FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 334:1287-1291 May 16, 1996 Number 20 Next

	Full Text PDF Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs.

Methods We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary end point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity.

Results Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P<0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent, P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity.

Conclusions In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine and hydroxychloroquine.

Source Information

From the University of Nebraska Medical Center and the Omaha Veterans Affairs Medical Center, Omaha (J.R.O., C.E.H., P.M., L.W.K., G.F.M.), and affiliated Rheumatoid Arthritis Investigational Network clinics (N.E., W.D., W.P., P.J.E., V.G., S.W., H.K.).

Address reprint requests to Dr. O'Dell at the University of Nebraska Medical Center, Department of Internal Medicine, 600 S. 42nd St., Omaha, NE 68198-3025.

Full Text of this Article

Related Letters:

Treatment of Rheumatoid Arthritis
Stohl W., Arkfeld D. G., Zurier R. B., DeMarco D. M., Liu N. Y., Schinagl E. F., Strauss P. C., O'Dell J. R.
Extract | Full Text  
N Engl J Med 1996; 335:821-823, Sep 12, 1996. Correspondence

This article has been cited by other articles:

• van Tuyl, L. H. D., Plass, A. M. C., Lems, W. F., Voskuyl, A. E., Kerstens, P. J. S. M., Dijkmans, B. A. C., Boers, M. (2008). Discordant perspectives of rheumatologists and patients on COBRA combination therapy in rheumatoid arthritis. Rheumatology (Oxford) 0: ken323v1-ken323 [Abstract] [Full Text]  
• Bruyn, G A W, Tate, G, Caeiro, F, Maldonado-Cocco, J, Westhovens, R, Tannenbaum, H, Bell, M, Forre, O, Bjorneboe, O, Tak, P P, Abeywickrama, K H, Bernhardt, P, van Riel, P L C, for the RADD study group, (2008). Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study. Ann Rheum Dis 67: 1090-1095 [Abstract] [Full Text]  
• Saleem, B, Mackie, S, Quinn, M, Nizam, S, Hensor, E, Jarrett, S, Conaghan, P G, Emery, P (2008). Does the use of tumour necrosis factor antagonist therapy in poor prognosis, undifferentiated arthritis prevent progression to rheumatoid arthritis?. Ann Rheum Dis 67: 1178-1180 [Abstract] [Full Text]  
• Kravitz, R. L., Duan, N., White, R. H. (2008). N-of-1 Trials of Expensive Biological Therapies: A Third Way?. Arch Intern Med 168: 1030-1033 [Abstract] [Full Text]  
• Cohen, J., Calabresi, P., Chakraborty, S., Edwards, K., Eickenhorst, T., Felton, W. III, Fisher, E., Fox, R., Goodman, A., Hara-Cleaver, C., Hutton, G., Imrey, P., Ivancic, D., Mandell, B., Perryman, J., Scott, T., Skaramagas, T., Zhang, H. for the AC (2008). Avonex Combination Trial in relapsing--remitting MS: rationale, design and baseline data. Mult Scler 14: 370-382 [Abstract]  
• Donahue, K. E., Gartlehner, G., Jonas, D. E., Lux, L. J., Thieda, P., Jonas, B. L., Hansen, R. A., Morgan, L. C., Lohr, K. N. (2008). Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis. ANN INTERN MED 148: 124-134 [Abstract] [Full Text]  
• Wasko, M. C. M., Hubert, H. B., Lingala, V. B., Elliott, J. R., Luggen, M. E., Fries, J. F., Ward, M. M. (2007). Hydroxychloroquine and Risk of Diabetes in Patients With Rheumatoid Arthritis. JAMA 298: 187-193 [Abstract] [Full Text]  
• Goekoop-Ruiterman, Y. P.M., de Vries-Bouwstra, J. K., Allaart, C. F., van Zeben, D., Kerstens, P. J.S.M., Hazes, J. M. W., Zwinderman, A. H., Peeters, A. J., de Jonge-Bok, J. M., Mallee, C., de Beus, W. M., de Sonnaville, P. B.J., Ewals, J. A.P.M., Breedveld, F. C., Dijkmans, B. A.C. (2007). Comparison of Treatment Strategies in Early Rheumatoid Arthritis: A Randomized Trial. ANN INTERN MED 146: 406-415 [Abstract] [Full Text]  
