Biologic Therapy For Rheumatoid Arthritis Research Articles

Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases

To assess the proportion of RA patients who discontinued biologics in world registries and health care databases and to identify causes and predictors of discontinuation. Medline, Embase, Cochrane Library and Web of Science electronic databases and ACR and EULAR meeting abstracts were used. The selection of studies from world registries and health care databases including RA patients treated with biologics was independently performed. Data extracted from articles and abstracts were combined using a random effects model. Meta-analyses of percentages and hazard ratios were used to assess discontinuation. Ninety-eight studies with >200 000 patients from 11 242 articles and 119 abstracts met the inclusion criteria. Overall discontinuation rates of TNF inhibitors at 0.5, 1, 2, 3 and 4 years were 21, 27, 37, 44 and 52%, respectively. Discontinuation of etanercept was significantly lower at 3 and 4 years (35% and 41%, respectively) than infliximab and adalimumab (46% and 52%, respectively). Predictors of time to discontinuation were etanercept [hazard ratios (HRs) 0.58 and 0.77 versus infliximab and adalimumab, respectively), concomitant use of DMARDs (HR 0.77), disease duration (HR 1.01) and female sex (HR 1.18). Studies from registries conducted after 2005 and from countries with lower biologics access showed higher percentages of discontinuation. Relevant data on abatacept and tocilizumab were missing. In RA, treatment with etanercept has a lower percentage of discontinuation than infliximab and adalimumab. Concomitant use of DMARDs, disease duration before treatment with a biologic and female sex predict time to discontinuation.

Factors determining long-term success of biologic therapy in rheumatoid arthritis

The necessity to achieve clinical remission or low disease activity in every patient with rheumatoid arthritis highlights the importance of combination therapy with methotrexate and biological agents for treatment of resistant to conventional disease-modifying anti-rheumatic drugs patients. Modern requirements mean not only the achievement of results but also long-term maintaining of success. The possibility to get stable results of treatment is determined by many factors such as: clinical efficacy, safety, low immunogenicity, persistence on therapy and the economic feasibility. Analysis of published data for last 5 years leads to the conclusion that etanercept has an optimal combination of these parameters among inhibitors of tumor necrosis factor alpha.

2014 Update of the Consensus Statement of the Spanish Society of Rheumatology on the Use of Biological Therapies in Rheumatoid Arthritis

ObjectiveTo establish recommendations for the management of patients with rheumatoid arthritis (RA) to serve as a reference for all health professionals involved in the care of these patients, and focusing on the role of available synthetic and biologic disease-modifying antirheumatic drugs (DMARDs). MethodsConsensual recommendations were agreed on by a panel of 14 experts selected by the Spanish Society of Rheumatology (SER). The available scientific evidence was collected by updating three systematic reviews (SR) used for the EULAR 2013 recommendations. A new SR was added to answer an additional question. The literature review of the scientific evidence was made by the SER reviewer's group. The level of evidence and the degree of recommendation was classified according to the Oxford Centre for Evidence-Based Medicine system. A Delphi panel was used to evaluate the level of agreement between panellists (strength of recommendation). ResultsThirteen recommendations for the management of adult RA were emitted. The therapeutic objective should be to treat patients in the early phases of the disease with the aim of achieving clinical remission, with methotrexate playing a central role in the therapeutic strategy of RA as the reference synthetic DMARD. Indications for biologic DMARDs were updated and the concept of the optimisation of biologicals was introduced. ConclusionsWe present the fifth update of the SER recommendations for the management of RA with synthetic and biologic DMARDs.

Leucine-rich α2 -glycoprotein as a potential biomarker for joint inflammation during anti-interleukin-6 biologic therapy in rheumatoid arthritis.

