubMed  Google Scholar 

  28. 28.

    L Klareskog D Heijde Particlevan der JP Jager Particlede et al. (2004) ArticleTitleTherapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial Lancet 363 675–681 Occurrence Handle1:CAS:528:DC%2BD2cXhs12jur4%3D Occurrence Handle15001324

    CAS  PubMed  Google Scholar 

  29. 29.

    R Maini EW St Clair F Breedveld et al. (1999) ArticleTitleInfliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial, ATTRACT Study Group Lancet 354 1932–1939 Occurrence Handle10.1016/S0140-6736(99)05246-0 Occurrence Handle1:CAS:528:DC%2BD3cXit1Oquw%3D%3D Occurrence Handle10622295

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    RN Maini FC Breedveld JR Kalden et al. (2004) ArticleTitleSustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate Arthritis Rheum 50 1051–1065 Occurrence Handle10.1002/art.20159 Occurrence Handle1:CAS:528:DC%2BD2cXjslGqsrk%3D Occurrence Handle15077287

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    ME Weinblatt EC Keystone DE Furst et al. (2003) ArticleTitleAdalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial Arthritis Rheum 48 35–45 Occurrence Handle10.1002/art.10697 Occurrence Handle1:CAS:528:DC%2BD3sXhtFGnsb0%3D Occurrence Handle12528101

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    ME Weinblatt JM Kremer AD Bankhurst et al. (1999) ArticleTitleA trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate N Engl J Med 340 253–259 Occurrence Handle10.1056/NEJM199901283400401 Occurrence Handle1:CAS:528:DyaK1MXht1Wqsbk%3D Occurrence Handle9920948

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    RS Pinals AT Masi RA Larsen (1981) ArticleTitlePreliminary criteria for clinical remission in rheumatoid arthritis Arthritis Rheum 24 1308–1315 Occurrence Handle1:STN:280:Bi2D28fmtFc%3D Occurrence Handle7306232

    CAS  PubMed  Google Scholar 

  34. 34.

    ML Prevoo AM Gestel Particlevan MA T'Hof Particlevan et al. (1996) ArticleTitleRemission in a prospective study of patients with rheumatoid arthritis. American Rheumatism Association preliminary remission criteria in relation to the disease activity score Br J Rheumatol 35 1101–1105 Occurrence Handle10.1093/rheumatology/35.11.1101 Occurrence Handle1:STN:280:ByiC3cvhtlQ%3D Occurrence Handle8948296

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Klareskog L, van der Heijde D, de Jager JP et al (2004) Clinical outcomes of a double-blind study of etanercept and methotrexate, alone and combined, in patients with active rheumatoid arthritis (TEMPO trial), year 2 results [Abstract]. Ann Rheum Dis 63

  36. 36.

    van der Heijde D, Klareskog L, Pedersen R et al (2004) Assessment of functional status among patients with active rheumatoid arthritis in a double-blind trial of etanercept and methotrexate, alone and combined (TEMPO trial) [Abstract]. Arthritis Rheum 50

  37. 37.

    D Heijde Particlevan der R Landewe L Klareskog et al. (2005) ArticleTitlePresentation and analysis of data on radiographic outcome in clinical trials: experience from the TEMPO study Arthritis Rheum 52 49–60 Occurrence Handle10.1002/art.20775 Occurrence Handle15641062

    Article  PubMed  Google Scholar 

  38. 38.

    SW Baumgartner RM Fleischmann LW Moreland et al. (2004) ArticleTitleEtanercept (Enbrel) in patients with rheumatoid arthritis with recent onset versus established disease: improvement in disability J Rheumatol 31 1532–1537 Occurrence Handle1:CAS:528:DC%2BD2cXnt1emu7k%3D Occurrence Handle15290731

    CAS  PubMed  Google Scholar 

  39. 39.

    EW St Clair DM Heijde Particlevan der JS Smolen et al. (2004) ArticleTitleCombination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial Arthritis Rheum 50 3432–3443 Occurrence Handle1:CAS:528:DC%2BD2cXhtVOqtrvJ Occurrence Handle15529377

    CAS  PubMed  Google Scholar 

  40. 40.

    Smolen J, van der Heijde DM, Emery P et al (2003) Methotrexate naive early rheumatoid arthritis (RA) patients with higher baseline ESR and CRP derive greater radiographic benefit from initiating treatment with a combination of infliximab and methotrexate [Abstract]. Arthritis Rheum 48

  41. 41.

    FC Breedveld P Emery E Keystone et al. (2004) ArticleTitleInfliximab in active early rheumatoid arthritis Ann Rheum Dis 63 149–155 Occurrence Handle1:CAS:528:DC%2BD2cXhsVGnsLY%3D Occurrence Handle14722203

    CAS  PubMed  Google Scholar 

  42. 42.

