Efficacy of etanercept in combination with methotrexate in moderate-to-severe rheumatoid arthritis is not dependent on methotrexate dosage

G Gallo, F Brock, U Kerkmann, B Kola, T W J Huizinga, G Gallo, F Brock, U Kerkmann, B Kola, T W J Huizinga

Abstract

Objective: To evaluate the impact of methotrexate (MTX) dosage on clinical, functional and quality of life outcomes in patients with rheumatoid arthritis (RA) from two previous etanercept (ETN) trials after 24 months of treatment.

Methods: Patients with active RA in the ETN+MTX combination treatment arms of the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) and COmbination of Methotrexate and ETanercept in Active Early Rheumatoid Arthritis (COMET) studies were pooled in this post hoc analysis and stratified by MTX dosage at 24 months, having MTX monotherapy groups as control: low dose, <10.0 mg/week; medium dose, 10.0-17.5 mg/week; and high dose, >17.5 mg/week. Data from these patient subgroups were included in descriptive summaries of demographic and disease characteristics at baseline. The following outcomes at 24 months were also evaluated for each subgroup: Disease Activity Score in 28 joints (DAS28) low disease activity (LDA) and remission; American College of Rheumatology 20%, 50% and 70% improvement criteria (ACR20, 50 and 70) responses; and changes from baseline in DAS28, Health Assessment Questionnaire Disease Index (HAQ-DI) and EuroQol 5-dimensions visual analogue scale (EQ-5D VAS).

Results: Baseline demographics were similar between the low, medium and high MTX dose groups in the ETN+MTX combination and MTX monotherapy arms, with the exception of disease duration (ETN+MTX low 5.5; medium 5.1; high 0.8 years vs MTX low 8.3; medium 4.7; high 0.8 years). Responses to ETN+MTX combination therapy at 24 months were consistently high across MTX dosage groups, with very similar rates of DAS28 LDA/remission and ACR20/50/70. Improvements in DAS28, HAQ-DI and EQ-5D VAS were also not dependent on MTX dosage in the combination treatment arm.

Conclusions: Patients with RA in the TEMPO and COMET trials who received ETN+MTX showed similar efficacy outcomes at 24 months, regardless of MTX dosage.

Trial registration numbers: NCT00195494 (COMET) and NCT00393471 (TEMPO).

Keywords: Anti-TNF; DMARDs (biologic); DMARDs (synthetic); Rheumatoid Arthritis.

Figures

Figure 1
Figure 1
Frequency of methotrexate (MTX) doses at 24 months (plot) and summary of MTX doses across the MTX dosing categories (low, medium, high) based on data at 6, 12 and 24 months (table). Data represent n values, mean (median). *Patients with no MTX dose data at 24 months were excluded from the remainder of the post hoc summaries in this paper.
Figure 2
Figure 2
Percentage of patients achieving (A) DAS28 remission and (B) DAS28 LDA at baseline and at 6, 12 and 24 months. DAS28 remission was defined as DAS28≤2.6 and LDA as >2.6 DAS28

Figure 3

Percentage of patients achieving (A)…

Figure 3

Percentage of patients achieving (A) ACR 20, (B) ACR 50 and (C) ACR…

Figure 3
Percentage of patients achieving (A) ACR 20, (B) ACR 50 and (C) ACR 70 responses at 6, 12 and 24 months. ACR 20/50/70, American College of Rheumatology 20%, 50% and 70% improvement criteria; ETN, etanercept; MTX, methotrexate.

Figure 4

(A) DAS28, (B) HAQ-DI and…

Figure 4

(A) DAS28, (B) HAQ-DI and (C) EQ-5D VAS scores at baseline and at…

Figure 4
(A) DAS28, (B) HAQ-DI and (C) EQ-5D VAS scores at baseline and at 6, 12 and 24 months. Values are mean±SD. DAS28, Disease Activity Score in 28 joints; EQ-5D VAS, EuroQol 5-dimensions visual analogue scale; ETN, etanercept; HAQ-DI, Health Assessment Questionnaire Disability Index; MTX, methotrexate.
Figure 3
Figure 3
Percentage of patients achieving (A) ACR 20, (B) ACR 50 and (C) ACR 70 responses at 6, 12 and 24 months. ACR 20/50/70, American College of Rheumatology 20%, 50% and 70% improvement criteria; ETN, etanercept; MTX, methotrexate.
Figure 4
Figure 4
(A) DAS28, (B) HAQ-DI and (C) EQ-5D VAS scores at baseline and at 6, 12 and 24 months. Values are mean±SD. DAS28, Disease Activity Score in 28 joints; EQ-5D VAS, EuroQol 5-dimensions visual analogue scale; ETN, etanercept; HAQ-DI, Health Assessment Questionnaire Disability Index; MTX, methotrexate.

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