Certolizumab pegol in severe rheumatoid arthritis. Real-life evidence in an Argentine cohort: goal achievement (t2t) at 3 months and predictive factors.
https://doi.org/10.46856/grp.10.e182
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Garcia Salinas R, Magri S, Ruta A. Certolizumab pegol en artritis reumatoidea severa. Evidencia de la vida real en una cohorte argentina: Logro de objetivos (T2T) a 3 meses y factores predictivos. Global Rheumatology. Vol 5/ Ene - Jun [2024]. Available from: https://doi.org/10.46856/grp.10.e182
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Certolizumab pegol in severe rheumatoid arthritis. Real-life evidence in an Argentine cohort: goal achievement (t2t) at 3 months and predictive factors.
Introduction: Certolizumab pegol (CTZ) is a tumor necrosis factor-alpha (TNF-α) inhibitor biological agent that has demonstrated efficacy in controlling rheumatoid arthritis (RA). Identifying predictive factors for treatment success and assessing its effectiveness in a real-world clinical setting are crucial for decision-making.
Objective: To evaluate the response to CTZ in patients with RA in a real-world cohort, measuring the reduction in DAS 28, HAQ, frequency of remission, and low disease activity (LDA) at three months, identifying predictive factors, and evaluating the reduction in the use of corticosteroids.
Methods: A prospective real-world observational study included patients over 18 years of age with RA (ACR/EULAR 2010 criteria) who initiated CTZ and were followed for three months. Demographic, clinical, comorbidity, treatment, and disease activity data were recorded.
Results: Out of 2092 RA patients treated with CTZ between 2016 and 2021, 90% had a poor prognosis, and 60% had high disease activity. Among 1673 patients followed for three months, a reduction in DAS 28 (-1.9) and HAQ (-0.63) was observed. At three months, 10.5% achieved remission, and 40% achieved LDA. Predictive factors for remission included age (OR: 0.97) and DAS 28 (OR: 0.58); for LDA, age (OR: 0.97), DAS 28 (OR: 0.61), first-line CTZ (OR: 1.6), and HAQ (OR: 0.61). Additionally, there was a reduction in the use of glucocorticoids (-3.1 mg prednisone).
Conclusions: CTZ is effective in RA, emphasizing patient selection and an early treatment approach. This study supports the efficacy of CTZ.
Rheumatoid Arthritis (RA) is an autoimmune disease that affects millions of people worldwide. It is characterized by chronic joint inflammation, which can lead to joint damage and disability. RA treatment has greatly benefited from advances in biological therapies, among which anti-TNFs are the most commonly used drugs in cases of DMARDs failure (1,2).
Certolizumab pegol (CZP) acts as a tumor necrosis factor-alpha (TNF-alpha) inhibitor, reducing inflammation and associated symptoms. Its main active ingredient is a humanized monoclonal antibody. The term "pegol" in its name indicates that the drug has been chemically modified with polyethylene glycol (PEG) to increase its half-life in the body and reduce the frequency of administration (3).
Certolizumab pegol has been the subject of various clinical studies in the treatment of RA to assess its efficacy and safety. The RAPID study (among others) evaluated its effectiveness in patients with active RA who had not responded adequately to prior therapies. The results demonstrated that CZP significantly improved RA symptoms and joint function compared to placebo and established the concept of predictability—meaning that if a response occurs within the first 3 months, it is likely to persist over time. This concept aligns with the goals of Treat-to-Target (T2T), including remission and low disease activity (LDA) (4–6).
The objective of this study was to estimate the reduction in DAS28 and HAQ scores, as well as the frequency of remission and low disease activity at 3 months in a real-world cohort of RA patients who began treatment with CZP. Additionally, the study aimed to identify baseline predictive factors associated with achieving these outcomes. A further goal was to assess corticosteroid dose reduction during the same period.
Observational prospective real-world practice study including consecutive patients aged ≥18 years with Rheumatoid Arthritis (RA) according to the ACR/EULAR 2010 classification criteria (7), who initiated treatment with Certolizumab pegol and had a follow-up visit at 3 months. Data were collected from the BIOARSITE registry.
The BIOARSITE registry is a prospective database that collects information on patients starting treatment with Certolizumab pegol under real-world clinical conditions. Sociodemographic, clinical characteristics, comorbidities, previous and current treatments, as well as the current glucocorticoid dose (GC-prednisone) were recorded. Disease activity was assessed using DAS28, HAQ, and glucocorticoid dose at baseline and at three months (8,9).
