Correction: Comparing Effects of Biologic Agents in Treating Patients with Rheumatoid Arthritis: A Multiple Treatment Comparison Regression Analysis.
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ABSTRACT:
SUBMITTER: Tvete IF
PROVIDER: S-EPMC4727918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rheumatoid arthritis patients have been treated with disease modifying anti-rheumatic drugs (DMARDs) and the newer biologic drugs. We sought to compare and rank the biologics with respect to efficacy. We performed a literature search identifying 54 publications encompassing 9 biologics. We conducted a multiple treatment comparison regression analysis letting the number experiencing a 50% improvement on the ACR score be dependent upon dose level and disease duration for assessing the comparable relative effect between biologics and placebo or DMARD. The analysis embraced all treatment and comparator arms over all publications. Hence, all measured effects of any biologic agent contributed to the comparison of all biologic agents relative to each other either given alone or combined with DMARD. We found the drug effect to be dependent on dose level, but not on disease duration, and the impact of a high versus low dose level was the same for all drugs (higher doses indicated a higher frequency of ACR50 scores). The ranking of the drugs when given without DMARD was certolizumab (ranked highest), etanercept, tocilizumab/ abatacept and adalimumab. The ranking of the drugs when given with DMARD was certolizumab (ranked highest), tocilizumab, anakinra/rituximab, golimumab/ infliximab/ abatacept, adalimumab/ etanercept [corrected]. Still, all drugs were effective. All biologic agents were effective compared to placebo, with certolizumab the most effective and adalimumab (without DMARD treatment) and adalimumab/ etanercept (combined with DMARD treatment) the least effective. The drugs were in general more effective, except for etanercept, when given together with DMARDs.
| S-EPMC4565694 | biostudies-literature
Project description:In England and Wales, the National Institute for Health and Clinical Excellence (NICE) has provided guidance [technology appraisals (TAs) 130, 186, 195, 198 and 225] on the use of biologic drugs for the treatment of RA. This is based on an analysis of efficacy, safety and cost-effectiveness, and has resulted in a complex management pathway that restricts freedom to prescribe biologics according to their licensed indications. Specifically, TNF antagonists are the only class of biologics that can be used first line in DMARD-inadequate responders, and only in patients with a persistent 28-joint DAS score of ≥5.1. Alternative biologic agents are denied to those with contraindications to anti-TNF drugs and are also not supported following intolerance to TNF antagonists. Rituximab is the only class of biologic permitted after TNF antagonist inefficacy, in the absence of a contraindication to its use, whereas abatacept and tocilizumab are licensed and may be a more efficacious choice at this stage in some patient groups. Furthermore, for patients who demonstrate sequential inadequate responses, treatment is restricted to one TNF antagonist, rituximab and tocilizumab, whereas abatacept is only a permitted choice when rituximab is contraindicated or has been withdrawn because of an adverse event. In this review, we discuss the treatment algorithm published by NICE, and suggest alternatives where perceived deficiencies exist.
| S-EPMC3276292 | biostudies-literature
Project description:The use of biologics has significantly changed the management of rheumatoid arthritis over the last decade, becoming the cornerstone treatment for many patients. The current therapeutic arsenal consists of just under 10 biologic agents, with four different mechanisms of action. Several studies have demonstrated a large interindividual pharmacokinetic variability, which translates to unpredictability in clinical response among individuals. The present review focuses on the pharmacokinetics and pharmacodynamics of biologic agents approved for rheumatoid arthritis. The literature relating to their concentration-effect relationship and the use of pharmacokinetic-pharmacodynamic modelling to optimize drug regimens is analysed. Due to the scarcity and complexity of these studies, the current dosing strategy is based on clinical indexes/aspects. In general, dose individualization for biologics should be implemented increasingly in clinical practice as there is a direct benefit for treated rheumatoid arthritis patients. Moreover, there is an indirect benefit in terms of cost-effectiveness.