    Breedveld FC, Kavanaugh AF, Cohen SB et al (2004) Early treatment of rheumatoid arthritis (RA) with adalimumab (Humira) plus methotrexate vs. adalimumab alone or methotrexate alone: the PREMIER study [Abstract]. Arthritis Rheum 50

  43. 43.

    EC Keystone B Haraoui VP Bykerk (2003) ArticleTitleRole of adalimumab in the treatment of early rheumatoid arthritis Clin Exp Rheumatol 21 S198–S199 Occurrence Handle1:STN:280:DC%2BD2c%2FotVSjuw%3D%3D Occurrence Handle14969077

    CAS  PubMed  Google Scholar 

  44. 44.

    Keystone EC, Kavanaugh A, Sharp J et al (2002) Adalimumab (D2E7), a fully human anti-TNF monoclonal antibody inhibits the progression of structural joint damage in patients with active RA despite concomitant methotrexate therapy [Abstract]. Arthritis Rheum 46

  45. 45.

    EC Keystone AF Kavanaugh JT Sharp et al. (2004) ArticleTitleRadiographic, 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, placebo-controlled, 52-week trial Arthritis Rheum 50 1400–1411 Occurrence Handle1:CAS:528:DC%2BD2cXkvFykur4%3D Occurrence Handle15146409

    CAS  PubMed  Google Scholar 

  46. 46.

    SB Cohen LW Moreland JJ Cush et al. (2004) ArticleTitleA multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate Ann Rheum Dis 63 1062–1068 Occurrence Handle1:CAS:528:DC%2BD2cXnvFWktrg%3D Occurrence Handle15082469

    CAS  PubMed  Google Scholar 

  47. 47.

    JF Fries (1999) ArticleTitleSafety, cost and effectiveness issues with disease modifying anti-rheumatic drugs in rheumatoid arthritis Ann Rheum Dis 58 IssueIDSuppl 1 I86–I89 Occurrence Handle1:CAS:528:DC%2BD3cXivFGktQ%3D%3D Occurrence Handle10577980

    CAS  PubMed  Google Scholar 

  48. 48.

    RH Mullan B Bresnihan (2003) ArticleTitleDisease-modifying anti-rheumatic drug therapy and structural damage in early rheumatoid arthritis Clin Exp Rheumatol 21 S158–S164 Occurrence Handle1:STN:280:DC%2BD2c%2FotVSjsw%3D%3D Occurrence Handle14969069

    CAS  PubMed  Google Scholar 

  49. 49.

    Goekoop-Ruiterman YPM, De Vries-Bouwstra JK, Zeben DV et al (2004) Treatment strategies in early rheumatoid arthritis: clinical and radiologic outcomes after 2 year follow-up of the BeST Study [Abstract]. Arthritis Rheum 50

  50. 50.

    C Grigor H Capell A Stirling et al. (2004) ArticleTitleEffect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial Lancet 364 263–269 Occurrence Handle10.1016/S0140-6736(04)16676-2 Occurrence Handle15262104

    Article  PubMed  Google Scholar 

  51. 51.

    D Aletaha JS Smolen (2002) ArticleTitleEffectiveness profiles and dose dependent retention of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. An observational study J Rheumatol 29 1631–1638 Occurrence Handle1:CAS:528:DC%2BD38Xms1Sisbk%3D Occurrence Handle12180721

    CAS  PubMed  Google Scholar 

  52. 52.

    AC Cannella JR O'Dell (2003) ArticleTitleIs there still a role for traditional disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis? Curr Opin Rheumatol 15 185–192 Occurrence Handle10.1097/00002281-200305000-00003 Occurrence Handle12707569

    Article  PubMed  Google Scholar 

  53. 53.

    T Mottonen P Hannonen M Leirisalo-Repo et al. (1999) ArticleTitleComparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial, FIN-RACo trial group Lancet 353 1568–1573 Occurrence Handle10.1016/S0140-6736(98)08513-4 Occurrence Handle1:CAS:528:DyaK1MXjsFyjsbw%3D Occurrence Handle10334255

    Article  CAS  PubMed  Google Scholar 

  54. 54.

    Wolfe F, Michaud K (2004) Prednisone but not biologics or DMARDs is associated with increased risk of myocardial infarction in persons with RA [Abstract]. Ann Rheum Dis 63

  55. 55.

    Wolfe F, Michaud K (2004) Rates and risk factors for herpes zoster in patients with rheumatoid arthritis [Abstract]. Ann Rheum Dis 63

  56. 56.

    Wolfe F, Michaud K (2004) Corticosteroids increase the risk of diabetes mellitus in RA and contribute to the risk of myocardial infarction and heart failure [Abstract]. Ann Rheum Dis 63

  57. 57.

