Biological Drugs In Rheumatoid Arthritis Research Articles

OP51 Use Of Real-World Data In Cost-effectiveness Analysis Of Sequential Biologic Treatment For Rheumatoid Arthritis

IntroductionIn health technology assessment (HTA), economic evaluations assessing biologic drugs for rheumatoid arthritis (RA) involve modeling patients’ responses to multiple treatments given sequentially over a lifetime horizon. When data from randomized controlled trials (RCTs) are scarce, data from non-randomized studies (e.g., single-arm trials [SATs] and disease registries) can be used to supplement the evidence base. This research aimed to demonstrate meta-analytic methods for combining effectiveness data from randomized and non-randomized studies and their corresponding impact on cost-effectiveness estimates.MethodsData comparing patients receiving second-line rituximab with continued background non-biologic treatment were extracted from one RCT and six SATs identified in an HTA assessing second-line rituximab for RA, and from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis, by applying a target trial emulation approach. A binomial meta-analysis model was used to estimate the probabilities of achieving the European League against Rheumatism (EULAR) response criteria by pooling data from the RCT, SATs, and the registry. The probabilities were entered into a decision model from a previous HTA to derive incremental cost-effectiveness ratio (ICER) estimates for treatment strategies with and without biologic drugs.ResultsCompared with the original analysis, the estimated probability of at least a moderate EULAR response on rituximab from combined sources was substantially lower. For example, the probability obtained from an RCT was 0.68 (95% credible interval [CrI]: 0.345, 0.907), but only 0.29 (95% [CrI]: 0.242, 0.333) when using RCT plus registry data and 0.29 (95% CrI: 0.244, 0.336) for combined RCT, registry, and SAT data. In the cost-effectiveness analysis, the median ICERs were higher when including real-world data.ConclusionsSynthesis of all relevant data, including RWD, provides additional information regarding the variability in cost-effectiveness estimates and can be considered in sensitivity analyses for HTA decision-making.

P138 Inequity in Clinical Commissioning Group funding across England for high-cost biologic drugs in rheumatoid arthritis

Abstract Background/Aims Biologic, and targeted, disease-modifying antirheumatic drugs (bDMARDs/tDMARDs) are recommended for patients in England with high disease activity score rheumatoid arthritis (HDAS-RA) who do not respond to two or more conventional synthetic DMARDs. To prescribe bDMARDs/tDMARDs in England, prescribers must apply for funding via their local clinical commissioning group (CCG). The project aim was to review whether CCGs across England had defined high cost drugs pathways for bDMARDs/tDMARDs use in HDAS-RA and if so, what this pathway looked like regarding drug choice, order of availability, and ability to prescribe as monotherapy. Methods We submitted a freedom of information (FOI) request in October 2021 to all CCGs within England to obtain their high cost drug pathway for bDMARDs/tDMARDs use in HDAS-RA. We then manually reviewed the pathways to determine whether the CCG specified an order of drug prescribing. Data was also gathered on whether CCGs allowed abatacept (ABT), rituximab (RTX), and golimumab (GOL) to be prescribed as monotherapy. Results All 107 CCGs in England responded to the FOI request. 69 out of 107 CCGs (65%) had a pathway for bDMARDs/tDMARDs prescribing. 60 out of 69 CCGs (87%) specified an order for drug prescribing in RA. Within their pathways, CCGs generally fell into 3 prescribing preferences. Table 1 summarises these pathway recommendations. 39 (57%), 59 (86%), and 6 (9%) CCGs allowed ABT/RTX/GOL to be prescribed as monotherapy respectively. RTX monotherapy was specifically allowed outside of special indications such as cancer, interstitial lung disease and multiple sclerosis. Conclusion These findings show there is significant variation across England regarding which bDMARDs/tDMARDs patients can receive for HDAS-RA resulting in a postcode lottery. Several studies support the use of ABT/RTX/GOL as monotherapy and registry data shows that 30-40% of RA patients are administered ABT/RTX/GOL as monotherapy for methotrexate intolerance/contraindication. Lack of NICE appraisal, however, means some CCGs mandate individual funding requests for monotherapy prescribing. We would like to use these results to help negotiate equitable access to bDMARDs/tDMARDs nationwide. Disclosure O. Buckeldee: None. R. Khanna: None. L. Snell: None. L. Attipoe: None.