To investigate whether leucine-rich α2 -glycoprotein (LRG) could be a biomarker for disease activity during interleukin-6 (IL-6) blockade treatment of rheumatoid arthritis (RA). In 59 RA patients who were treated with tocilizumab for 24 weeks, serum LRG levels were determined by enzyme-linked immunosorbent assay. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance of LRG and other biomarkers. In monkeys with experimental autoimmune arthritis, swollen joint counts, joint pathologic changes, and blood levels of C-reactive protein (CRP) and LRG were evaluated after treatment with anti-IL-6 receptor antibody. Among tocilizumab-treated RA patients, those with active disease (CDAI >2.8) had significantly higher serum LRG levels compared to those whose disease was in remission. ROC curve analysis suggested that the LRG level was more useful than the CRP or matrix metalloproteinase 3 level or the erythrocyte sedimentation rate in discriminating between remission and active disease during therapy with tocilizumab. In monkeys treated with IL-6 blockade, joint scores were more closely correlated with LRG levels than with CRP levels. Histologic analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration, and bone destruction in IL-6 blockade-treated monkeys with low levels of CRP. Under conditions of IL-6 inhibition, LRG was more useful than other biomarkers in discriminating between active and inactive disease in human RA and in detecting joint inflammation in experimental arthritis. LRG may serve as a convenient biomarker for RA disease activity during IL-6 blockade treatment.

180. Developing a New Commissioning Pathway for Biologic Therapy in Rheumatoid Arthritis

180. Developing a New Commissioning Pathway for Biologic Therapy in Rheumatoid Arthritis

Key data elements for use in cost-utility modeling of biological treatments for rheumatoid arthritis

Objectives:Economic evaluation is becoming more common and important as new biologic therapies for rheumatoid arthritis (RA) are developed. While much has been published about how to design cost-utility models for RA to conduct these evaluations, less has been written about the sources of data populating those models. The goal is to review the literature and to provide recommendations for future data collection efforts.Methods:This study reviewed RA cost-utility models published between January 2006 and February 2014 focusing on five key sources of data (health-related quality-of-life and utility, clinical outcomes, disease progression, course of treatment, and healthcare resource use and costs). It provided recommendations for collecting the appropriate data during clinical and other studies to support modeling of biologic treatments for RA.Results:Twenty-four publications met the selection criteria. Almost all used two steps to convert clinical outcomes data to utilities rather than more direct methods; most did not use clinical outcomes measures that captured absolute levels of disease activity and physical functioning; one-third of them, in contrast with clinical reality, assumed zero disease progression for biologic-treated patients; little more than half evaluated courses of treatment reflecting guideline-based or actual clinical care; and healthcare resource use and cost data were often incomplete.Conclusions:Based on these findings, it is recommended that future studies collect clinical outcomes and health-related quality-of-life data using appropriate instruments that can convert directly to utilities; collect data on actual disease progression; be designed to capture real-world courses of treatment; and collect detailed data on a wide range of healthcare resources and costs.

Pelvic peritonitis during biologic therapy for rheumatoid arthritis: a case report and review of the literature.

IntroductionInfections are recognized as major complications during therapy with biologics and other immunosuppressant drugs. The respiratory tract, bone, joint, skin, and soft tissues are well known sites of infection in patients with rheumatoid arthritis (RA) treated by biologics or other immunosuppressants. It is known that patients with intra-abdominal infections may develop tuberculous peritonitis during biologic therapy. However, non-tuberculous pelvic peritonitis is rare.Case descriptionA case of a 46-year-old patient with RA developed pelvic peritonitis during therapy with MTX, tacrolimus (TAC), and golimumab (GLM). The patient visited our hospital due to a fever and general malaise. Physical findings included lower abdominal tenderness and rebound tenderness. Abdominal computed tomography (CT) images showed an intrauterine foreign body and ascites. The contraceptive ring was removed. Streptococcus agalactiae and Streptococcus constellatus were cultured from the removed contraceptive ring. She was started on an antimicrobial agent, flomoxef (FMOX), at 2 g/day. The FMOX dosage was increased to 3 g/day from the 3rd day of disease and continued for 10 days. Her fever disappeared from the 4th disease day, and her inflammatory response then gradually decreased. No exacerbation of symptoms occurred even after the FMOX treatment was stopped, and the patient was discharged on the 14th disease day.Discussion and evaluationMTX and biologics were being administered at the time of onset of peritonitis. The peritonitis was diagnosed on the basis of the gynecological evaluation and CT imaging findings that were typical of peritonitis. The patient was in an immunosuppressed state during administration of anti-rheumatic drugs, and the peritonitis was thought to have developed due to an ascending infection via the long-term presence of the intrauterine contraceptive ring which had an attached string.ConclusionsBefore starting biological agents, patients must be questioned regarding the presence of an intrauterine foreign body.

