Predictive factors of response to biological disease modifying antirheumatic drugs: towards personalized medicine.
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ABSTRACT:
SUBMITTER: Daien CI
PROVIDER: S-EPMC3913459 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
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Predictive factors of response to biological disease modifying antirheumatic drugs: towards personalized medicine.
Daïen Claire I CI Morel Jacques J
Mediators of inflammation 20140112
Many therapies are now available for patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate including tumor necrosis factor inhibitors, abatacept, tocilizumab, and rituximab. Clinical response to drugs varies widely between individuals. A part of this variability is due to the characteristics of the patient such as age, gender, concomitant therapies, body mass index, or smoking status. Clinical response also depends on disease characteristics including disease ac ...[more]
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Project description:ObjectivesBiological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR).MethodsData were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed.Results2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs).ConclusionsTofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations.Trial registration numbers(NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385).
| S-EPMC4941182 | biostudies-literature
Project description:Background & Objectives: Biological disease-modifying antirheumatic drugs (bDMARDs) for the treatment of rheumatoid arthritis (RA) are not always accessible to all patients in accordance with international guidelines, partly owing to their high direct costs against a background of restricted healthcare budgets. This study compares the size of RA patient populations with access to reimbursed bDMARDs across 37 European countries, Russia, and Turkey, according to their treatment eligibility defined by European League Against Rheumatism (EULAR) recommendations and national reimbursement criteria. Methods: The size of the RA patient population eligible for bDMARD treatment was estimated in a population model using published RA epidemiological data and clinical criteria defined by 2013 EULAR recommendations along with national reimbursement criteria defined in a survey of the 39 countries in November 2015. Results: According to EULAR recommendations, 32% of the total RA population in the European region is eligible for bDMARD treatment. However, only an average 59% of this EULAR-eligible population remains eligible after applying national reimbursement criteria (from 86% in 'high access' to 13% in 'low-access' countries). Conclusion: Access to reimbursed bDMARDs remains unequal in the European region. As biosimilars of bDMARDs are introduced, changes in reimbursement criteria may increase access to bDMARDs and reduce this inequality.
| S-EPMC5508389 | biostudies-literature
Project description:ObjectiveThe study assessed persistence rates of biological disease-modifying antirheumatic drugs (bDMARDs) for the treatment of rheumatoid arthritis in Japan and compared resource utilization and treatment costs between persistence and non-persistence groups.MethodsData were extracted from a Japanese claims database between 2009 and 2015. bDMARD-naïve patients were identified and included in the final analysis. Survival analysis was used to estimate 1-year persistence rates for current bDMARDs. Propensity score matching was applied to control for potential treatment selection bias. Resource utilization and healthcare costs were calculated 1 year before and after initiation of bDMARDs and compared between persistence and non-persistence groups.ResultsA total of 6153 bDMARD-naïve patients were identified and the overall 1-year persistence rate was 85% (95% CI 84-86). Overall, 1-year outpatient visits increased from 10 at baseline to 16 after bDMARD treatment, while the number of hospital admissions declined from 3.3 to 1.6. The non-persistence group had a larger increase in outpatient visits after bDMARD initiation compared with the persistence group (8-16 vs. 10-16, respectively) and a smaller decrease in hospital admissions (3.1-1.9 vs. 3.5-1.4, respectively). Persistence was associated with a reduction in total healthcare costs of US$760.ConclusionsJapanese bDMARD-naïve patients with RA have a high persistence rate with those treatments. The reduction in medication costs in non-persistent patients is offset by higher hospitalization costs, making non-persistence more expensive.
| S-EPMC6119169 | biostudies-literature
Project description:OBJECTIVE:This study aims to explore the contribution of implicit attitudes and associations towards conventional disease-modifying antirheumatic drugs (cDMARDs), alongside explicit measures, on medication-taking behaviour and clinical outcomes in adult patients with rheumatoid arthritis (RA). METHODS:In this observational study, implicit attitudes (positive-negative) and health-related associations (health-sickness) were measured with Single Category Implicit Association Tests, whereas explicit outcomes were measured with a bipolar evaluative adjective scale and the Beliefs about Medicines Questionnaire Specific. The primary outcome of this study was medication-taking behaviour subjectively measured by self-report (i.e. validated Compliance Questionnaire on Rheumatology) and objectively measured with electronic drug monitors over a 3 month period. Spearman rank correlations were used to describe correlations between implicit and explicit outcomes. Nested linear regression models were used to assess the additional value of implicit measures over explicit measures and patient-, clinical-, and treatment-related characteristics. RESULTS:Of the 1659 initially-invited patients, 254 patients with RA agreed to participate in this study. Implicit attitudes correlated significantly with necessity-concerns differential (NCD) scores (? = 0.13, P = 0.05) and disease activity scores (? = -0.17, P = 0.04), whereas implicit health-related associations correlated significantly with mean scores for explicitly reported health-related associations (? = 0.18, P = 0.004). Significant differences in age, number of DMARDs, biologic DMARD use, NCD-scores, and self-reported correct dosing were found between the four attitudinal profiles. Nested linear regression models revealed no additional value of implicit measures in explaining self-reported medication-taking behaviour and clinical outcomes, over and above all other variables. CONCLUSION:Implicit attitudes and associations had no additional value in explaining medication-taking behaviour and clinical outcomes over and above often used explicitly measured characteristics, attitudes and outcomes in the studied population. Only age and NCD scores contributed significantly when the dependent variable was correct dosing measured with self-report.
