TEAR Trial Validates Methotrexate First Strategy for Early RA

CHICAGO – Methotrexate monotherapy is recommended and widely prescribed as the initial treatment approach for patients presenting with early rheumatoid arthritis, and now results of the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) Trial appear to validate the approach.

Findings from the randomized, double-blind 2-year trial involving 755 patients with early rheumatoid arthritis (RA) and a poor prognosis demonstrate that about 30% of those randomized to receive initial methotrexate monotherapy respond adequately and don’t need to step up to combination therapy. In addition, data from the study demonstrated that those who require step-up therapy because of inadequate response to methotrexate monotherapy do just as well radiographically as do those who receive combination therapy at the outset, according to Dr. James R. O’Dell, the Larson Professor of Medicine of the University of Nebraska and chief of rheumatology at the Veterans Affairs Medical Center, both in Omaha, and his colleagues reported at the annual meeting of the American College of Rheumatology.

"So there is no radiographic penalty for waiting to make that decision [to use combination therapy] clinically," said Dr. O’Dell, the new president of the American College of Rheumatology.

Patients in the TEAR Trial had active disease with a mean disease duration of 3.6 months and a mean disease activity 28 (DAS28) score of 5.8, had not received prior disease-modifying antirheumatic drug (DMARD) therapy, and had a poor prognosis based on the findings of rheumatoid factor positivity, a positive cyclic citrullinated peptide antibody test, or the presence of at least two erosions. They were randomized 2:1 to receive methotrexate monotherapy or combination therapy (either methotrexate plus etanercept or methotrexate plus sulfasalazine and hydroxychloroquine).

Methotrexate monotherapy patients who failed to achieve DAS28 of less than 3.2 within 24 weeks switched to one of the combinations.

Of 379 patients who received methotrexate monotherapy, 28% achieved a DAS28 below 3.2. Those who remained on monotherapy at week 102 had a mean DAS28 of 2.7, which both indicated durability of response and was nominally lower than the mean DAS28 of 3.0 in the initial combination therapy patients, Dr. O’Dell said.

Radiographic progression in the methotrexate monotherapy patients, compared with the immediate combination therapy patients was also nominally – and reassuringly – better (total sharp scores of 0.1 and 1.1, respectively), he noted. In addition, DAS28 scores as well as measures of radiographic progression were comparable in the step-up patients and the immediate combination patients beginning at 12 weeks after step-up through 102 weeks.

As for baseline differences between the patients on methotrexate monotherapy who did and did not require step-up therapy, those on step-up were more likely to be female and to have a higher DAS28 and an elevated body mass index.

"None of these differences were statistically significant, but one wonders about the overall accumulative effect of those factors on predicting response," Dr. O’Dell said.

Although methotrexate monotherapy is widely accepted as the appropriate approach to treatment in early RA patients and is recommended by both the ACR and the European League Against Rheumatism, this is the first blinded randomized trial to validate this approach, he noted.

Dr. O’Dell disclosed that he received grant money for the National Institutes of Health and the Department of Veterans Affairs. Other authors disclosed relationships with Abbott, American Shoulder and Elbow, Amgen, which provided grant money for the study, as well as BMS, Centacor, Corona, Crescendo, Genentech, Ortho Biotech Services, Pfizer, Roche, Teva Pharmaceuticals, and/or UCB.

CHICAGO – Methotrexate monotherapy is recommended and widely prescribed as the initial treatment approach for patients presenting with early rheumatoid arthritis, and now results of the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) Trial appear to validate the approach.

Findings from the randomized, double-blind 2-year trial involving 755 patients with early rheumatoid arthritis (RA) and a poor prognosis demonstrate that about 30% of those randomized to receive initial methotrexate monotherapy respond adequately and don’t need to step up to combination therapy. In addition, data from the study demonstrated that those who require step-up therapy because of inadequate response to methotrexate monotherapy do just as well radiographically as do those who receive combination therapy at the outset, according to Dr. James R. O’Dell, the Larson Professor of Medicine of the University of Nebraska and chief of rheumatology at the Veterans Affairs Medical Center, both in Omaha, and his colleagues reported at the annual meeting of the American College of Rheumatology.

"So there is no radiographic penalty for waiting to make that decision [to use combination therapy] clinically," said Dr. O’Dell, the new president of the American College of Rheumatology.

Patients in the TEAR Trial had active disease with a mean disease duration of 3.6 months and a mean disease activity 28 (DAS28) score of 5.8, had not received prior disease-modifying antirheumatic drug (DMARD) therapy, and had a poor prognosis based on the findings of rheumatoid factor positivity, a positive cyclic citrullinated peptide antibody test, or the presence of at least two erosions. They were randomized 2:1 to receive methotrexate monotherapy or combination therapy (either methotrexate plus etanercept or methotrexate plus sulfasalazine and hydroxychloroquine).

