Rheumatoid Arthritis: Why Are Some People Not Recovering and What They Can Do About This Right Now
A recent investigation, published in JAMA Network Open, explored the relationship between antibodies developed against certain drugs, such as monoclonal antibodies aimed at tumor necrosis factor (TNF) and interleukin-6 receptor, and the effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) used in treating rheumatoid arthritis.
Rheumatologists commonly use biologic drugs or bDMARDs as secondary treatment strategies for rheumatoid arthritis. However, patient retention for these treatments is not optimal, with approximately half of the patients ceasing treatment within two years.
The formation of antibodies against these biologic drugs could be one of the factors contributing to their ineffectiveness and subsequent decrease in concentration.
A pan-European investigation looked into the formation of these antibodies against biologic drugs among patients suffering from multiple sclerosis, Crohn’s disease, rheumatoid arthritis, and ulcerative colitis. The study noted that the use of antibiotics and immunosuppressants could decrease the likelihood of antidrug antibody formation.
Moreover, in patients with rheumatoid arthritis, the administration of methotrexate was also associated with a decrease in the creation of anti-drug antibodies. Nonetheless, the impact of these antibodies on the effectiveness of various bDMARDs used in treating rheumatoid arthritis remains a subject of ongoing research.
In the study under discussion, researchers utilized multi-center data from the European Anti-Biopharmaceutical Immunization study on the rheumatoid arthritis group, encompassing 27 recruitment centers across the United Kingdom, France, the Netherlands, and Italy.
Eligibility for participation in the study required patients to be over 18, have a rheumatoid arthritis diagnosis, and be starting treatment with rituximab (a CD20 inhibitor), tocilizumab (an interleukin-6 receptor monoclonal antibody), or TNF inhibitors such as infliximab, etanercept, and adalimumab.
Exclusion criteria included prior treatment with similar drugs, current pregnancy or breastfeeding, and inability to comply with study protocols. Study visits occurred every three months for 18 months, with C-reactive protein scores employed at each visit to evaluate disease severity.
Additionally, serum samples were collected during each visit to evaluate the levels of antidrug antibodies against all bDMARDs, and drug concentrations of the TNF inhibitors. Various biological tests and health-related data were also collected during these visits.
Antidrug antibody detection methods included electrochemiluminescence for binding antibodies and enzyme-linked immunosorbent assays for drug levels. The study defined antidrug antibody positivity as the detection of these antibodies at least once during one of the visits in the first year, with further subdivision based on subsequent test results.
The main goal was to evaluate the European League Against Rheumatism (EULAR) response after one year of rheumatoid arthritis therapy. Secondary objectives included responses at six months, and at various intervals up to 18 months, alongside drug levels at each visit.
The results highlighted that the presence of antidrug antibodies correlated with a reduced response to bDMARDs in rheumatoid arthritis patients. Notably, high levels of antibodies against TNF inhibitors, tocilizumab, and rituximab were found in these patients.
Moreover, the clinical response after a year of treatment with all bDMARDs, particularly the monoclonal antibodies against TNF, was negatively correlated with the levels of antidrug antibodies. Factors such as rheumatoid factor, body mass index (BMI), and antidrug antibody levels were found to independently inversely correlate with the therapeutic response for rheumatoid arthritis.
Pharmacokinetic analysis further indicated significantly lower concentrations of infliximab and adalimumab in patients testing positive for antidrug antibodies. The methotrexate concentration also showed an inverse correlation with persistent antidrug antibody positivity.
Overall, the study suggested that the formation of antidrug antibodies considerably reduces the effectiveness of bDMARDs in treating rheumatoid arthritis patients.
Hence, the study’s findings advocate for personalized management and careful monitoring of antidrug antibody levels in patients with rheumatoid arthritis.
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