Statistical analysis:
Descriptive statistics were used to summarize patient characteristics. Continuous variables were expressed as medians and interquartile ranges (IQR) or as means and standard deviations (SD), and categorical variables as percentages. Comparisons between groups were performed using parametric and non-parametric tests: Chi-square or Fisher’s exact test for categorical variables; and T-test, Mann-Whitney, ANOVA, or Kruskal-Wallis tests depending on the nature and distribution of the variables. Predictive factors for achieving remission or low disease activity (LDA) at three months were analyzed using binary logistic regression.
This observational study was approved by the institutional ethics committees of each participating center and conducted in accordance with current regulations, including the Declaration of Helsinki, resolution 1480/11 of the local Health Council, and applicable local regulations. Patient confidentiality was respected according to local laws, and informed consent was obtained for publication.
A total of 2,092 patients with RA who initiated treatment with CZP between 2016 and 2021 were enrolled. Ninety percent had poor prognostic factors, and 60% had high disease activity (see Table 1).
A total of 1,673 patients completed a follow-up visit at 3 months. The reduction in DAS28 was -1.9 (from 3.8 to 5.7, p = 0.001), and the reduction in HAQ was -0.63 (from 1.17 to 1.8, p = 0.001) (Figure 1). At 3 months, 10.5% (95% CI: 9-12) achieved remission, and 40% (95% CI: 38-42) achieved low disease activity (LDA) (see Figure 2).
In the multivariate analysis, baseline predictive factors for achieving remission were:
Age (OR: 0.97; 95% CI: 0.96-0.99; p = 0.04)
DAS28 (OR: 0.58; 95% CI: 0.45-0.54; p < 0.001)
For achieving LDA, predictive factors were:
Age (OR: 0.97; 95% CI: 0.96-0.99; p = 0.01)
DAS28 (OR: 0.61; 95% CI: 0.49-0.76; p < 0.001)
CZP as first-line therapy (OR: 1.6; 95% CI: 1.1-2.4; p = 0.03)
HAQ (OR: 0.61; 95% CI: 0.44-0.84)
The reduction in glucocorticoid dose at 3 months (prednisone mg) was -3.1 (from 5.4 to 8.5, p = 0.001) (see Figure 3).
This prospective study in patients with Rheumatoid Arthritis (RA) treated with Certolizumab (CZP) provides valuable information about predictive factors of therapeutic response at three months of follow-up. The results indicate that a significant percentage of patients experienced substantial improvements in disease activity and joint functionality after starting treatment with CZP, even in the presence of poor prognostic factors and previous treatment failure. These findings are consistent with previous research demonstrating the rapid response to CZP, with this early response being predictive of sustained effect over time (predictability) (4–6,10,11).
Response within the first three months is crucial, as pragmatic studies based on Treat-to-Target (T2T) have shown that clinical response during this period is also associated with long-term improvement in functional capacity measured by HAQ and less radiographic progression (12–14).
One key finding of this study is that age and disease activity at treatment initiation are important predictive factors for achieving remission and low disease activity. This suggests that younger patients and those with less active disease at baseline may have a higher probability of responding positively to CZP. Additionally, the use of CZP as a first-line treatment and improvements in joint functionality, assessed by the Health Assessment Questionnaire (HAQ), were also associated with a greater likelihood of achieving low disease activity. This indicates a population of RA patients with better prognosis and less prior use of biologic drugs (15,16).
It is important to highlight that, beyond the mentioned factors, other clinical and demographic aspects may influence response to treatment with CZP. Therefore, a comprehensive evaluation of patients is essential before deciding on the most appropriate therapy (17).
Rapid reduction of corticosteroids is also an important factor, as their adverse effects are well known, and generally their use is associated with a higher frequency of severe and opportunistic infections (18,19).
This study has limitations, including its observational design and lack of a control group, which may bias the results. However, the findings suggest the importance of careful evaluation of age, disease activity, and joint functionality when selecting patients for CZP treatment in RA.
In conclusion, the use of CZP in our cohort of RA patients with poor prognostic factors demonstrated a significant and rapid (3 months) reduction in disease activity and improvement in HAQ scores. Predictive factors at treatment initiation for remission and low disease activity (LDA) were low baseline disease activity, younger age, lower HAQ, and the use of CZP as first-line therapy. CZP also showed a rapid corticosteroid-sparing effect.
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