Biologics For Treatment Of Rheumatoid Arthritis Research Articles

Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis.

Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR2.84, p = 0.02). In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea.

OA40 Clinical and psychological factors associated with adherence based on a patient self-reported questionnaire: results from the biologics in rheumatoid arthritis genetics and genomics study syndicate (BRAGGS) cohort

Abstract Background/Aims To explore the relationship of clinical and psychological factors with adherence based on a patient self-reported questionnaire from a prospective longitudinal study of patients receiving TNFi biologic treatment for rheumatoid arthritis, recruited since 2008. Methods Analysis of data collected from a prospective longitudinal UK study (Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate [BRAGGSS]) of patients with moderate to severe RA commencing TNFi biologic treatment. Clinical data including Disease Activity Score-28 (DAS28), serological status (Rheumatoid Factor positivity) and body mass index (BMI) were collected. Patients also completed self-reported questionnaires, the health assessment questionnaire (HAQ), hospital anxiety and depression scale (HAD), beliefs about medicine questionnaire (BMQ), brief illness perception score (B-IPQ) and a self-reported adherence questionnaire. Adherence was defined as any deviation from prescribed medication regime such as altering the dose, forgetting a dose, stopping treatment, missing a dose, and taking less than instructed. Associations between demographic and psychological variables and adherence were evaluated using regression models and a multivariable logistic regression model was used to further evaluate associations, controlling for BMI. Results 1,513 patients (75.7% female, age 58.1 [IQR 16.0], disease duration 9.6 ± 9.6 years and pre-treatment DAS28 scores 5.7 ± 0.8) were included. 70% of patients self-reported adherence to their medication. When comparing the different TNFi treatments, etanercept had the lowest levels of adherence at the 3 and 6 month time-points. Adherence was higher in those with older age (β = 0.03, p&amp;lt; 0.01), higher baseline CRP levels (β = 0.01, p= 0.03) and higher necessity beliefs (β = 0.04, p= 0.03). Adherence was lower in those with higher tender joint counts at baseline (β=-0.03, p= 0.04) and 3 months (β = 0.03, p= 0.02) (Table I). These associations persisted after controlling for the effects of BMI using a multivariable logistic model. Conclusion Self-reported adherence was 70% in this BRAGGS population. Factors associated with non-adherence included higher tender joint counts and lower necessity beliefs pre-treatment, which may allow targeting of interventions to optimise adherence in these groups. Disclosure T.K.Y. Chong: None. N. Nair: None. A.W. Morgan: None. J.D. Isaacs: None. A.G. Wilson: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; K.H has grants from BMS and Pfizer. D. Plant: None. A. Barton: Grants/research support; A.B has received funding/speaker fees from BMS, Pfizer and Galapagos.

Treatment of rheumatoid arthritis with conventional, targeted and biological disease-modifying antirheumatic drugs in the setting of liver injury and non-alcoholic fatty liver disease.

Increased incidence of liver diseases emphasizes greater caution in prescribing antirheumatic drugs due to their hepatotoxicity. A transient elevation of transaminases to autoimmune hepatitis and acute liver failure has been described. For every 10 cases of alanine aminotransferase (ALT) elevation in a clinical trial, it is estimated that one case of more severe liver injury will develop once the investigated drug is widely available. Biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (tsDMARDs) are less likely to cause liver damage. However, various manifestations, from a transient elevation of transaminases to autoimmune hepatitis and acute liver failure, have been described. Research on non-alcoholic fatty liver disease (NAFLD) has provided insight into a pre-existing liver disease that may be worsen by medication. Diabetes and obesity could be an additional burden in drug-induced liver injury (DILI). In the intertwining of the inflammatory and metabolic pathways, the most important cytokines are IL-6 and TNF alpha, which are also the cornerstone of biological treatment for rheumatoid arthritis. This narrative review evaluates the complexity and prevention of DILI in RA and treatment options involving biological therapy and tsDMARDs.