• O'Dell, J. R. (2007). The BeSt Way to Treat Early Rheumatoid Arthritis?. ANN INTERN MED 146: 459-460 [Full Text]  
• Capell, H. A, Madhok, R., Porter, D. R, Munro, R. A L, McInnes, I. B, Hunter, J. A, Steven, M., Zoma, A., Morrison, E., Sambrook, M., Wui Poon, F., Hampson, R., McDonald, F., Tierney, A., Henderson, N., Ford, I. (2007). Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study. Ann Rheum Dis 66: 235-241 [Abstract] [Full Text]  
• Russell, A S, Wallenstein, G V, Li, T, Martin, M C, Maclean, R, Blaisdell, B, Gajria, K, Cole, J C, Becker, J-C, Emery, P (2007). Abatacept improves both the physical and mental health of patients with rheumatoid arthritis who have inadequate response to methotrexate treatment. Ann Rheum Dis 66: 189-194 [Abstract] [Full Text]  
• Fraenkel, L., Rabidou, N., Dhar, R. (2006). Are rheumatologists' treatment decisions influenced by patients' age?. Rheumatology (Oxford) 45: 1555-1557 [Abstract] [Full Text]  
• Douglas, K M J, Ladoyanni, E, Treharne, G J, Hale, E D, Erb, N, Kitas, G D (2006). Cutaneous abnormalities in rheumatoid arthritis compared with non-inflammatory rheumatic conditions. Ann Rheum Dis 65: 1341-1345 [Abstract] [Full Text]  
• Weinblatt, M E, Keystone, E C, Furst, D E, Kavanaugh, A F, Chartash, E K, Segurado, O G (2006). Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4 year extended study. Ann Rheum Dis 65: 753-759 [Abstract] [Full Text]  
• Pincus, T., Sokka, T. (2006). Should aggressive therapy for rheumatoid arthritis require early use of weekly low-dose methotrexate, as the first disease-modifying anti-rheumatic drug in most patients?. Rheumatology (Oxford) 45: 497-499 [Full Text]  
• Lev-Ari, S., Strier, L., Kazanov, D., Elkayam, O., Lichtenberg, D., Caspi, D., Arber, N. (2006). Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells. Rheumatology (Oxford) 45: 171-177 [Abstract] [Full Text]  
• Choy, E. H. S., Smith, C., Dore, C. J., Scott, D. L. (2005). A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic drugs in rheumatoid arthritis based on patient withdrawal. Rheumatology (Oxford) 44: 1414-1421 [Abstract] [Full Text]  
• Irvine, S, Capell, H C (2005). Great expectations of modern RA treatment. Ann Rheum Dis 64: 1249-1251 [Full Text]  
• Suresh, E, Lambert, C M (2005). Combination treatment strategies in early rheumatoid arthritis. Ann Rheum Dis 64: 1252-1256 [Abstract] [Full Text]  
• Cronstein, B. N. (2005). Low-Dose Methotrexate: A Mainstay in the Treatment of Rheumatoid Arthritis. Pharmacol. Rev. 57: 163-172 [Abstract] [Full Text]  
• Roberts, L. J., Kalil, A. C., Messori, A., Santarlasci, B., Vaiani, M. (2004). New Drugs for Rheumatoid Arthritis. NEJM 351: 2659-2661 [Full Text]  
• Lee, S J, Kavanaugh, A (2004). A need for greater reporting of socioeconomic status and race in clinical trials. Ann Rheum Dis 63: 1700-1701 [Full Text]  
• Choy, E. H. (2004). Two is better than one? Combination therapy in rheumatoid arthritis. Rheumatology (Oxford) 43: 1205-1207 [Full Text]  
• O'Dell, J. R. (2004). Therapeutic Strategies for Rheumatoid Arthritis. NEJM 350: 2591-2602 [Full Text]  
• Breedveld, F C, Kalden, J R (2004). Appropriate and effective management of rheumatoid arthritis. Ann Rheum Dis 63: 627-633 [Abstract] [Full Text]  
