Objective To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA).
Methods Patients with active early RA (disease duration of ≤12 months) were randomly assigned to receive 40 mg ADA subcutaneously every other week (eow) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks. Thereafter, all patients received MTX monotherapy up to week 48. The primary outcome was the Disease Activity Score 28 (DAS28) at week 48. Secondary outcomes included proportions of patients in remission (DAS28<2.6), ACR responses, Health Assessment Questionnaire (HAQ) score and radiographic progression.
Results 87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX. At baseline, DAS28 was 6.2±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups. At week 24, treatment with ADA/MTX compared with PBO/MTX resulted in a greater reduction in DAS28 (3.0±1.2 vs 3.6±1.4; p=0.009) and other secondary outcomes such as DAS28 remission rate (47.9% vs 29.5%; p=0.021) and HAQ (0.49±0.6 vs 0.72±0.6; p=0.0014). At week 48, the difference in clinical outcomes between groups was not statistically significant (DAS28: 3.2±1.4 vs 3.4±1.6; p=0.41). Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX (Sharp/van der Heijde score: ADA/MTX 2.6 vs PBO/MTX 6.4; p=0.03, Ratingen score: 1.7 vs 4.2; p=0.01).
Conclusions A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).
Statistics from Altmetric.com
Trial registration http://www.controlled-trials.com: ISRCTN36745608; EudraCT Number: 2006-003146-41.
Funding This study was funded by the German Federal Ministry of Education and Research (BMBF, grant number: 01KG0602), trial designation: High Induction Therapy with Anti-Rheumatic Drugs–HIT HARD. Adalimumab was provided by Abbott Co., Wiesbaden, Germany, under an unconditional scientific grant. Abbott had no influence on trial design, interpretation of the data or writing of the paper.
Competing interests GRB and KK have received honoraria from Abbott for speaking, board membership and lectures.
Ethics approval This study was conducted with the approval of the Berlin State ethics committee (Landesethikkommission Berlin).
Provenance and peer review Not commissioned; externally peer reviewed.
Correction notice This article has been corrected since it was published online first. The Acknowledgements section has been altered.