Economics of non-adherence to biologic therapies in rheumatoid arthritis.

Adherence to biologic therapies among patients with rheumatoid arthritis is sub-optimal, with the proportion of adherent patients reported to be as low as 11%. We found few studies evaluating economic outcomes, including health care costs, associated with non-adherence with biologic therapies. Findings suggest that while higher pharmacy costs drive total health care costs among adherent patients, non-adherent patients incur greater health care utilization including inpatient, outpatient, and laboratory services. Finally, economic factors are important determinants of adherence to biologics in patients with rheumatoid arthritis. Evidence to date has shown that higher out-of-pocket payments have a negative association with adherence to biologics. Furthermore, cost-related non-adherence is a highly prevalent problem in rheumatoid arthritis. Given the high costs of biologics and continued expansion of use in rheumatoid arthritis, there is need for more research to understand the economic implications of adherence to these therapies.

Persistence and dose escalation of tumor necrosis factor inhibitors in US veterans with rheumatoid arthritis.

Limited evidence exists comparing the persistence, effectiveness, and costs of biologic therapies for rheumatoid arthritis in clinical practice. Comparative effectiveness studies are needed to understand real-world experience with these agents. We evaluated treatment patterns, costs, and effectiveness of tumor necrosis factor inhibitor (TNFi) agents in patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry. Observational data from the VARA registry and linked administrative databases were analyzed. Longitudinal data from VARA patients initiating adalimumab (ADA), etanercept (ETN), or infliximab (IFX) from 2003 (the date all agents were available within the Veteran Affairs) to 2010 were analyzed. Outcomes included Disease Activity Score using 28 joints (DAS28), treatment persistence, dose escalation, and direct costs of drugs and drug administration. For 563 eligible patients, baseline DAS28, DAS28 improvements, and persistence on initial treatment were similar across agents. Fewer patients receiving ETN (n = 5/290; 2%) underwent dose escalation than did patients taking ADA (n = 32/204; 16%) or IFX (n = 44/69; 64%). Annual costs for first course of TNFi therapy were lower for injectable ADA ($13,100 US) and ETN ($13,500 US) than for intravenously administered IFX ($16,900 US). Despite similar persistence and clinical disease activity for these TNFi agents, rates of dose escalation were highest with ADA and IFX. Higher overall costs were noted for IFX without increases in effectiveness.

The effect of antidrug antibodies on the sustainable efficacy of biologic therapies in rheumatoid arthritis: practical consequences

Biologic therapies, predominantly TNF-α inhibitors, have revolutionized the treatment of rheumatoid arthritis (RA). However, their clinical utility can be limited by the development of antidrug antibodies (ADAs). Immunogenicity is a complex phenomenon related to various drug, disease, and patient characteristics, and may be more common with the monoclonal antibodies than with etanercept, a soluble TNF receptor-Fc immunoglobulin fusion protein. Neutralizing antibodies – those that hinder bioactivity by preventing drug molecules from binding to TNF – are correlated with reduced serum drug concentrations, loss of therapeutic response, adverse events, and treatment discontinuation. Cost-effective use of these agents will depend on further research into drug and ADA assays, and how they should guide dose reduction or switching strategies.

THU0431 Area of Residence and Socio-Economic Factors Significantly Affect ACCESS to Biological Therapy for Rheumatoid Arthritis Patients in Romania

BackgroundClinical trials have proven the efficacy of biological therapy for rheumatoid arthritis (RA) worldwide. However, high costs have set boundaries to their use, especially in developing countries. Whereas in Europe,...

THU0262 Comparing Abatacept to Adalimumab, Etanercept and Infliximab as First or Second Line Agents in Patients with Rheumatoid Arthritis. Experience from the Rhumadata® Clinical Database and Registry

BackgroundThe order of use of biologic agents is still a question for debate. Phase III trial data in MTX-IR patients show comparable efficacy results across biologic agents and limited head-to-head...