How long does it take to translate research findings into routine healthcare practice?-the case of biological drugs for rheumatoid arthritis in Brazil.

BackgroundThe literature reports long time lags between the several processes involved in the translation of drug research and development into clinical application. To expedite these processes, translational research has emerged as a process that can be applied to reduce the lag between scientific discoveries and their practical application. Thus, the objective of this study was to estimate the time lag in translational research of biological drugs for the treatment of rheumatoid arthritis included in the Brazilian Unified Health System [Sistema Único de Saúde (SUS)].MethodsA descriptive retrospective study was conducted based on secondary data loaded by SUS users in public sources and systems to estimate the time lag between the publication of phase I clinical trial results to drug use in clinical settings. The dates of translational research activities were identified from markers and steps. Structured searches were conducted in the literature and reports from the National Commission for the Incorporation of Technologies in the SUS (Conitec) as well as from health authorities, and analyzed.ResultsBetween 2012 and 2019, SUS included five biological agents for the treatment of rheumatoid arthritis. The mean time lag from clinical development to use of these agents was 11.13 years (range, 8.57 to 12.90 years). The mean time lag for the stages of translational research were 5.30 (T1—basic research to clinical research), 5.08 (T2—clinical research to research synthesis), and 0.75 (T3—research synthesis to evidence-based practice) years. A shorter time lag was observed in the Brazilian case when it was possible to compare with other studies.ConclusionsThe estimated time lag of biological drugs used in the treatment of rheumatoid arthritis was determined based on the translational research steps model adapted to the Brazilian context. Brazil has instituted legal frameworks that set deadlines for sanitary registration, health technology assessment (HTA), and the availability of drugs in the SUS, thus, allowing for a reduced stage T2 time lag. Nevertheless, improvements are still required in stages T1 and T2, especially in publishing the results of clinical trials.

Review on pain reduction when using Golimumab, Tofacilinib and Etanercept

Research Background: Biologic drugs are TNF alpha inhibitors, or similar drugs effective in treating AR that do not respond to NSAIDs and DMARDs. They are generally classified as potent drugs in the treatment of Rheumatoid Arthritis, Psoriatic Arthritis and other autoimmune forms of inflammatory arthritis. Biologic drugs are seen as the best way to treat chronic pain that has previously been incurable. Purpose: To identify the effectiveness of the use of biological drugs in Rheumatoid Arthritis to reduce pain. Methodology: The methodology that will be used in this study is an observational, cohort study, conducted at the Mother Teresa University Hospital Center in Albania. The sample taken in the study consists of 36 individuals who are currently undergoing biological drug therapy, and in previous treatments have been treated with Methotrexate or NSAIDs. The biological drugs used are Golimumab, Tofacilinib and Etanercept as a change therapy. Results: The expected results suggest a reduction of pain after the use of biological drugs in the first 6 months of treatment. Conclusions: Biologic drugs are 70-100% effective in reducing AR pain, mainly joint pain in the small joints of the hands and feet, knee and in advanced stages in the articular pain of the pelvis and spine. A therapeutic approach with biological drugs for patients suffering from chronic pain can improve pain reduction, the patient's daily life, and reduce disability states.

A novel multi-biomarker combination predicting relapse from long-term remission after discontinuation of biological drugs in rheumatoid arthritis

Biological disease modifying anti-rheumatic drugs (bDMARDs) show dramatic treatment efficacy in rheumatoid arthritis (RA). Long-term use of bDMARDs, however, has disadvantages such as high costs and infection risk. Therefore, a methodology is needed to predict any future RA relapse. Herein, we report a novel multi-biomarker combination which predicts relapse after bDMARDs-withdrawal in patients in remission. Forty patients with RA in remission for more than 12 months were enrolled. bDMARDs were withdrawn and they were followed monthly for the next 24 months. Fourteen patients (35%) of 40 in the cohort remained in remission at 24 months, whereas 26 (65%) relapsed at various time-points. Serum samples obtained longitudinally from patients in remission were assessed for the relapse-prediction biomarkers and index from 73 cytokines by the exploratory multivariate ROC analysis. The relapse-prediction index calculated from the 5 cytokines, IL-34, CCL1, IL-1β, IL-2 and IL-19, strongly discriminated between patients who relapsed and those who stayed in remission. These findings could contribute to clinical decision-making as to the timing of when to discontinue bDMARDs in RA treatment.

