Background In patients (pts) with rheumatoid arthritis (RA), rheumatoid factor (RF) and anti-citrillunated peptide antibody (ACPA) are associated with higher disease activity and damage progression.
Objectives To explore whether early initiation of combination therapy with the TNF-inhibitor, adalimumab (ADA) + methotrexate (MTX) is associated with conversion in RF or ACPA status.
Methods Data were from the OPTIMA trial1, where pts with early RA were initially treated for 26 weeks (wks, period 1) with ADA+MTX, or placebo (PBO) +MTX. In total, 708/900 (78.7%) were RF+, 728/884 (82.4%) were ACPA+ at wk 26. If pts on ADA+MTX attained 28-joint disease activity score based on C - reactive protein (DAS28-CRP) <3.2 at wks 22 and 26 (responders), they were randomized to withdraw ADA, continue PBO+MTX, or continue ADA+MTX until wk 78 (period 2). Pts on PBO+MTX, who were responders at wks 22 and 26, received PBO+MTX until wk 78. Pts who did not reach DAS28-CRP <3.2 either on ADA+MTX or MTX alone (non-responders, NR), received Open Label (OL) ADA+MTX until wk 78. Levels of RF and ACPA were measured at baseline (BL), wks 26, 52 and 78. Results obtained in OPTIMA were validated with data from PREMIER (early RA; RF levels at BL, wks 26 and 52)2 and DE019 trials (established RA; RF at screening, wks 24 and 52).3
Results In OPTIMA, pts on ADA in period 1 tended to have lower RF levels than pts in the PBO+MTX arm at wks 26 and 78, irrespective of the treatment after wk 26. In pts who switched to or continued ADA in period 2 [ADA+MTX/ADA+MTX, ADA+MTX/OL ADA+MTX and PBO+MTX/ADA+MTX arms], RF levels decreased from wk 26 to 78 (table); pts in the PBO+MTX/ADA+MTX arm had the largest decrease from wk 26, in line with a decrease of clinical disease activity. In pts who switched to or continued on PBO+MTX in period 2 (ADA+MTX/PBO+MTX and the PBO+MTX/PBO+MTX arms), the RF levels increased from wk 26 to 78, despite overall maintenance of a low disease activity. A similar pattern was observed for ACPA levels. In PREMIER, combination ADA+MTX therapy was also more effective in reducing RF levels vs ADA or MTX monotherapy (table). More pts on ADA+MTX (19.4%) vs ADA (10.2%) or MTX (8.8%) monotherapy, who were RF+ at BL became RF- after 26 wks. In DE019, ADA+MTX therapy was effective in reducing RF levels compared to PBO (on background MTX), and more pts in the ADA arms vs PBO, who were RF+ at screening became RF- after 24 wks (ADA 20 mg: 7.5%; ADA 40 mg: 7.1%; PBO: 2.3%).
Conclusions Early combination treatment with ADA+MTX resulted in lower levels of RF and ACPA. The withdrawal of ADA led to increases in levels of RF and ACPA. These data suggest that effective therapy reduces autoantibody levels. Further studies are needed to elucidate the consequences of these changes.
Smolen et al. 2014. Lancet; 383:321–32
Breedveld et al. 2006. Arth and Rheum; 54:26–37
Keystone et al. 2004. Arth and Rheum; 5:1400–11
Acknowledgement AbbVie: study sponsor, contributed to design, data collection, analysis & interpretation; writing, reviewing, and approval of final version. Medical writing support: Naina Barretto, of AbbVie.
Disclosure of Interest J. Smolen Grant/research support from: AbbVie, Consultant for: AbbVie, A. Kavanaugh Grant/research support from: AbbVie, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Consultant for: AbbVie, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, D. Aletaha Grant/research support from: AbbVie, Pfizer, Grünenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche, Consultant for: AbbVie, Pfizer, Grünenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche, S. Florentinus Shareholder of: AbbVie, Employee of: AbbVie, Y. Li Shareholder of: AbbVie, Employee of: AbbVie, I. Lagunes Shareholder of: AbbVie, Employee of: AbbVie