| S-EPMC6716669 | biostudies-literature
Project description:In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at 3 months). Tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, biosimilars), abatacept, tocilizumab and, under certain circumstances, rituximab are essentially considered to have similar efficacy and safety. If the first bDMARD strategy fails, any other bDMARD may be used. The recommendations also address tofacitinib as a targeted sDMARD (tsDMARD), which is recommended, where licensed, after use of at least one bDMARD. Biosimilars are also addressed. These recommendations are intended to inform rheumatologists, patients, national rheumatology societies and other stakeholders about EULAR's most recent consensus on the management of RA with sDMARDs, glucocorticoids and bDMARDs. They are based on evidence and expert opinion and intended to improve outcome in patients with RA.
| S-EPMC3933074 | biostudies-literature
Project description:ObjectiveTo assess the association between the use of biological disease-modifying antirheumatic drugs (bDMARDs) and the risk of cardiovascular events in patients with systemic inflammatory conditions.MethodsEligible cohort studies or randomized controlled trials (RCTs) from inception to January 2021 were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for cardiovascular outcomes were calculated in the fixed- and random-effects model accordingly. Associated factors with risks of cardiovascular events were also studied in sensitivity analyses and metaregression analyses.ResultsCompared with non-bDMARD users, the risks of myocardial infarction (MI) (OR = 0.74, 95% CI, 0.63 to 0.87), heart failure (OR = 0.84, 95% CI, 0.74 to 0.95), cardiovascular (CV) death (OR = 0.62, 95% CI, 0.40 to 0.95), all-cause mortality (OR = 0.64, 95% CI, 0.58 to 0.70), and 3P-MACE (composite endpoint of MI, stroke, and CV death) (OR = 0.69, 95% CI, 0.53 to 0.89) were significantly reduced in bDMARD users, which were mainly driven by the risk reduction in patients with rheumatoid arthritis (RA). TNF-α inhibitors exhibited consistent benefits in reducing the risks of MI, heart failure, CV death, all-cause mortality, and 3P-MACE. Moreover, the risks of heart failure, CV death, all-cause mortality, and 3P-MACE were significantly reduced in bDMARD users with follow-up over one year.ConclusionsThe use of bDMARDs might be associated with the reduced risks of CV events, especially in patients with RA. The CV events might be less frequent in bDMARD users with TNF-α inhibitors or follow-up over one year. More investigations are needed to validate conclusions.
| S-EPMC8423578 | biostudies-literature
Project description:Current recommendations advocate treatment with disease-modifying antirheumatic drugs (DMARD) in all patients with active rheumatoid arthritis (RA). We investigated the frequency of and reasons for inconsistent DMARD use among patients in a clinical rheumatology cohort.Patients in the Brigham Rheumatoid Arthritis Sequential Study were studied for DMARD use (any or none) at each semiannual study timepoint during the first 2 study years. Inconsistent use was defined as DMARD use at ? 40% of study timepoints. Characteristics were compared between inconsistent and consistent users (> 40%), and factors associated with inconsistent DMARD use were determined through multivariate logistic regression. A medical record review was performed to determine the reasons for inconsistent use.Of 848 patients with ? 4 out of 5 visits recorded, 55 (6.5%) were inconsistent DMARD users. Higher age, longer disease duration, and rheumatoid factor negativity were statistically significant correlates of inconsistent use in the multivariate analyses. The primary reasons for inconsistent use identified through chart review, allowing for up to 2 co-primary reasons, were inactive disease (n = 28, 50.9%), intolerance to DMARD (n = 18, 32.7%), patient preference (n = 7, 12.7%), comorbidity (n = 6, 10.9%), DMARD not being effective (n = 3, 5.5%), and pregnancy (n = 3, 5.5%). During subsequent followup, 14/45 (31.1%) inconsistent users with sufficient data became consistent users of DMARD.A small proportion of patients with RA in a clinical rheumatology cohort were inconsistent DMARD users during the first 2 years of followup. While various patient factors correlate with inconsistent use, many patients re-start DMARD and become consistent users over time.