    AA Everdingen Particlevan DR Siewertsz van Reesema JW Jacobs et al. (2003) ArticleTitleLow-dose glucocorticoids in early rheumatoid arthritis: discordant effects on bone mineral density and fractures? Clin Exp Rheumatol 21 155–160 Occurrence Handle12747268

    PubMed  Google Scholar 

  58. 58.

    Genovese MC, Martin RW, Fleischmann RM et al (2003) Etanercept (Enbrel) in early erosive rheumatoid arthritis (ERA trial): clinical and radiographic data [Abstract]. Arthritis Rheum 47(Suppl)

  59. 59.

    Singh A, Van der Heijde D, Klareskog L et al (2004) Assessment of treatment satisfaction among patients with active rheumatoid arthritis in a double-blind trial of etanercept and methotrexate, alone and combined (TEMPO trial) [Abstract]. Arthritis Rheum 50(Suppl)

  60. 60.

    JF Maillefert B Combe P Goupille et al. (2003) ArticleTitleLong term structural effects of combination therapy in patients with early rheumatoid arthritis: five year follow up of a prospective double blind controlled study Ann Rheum Dis 62 764–766 Occurrence Handle1:STN:280:DC%2BD3szlsVSquw%3D%3D Occurrence Handle12860733

    CAS  PubMed  Google Scholar 

  61. 61.

    MC Genovese S Cohen L Moreland et al. (2004) ArticleTitleCombination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate Arthritis Rheum 50 1412–1419 Occurrence Handle10.1002/art.20221 Occurrence Handle1:CAS:528:DC%2BD2cXkvFykurw%3D Occurrence Handle15146410

    Article  CAS  PubMed  Google Scholar 

  62. 62.

    KR Wilske LA Healey (1989) ArticleTitleRemodeling the pyramid—a concept whose time has come J Rheumatol 16 565–567 Occurrence Handle1:STN:280:BiaA38fovFM%3D Occurrence Handle2754660

    CAS  PubMed  Google Scholar 

  63. 63.

    JM Kremer ME Weinblatt AD Bankhurst et al. (2003) ArticleTitleEtanercept added to background methotrexate therapy in patients with rheumatoid arthritis: continued observations Arthritis Rheum 48 1493–1499 Occurrence Handle1:CAS:528:DC%2BD3sXltlSgtbY%3D Occurrence Handle12794815

    CAS  PubMed  Google Scholar 

  64. 64.

    JF Fries (1990) ArticleTitleReevaluating the therapeutic approach to rheumatoid arthritis: the “sawtooth” strategy J Rheumatol, Suppl 22 12–15 Occurrence Handle1:CAS:528:DyaK3cXltVymt7Y%3D

    CAS  Google Scholar 

  65. 65.

    TM Sokka K Kaarela TT Mottonen et al. (1999) ArticleTitleConventional monotherapy compared to a “sawtooth” treatment strategy in the radiographic progression of rheumatoid arthritis over the first eight years Clin Exp Rheumatol 17 527–532 Occurrence Handle1:STN:280:DC%2BD3c%2Fht1SktQ%3D%3D Occurrence Handle10544834

    CAS  PubMed  Google Scholar 

  66. 66.

    T Mottonen L Paimela J Ahonen et al. (1996) ArticleTitleOutcome in patients with early rheumatoid arthritis treated according to the “sawtooth” strategy Arthritis Rheum 39 996–1005 Occurrence Handle1:STN:280:BymB3s3ktlQ%3D Occurrence Handle8651994

    CAS  PubMed  Google Scholar 

  67. 67.

    De Vries-Bouwstra JK, Goekoop-Ruiterman YPM, Van Zeben D et al (2004) A comparison of clinical and radiologic outcomes of four treatment strategies for early rheumatoid arthritis: results of the BEST trial [Abstract]. Ann Rheum Dis 63

  68. 68.

    De Vries-Bouwstra JK, Goekoop-Ruiterman YPM, Kerstens PJSM et al (2004) Patient preferences for treatment of newly diagnosed rheumatoid arthritis [Abstract]. Ann Rheum Dis 63

  69. 69.

    Breedveld FC et al (June 8–11, 2005) Presented at: EULAR Annual Meeting; Vienna, Austria. Abstract OP0013

Download references


The thoughtful suggestions of Dr. C. Ronald MacKenzie and Dr. Sergio Schwartzman are gratefully appreciated. I thank Ting Chang and Ruth Pereira for editorial support.

Author information



Corresponding author

Correspondence to Allan Gibofsky MD, JD, FACP, FCLM.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Gibofsky, A. Combination Therapy for Rheumatoid Arthritis in the Era of Biologicals. HSS Jrnl 2, 30–41 (2006).

Download citation

Key words

  • combination therapy
  • disease-modifying antirheumatic drugs
  • joint destruction
  • rheumatoid arthritis
  • tumor necrosis factor antagonists