| S-EPMC5401978 | biostudies-literature
Project description:Rheumatoid arthritis is associated with reduced kidney function, possibly due to chronic inflammation or the use of nephrotoxic therapies. However, little is known about the effects of using the newer novel non-nephrotoxic biologic agents on the risk of incident chronic kidney disease (CKD). To study this we used a cohort of 20,757 United States veterans diagnosed with rheumatoid arthritis with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2 or more, recruited between October 2004 and September 2006, and followed through 2013. The associations of biologic use with incident CKD (eGFR under 60 with a decrease of at least 25% from baseline, and eGFR under 45 mL/min/1.73m2) and change in eGFR (<-3, -3 to <0 [reference], and ?0 mL/min/1.73m2/year) were examined in propensity-matched patients based on their likelihood to initiate biologic treatment, using Cox models and multinomial logistic regression models, respectively. Among 20,757 patients, 4,617 started biologic therapy. In the propensity-matched cohort, patients treated (versus not treated) with biologic agents had a lower risk of incident CKD (hazard ratios 0.95, 95% confidence interval [0.82-1.10] and 0.71 [0.53-0.94] for decrease in eGFR under 60 and under 45 mL/min/1.73m2, respectively) and progressive eGFR decline (multinomial odds ratios [95% CI] for eGFR slopes <-3 and ?0 [versus -3 to <0] mL/min/1.73m2/year, 0.67 [0.58-0.79] and 0.76 [0.69-0.83], respectively). A significant deceleration of eGFR decline was also observed after biologic administration in patients treated with biologics (-1.0 versus -0.4 [mL/min/1.73m2/year] before and after biologic use). Thus, biologic agent administration was independently associated with lower risk of incident CKD and progressive eGFR decline.
| S-EPMC5911428 | biostudies-literature
Project description:IntroductionTo compare biologic disease-modifying antirheumatic drug therapy persistence between biologics among patients with rheumatoid arthritis (RA) who previously used ?1 other biologic.MethodsUsing a large United States administrative claims dataset, we identified adult patients with RA initiating abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, or tocilizumab between January 1, 2010 and January 1, 2012 (initiation date = index). Patients were required to have used ?1 other biologic before index. Outcomes were biologic persistence, defined in two alternative ways: (1) time from initiation until switching to a different biologic (time to switch) and (2) time from initiation until switching or the first occurrence of a 90-day gap in treatment with the initiated biologic (time to switch/discontinuation). Rituximab was excluded from analyses due to retreatment based on clinical evaluation, which complicates the measurement of persistence. Multivariable survival analyses compared persistence outcomes between tocilizumab and the other biologics, adjusting for patient characteristics.ResultsThe sample comprised 9,782 biologic initiations; mean age 54 years and 82% female. Compared with tocilizumab, the hazards of switching biologic therapy were significantly higher for abatacept [hazard ratio (HR) = 1.19, P = 0.041], adalimumab (HR = 1.39, P < 0.001), certolizumab (HR = 1.39, P < 0.001), golimumab (HR = 1.20, P = 0.047), and infliximab (HR = 1.33, P < 0.001), but not significantly different for etanercept (HR = 1.19, P = 0.095); the hazards of switching/discontinuing biologic therapy were significantly higher for adalimumab (HR = 1.16, P = 0.014) and certolizumab (HR = 1.15, P < 0.012), but not significantly different for abatacept (HR = 1.08, P = 0.229), etanercept (HR = 0.97, P = 0.644), golimumab (HR = 0.99, P = 0.829), and infliximab (HR = 0.97, P = 0.721).ConclusionsThis is one of the first studies of biologic persistence to focus specifically on patients with RA who are not naïve to biologic treatment. Among patients with RA who previously used ?1 other biologic, tocilizumab-treated patients had similar or significantly better biologic persistence compared with other biologics.
| S-EPMC4883249 | biostudies-literature
Project description:BackgroundBiologic disease modifying agents (bDMARDs) are an integral part of rheumatoid arthritis treatment guidelines but are associated with significant cost in the US. We present the trends in total spending and unit cost of conventional DMARDs (cDMARDs) as compared to bDMARDs in Medicare program.MethodsWe used the Medicare drug spending data for the year 2012-2017 covering all part B (fee-for-service) and part D drugs. Total spending was calculated by summing spending across various drug formulations and unit drug cost by dividing total spending by number of doses dispensed. We present the 6-year trends in total spending, total beneficiary count and unit costs of each of the commonly used cDMARDs and bDMARDs.ResultsBetween 2012 and 2017, the total spending on the cDMARDs increased 5-folds from $98 million to $579 million; this was fraction of total spending on bDMARDs which increased from $4.3 to $10.0 billion. This increase was driven largely by unit costs of drug rather than number of beneficiaries. There was a 6-fold increase in the unit cost of generic hydroxychloroquine followed by methotrexate and leflunomide. Amongst bDMARDs, adalimumab and etanercept unit cost increased by 2-folds. The increase was less pronounced for office-administered products.ConclusionsDespite the availability of several generic cDMARDs over decades, there were steep increases in the unit cost of these agents to "keep pace" with the increases in bDMARDs. As the number of elderly rheumatoid arthritis patients increases, policy interventions might be required to reduce the spending on both biologics and conventional DMARDs.