Biological Disease-Modifying Antirheumatic Drugs and Osteoporotic Fracture Risk in Patients with Rheumatoid Arthritis: A Danish Cohort Study

ObjectivesClinical trials have shown a beneficial effect from biological disease-modifying antirheumatic drugs (bDMARDs) on hand or axial bone loss in patients with rheumatoid arthritis; however, it is unclear if this translates to a reduced fracture risk. We investigated the effect of bDMARDs on osteoporotic fracture risk compared to no biological treatment in rheumatoid arthritis. MethodsA cohort of patients with rheumatoid arthritis aged 18+ from DANBIO was linked to population-based health registries in Denmark (2006-2016). Adopting a prevalent new-user design, we matched bDMARD users to bDMARD-naïve patients using time-conditional propensity scores. The risk of incident osteoporotic fractures (including hip, vertebrae, humerus, and forearm) was estimated among the matched patients by Cox proportional hazards models. ResultsOut of 24,678 patients with rheumatoid arthritis, 4265 bDMARD users were matched to the same number of bDMARD-naïve patients (mean age 56.2 years, 74% female). During follow-up, 229 osteoporotic fractures occurred among bDMARD users and 205 fractures among bDMARD-naïve patients (incidence rates 12.1 and 13.0 per 1000 person-years, respectively). The use of bDMARDs was not associated with a reduced risk of osteoporotic fractures among patients with rheumatoid arthritis (hazard ratio 0.97, 95% confidence interval 0.78-1.20), compared with no biological treatment. The risk estimates were similar for all osteoporotic fracture sites. ConclusionWe found no independent beneficial effect from using bDMARDs on reducing the risk of osteoporotic fractures in patients with rheumatoid arthritis.

Polymorphisms Involved in Response to Biological Agents Used in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic disease that leads to joint destruction. During the last decade, the therapy of RA has been principally based on biological drugs. Although the efficacy of biological therapy has been established, patients demonstrated a high heterogeneity in clinical response to treatment. Several genetic polymorphisms play a part in the different response to biological drugs. This review summarizes the pharmacogenetics of biological agents approved for clinical RA treatment. We reviewed PubMed papers published over the past 20 years (2000–2020), inserting as the search term “rheumatoid arthritis and polymorphisms”. Despite some studies showing important correlations between genetic polymorphisms and response to biological therapy in RA patients, most of these findings are still lacking and inconsistent. The personalized treatment according to a pharmacogenetics approach is promising but the available pharmacogenetics data on biological treatment in RA are not adequate and reliable to recommend pharmacogenetic tests before starting biological therapy in RA patients.

Cardiovascular risk estimation with 5 different algorithms before and after 5 years of bDMARD treatment in rheumatoid arthritis.

Assessing cardiovascular (CV) risk represents a challenge for clinicians because more variables can impact CV risk. The aim of this study was to evaluate the change of CV risk after 5years of biological treatment in rheumatoid arthritis (RA) patients and impact of prolonged low disease activity on 5 different CV risk algorithms. We estimated the CV risk, at baseline and at 5-year follow-up (FU), with the Systematic COronary Risk Evaluation(SCORE) charts, the algorithm 'Progetto Cuore', the QRISK3-2018 score, the Reynold Risk Score(RRS) and the Expanded Risk Score in RA(ERS-RA). Clinical disease activity index(CDAI) was used to define RA activity. Wilcoxon signed-rank test was used to compare CV risk scores. In 110 patients with a 5-year FU on biological disease-modifying anti-rheumatic drug treatment, we observed an increase in the 10-year CV risk estimated by SCORE charts [from mean (SD) 0.9% (1.4) to 1.1% (1.5), P<.001], 'Progetto Cuore' [from mean (SD) 5.5% (7.2) to 6.2% (6.8), P<.001], QRISK3-2018 [from mean (SD) 9.3% (10.1) to 11.9% (10.8), P<.001) and RRS [from mean (SD) 5.6% (6.4) to 6.2% (7.5), P<.05], mainly due to age raise. ERS-RA highlighted a significant decrease of estimated CV risk in patients with persistent CDAI≤10[from mean (SD) 9.6% (11.2) to 7.3% (6.4), P<.05], despite age increase and its impact on the CV risk score. Algorithms commonly used to estimate 10-year CV risk in RA perform differently. Scores that include specific inflammatory RA-related variables seem to decrease with amelioration of disease activity. Further investigations are warranted to explore the predictive value of their changing over time.