AB0408 Study of the Efficacy of Golimumab and Tocilizmab in Rheumatoid Arthritis with Anti-Ro/Ss-A Antibody

BackgroundWe reported that the presence of anti-Ro/SS-A antibody (anti-Ro) in rheumatoid arthritis (RA) patients might be related to the inefficacy and the discontinuation of infliximab (IFX) compared to the other...

FRI0024 Contribution of the Individual Components of the Disease Activity Score (DAS28) to the Total DAS28 Score among Responders and Non-Responders to Biological Therapy for Rheumatoid Arthritis

BackgroundThe commonly used Disease Activity Score based on 28 joints (DAS28) is a composite index composed of two somewhat subjective components (tender joint count and visual analogue scale general well-being)...

AB1041 Prevalence of Latent Tuberculosis Infection in Rheumatoid Arthritis Patients: Findings from A United Nations National Study

BackgroundThe risk of latent tuberculosis infection (LTBI) is increased in patients with rheumatoid arthritis (RA) than in the general population. Additionally, RA patients may develop pulmonary complications and are more...

AB0403 Dose Optimization of Biological Therapies in Rheumatoid Arthritis in Clinical Practice

BackgroundBiological therapies (BT) have resulted in a remarkable improvement in the treatment of rheumatoid arthritis (RA). One of the limiting factors for its use is cost. For this reason, the...

OP0277 Effect of Disease Modifying Drugs on Bone Mineral Density in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, Psoriasis, and Ankylosing Spondylitis: A Meta-Analysis

OP0277 Effect of Disease Modifying Drugs on Bone Mineral Density in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, Psoriasis, and Ankylosing Spondylitis: A Meta-Analysis

Comparative clinical utility of once-weekly subcutaneous abatacept in the management of rheumatoid arthritis.

Biologic therapies in rheumatoid arthritis are now part of standard practice for disease that proves difficult to control with conventional disease-modifying anti-rheumatic drugs. While anti-tumor necrosis factor therapies have been commonly used, other targeted biologic therapies with different mechanisms of action are becoming increasingly available. Abatacept is a recombinant fusion protein that inhibits the T-cell costimulatory molecules required for T-cell activation. Intravenous abatacept has good clinical efficacy with an acceptably low toxicity profile in rheumatoid arthritis, but the subcutaneous mode of delivery has only recently become available. In this article, we examine key efficacy and safety data for subcutaneous abatacept in rheumatoid arthritis, incorporating evidence from five large Phase III studies that included people with an inadequate response to methotrexate and an inadequate response to biologic disease-modifying anti-rheumatic drugs. The results demonstrate that subcutaneous abatacept has efficacy and safety comparable with that of intravenous abatacept and adalimumab. In addition, inhibition of radiographic progression at year 1 in relatively early rheumatoid arthritis is consistent with that of adalimumab. Subcutaneous abatacept is well tolerated, with very low rates of discontinuation in both short-term and long-term follow-up.

Biologic therapy for rheumatoid arthritis in developing countries--a place for non-TNF inhibitors as first-line treatment?

Biologic therapy for rheumatoid arthritis in developing countries--a place for non-TNF inhibitors as first-line treatment?

Open questions in autoimmunity: discussions from the 2013 Controversies in Rheumatology and Autoimmunity Meeting

The recent CORA (Controversies in Rheumatology and Autoimmunity) meeting held in 2013 represented a unique opportunity for rheumatologists to address several topics. Among these, four topics include: (i) the role of epigenetic changes in the pathogenesis of rheumatoid arthritis (RA), as shown by studies in monozygotic twins; (ii) the cardiovascular and atherosclerotic risk in patients with RA treated with biologics; (iii) the use of new biomarkers for the diagnosis and follow-up of RA and other autoimmune diseases, as represented by the new automatic machines for anti-nuclear antibodies detection, or ultrasound imaging to follow RA progression; and (iv) the latest guidelines on how to use and manage biologic therapies in RA and other autoimmune diseases, such as lupus. In summary, we will herein present these topics of discussion and underline the conclusions obtained by rheumatologists during the 2013 CORA Meeting.