Biologic Drugs for Rheumatoid Arthritis in the Context of Biosimilars, Genetics, Epigenetics and COVID-19 Treatment.

Rheumatoid arthritis (RA) affects around 1.2% of the adult population. RA is one of the main reasons for work disability and premature retirement, thus substantially increasing social and economic burden. Biological disease-modifying antirheumatic drugs (bDMARDs) were shown to be an effective therapy especially in those rheumatoid arthritis (RA) patients, who did not adequately respond to conventional synthetic DMARD therapy. However, despite the proven efficacy, the high cost of the therapy resulted in limitation of the widespread use and unequal access to the care. The introduction of biosimilars, which are much cheaper relative to original drugs, may facilitate the achievement of the therapy by a much broader spectrum of patients. In this review we present the properties of original biologic agents based on cytokine-targeted (blockers of TNF, IL-6, IL-1, GM-CSF) and cell-targeted therapies (aimed to inhibit T cells and B cells properties) as well as biosimilars used in rheumatology. We also analyze the latest update of bDMARDs’ possible influence on DNA methylation, miRNA expression and histone modification in RA patients, what might be the important factors toward precise and personalized RA treatment. In addition, during the COVID-19 outbreak, we discuss the usage of biologicals in context of effective and safe COVID-19 treatment. Therefore, early diagnosing along with therapeutic intervention based on personalized drugs targeting disease-specific genes is still needed to relieve symptoms and to improve the quality of life of RA patients.

Medicolegal Aspects of Disclosure of Side Effects of Biologic Drugs in Rheumatology: A Pilot Study

Background: Management of rheumatoid arthritis is complicated due to different disease presentations and the multiplicity of drugs. Although most patients are informed about the risks of treatment, there remain possible side-effects, which patients are not informed about to avoid the 'information dump.’ Rheumatologists have to balance what they believe is essential to tell patients versus what reasonable patients believe they need to know to make an informed consent. Objectives: To determine differences in information that the physicians give, regarding the possible side effects of treatment options for rheumatoid arthritis, and what the patients actually want to know. Methods: To conduct this pilot study, a questionnaire was devised to assess what patients and prescribing rheumatologists, from the Gulf Cooperative Council, consider important for being informed about, including the possible adverse events with biologic drugs in rheumatoid arthritis. Results: A total of 20 patients and 13 physicians completed the questionnaire. Physicians routinely discussed the increased risk of infections (100%), skin rashes at injection sites (92%),falling white blood cell counts, and alterations in liver enzymes (84%). Patients were less interested in learning about infections (72%) and more interested in learning about rare complications, such as an increased risk of heart failure and cancer (81%), which doctors were less likely to discuss. Conclusions: There is a discordance between what doctors inform patients about and what patients want to know regarding the risks of biologic therapy in rheumatoid arthritis. This information gap can have a significant legal implications in routine practice if a patient develops a rare side effect of which they have not been informed. We propose a solution of both verbal and signed informed consent to bridge the gap.

New lessons for an old problem: ASSET open-label extension.

Abatacept is a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) immunoglobulin fusion protein, which is effective for the treatment of rheumatoid arthritis and is approved in Europe and the USA for this indication.1 By contrast with the first generation of anti-cytokine biological drugs for rheumatoid arthritis, abatacept acts by directly inhibiting T-cell co-stimulation and preventing T-cell-dependent B-cell maturation and activation. The role of the CD28–CTLA-4 pathway in autoimmunity has been increasingly recognised, from the first single nucleotide polymorphism reported to bring higher risk of autoimmunity2 to the clinical benefit of CTLA4 checkpoint inhibitors in cancer immunotherapy.

Using the Immunophenotype to Predict Response to Biologic Drugs in Rheumatoid Arthritis.

Tumour necrosis factor (TNF)-α is a key mediator of inflammation in rheumatoid arthritis, and its discovery led to the development of highly successful anti-TNF therapy. Subsequently, other biologic drugs targeting immune pathways, namely interleukin-6 blockade, B cell depletion, and T cell co-stimulation blockade, have been developed. Not all patients respond to a biologic drug, leading to a knowledge gap between biologic therapies available and the confident prediction of response. So far, genetic studies have failed to uncover clinically informative biomarkers to predict response. Given that the targets of biologics are immune pathways, immunological study has become all the more pertinent. Furthermore, advances in single-cell technology have enabled the characterization of many leucocyte subsets. Studying the blood immunophenotype may therefore, define biomarker profiles relevant to each individual patient’s disease and treatment outcome. This review summarises our current understanding of how immune biomarkers might be able to predict treatment response to biologic drugs.