DAS28-ESR and DAS28-CRP - are they Interchangeable in Measuring the Activity of Rheumatoid Arthritis in Response to Treatment with Biological Agents?

The European League Against Rheumatism updates the recommendations for managing rheumatoid arthritis. Again, it is not specified which DAS28 is there in view (with erythrocyte sedimentation rate or C-reactive protein). The aim of the study is to check whether Disease Activity Score-28 (erythrocyte sedimentation rate) and Disease Activity Score-28 (C-reactive protein) represent equally the activity of rheumatoid arthritis in the course of treatment with biological agents. In a retrospective study we analyzed the database of real clinical practice over a 12-month period of biological treatment of rheumatoid arthritis. Disease Activity Score-28 (erythrocyte sedimentation rate) and (C-reactive protein) are compared at the start and at the end of the study. The mean difference between the two variants of disease activity scores at baseline and at the end of the study is significant (p < 0.001). The Disease Activity Score-28 (erythrocyte sedimentation rate) represents a remarkably small proportion of patients with remission and low activity (<3.2) at baseline (18.46%) and at the end of the study (40.51%). Disease Activity Score-28 (C-reactive protein) represents a significantly high proportion of patients in remission and low activity (<3.2) at the end of the study (69.74%). Estimates of activity according to the two variants show significant discrepancy between each other and low level of agreement (kappa = 0.235-0.464). Discrepancies are not related to the type of biological drug (anti-TNF or not). The two DAS28 variants are not interchangeable with the same threshold for low activity in measuring the response to biological therapy.

Association of Patient, Prescriber, and Region With the Initiation of First Prescription of Biologic Disease-Modifying Antirheumatic Drug Among Older Patients With Rheumatoid Arthritis and Identical Health Insurance Coverage

Prescribing the first biologic treatment for rheumatoid arthritis (RA) is an important decision for patients, their physicians, and payers, with considerable costs and clinical implications. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have known effectiveness and safety profiles and are less expensive; therefore, determining the variables contributing to csDMARD treatment duration is an essential question for patients, physicians, and payers. To describe access to the first biologic DMARD prescription in a population of patients with RA and identical comprehensive health insurance coverage in Ontario, Canada, and to explore the associations of patient, prescriber, and geographic region with differences in time to first biologic prescription. This cohort study of incident patients with RA used administrative data with surveillance and patient-level data collected at yearly intervals. A total of 17 672 patients were included in the study; they were residents of Ontario, Canada, had an incident RA diagnosis at age 67 or older between 2002 and 2015, and received at least 1 csDMARD. Data were analyzed in November 2017. Patient variables were age, sex, disease duration, socioeconomic status, distance to care, and supply of care in the patient's area of residence. Prescriber covariates were year of graduation, specialty of practice, and supply of rheumatologic care in the patient's geographic region. Time from first csDMARD prescription to receipt of first biologic medication. Of 17 672 patients, 11 598 (65.6%) were women, and the mean (SD) age was 75.2 (5.8) years. Characteristics associated with longer time to receipt of a biologic prescription were older age (HR for every 5-year increase, 0.66; 95% CI, 0.62-0.71; P < .001), male sex (HR, 0.76; 95% CI, 0.66-0.89; P < .001), and distance to the nearest rheumatologist (HR per 10-km increase, 0.99; 95% CI, 0.98-0.99; P < .001). Prescribers were primarily rheumatologists (151 of 214 [70.6%]) and primary care physicians (26 of 214 [12.1%]). After adjusting for the number of patients eligible to receive biologic DMARDs, rheumatologists' preferences (ie, yearly prescription rates) for using biologic DMARDs increased over time, from 1.7% in 2001 to 4.9% in 2015. After adjusting for calendar year and patient-, prescriber-, and region-level characteristics, substantial variation between prescribers in rates of prescribing a first biologic DMARD were found (65% variance). This study found variation in time to receipt of first biologic DMARD after prescription of first csDMARD in a population with RA after adjustment for individual-level patient, prescriber, and geographic area covariates, despite identical universal health insurance coverage.

