Background HOPEFUL-1 trial and HIT HARD trial showed the effect of combination therapy of methotrexate (MTX) plus adalimumab (ADA) for MTX naïve patients with active early rheumatoid arthritis (RA). Although the biologic disease modified anti rheumatic drugs (bDMARDs) are the most effective treatment of RA, the costs are much higher than that of conventional synthetic DMARDs (csDMARDs). Considering the total medical cost, strategies such as tapering and withdrawal of bDMARDs without disease flare can be an important option. However, the condition for discontinuation of bDMARDs in a real clinical setting has not been fully investigated.
Objectives To analyze the bio-free condition of ADA and the effect of early introduction of ADA in RA patients in a real world.
Methods We used ADA in 132 RA patients. Study 1: Twenty three patients discontinued ADA. We analyzed 14 patients who were followed up for more than 24 weeks after discontinuation. Study 2: Twenty four patients started ADA within 3 months from the introduction of MTX. Two patients stopped ADA due to inefficacy. We analyzed 14 patients who were followed up for more than 52 weeks.
Results Study 1. Patients were 54.6 ± 10.5 years old, disease duration 3.2 ± 2.7 years, Bio-naïve: 13 patients, switch: 1 patient, Prednisolone was increased in 1 patient. csDMARDs were added in 8 patients (4 patients before and 4 patients after discontinuation of ADA). DAS28-CRP did not change until 24 weeks and no patient re-started bDMARDs. Study 2. Patients were 45.0 ± 14.9 years old, disease duration 1.5 ± 2.7 years, 6 patients used MTX alone as csDMARD and 5 patients among them started other csDMARDs additionally. DAS28-CRP decreased from 4.9 ± 1.1 to 1.8 ± 0.6 (p<0.0001), 9 patients achieved clinical remission (64.3%), and 3 patients (21.4%) achieved bio-free condition without relapse.
Conclusions In Study 1, ADA made bio-free condition in 17.5% of RA patients without relapse until 24 weeks, which indicates the possibility of sustainable bio-free in the real clinical setting. In Study 2, patients with early RA who started ADA within 3 months from the introduction of MTX achieved clinical remission (64.3%) and bio-free condition (21.4%). This result shows early introduction of ADA for bio-free condition might be a good choice in terms of reducing a total medical cost in the long term. In these studies, additional use of csDMARDs after bDMARDs discontinuation is thought to be important for maintaining bio-free condition without disease flare.
Hisashi Yamanaka et al. Recovery of clinical but not radiographic outcomes by the delayed addition of adalimumab to methotrexate-treated Japanese patients with early rheumatoid arthritis: 52-week results of the HOPEFUL-1 trial. Rheumatology 2014;53:904–913
Jacqueline Detert et al. Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naïve patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study. Ann Rheum Dis 2013;72:844–850
Disclosure of Interest S. Ito Speakers bureau: AbbVie, Eisai, D. Kobayashi: None declared, C. Takai: None declared, T. Nemoto: None declared, H. Lee: None declared, A. Abe: None declared, H. Otani: None declared, H. Ishikawa: None declared, A. Murasawa: None declared, I. Narita: None declared, K. Nakazono: None declared