Study Outlines Path for Treating Early RA

PHILADELPHIA — Methotrexate monotherapy, with the addition of either the combination of sulfasalazine plus hydroxychloroquine or etanercept alone at 6 months, if needed, is a reasonable treatment strategy for early rheumatoid arthritis, according to findings presented at the annual meeting of the American College of Rheumatology.

Reporting findings from the TEAR (Treatment of Early Aggressive RA) trial, principal investigator Dr. Larry W. Moreland described the trial, in which 755 patients (72% female; 80% white; 11% black) were randomized to either an immediate or a stepped-up strategy that involved methotrexate, etanercept, and triple disease-modifying antirheumatic drug (DMARD) therapy in four arms.

Patients were randomized to one of the following four strategies:

▸ Immediate methotrexate and etanercept.

▸ Immediate triple DMARD therapy with methotrexate, sulfasalazine, and hydroxychloroquine.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus etanercept.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus triple DMARD therapy.

At trial entry, patients had a mean Disease Activity Score 28 of 5.8; the primary end point was mean DAS28 from weeks 48 to 102. Their entry 28-joint count showed that they had a mean of 14.3 painful joints and 12.8 swollen joints.

Findings from the TEAR trial, which began in 2004, showed that by the end of the second year of therapy, patients who were randomized to a stepped-up drug regimen and those treated immediately with either combination regimen had similar clinical responses, Dr. Moreland said.

Specifically, the DAS28 at week 102 was 3.0 for patients who were treated immediately with methotrexate plus etanercept, 3.1 for those on methotrexate stepped up to etanercept, and 2.8 for those who were treated with methotrexate stepped up to triple DMARD therapy.

The cost of care with three conventional oral disease-modifying antirheumatic drugs is going to be lower than the cost of using a biologic, said Dr. Moreland, who is the Margaret Jane Miller Endowed Professor of Arthritis Research and chief of rheumatology and clinical immunology at the University of Pittsburgh, although he did not cite specific costs of care.

The American College of Rheumatology has developed guidelines on the treatment of RA that call for initial treatment with methotrexate, but they go only so far, Dr. Moreland noted. They do not cover how to deal with patients who do not respond to methotrexate. Factors such as clinical judgment and insurance coverage may decide whether a nonresponder goes onto DMARDs or a biologic, he said.

Dr. Moreland said that the investigators undertook this research to provide much-needed direct data comparing triple DMARD therapy (methotrexate, sulfasalazine, and hydroxychloroquine) vs. methotrexate plus etanercept in patients with early RA. The study is designed to fill another data shortcoming: It evaluates the relative benefit of either combination vs. methotrexate monotherapy with a step-up after 6 months, if necessary.

Dr. Moreland reported research funding and other support from Amgen Inc., Barr Pharmaceuticals Inc., Immunex Corp., and Pharmacia Corp. Additional funding for the research was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

PHILADELPHIA — Methotrexate monotherapy, with the addition of either the combination of sulfasalazine plus hydroxychloroquine or etanercept alone at 6 months, if needed, is a reasonable treatment strategy for early rheumatoid arthritis, according to findings presented at the annual meeting of the American College of Rheumatology.

Reporting findings from the TEAR (Treatment of Early Aggressive RA) trial, principal investigator Dr. Larry W. Moreland described the trial, in which 755 patients (72% female; 80% white; 11% black) were randomized to either an immediate or a stepped-up strategy that involved methotrexate, etanercept, and triple disease-modifying antirheumatic drug (DMARD) therapy in four arms.

Patients were randomized to one of the following four strategies:

▸ Immediate methotrexate and etanercept.

▸ Immediate triple DMARD therapy with methotrexate, sulfasalazine, and hydroxychloroquine.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus etanercept.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus triple DMARD therapy.

At trial entry, patients had a mean Disease Activity Score 28 of 5.8; the primary end point was mean DAS28 from weeks 48 to 102. Their entry 28-joint count showed that they had a mean of 14.3 painful joints and 12.8 swollen joints.

Findings from the TEAR trial, which began in 2004, showed that by the end of the second year of therapy, patients who were randomized to a stepped-up drug regimen and those treated immediately with either combination regimen had similar clinical responses, Dr. Moreland said.

