Treatment 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

James Robert O'Dell, Robert Leff, Gail Paulsen, Claire Haire, Jack Mallek, P. James Eckhoff, Ana Fernandez, Kent Blakely, Steven Wees, Julie Stoner, Stephen Hadley, Jeffrey Felt, William Palmer, Paul Waytz, Melvin Churchill, Lynell Warren Klassen, Gerald Francis Moore

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

Objective. To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). Methods. RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. Results. Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. Conclusion. The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ.

Original languageEnglish (US)
Pages (from-to)1164-1170
Number of pages7
JournalArthritis and rheumatism
Volume46
Issue number5
DOIs
StatePublished - May 28 2002

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Hydroxychloroquine
Sulfasalazine
Methotrexate
Rheumatoid Arthritis
Placebos
Therapeutics
Rheumatology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

Treatment 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. / O'Dell, James Robert; Leff, Robert; Paulsen, Gail; Haire, Claire; Mallek, Jack; Eckhoff, P. James; Fernandez, Ana; Blakely, Kent; Wees, Steven; Stoner, Julie; Hadley, Stephen; Felt, Jeffrey; Palmer, William; Waytz, Paul; Churchill, Melvin; Klassen, Lynell Warren; Moore, Gerald Francis.

In: Arthritis and rheumatism, Vol. 46, No. 5, 28.05.2002, p. 1164-1170.

Research output: Contribution to journalArticle

O'Dell, James Robert ; Leff, Robert ; Paulsen, Gail ; Haire, Claire ; Mallek, Jack ; Eckhoff, P. James ; Fernandez, Ana ; Blakely, Kent ; Wees, Steven ; Stoner, Julie ; Hadley, Stephen ; Felt, Jeffrey ; Palmer, William ; Waytz, Paul ; Churchill, Melvin ; Klassen, Lynell Warren ; Moore, Gerald Francis. / Treatment 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. In: Arthritis and rheumatism. 2002 ; Vol. 46, No. 5. pp. 1164-1170.
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abstract = "Objective. To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). Methods. RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20{\%} response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. Results. Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78{\%} achieving an ACR 20{\%} response at 2 years, compared with 60{\%} of those treated with MTX and HCQ (P = 0.05) and 49{\%} of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50{\%} response, with 55{\%}, 40{\%}, and 29{\%} of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. Conclusion. The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ.",
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T1 - Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications

T2 - Results of a two-year, randomized, double-blind, placebo-controlled trial

AU - O'Dell, James Robert

AU - Leff, Robert

AU - Paulsen, Gail

AU - Haire, Claire

AU - Mallek, Jack

AU - Eckhoff, P. James

AU - Fernandez, Ana

AU - Blakely, Kent

AU - Wees, Steven

AU - Stoner, Julie

AU - Hadley, Stephen

AU - Felt, Jeffrey

AU - Palmer, William

AU - Waytz, Paul

AU - Churchill, Melvin

AU - Klassen, Lynell Warren

AU - Moore, Gerald Francis

PY - 2002/5/28

Y1 - 2002/5/28

N2 - Objective. To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). Methods. RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. Results. Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. Conclusion. The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ.

AB - Objective. To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA). Methods. RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX was accelerated from 7.5 mg/week to 17.5 mg/week in all patients who were not in remission. Similarly, the dosage of SSZ was escalated from 500 mg twice a day to 1 gm twice a day in patients who were not in remission. The primary end point of the study was the percentage of patients who had a 20% response to therapy according to the American College of Rheumatology (ACR) criteria at 2 years. Results. Intent-to-treat analysis revealed that patients receiving the triple combination responded best, with 78% achieving an ACR 20% response at 2 years, compared with 60% of those treated with MTX and HCQ (P = 0.05) and 49% of those treated with MTX and SSZ (P = 0.002). Similar trends were seen for the ACR 50% response, with 55%, 40%, and 29% of patients in the 3 treatment groups, respectively, achieving these results at 2 years (P = 0.005 for the triple combination group versus the MTX and SSZ group). All combination treatments were well-tolerated. Fourteen patients (evenly distributed among the 3 groups) withdrew from the protocol because of symptoms that were potentially related to the study medication. Conclusion. The triple combination of MTX, SSZ, and HCQ is well-tolerated, and its efficacy is superior to that of the double combination of MTX and SSZ and is marginally superior to that of the double combination of MTX and HCQ.

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