Disease activity, physical function, and radiographic progression after longterm therapy with adalimumab plus methotrexate: 5-year results of PREMIER.
OBJECTIVE
To evaluate the efficacy and safety of initial combination treatment with adalimumab (ADA) and methotrexate (MTX) versus monotherapy with ADA or MTX during an open-label extension of PREMIER.


METHODS
Patients with early rheumatoid arthritis (RA) received blinded ADA plus MTX, ADA alone, or MTX alone for 2 years in PREMIER. At Year 2, patients could enroll in an open-label extension and receive ADA monotherapy; MTX could be added at the investigator's discretion. Longterm efficacy results are presented as observed data.


RESULTS
In the open-label period, 497 of the original 799 randomized patients had ≥ 1 dose of ADA (by original randomization: ADA plus MTX, n = 183; ADA, n = 159; MTX, n = 155). In the completers cohort [patients with available Year-5 ACR responses and modified total Sharp scores (mTSS)], the Year-5 mean change from baseline in mTSS for the ADA+MTX arm (n = 124) was 2.9, compared with 8.7 and 9.7 in the ADA (n = 115) and MTX (n = 115) arms. Comprehensive disease remission, defined as the combination of DAS28 remission, normal function (Health Assessment Questionnaire ≤ 0.5), and radiographic nonprogression (ΔmTSS ≤ 0.5), was achieved by more patients in the initial ADA+MTX arm (35%) than in the ADA (13%) or MTX (14%) arms.


CONCLUSIONS
Initial combination treatment with ADA plus MTX, followed by open-label ADA, led to better longterm clinical, functional, and radiographic outcomes than either initial ADA or MTX monotherapy during 5 years of treatment.
van der Heijde
Désirée
D
Leiden University Medical Center, Leiden, The Netherlands.
Breedveld
Ferdinand C
FC
Kavanaugh
Arthur
A
Keystone
Edward C
EC
Landewé
Robert
R
Patra
Kaushik
K
Pangan
Aileen L
AL
D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D001175:Arthrography; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007596:Joints / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D008727:Methotrexate