| S-EPMC4843119 | biostudies-literature
Project description:Over the past several years, the success of genome-wide association studies (GWAS) and pharmacogenomics has gradually begun to enable personalized medicine in some fields. In the field of liver diseases, host genetic factors are now very useful in clinical practice for predicting treatment outcome and adverse reactions for pegylated interferon plus ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. Recently, three virus-related hepatocellular carcinoma (HCC) GWAS were reported from Asia. One study examined hepatitis B virus-related HCC in China, where hepatitis B is very prevalent, and the other two examined HCV-related HCC in Japan. We identified a common variant in the DEPDC5 locus associated with HCV-related HCC, and another group identified an association involving the MICA locus. In this review, we compare the results of these GWAS and earlier candidate gene studies. Further research is needed to determine the role of these single nucleotide polymorphisms on HCC risk, but identification of these markers could make it possible to assess the magnitude of the risk of cancer based on each patient's genetic background. Consideration of the genetic background of the patients will likely play a role in personalized medicine for HCC, and understanding the mechanism underlying the association could suggest novel promising therapeutic targets in the future.
| S-EPMC7659374 | biostudies-literature
Project description:BackgroundAdvances in Disease-Modifying Antirheumatic Drugs (DMARDs) have expanded the treatment landscape for Rheumatoid Arthritis (RA). Guidelines recommend adding either conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs to methotrexate (MTX) for managing RA. Limited evidence exists regarding the factors that contribute to adding a DMARD agent to the MTX regimen. This study examined the factors associated with adding the first DMARD in RA patients initiating MTX.MethodsThis retrospective cohort study utilized the MarketScan data (2012-2014) involving adults (aged ≥18) with RA initiating an MTX (index date) between Jul 1, 2012 and Dec 30, 2013, and with continuous enrollment for the 6-month pre-index period. The combination therapy users received the first treatment addition of DMARD starting from day 30 after the index MTX over one year period. The study focused on the addition of csDMARDs, Tumor Necrosis Factor Inhibitors (TNFi) bDMARDs, non-TNFi bDMARDs, or tsDMARDs. Baseline covariates were measured in the 6-month pre-index and grouped into predisposing, enabling, and need factors, as per the Andersen Behavior Model. Multivariable logistic regression examined the factors associated with the addition of TNFi compared to adding a csDMARD. An additional regression model evaluated the factors associated with adding any biologic (combining TNFi and non-TNFi biologics).ResultsAmong 8350 RA patients starting MTX, 31.92% (n = 2665) initiated any DMARD within the 1-year post-index period. Among RA patients initiating a DMARD prescription after starting MTX, 945 (11.32%) received combination therapy with treatment addition of a DMARD to MTX regimen; majority added TNFi (550, 58%), followed by csDMARD (352, 37%); non-TNF biologic (40, 4%), or tsDMARD (3, 0.3%). The tsDMARD group was limited and was not included for further analysis. The multivariable model found Preferred Provider Organization insurance coverage (odds ratio [OR], 1.43; 95% confidence interval (CI), 1.06-1.93), chronic pulmonary disease (OR, 1.98; 95% CI, 1.14-3.44), liver disease (OR, 5.24; 95% CI, 1.77-15.49), and Elixhauser score (OR, 0.91; 95% CI, 0.86-0.97) were significantly associated with the addition of TNF-α inhibitors. The separate multivariable model additionally found that patients from metropolitan areas (OR, 1.50; 95% CI, 1.04-2.16) were positively associated with adding any biological agent.ConclusionsTNFi are often added to MTX for managing RA. Enabling and need factors contribute to the prescribing of a TNFi add-on therapy in RA. Future research should examine the impact of these combination therapies on RA management.
| S-EPMC10372178 | biostudies-literature
Project description:To describe patterns of disease-modifying antirheumatic drug (DMARD) use during pregnancy in a population-based cohort, and to evaluate the association between autoimmune disease, DMARDs, corticosteroids, and nonsteroidal antiinflammatory drugs (NSAIDs) and preeclampsia.Using health care utilization databases from British Columbia (1997-2006), we compared the risk for preeclampsia among 44,786 women with and without autoimmune disease with study drug dispensings before pregnancy (past users) and before and during the first 20 gestational weeks (continuous users). Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated.Only 414 women (0.1%) had a DMARD dispensing during pregnancy. The incidence of preeclampsia was 2.3% for past DMARD users, 2.7% for past corticosteroid users, and 2.9% for past NSAID users. Compared to past users, the continuous DMARD user RR was 2.29 (95% CI 0.81-6.44), and was 0.89 (95% CI 0.51-1.56) for corticosteroid and 0.84 (95% CI 0.63-1.10) for NSAID users. Compared to women without autoimmune disease, the delivery year-adjusted RR was 2.02 (95% CI 1.11-3.64) for women with systemic lupus erythematosus (SLE). The DMARD results were attenuated when antimalarials were excluded, and the delivery year-adjusted RR was 0.95 (95% CI 0.25-3.55) when the DMARD analysis was restricted to women with autoimmune disease.Few women were exposed to DMARDs during pregnancy. We observed a 2-fold increased risk of preeclampsia among women with SLE and a nonsignificant increase in risk in DMARD users. The DMARD and preeclampsia association was attenuated when antimalarials were excluded and null when restricted to women with autoimmune disease, which suggests the association is likely due to greater autoimmune disease severity in DMARD users.
| S-EPMC3514881 | biostudies-literature