Discordance between doctor and patient assessments and non-adherence to subcutaneous biological drugs.

To estimate the agreement level between patient and physician assessment of disease activity and to explore whether agreement is associated with adherence to subcutaneous (SC) biological drugs in rheumatoid arthritis (RA). Cross-sectional study of RA patients who had been prescribed a SC biological drug in the past 12-18monthswas performed. Patients and physicians global disease activity on visual analogue scale (VAS) were collected. Disagreement was defined as an absolute difference ≥ 3 points between VAS scores. Adherence was assessed by the Medication Possession Ratio (MPR), considering adherence an MPR > 80%. We analysed 360 patients of whom 15.5% presented disagreement with their physicians. The mean patient global VAS was 5.75 ± 1.8 (median 5.5 [5-7]) in the disagreement group versus 2.7 ± 2.2 (median 2 [1-4]) in the agreement group (p < 0.001). There were also differences in physicians global VAS between groups (p = 0.01). The non-adherence to SC biological drugs rate was 10.7% and 14.5% in the disagreement and agreement groups (p = 0.45). No association between adherence and discordance was found. Disagreement in the global disease activity between patients and physicians was detected in 15.5% of patients. In general, patients perceived higher disease activity. No associations between patient-physician disagreement in VAS and adherence were observed.

PREDICTION OF TOCILIZUMAB AND RITUXIMAB EFFECTIVENESS IN RHEUMATOID ARTHRITIS

Objective: to study the possibility of prediction of treatment effectiveness with tocilizumab and rituximab in rheumatoid arthritis (RA), taking into account the clinical and immunological characteristics of patients. Material and methods. The efficacy of treatment with tocilizumab in 53 patients and rituximab in 22 patients with RA within 12 months was analyzed, the prognostic role of the initial values of activity indices, the presence of systemic manifestations, the duration of RA, levels of autoantibodies and acute phase proteins was evaluated. Results. The high efficacy of treatment with biological drugs in RA was established, the treatment goals were achieved by 84.91% of patients in the group of tocilizumab and 72.72% in the group of rituximab, but the remaining patients did not reach the treatment goal after 12 months of follow-up. Conclusions. Reliable predictors of a good response to tocilizumab in RA may be high activity of the joint syndrome, rituximab – seropositive variant of RA, as well as the presence of systemic manifestations.

OP45 Biological Drugs And Rheumatoid Arthritis In Brazil: An Overview

IntroductionThe Brazilian Unified Health System (SUS) is known worldwide for ensuring universal assistance to citizens, which includes the supply of medicines free of charge. Biological drugs consume about 40 percent of the public budget for pharmaceutical services in the SUS and Rheumatoid Arthritis (RA) is the largest consumer of these resources, serving about 110,000 patients. Since 2002 there has been a clinical guideline for the care of patients with rheumatoid arthritis in Brazil, currently providing 10 biological drugs for treatment of RA. The objective of this study is to present data about the provision, expenditure and profile of users of biological drugs for rheumatoid arthritis in SUS.MethodsRetrospective and exploratory study, using administrative data regarding the purchase and consumption of biological drugs Infliximab, Etanercept, Adalimumab, Rituximab, Abatacept (intravenous and subcutaneous), Tocilizumab, Golimumab and Certolizumab pegol for the treatment of RA between 2012 and 2017 in SUS.ResultsThere was an expenditure of approximately USD 421.7 million from the Brazilian Ministry of Health with the supply of about 2 million pharmaceutical units of biological drugs for treatment of rheumatoid arthritis, 79 percent of them destined for female users and 89.2 percent for the 40-69 age group. The M05.8 and M.06.0 codes of the International Classification of Diseases (ICD-10) were the most prevalent among the arthritic population served. Adalimumab and Etanercept accounted for 68.3 percent of total expenditure. A reduction in the use of these medicines were observed after the availability of new drugs for the treatment of the disease between 2014 and 2017.ConclusionsBrazil is one of the largest consumers of biological medicines in the world. The use of real-life data allows monitoring trends and costs of the use of these drugs as well as changes with the entry of new therapies and biosimilar medicines.