Axillary lymph-node metabolic activity assessment on 18F-FDG-PET/CT in rheumatoid arthritis patients treated with biologic therapies

Objective: Recent studies have provided new insights into the role of lymph nodes (LNs) in rheumatoid arthritis (RA). The aim of this study was to evaluate the metabolic activity of the axillary LNs in relation to that of the upper limb joints and the clinical assessment of disease activity in RA patients treated with biologic therapies.Method: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) scans were acquired for 64 patients with RA at baseline and after 6 months of biologic therapy, and the patients’ clinical status was evaluated. The maximum standardized uptake value (SUVmax), metabolic active volume, and total lesion glycolysis (TLG) were used to assess glucose metabolism in the LNs and 12 joints. Clinical evaluations included serum markers and the Disease Activity Score based on 28-joint count–erythrocyte sedimentation rate (DAS28-ESR).Results: Changes in the SUVmax and TLG for the axillary LNs correlated significantly with those of the ipsilateral wrist joints. There was a positive correlation between the changes in the three metabolic parameters of the axillary LNs and the changes in disease activity after treatment. After 6 months of biologic therapy, all metabolic parameters for the axillary LNs in patients with a DAS28-ESR < 3.2 were significantly lower than those of patients with a DAS28-ESR ≥ 3.2.Conclusion: A relationship between the glucose metabolism of the axillary LNs and the ipsilateral wrist joints was demonstrated by the 18F-FDG-PET/CT parameters. The metabolic activity and active volume of axillary LNs may reflect the therapeutic response to the biologic treatment of RA.

Indicator opportunistic infections after biological treatment in rheumatoid arthritis, 10 years follow-up in a real-world setting.

Background:This research describes the incidence and factors associated with opportunistic infections in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs).Methods:A retrospective longitudinal study was carried out from 2007 to 2018. We included RA patients treated with a tumor necrosis factor (TNF)-targeted bDMARD or non-TNF-targeted bDMARD from the start of bDMARDs. An independent variable was the development of an indicator of opportunistic infection after biological (IOIb) treatment. Secondary variables included sociodemographic, clinical, and treatments. We used survival techniques to estimate the incidence of IOIb, per 1000 patient-years (95% CI). We performed a Cox multivariate regression analysis model to compare the risk of IOIb. Results were expressed as a hazard ratio (HR).Results:A total of 441 RA patients were included, that started 761 different courses of bDMARDs. A total of 81% were women with a mean age at first bDMARD of 57.3 ± 14 years. A total of 71.3% of the courses were TNF-targeted bDMARDs and 28.7% were non-TNF-targeted bDMARDs. There were 37 IOIb (25 viral, 6 fungal, 5 bacterial, 1 parasitic). Nine of these required hospitalization and one died. The global incidence of IOIb was 23.2 (16.8–32). TNF-targeted bDMARDs had 25 IOIb, incidence 20.5 (13.9–30.4), and non-TNF-targeted bDMARDs had 12 IOIb, incidence 31.7 (18–55.9). In the multivariate analysis, glucocorticosteroids (HR 2.17, p = 0.004) and lower lymphocyte count increased the risk for IOIb (HR 0.99, p = 0.005).Conclusions:The incidence of IOIb due to bDMARDs was 23 cases per 1000 patient-years. Close monitoring should be taken in the RA patients treated with bDMARDs and glucocorticosteroids, mainly in elderly patients and those with a low total lymphocyte count at the beginning of bDMARD treatment.

