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This study is among the first to show that aggressive treatment of early rheumatoid arthritis with biologic DMARDs benefits high-risk patients.
A clinical trial assessing the sustainability of radiographic and clinical benefits achieved with the combination of biological DMARDs and methotrexate for early rheumatoid arthritis, shows that patients maintained improvements one year after the biological DMARDs were removed from treatment.
The trial included 316 methotrexate naÃ¯ve patients with early rheumatoid arthritis. They were treated with the combination of certolizumab pegol with methotrexate treatment for one year, then methotrexate monotherapy in the second year. Patients were largely able to maintain clinical benefits through two years.
“These results suggest that early treatment with certolizumab pegol during the initial stages of the disease - when rapid joint damage may take place - could prevent long-term progression of joint damage and functional disability as previously suggested in the ‘window of opportunity’ concept,” researchers wrote in the May 31 online issue of Annals of the Rheumatic Diseases.
The researchers, led by Tatsuya Atsumi of Hokkaido University in Japan, suggest that biological DMARDs (bDMARDs) could be used as a first-line treatment in early rheumatoid arthritis, especially for high-risk patients who are candidates for aggressive treatment. Currently, biological DMARDs are considered second-line therapies for patients who do not meet treatment targets. Instead, these patients are typically treated with conventional synthetic DMARDs (csDMARDs), even though some studies have shown that bDMARDs are superior to csDMARDs in preventing more joint damage.
The study is among the first to show that aggressive early treatment of rheumatoid arthritis can stave off symptoms one year after the initial therapy has stopped.
“The results suggest that initial aggressive treatment with a bDMARD could be a potential treatment option at the early stage of disease, especially for patients who have a poor prognosis. Once patients achieve their treatment targets, bDMARD treatment could be withdrawn. This treatment approach has the potential to prevent irreversible joint damage, reduce patient risk of adverse events and be a more cost-effective way to manage rheumatoid arthritis over the long term,” the researchers wrote.
In this study, researchers examined whether the symptoms of rheumatoid arthritis would remain under control after the treatment stopped.
Certolizumab-Optimal Prevention of joint damage for Early RA (C-OPERA) is a multi-center, double-blind, placebo-controlled, randomized, parallel-group two-year study of 316 rheumatoid arthritis patients with poor prognostic factors, high concentrations of anticyclic citrullinated peptide antibody and were either positive for rheumatoid factor or bone erosions.
The first 52 weeks was a double-blind trial of rheumatoid arthritis patients who received either certolizumab pegol with methotrexate (159 patients) or a placebo with methotrexate (157 patients). In the first year, 50 percent of patients achieved remission and 80 percent achieved radiographic non-progression, “suggesting that the introduction of certolizumab pegol at a very early stage led to substantial therapeutic effects, despite poor prognosis.”
During the second year, 179 patients received methotrexate without certolizumab pegol or a placebo for 52 weeks. 131 patients completed the study through week 104: specifically, 68.5 percent of the certolizumab pegol with methotrexate group and 80.3 percent in the placebo with methotrexate group.
In the certolizumab pegol and methotrexate combination treatment group, 84.2 percent of patients experienced significant inhibition of disease progression as compared to 67.5 percent of the placebo plus methotrexate group. Remission rates decreased after certolizumab pegol was discontinued, however, the certolizumab pegol and methotrexate combination group experienced 41.5 percent of remission as compared to the second group at 24.2 percent.
After certolizumab pegol was discontinued, 28 patients experienced a flare-up, but they quickly responded to a second round of treatment with certolizumab pegol achieving pre-flare disease activity levels.
Joint destruction was consistently prevented in the second year with methotrexate monotherapy, but clinical remission was sometimes lost after 16 weeks.
The clinical benefits observed in year one were evident in year two. The patients overwhelmingly experienced a reduction in the severity of their symptoms as well as significant inhibition of structural damage.
“A key finding from the post treatment period reported here, was that the beneficial effect seen after an initial one year of treatment with certolizumab pegol was observed after discontinuing certolizumab pegol therapy when the dose of methotrexate remained optimized,” the researchers wrote.
The safety analyses showed similar rates of serious adverse events for both treatment groups over the course of the two-year study with no major safety concerns.
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Astellas Pharma. and UCB Pharma funded this study and manuscript.
Atsumi T, Tanaka Y, Yamamoto K, et al. “Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomized trial.” Annals of the Rheumatic Diseases. Published Online First: 02 February 2017. DOI: 10.1136/annrheumdis-2016-210246