• Matteson, E. L., Weyand, C. M., Fulbright, J. W., Christianson, T. J. H., McClelland, R. L., Goronzy, J. J. (2004). How aggressive should initial therapy for rheumatoid arthritis be? Factors associated with response to 'non-aggressive' DMARD treatment and perspective from a 2-yr open label trial. Rheumatology (Oxford) 43: 619-625 [Abstract] [Full Text]  
• Maillefert, J F, Combe, B, Goupille, P, Cantagrel, A, Dougados, M (2003). Long 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 [Abstract] [Full Text]  
• Gerards, A H, Landewe, R B M, Prins, A P A, Bruijn, G A W, Goei The, H S, Laan, R F J M, Dijkmans, B A C (2003). Cyclosporin A monotherapy versus cyclosporin A and methotrexate combination therapy in patients with early rheumatoid arthritis: a double blind randomised placebo controlled trial. Ann Rheum Dis 62: 291-296 [Abstract] [Full Text]  
• Gause, A. (2003). Progress in the treatment of rheumatic disease. Nephrol Dial Transplant 18: 13-16 [Full Text]  
• Canvin, J. M. G., Bernatsky, S., Hitchon, C. A., Jackson, M., Sowa, M. G., Mansfield, J. R., Eysel, H. H., Mantsch, H. H., El-Gabalawy, H. S. (2003). Infrared spectroscopy: shedding light on synovitis in patients with rheumatoid arthritis. Rheumatology (Oxford) 42: 76-82 [Abstract] [Full Text]  
• Kremer, J. M., Genovese, M. C., Cannon, G. W., Caldwell, J. R., Cush, J. J., Furst, D. E., Luggen, M. E., Keystone, E., Weisman, M. H., Bensen, W. M., Kaine, J. L., Ruderman, E. M., Coleman, P., Curtis, D. L., Kopp, E. J., Kantor, S. M., Waltuck, J., Lindsley, H. B., Markenson, J. A., Strand, V., Crawford, B., Fernando, I., Simpson, K., Bathon, J. M. (2002). Concomitant 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 [Abstract] [Full Text]  
• Temekonidis, T I, Georgiadis, A N, Alamanos, Y, Bougias, D V, Voulgari, P V, Drosos, A A (2002). Infliximab treatment in combination with cyclosporin A in patients with severe refractory rheumatoid arthritis. Ann Rheum Dis 61: 822-825 [Abstract] [Full Text]  
• Ferraccioli, G. F., Gremese, E., Tomietto, P., Favret, G., Damato, R., Di Poi, E. (2002). Analysis of improvements, full responses, remission and toxicity in rheumatoid patients treated with step-up combination therapy (methotrexate, cyclosporin A, sulphasalazine) or monotherapy for three years. Rheumatology (Oxford) 41: 892-898 [Abstract] [Full Text]  
• Machein, U., Buss, B., Spiller, I., Braun, J., Rudwaleit, M., Faerber, L., Sieper, J. (2002). Effective treatment of early rheumatoid arthritis with a combination of methotrexate, prednisolone and cyclosporin. Rheumatology (Oxford) 41: 110-111 [Full Text]  
• Pisetsky, D. S., St.Clair, E. W. (2001). Progress in the Treatment of Rheumatoid Arthritis. JAMA 286: 2787-2790 [Full Text]  
• Lai, J.-H., Ho, L.-J., Lu, K.-C., Chang, D.-M., Shaio, M.-F., Han, S.-H. (2001). Western and Chinese Antirheumatic Drug-Induced T Cell Apoptotic DNA Damage Uses Different Caspase Cascades and Is Independent of Fas/Fas Ligand Interaction. J. Immunol. 166: 6914-6924 [Abstract] [Full Text]  
• Kim, W-U, Seo, Y-I, Park, S-H, Lee, W-K, Lee, S-K, Paek, S-I, Cho, C-S, Song, H-H, Kim, H-Y (2001). Treatment with cyclosporin switching to hydroxychloroquine in patients with rheumatoid arthritis. Ann Rheum Dis 60: 514-517 [Abstract] [Full Text]  
• Zink, A, Listing, J, Niewerth, M, Zeidler, H (2001). The national database of the German Collaborative Arthritis Centres: II. Treatment of patients with rheumatoid arthritis. Ann Rheum Dis 60: 207-213 [Abstract] [Full Text]  
• Koopman, W. J. (2001). Prospects for Autoimmune Disease: Research Advances in Rheumatoid Arthritis. JAMA 285: 648-650 [Abstract] [Full Text]  
