Treatment response and disease remission rates were lowest with infliximab and highest with adalimumab in a large Danish cohort analysis of patients who were treated for rheumatoid arthritis with tumor necrosis factor–alpha inhibitors, judging from recent findings.
Data from the DANBIO (Dansk Reumatologisk Database) registry also revealed that TNF-alpha adherence was lowest with infliximab and highest with etanercept, and that older age, low functional status, and concomitant prednisolone treatment were negative predictors of clinical response and remission, according to Dr. Merete Lund Hetland of Copenhagen University and her associates.
The DANBIO registry has monitored and reported details of TNF-alpha inhibitor therapy for RA patients since October 2000.
Sponsored by Danish hospital owners and the pharmaceutical companies that offer biologic treatments for rheumatologic disease (Abbott, Wyeth, Schering-Plough, Bristol-Myers Squibb, Roche, and UCB-Nordic), DANBIO is approved by the Danish National Board of Health as a national quality registry, Dr. Hetland and her associates wrote (Arthritis Rheum. 2010;62:22-32).
This study is believed to be the first direct comparison between adalimumab, etanercept, and infliximab and the ability of the three agents to elicit treatment goals including remission, they noted.
All patients included in the study had RA and had been treated with one or more conventional disease-modifying antirheumatic drugs (DMARDs), but those treatments had failed, and one of the three biologic agents was initiated. Concomitant methotrexate or other DMARD and prednisolone were administered based on the decision of the treating rheumatologist.
The initial study population comprised 2,326 patients, of whom 449 withdrew prior to the first 6 months of the study. Of those 449, 52% withdrew because of lack of efficacy and 38% from adverse events.
Among the 1,877 patients who had not withdrawn, an ACR 70 (American College of Rheumatology 70) response was achieved after 6 months in 19% of them (Arthritis Rheum. 1995;38:727-35), a good response by the EULAR (European League Against Rheumatism) criteria in 41% of them (Arthritis Rheum. 1996;39:34-40), remission by DAS28 (Disease Activity Score in 28 joints) in 25% of them, and CDAI (Clinical Disease Activity Index) remission in 13%.
Older age, low functional status as reflected in a high score on the Health Assessment Questionnaire, and concomitant prednisolone treatment were negative predictors of an ACR 70 response, whereas concomitant methotrexate, male sex, number of previous DMARD treatments, and disease duration were not predictors.
The patterns were similar for all outcome measures at 6 and 12 months, according to Dr. Hetland and her associates.
Overall, the crude treatment response rates after 6 and 12 months were highest for adalimumab (544 patients), intermediate for etanercept (425), and poorest for infliximab (908).
After correction for withdrawals from the study, ACR 70 was achieved at 6 months by 19% of those receiving adalimumab, by 17% of those using etanercept, and by 11% of those on infliximab. A good EULAR response was reported at 6 months in 41%, 34%, and 27%, respectively.
Similarly, DAS28 remission at 6 months occurred in 26% with adalimumab, 21% with etanercept, and 17% with infliximab; CDAI remission occurred in 15%, 10%, and 8%, respectively.
Combination therapy with methotrexate and prednisolone was used more often by those taking infliximab than by those using the other two TNF-alpha inhibitors.
After adjustment for that, as well as previous DMARD use, sex, age, disease duration, seropositivity, and baseline functional status, the odds ratios for achieving an ACR 70 response after 6 months of treatment were 2.05 for adalimumab and 1.78 for etanercept, compared with infliximab.
Adalimumab and etanercept were not significantly different, the investigators reported.
The odds ratios for adalimumab vs. infliximab were statistically significant for all outcome measures, ranging from 1.78 to 2.76. For etanercept vs. infliximab, odds ratios ranged from 1.16 to 1.99, which were statistically significant for ACR 70 and EULAR response measures, but not for the two remission outcomes.
Adalimumab produced a significantly higher EULAR good response (OR, 1.49) and CDAI remission (OR, 1.58) than did etanercept.
Drug adherence was highest for etanercept and lowest for infliximab. At 48 months, unadjusted adherence rates were 52% for adalimumab, 56% for etanercept, and 41% for infliximab, Dr. Hetland and her associates said.
Disclosures: This study was supported by unrestricted grants to DANBIO from its participating companies, which had no role in the study design, nor the collection, analysis, or interpretation of the data or the decision to submit the manuscript for publication.
Dr. Hetland's work on this study was supported by a grant from the Danish Rheumatism Association and a private foundation.
She has received consulting fees, speaking fees, and/or research grants of less than $10,000 each from all of the companies (except Bristol-Myers Squibb) that were involved in DANBIO, and grants of more than $10,000 each from all the participating companies on behalf of DANBIO.