Two-Year Safety and Efficacy Experience in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis Treated with Etanercept and Conventional Disease-Modifying Anti-rheumatic Drugs in the Latin American Region

Daniel A Machado, Renato Guzman, Ricardo M Xavier, Jesus A Simon, Linda Mele, Qi Shen, Ronald Pedersen, Sameer Kotak, Bonnie Vlahos, Daniel A Machado, Renato Guzman, Ricardo M Xavier, Jesus A Simon, Linda Mele, Qi Shen, Ronald Pedersen, Sameer Kotak, Bonnie Vlahos

Abstract

Background: Although long-term data are available from biologic studies in North American/European populations with rheumatoid arthritis (RA), long-term findings in Latin American RA populations are limited.

Objective: To examine long-term safety/efficacy of etanercept, methotrexate, and/or other disease-modifying anti-rheumatic drugs (DMARDs) in Latin American patients with moderate-to-severe active RA.

Methods: In the first phase of this open-label study, patients were randomized to etanercept 50 mg weekly plus methotrexate or conventional DMARD (hydroxychloroquine or sulfasalazine) plus methotrexate for 24 weeks. At the start of the second phase (week 24), investigators selected a treatment regimen that included any combination/dosage of etanercept, methotrexate, hydroxychloroquine, or sulfasalazine based on previous treatment response, preference, and local product labeling, and was continued for the 104-week extension.

Results: In the extension, in the group previously randomized to etanercept-plus-methotrexate therapy, etanercept was continued in 259/260 patients; methotrexate continued in 260/260; and hydroxychloroquine and sulfasalazine added in 8/260 and 3/260, respectively. In the group previously randomized to conventional DMARD-plus-methotrexate therapy, conventional DMARD was discontinued in 86/126 and etanercept added in 105/126. Among etanercept-exposed patients (total exposure, 798.1 patient-year [PY]), rates of adverse events, serious adverse events, and serious infections per PY were 1.7, 0.07, and 0.02 events per PY. In both groups, after treatment modification was permitted, clinical response rates and improvements in clinical/patient-reported outcomes from baseline were sustained to week 128.

Conclusion: After investigators were permitted to modify treatment, etanercept was part of the treatment regimen in 95% of patients. Continuation or addition of etanercept in the 2-year extension resulted in a consistently good risk:benefit profile.

Trial registration: Open-Label Study Comparing Etanercept to Conventional Disease Modifying Antirheumatic Drug (DMARD) Therapy; ClinicalTrials.gov, number NCT00848354; https://ichgcp.net/clinical-trials-registry/NCT00848354.

Keywords: Disease-modifying antirheumatic drugs; Latin America; etanercept; methotrexate; rheumatoid arthritis.

Figures

Fig. (1)
Fig. (1)
Proportion of patients achieving (A) ACR20 response, (B) ACR50 response, (C) ACR70 response, (D) DAS28 LDA, (E) DAS28 remission, and (F) normal HAQ (≤0.5). Treatment modification was permitted at the start of the extension (i.e., after week 24); during the extension, 259/260 patients in the ETN + MTX group continued to receive etanercept and 105/126 patients in the DMARD + MTX group received etanercept. ACR, American College of Rheumatology; DAS28, Disease Activity Score in 28 joints; DMARD, disease-modifying antirheumatic drug; ETN, etanercept; HAQ, Health Assessment Questionnaire; LDA, low disease activity; LOCF, last observation carried forward; MTX, methotrexate. Analyses included patients who received at least one dose of study drug in the extension phase; LOCF.
Fig. (2)
Fig. (2)
Mean scores (SD) for (A) DAS28, (B) total HAQ Disability Index,(C) SF-36 PCS, (D) SF-36 MCS, and (E) SF-36 vitality domain. Treatment modification was permitted at the start of the extension (i.e., after week 24); during the extension, 259/260 patients in the ETN + MTX group continued to receive etanercept and 105/126 patients in the DMARD + MTX group received etanercept. DAS28, Disease Activity Score in 28 joints; DMARD, disease-modifying anti-rheumatic drug; ETN, etanercept; HAQ, health assessment questionnaire; MCS, mental component summary; MTX, methotrexate; PCS, physical component summary; SF-36, 36-item short-form health survey. Analyses included patients who received at least 1 dose of study drug in the extension phase; LOCF.
Fig. (3)
Fig. (3)
The percentage of (A) work time missed and (B) overall work impairment due to RA in the past 7 days based on patient responses on the WPAI:RA questionnaire. Proportions of patients who are (C) currently employed; who have required (D) a rheumatologist visit or (E) an emergency department visit in the past 6 months; and who have required (F) caregiver assistance in the past month based on responses on the CBRU questionnaire. Treatment modification was permitted at the start of the extension (i.e., after week 24); during the extension, 259/260 patients in the ETN + MTX group continued to receive etanercept and 105/126 patients in the DMARD + MTX group received etanercept. Analyses included patients who received at least one dose of study drug in the extension phase. WPAI:RA and CBRU employment findings analyzed using LOCF; all other CBRU findings based on observed cases. CBRU, caregiver burden and resource utilization questionnaire; DMARD, disease-modifying anti-rheumatic drug; ETN, etanercept; LOCF, last observation carried forward; MTX, methotrexate; RA, rheumatoid arthritis; WPAI:RA, work productivity and activity impairment: rheumatoid arthritis questionnaire.

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