Variability in the prescription of biological drugs in rheumatoid arthritis in Spain: a multilevel analysis.

To describe variability in the prescription of biologics (B-DMARDs) for patients with rheumatoid arthritis (RA) in hospitals in Spain, and to explore which characteristics of the patient, the doctor and the hospital are associated with this variability. Cross-sectional multicentric study in 46 rheumatology services of the National Health System. Medical records of 1188 randomly selected patients were reviewed. The association of each variable with B-DMARD prescription was analyzed using simple logistic regressions. Multilevel logistic regression models were created to analyze variability among centers. 36.8% of patients had received B-DMARD. The proportion of patients being treated with B-DMARDs varied between 3.6 and 71.4% depending on the center. Association of prescription of B-DMARD with patient age (OR = 0.958, 95% CI = 0.947-0.968, p < 0.001), longer disease duration (OR = 1.05, 95% CI = 1.032-1.069, p < 0.001), higher CRP levels (OR = 1.022, 95% CI = 1.003-1.042, p = 0.023), and higher number of hospitalizations (OR = 1.286, 95% CI = 1.145-1.446, p < 0.001) was observed. With regard to the center characteristics, the existence of telephone consultations (OR = 1.438, 95% CI = 1.037-1.994, p = 0.03) and the number of beds (OR = 1.045, 95% CI = 1.001-1.091, p = 0.044) were positively associated with prescription of B-DMARDs. Patient variables explained 34.04% of the variability among centers. By adjusting for patient and hospital characteristics, it went up to 83.71%. There is variability in the prescription of B-DMARDs for patients with RA among hospitals which is associated, to a greater extent, with the center characteristics. B-DMARDs prescription could be partly explained by other factors not covered by the current study including the provider's attitudes towards biologics and other hospital characteristics.

PMS25 - Switching of Biological Drugs in Rheumatoid Arthritis: A Cohort of Users from the Brazilian Public Health System

PMS25 - Switching of Biological Drugs in Rheumatoid Arthritis: A Cohort of Users from the Brazilian Public Health System

Risks of malignancies related to tofacitinib and biological drugs in rheumatoid arthritis: Systematic review, meta-analysis, and network meta-analysis.

To summarize and compare the risks of malignancies accompanying biologic DMARDs (b-DMARDs) and tofacitinib in rheumatoid arthritis (RA) in randomized clinical trials (RCTs) and long-term extension studies (LTEs). Articles in Medline, Embase, Cochrane Library, and the Web of Science dated from 2000 to February 2015. Selection criteria were as follows: (1) focus on RCTs or LTEs in RA; (2) treatment with b-DMARDs or tofacitinib; (3) data on malignancies; and (4) a minimum follow-up of 12 weeks. Data included publication details, study design, risk of bias, number and types of malignancies, and patient characteristics and treatments. Of 113 articles and one updated report that were meta-analyzed, overall malignancies in RCTs showed odds ratio (95% confidence intervals) of 1.01 (0.72, 1.42) for all TNF antagonists, 1.12 (0.33, 3.81) for abatacept, 0.54 (0.20, 1.50) for rituximab, 0.70 (0.20, 2.41) for tocilizumab, and 2.39 (0.50, 11.5) for tofacitinib. Network meta-analysis of overall malignancies showed odds ratio (95% predictive intervals) of 1.68 (0.48-5.92) for infliximab, 0.79 (0.44-1.40) for etanercept, 0.93 (0.43-2.03) for adalimumab, 0.87 (0.28-2.75) for certolizumab, 0.87 (0.39-1.95) for golimumab, 1.04 (0.32-3.32) for abatacept, 0.58 (0.21-1.56) for rituximab, 0.60 (0.16-2.28) for tocilizumab, and 1.15 (0.24-5.47) for tofacitinib. Marginal numerical differences in the incidence rate of solid and hematological malignancies and non-melanoma skin cancers appeared in LTEs. In RCTs, treatment of RA with b-DMARDs or tofacitinib does not increase the risk for malignancies. Generalizability of the differences in the rate of specific malignancies encountered in LTEs requires continuous pharmacovigilance of real-world patients.