Methotrexate monotherapy patients who failed to achieve DAS28 of less than 3.2 within 24 weeks switched to one of the combinations.

Of 379 patients who received methotrexate monotherapy, 28% achieved a DAS28 below 3.2. Those who remained on monotherapy at week 102 had a mean DAS28 of 2.7, which both indicated durability of response and was nominally lower than the mean DAS28 of 3.0 in the initial combination therapy patients, Dr. O’Dell said.

Radiographic progression in the methotrexate monotherapy patients, compared with the immediate combination therapy patients was also nominally – and reassuringly – better (total sharp scores of 0.1 and 1.1, respectively), he noted. In addition, DAS28 scores as well as measures of radiographic progression were comparable in the step-up patients and the immediate combination patients beginning at 12 weeks after step-up through 102 weeks.

As for baseline differences between the patients on methotrexate monotherapy who did and did not require step-up therapy, those on step-up were more likely to be female and to have a higher DAS28 and an elevated body mass index.

"None of these differences were statistically significant, but one wonders about the overall accumulative effect of those factors on predicting response," Dr. O’Dell said.

Although methotrexate monotherapy is widely accepted as the appropriate approach to treatment in early RA patients and is recommended by both the ACR and the European League Against Rheumatism, this is the first blinded randomized trial to validate this approach, he noted.

Dr. O’Dell disclosed that he received grant money for the National Institutes of Health and the Department of Veterans Affairs. Other authors disclosed relationships with Abbott, American Shoulder and Elbow, Amgen, which provided grant money for the study, as well as BMS, Centacor, Corona, Crescendo, Genentech, Ortho Biotech Services, Pfizer, Roche, Teva Pharmaceuticals, and/or UCB.

CHICAGO – Methotrexate monotherapy is recommended and widely prescribed as the initial treatment approach for patients presenting with early rheumatoid arthritis, and now results of the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) Trial appear to validate the approach.

Findings from the randomized, double-blind 2-year trial involving 755 patients with early rheumatoid arthritis (RA) and a poor prognosis demonstrate that about 30% of those randomized to receive initial methotrexate monotherapy respond adequately and don’t need to step up to combination therapy. In addition, data from the study demonstrated that those who require step-up therapy because of inadequate response to methotrexate monotherapy do just as well radiographically as do those who receive combination therapy at the outset, according to Dr. James R. O’Dell, the Larson Professor of Medicine of the University of Nebraska and chief of rheumatology at the Veterans Affairs Medical Center, both in Omaha, and his colleagues reported at the annual meeting of the American College of Rheumatology.

"So there is no radiographic penalty for waiting to make that decision [to use combination therapy] clinically," said Dr. O’Dell, the new president of the American College of Rheumatology.

Patients in the TEAR Trial had active disease with a mean disease duration of 3.6 months and a mean disease activity 28 (DAS28) score of 5.8, had not received prior disease-modifying antirheumatic drug (DMARD) therapy, and had a poor prognosis based on the findings of rheumatoid factor positivity, a positive cyclic citrullinated peptide antibody test, or the presence of at least two erosions. They were randomized 2:1 to receive methotrexate monotherapy or combination therapy (either methotrexate plus etanercept or methotrexate plus sulfasalazine and hydroxychloroquine).

Methotrexate monotherapy patients who failed to achieve DAS28 of less than 3.2 within 24 weeks switched to one of the combinations.

Of 379 patients who received methotrexate monotherapy, 28% achieved a DAS28 below 3.2. Those who remained on monotherapy at week 102 had a mean DAS28 of 2.7, which both indicated durability of response and was nominally lower than the mean DAS28 of 3.0 in the initial combination therapy patients, Dr. O’Dell said.

Radiographic progression in the methotrexate monotherapy patients, compared with the immediate combination therapy patients was also nominally – and reassuringly – better (total sharp scores of 0.1 and 1.1, respectively), he noted. In addition, DAS28 scores as well as measures of radiographic progression were comparable in the step-up patients and the immediate combination patients beginning at 12 weeks after step-up through 102 weeks.

As for baseline differences between the patients on methotrexate monotherapy who did and did not require step-up therapy, those on step-up were more likely to be female and to have a higher DAS28 and an elevated body mass index.

"None of these differences were statistically significant, but one wonders about the overall accumulative effect of those factors on predicting response," Dr. O’Dell said.

Although methotrexate monotherapy is widely accepted as the appropriate approach to treatment in early RA patients and is recommended by both the ACR and the European League Against Rheumatism, this is the first blinded randomized trial to validate this approach, he noted.

Dr. O’Dell disclosed that he received grant money for the National Institutes of Health and the Department of Veterans Affairs. Other authors disclosed relationships with Abbott, American Shoulder and Elbow, Amgen, which provided grant money for the study, as well as BMS, Centacor, Corona, Crescendo, Genentech, Ortho Biotech Services, Pfizer, Roche, Teva Pharmaceuticals, and/or UCB.