Specifically, the DAS28 at week 102 was 3.0 for patients who were treated immediately with methotrexate plus etanercept, 3.1 for those on methotrexate stepped up to etanercept, and 2.8 for those who were treated with methotrexate stepped up to triple DMARD therapy.

The cost of care with three conventional oral disease-modifying antirheumatic drugs is going to be lower than the cost of using a biologic, said Dr. Moreland, who is the Margaret Jane Miller Endowed Professor of Arthritis Research and chief of rheumatology and clinical immunology at the University of Pittsburgh, although he did not cite specific costs of care.

The American College of Rheumatology has developed guidelines on the treatment of RA that call for initial treatment with methotrexate, but they go only so far, Dr. Moreland noted. They do not cover how to deal with patients who do not respond to methotrexate. Factors such as clinical judgment and insurance coverage may decide whether a nonresponder goes onto DMARDs or a biologic, he said.

Dr. Moreland said that the investigators undertook this research to provide much-needed direct data comparing triple DMARD therapy (methotrexate, sulfasalazine, and hydroxychloroquine) vs. methotrexate plus etanercept in patients with early RA. The study is designed to fill another data shortcoming: It evaluates the relative benefit of either combination vs. methotrexate monotherapy with a step-up after 6 months, if necessary.

Dr. Moreland reported research funding and other support from Amgen Inc., Barr Pharmaceuticals Inc., Immunex Corp., and Pharmacia Corp. Additional funding for the research was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

PHILADELPHIA — Methotrexate monotherapy, with the addition of either the combination of sulfasalazine plus hydroxychloroquine or etanercept alone at 6 months, if needed, is a reasonable treatment strategy for early rheumatoid arthritis, according to findings presented at the annual meeting of the American College of Rheumatology.

Reporting findings from the TEAR (Treatment of Early Aggressive RA) trial, principal investigator Dr. Larry W. Moreland described the trial, in which 755 patients (72% female; 80% white; 11% black) were randomized to either an immediate or a stepped-up strategy that involved methotrexate, etanercept, and triple disease-modifying antirheumatic drug (DMARD) therapy in four arms.

Patients were randomized to one of the following four strategies:

▸ Immediate methotrexate and etanercept.

▸ Immediate triple DMARD therapy with methotrexate, sulfasalazine, and hydroxychloroquine.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus etanercept.

▸ Immediate methotrexate monotherapy with a step-up to methotrexate plus triple DMARD therapy.

At trial entry, patients had a mean Disease Activity Score 28 of 5.8; the primary end point was mean DAS28 from weeks 48 to 102. Their entry 28-joint count showed that they had a mean of 14.3 painful joints and 12.8 swollen joints.

Findings from the TEAR trial, which began in 2004, showed that by the end of the second year of therapy, patients who were randomized to a stepped-up drug regimen and those treated immediately with either combination regimen had similar clinical responses, Dr. Moreland said.

Specifically, the DAS28 at week 102 was 3.0 for patients who were treated immediately with methotrexate plus etanercept, 3.1 for those on methotrexate stepped up to etanercept, and 2.8 for those who were treated with methotrexate stepped up to triple DMARD therapy.

The cost of care with three conventional oral disease-modifying antirheumatic drugs is going to be lower than the cost of using a biologic, said Dr. Moreland, who is the Margaret Jane Miller Endowed Professor of Arthritis Research and chief of rheumatology and clinical immunology at the University of Pittsburgh, although he did not cite specific costs of care.

The American College of Rheumatology has developed guidelines on the treatment of RA that call for initial treatment with methotrexate, but they go only so far, Dr. Moreland noted. They do not cover how to deal with patients who do not respond to methotrexate. Factors such as clinical judgment and insurance coverage may decide whether a nonresponder goes onto DMARDs or a biologic, he said.

Dr. Moreland said that the investigators undertook this research to provide much-needed direct data comparing triple DMARD therapy (methotrexate, sulfasalazine, and hydroxychloroquine) vs. methotrexate plus etanercept in patients with early RA. The study is designed to fill another data shortcoming: It evaluates the relative benefit of either combination vs. methotrexate monotherapy with a step-up after 6 months, if necessary.

Dr. Moreland reported research funding and other support from Amgen Inc., Barr Pharmaceuticals Inc., Immunex Corp., and Pharmacia Corp. Additional funding for the research was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.