• Schattner, A. (2000). A new era in rheumatoid arthritis treatment--time to introduce a modified treatment pyramid. QJM 93: 757-760 [Full Text]  
• Uitz, E., Fransen, J., Langenegger, T., Stucki, G., , f. t. m. o. t. S. C. Q. M. i. R. A. (2000). Clinical quality management in rheumatoid arthritis: putting theory into practice. Rheumatology (Oxford) 39: 542-549 [Abstract] [Full Text]  
• Goldring, S. R. (2000). A 55-Year-Old Woman With Rheumatoid Arthritis. JAMA 283: 524-531 [Full Text]  
• Bingham, S., Emery, P. (2000). Resistant rheumatoid arthritis clinics-- a necessary development?. Rheumatology (Oxford) 39: 2-5 [Full Text]  
• Pincus, T., O'Dell, J. R., Kremer, J. M. (1999). Combination Therapy with Multiple Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis: A Preventive Strategy. ANN INTERN MED 131: 768-774 [Abstract] [Full Text]  
• Verhoeven, A. C., Boers, M., Tugwell, P. (1999). Combination therapy in rheumatoid arthritis. Rheumatology (Oxford) 38: 789a-790a [Full Text]  
• Dougados, M., Combe, B., Cantagrel, A., Goupille, P., Olive, P., Schattenkirchner, M., Meusser, S, Paimela, L, Rau, R., Zeidler, H., Leirisalo-Repo, M., Peldan, K. (1999). Combination 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 [Abstract] [Full Text]  
• Weinblatt, M. E., Kremer, J. M., Bankhurst, A. D., Bulpitt, K. J., Fleischmann, R. M., Fox, R. I., Jackson, C. G., Lange, M., Burge, D. J. (1999). A Trial of Etanercept, a Recombinant Tumor Necrosis Factor Receptor:Fc Fusion Protein, in Patients with Rheumatoid Arthritis Receiving Methotrexate. NEJM 340: 253-259 [Abstract] [Full Text]  
• O'Dell, J. R. (1999). Anticytokine Therapy -- A New Era in the Treatment of Rheumatoid Arthritis?. NEJM 340: 310-312 [Full Text]  
• Campbell, S. M., Wernick, R. (1999). Update in Rheumatology. ANN INTERN MED 130: 135-142 [Full Text]  
• Brooks, P. (1998). Recent advances: Rheumatology. BMJ 316: 1810-1812 [Full Text]  
• Porro, G., Bertolini, G., Bonardi, M. A., Giovanetti, E., Lento, P., Leoni, F., Modena, D., Pavich, G., Marcucci, F. (1998). Diaminic Carbonates, a New Class of Anti-inflammatory Compounds: Their Biological Characterization and Mode of Action. J. Pharmacol. Exp. Ther. 285: 193-200 [Abstract] [Full Text]  
• O'Dell, J. R, Nepom, B. S, Haire, C., Gersuk, V. H, Gaur, L., Moore, G. F, Drymalski, W., Palmer, W., Eckhoff, P J., Klassen, L. W, Wees, S., Thiele, G., Nepom, G. T (1998). HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments. Ann Rheum Dis 57: 209-213 [Abstract] [Full Text]  
• Harvey, S., Weisman, M., O'Dell, J., Scott, T., Visor, M. K. J., Swindlehurst, C. (1998). Chondrex: new marker of joint disease. Clin. Chem. 44: 509-516 [Abstract] [Full Text]  
• (1998). Modifying disease in rheumatoid arthritis. DTB 36: 3-6 [Abstract] [Full Text]  
• FERRACCIOLI, G F, CASATTA, L, DI POI, E, DAMATO, R, BARTOLI;, E, O'DELL, J. R (1997). Combination DMARD therapy for rheumatoid arthritis. Full or low DMARD doses?. Ann Rheum Dis 56: 336a-337 [Full Text]  
• MASI, A. T, CHROUSOS, G. P (1997). Dilemmas of low dosage glucocorticoid treatment in rheumatoid arthritis: considerations of timing. Ann Rheum Dis 56: 1-4 [Full Text]  
• Stohl, W., Arkfeld, D. G., Zurier, R. B., DeMarco, D. M., Liu, N. Y., Schinagl, E. F., Strauss, P. C., O'Dell, J. R. (1996). Treatment of Rheumatoid Arthritis. NEJM 335: 821-823 [Full Text]  
• (1996). COMBINING DISEASE-MODIFYING DRUGS FOR RHEUMATOID ARTHRITIS. JWatch General 1996: 4-4 [Full Text]