Background The PREMIER trial demonstrated the superiority of initial adalimumab (ADA)+MTX vs the individual monotherapies in MTX-naïve patients (pts) with early, aggressive rheumatoid arthritis (RA)1.
Objectives To assess long-term outcomes in pts treated with ADA, with or without MTX, for up to 10 years (yrs).
Methods Pts completing the 2yr blinded study were eligible to receive open-label (OL) ADA for up to an additional 8 yrs; MTX could be added at the investigator’s discretion. This post hoc analysis evaluated data as observed (ie, no imputation for missing data); results are summarized overall and by initial treatment arm. DAS28(CRP) and HAQ-DI were used to assess clinical and functional outcomes, respectively. Radiographic progression (change from baseline in mTSS) was assessed in 10yr completers with radiographic data available at baseline and yr 10. Adverse events (E) of interest were summarized for pts receiving ≥1 ADA dose and presented as E/100-pt yrs (PY).
Results Of the 799 pts randomized, 497 (62%) entered the OL extension; 250 (31%) maintained OL ADA±MTX through yr 10. MTX co-therapy was (re)initiated in 261 pts (53%) during the OL extension. Overall, pts completing 10 yrs of therapy continued to demonstrate effective disease control (mean DAS28=2.4; mean HAQ-DI=0.6; mean ΔmTSS=7.8). Although the addition of OL ADA±MTX to the initial MTX and ADA arms at yr 2 led to increases in the proportions achieving DAS28(CRP) <2.6 and HAQ-DI <0.5 over time, differences between initial treatment arms persisted through yr 10 (Table). Further, ΔmTSS remained significantly lower over time in the initial ADA+MTX arm compared with the 2 monotherapy arms (ΔmTSS =4.0, 11.0, and 8.8 at yr 10 for the initial ADA+MTX, MTX, and ADA arms, respectively; both P <0.05), despite OL ADA±MTX slowing progression comparably in each of the arms (both P >0.05). No new safety signals arose following 3708 PY of ADA exposure (N=697 pts): serious infections =2.6 E/100-PY; TB =0.2 E/100-PY; malignancy (other than NMSC) SIR (95% CI) =0.89 (0.62, 1.26). There were 23 deaths during this 10yr study, resulting in an SMR (95% CI) of 0.72 (0.49, 1.02).
Conclusions ADA±MTX maintained effective disease control for up to 10 yrs in pts with early, aggressive RA. Of the pts who continued in the study, those who initiated ADA+MTX combination therapy retained better outcomes through 10 yrs than pts who began treatment with MTX or ADA monotherapy.
Breedveld et al. Arthritis & Rheum. 2006; 54(1):26-37.
Acknowledgements AbbVie Inc. sponsored the study (NCT00195663), contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. Medical writing support was provided by Benjamin Wolfe, PhD, of AbbVie Inc.
Disclosure of Interest E. Keystone Grant/research support from: AbbVie Inc., Amgen, AstraZeneca, BMS, Centocor, Genzyme, Merck, Novartis, Pfizer, Roche, UCB, Consultant for: AbbVie Inc., AstraZeneca, Biotest, BMS, Centocor, Genentech, Merck, Nycomed, Pfizer, Roche, UCB, Speakers bureau: AbbVie Inc., Amgen, BMS, Janssen, Merck, Pfizer, Roche, UCB, F. Breedveld Consultant for: Centocor, Schering-Plough, Amgen/Wyeth, AbbVie Inc, D. van der Heijde Consultant for: AbbVie Inc., Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Wyeth, and is the director of Imaging Rheumatology bv, R. Landewé Consultant for: AbbVie Inc., Amgen, BMS, Centocor, GSK, Merck, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, and is the owner of Rheumatology Consultancy bv, S. Florentinus Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., U. Arulmani Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., S. Liu Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., H. Kupper Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., A. Kavanaugh Grant/research support from: AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB, Consultant for: AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB