Effectiveness, safety, and methotrexate dose-tapering pattern over two years of treatment with adalimumab and ≥12 mg/week methotrexate for early rheumatoid arthritis: Results of the HAWK postmarketing surveillance study in Japan

<b>Objectives:</b> To investigate the long-term effectiveness, safety, and methotrexate (MTX) dose-tapering patterns in patients with rheumatoid arthritis (RA) receiving adalimumab plus high-dose MTX. <b>Methods:</b> In this prospective, postmarketing study (2012–2017), conducted at 128 sites in Japan, biologic-naïve patients with RA (duration ≤2 years) previously treated with MTX for ≥3 months, initiated treatment with adalimumab and MTX (≥12 mg/week). Effectiveness by Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), safety, and MTX dose-tapering were assessed from baseline to 104 weeks. <b>Results:</b> In the effectiveness analysis set (<i>n</i> = 292), DAS28-CRP remission (&lt;2.6) was achieved in 92.3% (<i>n</i> = 120/130) of patients at week 104. The proportions of patients receiving MTX dose &lt;10 mg/week increased to 32.3% (<i>n</i> = 50/155) and ≥12 mg/week reduced to 52.9% (<i>n</i> = 82/155) by week 104. Per univariate regression analysis, MTX dose tapering was associated with longer adalimumab drug survival. Of 70 patients with joint X-rays available, 59 (84.3%) achieved Δ modified total Sharp score ≤1.0 at 104 weeks. In the safety analysis set (<i>n</i> = 300), 143 adverse drug reactions were reported in 92 patients (30.7%, non-serious; 24.7%, serious 8.7%). <b>Conclusion:</b> The long-term effectiveness and safety of adalimumab with high-dose MTX was confirmed in biologic-naïve patients with early RA in a real-world setting in Japan. <b>Clinical Trial Registration:</b> This study is registered at ClinicalTrials.gov (identifier: NCT01736189; retrospectively registered 29 November 2012, due to administrative reasons).