Results from a clinical trial revealed that patients with early rheumatoid arthritis (RA) who stopped taking Humira (adalimumab) once their RA was under control maintained a low disease activity for up to three years and showed an improvement in the incidence of adverse effects.
The patients in the HOPEFUL-3 study were taking a combination of Humira plus methotrexate (MTX) to get their RA under control. Once their RA was found to be at a low activity, they discontinued treatment with Humira but continued taking MTX. After three years without Humira, their disease was still under control and at a low activity.
The study, “Low disease activity for up to 3 years after adalimumab discontinuation in patients with early rheumatoid arthritis: 2-year results of the HOPEFUL-3 Study,” was published in the journal Arthritis Research & Therapy.
Therapeutic combinations for RA treatment have shown improved results in disease remission compared to a single drug. In particular, an anti-inflammatory tumor necrosis factor (TNF) inhibitor combined with MTX is more beneficial than MTX alone. However, the continuous use of biological agents may lead to serious infections and can be costly for patients.
Recent research has evaluated the possibility of discontinuing treatment with biological agents in RA patients who have achieved low disease activity. However, there was no data on the effects of stopping Humira for periods longer than one year.
In the HOPEFUL-1 study, early RA patients in Japan received initial therapy with either Humira plus MTX (intensive therapy) or MTX alone (standard therapy) for 26 weeks, followed by Humira plus MTX for an additional 26 weeks. Results showed that treatment with Humira combined with MTX was well-tolerated and effective in improving clinical responses.
In the HOPEFUL-2 study, Japanese patients received Humira plus MTX (Humira continuation) or MTX alone (where they stopped taking Humira) for 52 weeks. Most patients who discontinued Humira still had a low disease activity after one year.
HOPEFUL-3 (NCT01346501) was an observational study in participants who had completed the HOPEFUL-2 trial. A total of 172 patients were followed for an additional 104 weeks, or two years. The researchers evaluated the effects of long-term (three years) Humira discontinuation after the patients achieved low disease activity. The team also aimed to identify predictors of low disease activity maintenance.
In the end, the analysis included data from 135 patients. At the conclusion of the two-year follow-up in HOPEFUL-3, 58 (95.1%) of the 61 patients in the Humira continuation group in HOPEFUL-2, and 59 (79.7%) of 74 patients in the Humira discontinuation group had a low disease activity.
Initial intensive therapy with Humira plus MTX was associated with a better outcome in terms of suppression of joint destruction, compared to standard therapy with MTX alone.
The team also observed that the incidence of adverse events was lower when Humira treatment was discontinued (9.7%) than in the Humira continuation group (32.9%).
“Approximately 80% of patients who discontinued [Humira] for three years after achieving LDA [low disease activity] with [Humira plus] MTX were still in LDA, with a lower incidence of adverse events than patients who continued [Humira],” the team concluded. “However, it must be noted that there was a significant difference in the proportion of patients who achieved LDA among patients who discontinued [Humira] compared with patients who continued to receive [Humira].”
Because discontinuing Humira is associated with a lower incidence of adverse events, doctors should weigh the risks and benefits of discontinuing the drug, the researchers added.