Physician Preferences and Variations in Prescription of Biologic Drugs for Rheumatoid Arthritis: A Register-Based Study of 4,010 Patients in Sweden.

The prescription of biologic drugs for rheumatoid arthritis (RA) patients has varied considerably across different regions. Previous studies have shown physician preferences to be an important determinant in the decision to select biologic disease-modifying antirheumatic drugs (bDMARDs) rather than nonbiologic, synthetic DMARDs (sDMARDs) alone. The aim of this study was to test the hypothesis that physician preferences are an important determinant for prescribing bDMARDs for RA patients in Sweden. Using data from the Swedish Rheumatology Quality Register, we identified 4,010 RA patients who were not prescribed bDMARDs during the period 2008-2012, but who, on at least 1 occasion, had an sDMARD prescription and changed treatment for the first time to either a new sDMARD or a bDMARD. Physician preference for the use of bDMARDs was calculated using data on each physician's prescriptions during the study period. The relationship between prescription of a bDMARD and physician preference, controlling for patient characteristics, disease activity, and the physician's local context was evaluated using multivariate logistic regression. When adjusting for patient characteristics, disease activity, and the physician's local context, physician preference was an important predictor for prescription of bDMARDs. Compared with patients of a physician in the lowest preference tertile, patients of physicians in the highest and middle tertiles had an odds ratio for receiving bDMARDs of 2.8 (95% confidence interval [95% CI] 2.13-3.68) and 1.28 (95% CI 1.05-1.57), respectively. Physician preference is an important determinant for prescribing bDMARDs.

Use and Spending for Biologic Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis Among US Medicare Beneficiaries.

Biologic therapies have assumed an important role in treating rheumatoid arthritis (RA). We sought to investigate use, spending, and patient cost-sharing for Medicare beneficiaries using biologic drugs for RA, comparing patients exposed to minimal cost-sharing because of a Part D low-income subsidy (LIS) to those facing substantial out-of-pocket costs (OOP). We performed a retrospective, nationwide study using 2009 Medicare claims for a 5% random sample of beneficiaries with RA who had at least 1 RA drug dispensed. We analyzed biologic drug utilization and costs across the Part B (medical benefit) and Part D (pharmacy benefit) programs by LIS status using multinomial regression. We also projected OOP costs as the Affordable Care Act (ACA) mandates closure of the Part D coverage gap by 2020. Among 6,932 beneficiaries, 1,812 (26.1%) received a biologic drug. LIS beneficiaries were significantly more likely to obtain Part D home-administered biologics (relative risk ratio [RRR] 2.98, 95% confidence interval [95% CI] 2.50-3.56), while non-LIS beneficiaries were less likely to receive Part D biologic agents (RRR 0.58, 95% CI 0.48-0.69). OOP costs in Part D were lower, as expected, for LIS beneficiaries ($72 versus $3,751 per year for non-LIS). Non-LIS beneficiaries had lower costs for Part B facility-administered biologic agents (range $0-$2,584) than for Part D home-administered biologic agents. ACA reforms will narrow OOP differences between Part D and B for non-LIS beneficiaries. In contrast to LIS beneficiaries who receive mostly Part D home-administered biologic DMARDs, nonsubsidized beneficiaries have significant cost-based incentives to obtain facility-administered biologic DMARDs through Part B. The ACA will result in only slightly lower costs for Part D biologic drugs for these beneficiaries.

Risk of hospitalized infection among rheumatoid arthritis patients concurrently treated with a biologic agent and denosumab.