Biological treatment for rheumatoid arthritis: a review of the main approved monoclonal antibodies

Biological treatment for rheumatoid arthritis: a review of the main approved monoclonal antibodies

PMS29 - Consumption of Biologic Treatments for Rheumatoid Arthritis in the Brazilian Public Health System

PMS29 - Consumption of Biologic Treatments for Rheumatoid Arthritis in the Brazilian Public Health System

Biologic Treatment of Rheumatoid Arthritis, Current Status and Future Perspectives

Biologic Treatment of Rheumatoid Arthritis, Current Status and Future Perspectives

Persistence, switch rates, drug consumption and costs of biological treatment of rheumatoid arthritis: an observational study in Italy.

ObjectivesThe aim of this analysis was to provide an estimate of drug utilization indicators (persistence, switch rate and drug consumption) on biologics and the corresponding costs (drugs, admissions and specialist care) incurred by the Italian National Health Service in the management of adult patients with rheumatoid arthritis (RA).MethodsWe conducted an observational retrospective cohort analysis using the administrative databases of three local health units. We considered all patients aged ≥18 years with a diagnosis of RA and at least one biologic drug prescription between January 2010 and December 2012 (recruitment period). Persistence was defined as maintenance over the last 3 months of the follow-up period of the same biological therapy administered at the index date. A switch was defined as the presence of a biological therapy other than that administered at the index date during the last 3 months of the follow-up period. Hospital admissions (with a diagnosis of RA or other RA-related diagnoses), specialist outpatient services, instrumental diagnostics and pharmaceutical consumption were assessed.ResultsThe drug utilization analysis took into account only biologics with at least 90 patients on treatment at baseline (adalimumab n=144, etanercept n=236 and infliximab n=94). In each year, etanercept showed better persistence with initial treatment than adalimumab or infliximab. Etanercept was characterized by the lowest number of patients increasing the initial drug consumption (2.6%) and by the highest number of patients reducing the initial drug consumption (10.5%). The mean cost of treatment for a patient persisting with the initial treatment was €12,388 (€14,182 for adalimumab, €12,103 for etanercept and €11,002 for infliximab). The treatment costs for patients switching from initial treatment during the first year of follow-up were higher than for patients who did not switch (€12,710 vs. €11,332).ConclusionPersistence, switch rate and drug consumption seem to directly influence treatment costs. In subjects not persisting with initial treatment, other health care costs were approximately three times higher than for persistent patients. This difference could suggest a positive effect on the quality of life for persistent patients. Etanercept showed the highest persistence with treatment.

PMS26 - Tocilizumab Monotherapy As The First Line of Biological Treatment In Rheumatoid Arthritis: Budget Impact Analyses From The Perspective of Brazilian Public Healthcare System (SUS)

PMS26 - Tocilizumab Monotherapy As The First Line of Biological Treatment In Rheumatoid Arthritis: Budget Impact Analyses From The Perspective of Brazilian Public Healthcare System (SUS)

Personalized biological treatment for rheumatoid arthritis: a systematic review with a focus on clinical applicability.

To review studies that address prediction of response to biologic treatment in RA and to explore the clinical utility of the studied (bio)markers. A search for relevant articles was performed in PubMed, Embase and Cochrane databases. Studies that presented predictive values or in which these could be calculated were selected. The added value was determined by the added value on prior probability for each (bio)marker. Only an increase/decrease in chance of response ⩾15% was considered clinically relevant, whereas in oncology values >25% are common. Of the 57 eligible studies, 14 (bio)markers were studied in more than one cohort and an overview of the added predictive value of each marker is presented. Of the replicated predictors, none consistently showed an increase/decrease in probability of response ⩾15%. However, positivity of RF and ACPA in case of rituximab and the presence of the TNF-α promoter 308 GG genotype for TNF inhibitor therapy were consistently predictive, yet low in added predictive value. Besides these, 65 (bio)markers studied once showed remarkably high (but not validated) predictive values. We were unable to address clinically useful baseline (bio)markers for use in individually tailored treatment. Some predictors are consistently predictive, yet low in added predictive value, while several others are promising but await replication. The challenge now is to design studies to validate all explored and promising findings individually and in combination to make these (bio)markers relevant to clinical practice.

