10-Year Follow-up Study on Safety and Efficacy of Adalimumab

One of the great evolutions of clinical research over the past two decades is the development of longitudinal studies that look beyond the short-term safety and effectiveness of a therapy. This can be particularly important for conditions like severe-to-moderate rheumatoid arthritis (RA), for which patients may receive a medication—or a combination of medications—over a period that can span decades.

DE020 was a long-term, open-label, follow-up trial that looked at the safety and efficacy of adalimumab (Humira^®) in 846 methotrexate (MTX)-resistant patients over a 10-year period. Although preliminary results were presented at the 2012 European League Against Rheumatism (EULAR) 2012 Congress, the final 10-year results of the study were recently published in Rheumatology. In short, adalimumab led to sustained clinical and functional responses in the 33.8% of treatment-refractory RA patients who completed 10 years of treatment. Patients with shorter disease duration achieved better outcomes, highlighting the need for early treatment.

DE020 itself enrolled patients from earlier studies (including ARMADA and STAR and another smaller study).All four studies included patients with active RA and an inadequate response to MTX and/or other disease-modifying antirheumatic drugs (DMARDs). Patients could receive supplemental DMARD therapy at the investigator’s discretion after inclusion in DE020. A total of 846 patients were enrolled in the follow-up study.

Clinical and functional responses were assessed as the percentage of patients observed to achieve American College of Rheumatology (ACR) criteria 20/50/70 responses, disease activity score (DAS)28 <3.2 (a measure of low disease activity), DAS28 <2.6 and HAQ-DI <0.5 at year 10. ACR response criteria measure the percent improvement in tender and swollen joints, as well as patient and physician global assessment, pain, disability and inflammatory markers.

The large-scale study included patients with a mean baseline age of 55.6 years, 78.1% were women, and mean disease duration was 11.7 years. Twenty-seven percent were rheumatoid factor negative (RF⁻). Among 286 (33.8%) patients who completed 10 years of adalimumab, 71.2% achieved DAS28-C-reactive protein (CRP) ≤3.2, 42.4% achieved HAQ-DI <0.5 and 90/241 (37.3%) achieved DAS28-CRP ≤3.2 plus HAQ-DI <0.5. DAS28-CRP- or SDAI-based remission was observed in 57.2% and 29.7% patients, respectively.

The EULAR Congress report also noted the following at year 10 of the DE020 study:

• 78.6 percent of patients achieved at least 20 percent improvement in the ACR criteria (ACR20)
• 55.5 percent achieved at least 50 percent improvement in the ACR criteria
• 32.8 percent achieved at least 70 percent improvement in the ACR criteria
• 42.4 percent achieved a Health Assessment Questionnaire Disability Index (HAQ-DI) <0.5

The results complement other findings related to adalimumab effectiveness and safety, including the 2013 PREMIER study published in TheJournal of Rheumatology, which found that intensive therapy with adalimumab + MTX combination in patients with early RA has long-term benefits compared to patients initiating with 2-year adalimumab or MTX monotherapy.