| S-EPMC7453205 | biostudies-literature
Project description:Biologics, possibly in combination with a conventional disease-modifying antirheumatic drug (DMARD) - preferably methotrexate (MTX), are used in accordance with the recommendations of the international rheumatological societies. However, in clinical practice, this recommendation is often problematic, as many rheumatologists know from personal experience. The quality of life of the patient is affected mainly by drug-induced intolerances (eg, MTX). Thus, the acceptance of the patient to treatment is often so inadequate that a discontinuation of the drug is necessary. In daily practice, approximately 30% of patients with biological therapy receive no concomitant DMARD according to the register data.
| S-EPMC4440355 | biostudies-literature
Project description:ObjectiveThe purpose of the study is to evaluate the effects of biologic therapy on cardiovascular risk factors in rheumatoid arthritis patients to determine its clinical efficacy.MethodsRelevant literature was systematically searched in PubMed, Embase, and Cochrane Library databases. Meta-analysis was conducted using standardized mean differences (SMDs) and 95% confidence intervals (CIs) to evaluate cardiovascular risk factors and atherosclerosis. Heterogeneity, sensitivity analysis, and publication bias were assessed. Statistical significance was set at P<0.05.ResultsThe meta-analysis revealed that biologic treatment in RA patients was associated with decreased high-density lipoprotein cholesterol (HDL-C) levels compared to controls (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). Subgroup analysis based on treatment duration showed heterogeneity and a potential decrease in total cholesterol levels after 12 months of treatment (MD = -0.03, 95% CI [-0.21, -0.15], P = 0.76). Biologic therapy significantly reduced triglyceride levels compared to controls (MD = -0.23, 95% CI [-0.37, -0.09], P = 0.001), as observed in subgroup analysis. Moreover, biologics effectively decreased low-density lipoprotein cholesterol (LDL-C) levels (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). However, biologic treatment was associated with increased inner carotid artery thickness (MD: 0.05, 95% CI: [0.03, 0.07], P<0.0001), indicating potential adverse effects on cardiovascular health. No significant effect on pulse wave velocity (PWV) was observed (MD: -0.23, 95% CI: [-0.80, 0.34], P = 0.43, I2 = 0%, P = 0.55).ConclusionBiologic agents may improve lipid profiles in RA patients but could also have adverse effects on cardiovascular health. Further research is needed to comprehensively understand the impact of biologic therapy on lipid metabolism and cardiovascular outcomes in RA patients.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42024504911.
| S-EPMC11361434 | biostudies-literature
Project description:With the advent of biological therapies, considerable progress has been made in the treatment of rheumatoid arthritis (RA). These revolutionary therapies owe their origin to the role that cytokines play in the pathophysiology of the disease and are best exemplified by the wide use of tumor necrosis factor (TNF) blockade. The identification of additional pro-inflammatory factors and an understanding of their effector function now offer major possibilities for the generation of additional novel biological therapeutics to address unmet clinical needs. Such interventions will ideally fulfill several of the following criteria: control of inflammation, modulation of underlying immune dysfunction by promoting the reestablishment of immune tolerance, protection of targeted tissues such as bone and cartilage, and preservation of host immune capability to avoid profound immune suppression and amelioration of co-morbidity associated with underlying RA. The identification and characterization of the intracellular signaling pathways, in particular, the mitogen-activated protein kinase pathway, the nuclear factor-?B pathway and the cross-talk between these pathways offer several potential therapeutic opportunities. This review will provide an update on cytokine activities and signal transduction pathways that represent, in our opinion, optimal utility as future therapeutic targets.
| S-EPMC2822346 | biostudies-other
Project description:The aim of this study was to identify the specific molecular biological features predicting the therapeutic outcomes of three bDMARDs, infliximab (IFX), tocilizumab (TCZ), and abatacept (ABT) by studying blood gene expression signature of patients prior to biologic treatment in a unified test platform. GSEA analyses showed that inflammasome genes were significantly upregulated in IFXâs NON-REM compared with its REM. In TCZâs REM, B cell-specifically expressed genes were upregulated. RNA elongation, apoptosis-related, and NK cell-specifically expressed genes were upregulated in ABTâs NON-REM. RA patients who responded inadequately to methotrexate and were later commenced with any one of IFX (n=140), TCZ (n=38), and ABT (n=31) as their first biologic between May 2007 and November 2011 were enrolled. Whole blood gene expression data were obtained prior to their biologic administration. They were defined as remission and non-remission groups, according to CDAI at 6 months of biologic therapy.
2016-07-21 | E-GEOD-78068 | biostudies-arrayexpress