Biologics Prescribing for Rheumatoid Arthritis in Older Patients: A Single-Center Retrospective Cross-Sectional Study.

IntroductionAppropriate medical treatment can reduce the morbidity and mortality associated with rheumatoid arthritis (RA). Studies have shown that older patients with RA may be treated less aggressively than their younger counterparts, despite evidence suggesting that biologic treatments may be safe and efficacious in older age groups. The aim of this study was to assess whether patient age was associated with biologic treatment for RA in a single center in the United Kingdom.MethodsThis was a retrospective cross-sectional analysis of clinic records for all patients with RA reviewed over 1 year in our center. Data were also collected on healthcare use in patients aged 65 years and older as a surrogate marker of comorbidity.ResultsIn total, 856 patients with RA were identified, of which 22.8% were on biologic treatment. Patients on biologics were younger (mean age 58.9 years) compared to the mean age of all patients (61.4 years). Of patients aged less than 65 years, 27.2% were receiving biologic treatment, while only 15.2% of patients aged 65 years or older were on biologics. Increasing age was significantly associated with a lower likelihood of receiving biologic treatment. However, in patients 65 years or older, there was no significant difference in overall healthcare use between those on biologic treatment and those not. Patients treated with prednisolone were found to have a greater number of admissions.ConclusionIn our center, older patients are less likely to receive biologic treatment than younger patients. Among older patients we found no difference in healthcare use between those treated with biologics and those not, suggesting similar levels of comorbidity. Potential contributors are discussed, but further assessment is required to determine the reasons for this observation.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-015-0021-z) contains supplementary material, which is available to authorized users.

Projected Economic Impact of Increased Use of Biologic Treatments For Rheumatoid Arthritis In Argentina, Colombia, And Mexico Over 10 Years

Projected Economic Impact of Increased Use of Biologic Treatments For Rheumatoid Arthritis In Argentina, Colombia, And Mexico Over 10 Years

Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis

Serious infections are a major concern for patients considering treatments for rheumatoid arthritis. Evidence is inconsistent as to whether biological drugs are associated with an increased risk of serious infection compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did a systematic review and meta-analysis of serious infections in patients treated with biological drugs compared with those treated with traditional DMARDs. We did a systematic literature search with Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to Feb 11, 2014. Search terms included "biologics", "rheumatoid arthritis" and their synonyms. Trials were eligible for inclusion if they included any of the approved biological drugs and reported serious infections. We assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian network meta-analysis of published trials using a binomial likelihood model to assess the risk of serious infections in patients with rheumatoid arthritis who were treated with biological drugs, compared with those treated with traditional DMARDs. The odds ratio (OR) of serious infection was the primary measure of treatment effect and calculated 95% credible intervals using Markov Chain Monte Carlo methods. The systematic review identified 106 trials that reported serious infections and included patients with rheumatoid arthritis who received biological drugs. Compared with traditional DMARDs, standard-dose biological drugs (OR 1.31, 95% credible interval [CrI] 1.09-1.58) and high-dose biological drugs (1.90, 1.50-2.39) were associated with an increased risk of serious infections, although low-dose biological drugs (0.93, 0.65-1.33) were not. The risk was lower in patients who were methotrexate naive compared with traditional DMARD-experienced or anti-tumour necrosis factor biological drug-experienced patients. The absolute increase in the number of serious infections per 1000 patients treated each year ranged from six for standard-dose biological drugs to 55 for combination biological therapy, compared with traditional DMARDs. Standard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditional DMARDs, although low-dose biological drugs are not. Clinicians should discuss the balance between benefit and harm with the individual patient before starting biological treatment for rheumatoid arthritis. Rheumatology Division at the University of Alabama at Birmingham.

What is the best biological treatment for rheumatoid arthritis? A systematic review of effectiveness

What is the best biological treatment for rheumatoid arthritis? A systematic review of effectiveness