Denosumab is a biologic agent used to treat osteoporosis. Its safety profile given concurrently with biologic drugs for rheumatoid arthritis (RA) has not been well studied. We evaluated hospitalized infections among patients treated with biologic agents for RA who initiated denosumab or zoledronic acid (ZA), a parenteral bisphosphonate without known associations with infection. We hypothesized that the rate of hospitalized infection with denosumab would be noninferior to ZA. We identified RA patients enrolled in Medicare in 2006-2012 treated with biologic agents who initiated denosumab or ZA. Cox proportional hazards models compared the risk for hospitalized infection, comparing denosumab users to ZA users and adjusting for potentially confounding factors. A noninferiority margin was specified a priori to demonstrate that denosumab had no greater infection risk than ZA if the upper bound of the 95% confidence interval (95% CI) of the hazard ratio (HR) was <1.5. Eligible RA patients receiving biologic agents initiated denosumab (n = 1,354) or ZA (n = 4,460). Characteristics of the denosumab users were as follows: mean ± SD age 73.0 ± 8.9, 98.2% women, with a majority receiving infliximab (35.7%) or abatacept (18.6%). Denosumab users had a higher prevalence of prior infections (11.5% hospitalized and 48.3% outpatient) and infection-related risk factors. The crude rate of hospitalized infections for denosumab (14.9/100 person-years [95% CI 12.2-18.1]) was comparable to that for ZA (13.9/100 person-years [95% CI 12.5-15.4]). After adjustment, the HR of hospitalized infection for denosumab users was noninferior to that for ZA users (HR 0.89 [95% CI 0.69-1.15]). The rate of hospitalized infection among RA patients receiving denosumab concurrently with biologic agents for RA was not increased compared to those receiving zoledronate.

Individual variations in treatment decisions by Swedish rheumatologists regarding biological drugs for rheumatoid arthritis

Objectives: In Sweden, reports indicate surprisingly large regional variation in prescription of biological drugs despite a growing number of clinical studies describing their beneficial effects and guidelines by professional organizations and agencies. Our objectives were to ascertain whether there is also variation between individual rheumatologists in prescribing biologics to patients with rheumatoid arthritis (RA) and to evaluate reasons for treatment choices.Method: Ten hypothetical patient cases were constructed and presented to 26 rheumatologists in five regions in Sweden. The cases were based on actual cases and were thoroughly elaborated by a senior rheumatologist and pre-tested in a pilot study. The respondents were asked whether they would treat the patients with a biological agent (Yes/No) and to explain their decisions.Results: The response rate was 26/105 (25%). Treatment choices varied considerably between the rheumatologists, some prescribing biologics to 9/10 patients and others to 2/10. In five of the 10 hypothetical cases, approximately half of the respondents would prescribe biologics. No regions with particularly high or low prescription were identified. Both the decisions to prescribe biologics and also not to prescribe biologics were mainly motivated by medical reasons. Some rheumatologists also referred to lifestyle-related factors or the social function of the patient.Conclusions: The choice of initiation of biologics varied substantially among rheumatologists presented with hypothetical patient cases, and there were also disparities between rheumatologists practicing at the same clinic. Treatment choices were motivated primarily by medical reasons. This situation raises concerns about a lack of consensus in RA treatment strategies.

The perplexity of prescribing and switching of biologic drugs in rheumatoid arthritis: a UK regional audit of practice.

BackgroundBiologic drugs are expensive treatments used in rheumatoid arthritis (RA). Switching among them is common practice in patients who have had an inadequate response or intolerable adverse events. The National Institute of Health and Clinical Excellence (NICE) UK, which aims to curtail postcode prescribing, has provided guidance on the sequential prescription of these drugs. This study sought to evaluate the extent to which rheumatology centres across the Midlands were complying with NICE guidance on the switching of biologic drugs in RA, as well as analyse the various prescribing patterns of these drugs.MethodsData was collected via a web-based tool on RA patients who had undergone at least one switch of a biologic drug during 2011. The standards specified in NICE technology appraisals (TA130, TA186, TA195, TA198, and TA225) were used to assess compliance with NICE guidance. Descriptive statistical analysis was performed.ResultsThere were 335 biologic drug switches in 317 patients. The most common reason given for switching to a drug was NICE guidelines (242, 72.2%), followed by Physician's choice (122, 33.4%). Lack of effect was the most common reason for discontinuing a drug (224, 67%). For patients on Rituximab, Methotrexate was used in 133 switches (76.9% of the time). Overall NICE compliance for all units was 65% (range 50 to 100%), with anti-TNFα to anti-TNFα switches for inefficacy making up the majority of non-compliant switches.ConclusionThis study draws attention to the enigma and disparity of commissioning and prescribing of biologic drugs in RA. Currently the evidence would not support switching of a biologic drug for non-clinical purposes such as economic pressures. Flexibility in prescribing should be encouraged: biologic therapy should be individualised based on the mode of action and likely tolerability of these drugs. Further work should focus on the evidence for using particular sequences of biologic drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-290) contains supplementary material, which is available to authorized users.