Biologic Therapy For Rheumatoid Arthritis Research Articles

Update of the Consensus Statement of the Spanish Society of Rheumatology on the use of biological and synthetic targeted therapies in rheumatoid arthritis

ObjectiveTo update the consensus document of the Spanish Society of Rheumatology (SER) regarding the use of targeted biological and synthetic therapies in rheumatoid arthritis (RA) with the aim of assisting clinicians in their therapeutic decisions. MethodsA panel of 13 experts was assembled through an open call by SER. We employed a mixed adaptation-elaboration-update methodology starting from the 2015 Consensus Document of the Spanish Society of Rheumatology on the use of biological therapies in RA. Starting with systematic reviews (SR) of recommendations from EULAR 2019, American College of Rheumatology 2021, and GUIPCAR 2017, we updated the search strategies for the PICO questions of GUIPCAR. An additional SR was conducted on demyelinating disease in relation to targeted biological and synthetic therapies. Following the analysis of evidence by different panelists, consensus on the wording and level of agreement for each recommendation was reached in a face-to-face meeting. ResultsThe panel established 5 general principles and 15 recommendations on the management of RA. These encompassed crucial aspects such as the importance of early treatment, therapeutic goals in RA, monitoring frequency, the use of glucocorticoids, the application of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs. Additionally, recommendations on dose reduction of these drugs in stable patients were included. This update also features recommendations on the use of bDMARDs and Janus Kinase inhibitors in some specific clinical situations, such as patients with lung disease, a history of cancer, heart failure, or demyelinating disease. ConclusionsThis update provides recommendations on key aspects in the management of RA using targeted biological and synthetic therapies.

Initial Treatment with Biological Therapy in Rheumatoid Arthritis.

We aimed to analyse the effectiveness, efficiency, and safety of initial treatment with biological therapies in rheumatoid arthritis (RA). Qualitative study. A group of RA experts was selected. A scoping review in Medline was conducted to analyse the evidence of initial RA treatment with biological therapies. Randomised clinical trials were selected. Two reviewers analysed the articles and compiled the data, whose quality was assessed using the Jadad scale. The experts discussed the review's findings and generated a series of general principles: Results: Seventeen studies were included. Most of the included patients were middle-aged women with early RA (1-7 months) and multiple poor prognostic factors. Initial treatment with TNF-alpha inhibitors combined with methotrexate (MTX) and an IL6R inhibitor (either in mono or combination therapy) is effective (activity, function, radiographic damage, quality of life), safe, and superior to MTX monotherapy in the short and medium term. In the long term, patients who received initial treatment with biologicals presented better results than those whose initial therapy was with MTX. Initial treatment of RA with biological therapies is effective, efficient, and safe in the short, medium, and long term, particularly for patients with poor prognostic factors.

Association between the functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to biologics in rheumatoid arthritis patients: A meta-analysis.

This study aimed to investigate the association between functional Fc gamma receptor 3A (FCGR3A) V158F and FCGR2A R131H polymorphisms and biologic therapy in rheumatoid arthritis (RA) patients. We searched Medline, Embase, and Cochran databases for available articles. This study is a meta-analysis of the association between the FCGR3A V158F and FCGR2A R131H polymorphisms and their responsiveness to biologics in RA patients. Seventeen studies involving RA patients with FCGR3A V158F (n = 1884) and FCGR2A R131H (n = 1118) polymorphisms were considered. This meta-analysis showed that the FCGR3A V allele was associated with responsiveness to rituximab (odds ratio [OR] = 1.431, 95% CI = 1.081-1.894, P = 0.012), but not with tumor necrosis factor (TNF) blockers, tocilizumab, or abatacept. A significant association was also found between the FCGR3A V158F polymorphism and responsiveness to biologics using the dominant-recessive model. Additionally, the FCGR3A V158F polymorphism was associated with responsiveness to TNF blockers in the homozygous contrast model. Meta-analysis revealed an association between the FCGR2A RR + RH genotype and responsiveness to biologics (OR = 1.385, 95% CI = 1.007-1.904, P = 0.045). This meta-analysis demonstrates that FCGR3A V allele carriers show better responsiveness to rituximab, and FCGR2A R allele carriers may show a better response to biologics in RA treatment. Genotyping of these polymorphisms could be a useful tool to find associations with the responsiveness of personalized medicine to biologics.

Biological therapy in rheumatoid arthritis: A review of adverse reactions

IntroductionThe relationship between adverse events and the application of biological drugs in patients with a diagnosis of rheumatoid arthritis has been documented worldwide, but with little evidence of the situation in Colombia. If adverse events and/or drug reactions with relevant clinical findings in health because of this therapeutic treatment affect the patient's quality of life and influence health indicators at the national level and system resources, it is important to assess their impact. ObjectivesTo determine the frequency of adverse events and/or adverse reactions related to the use of biological drugs in a cohort of patients diagnosed with rheumatoid arthritis from a national insurer, in the period from 2000 to 2019. MethodologyA descriptive, cross-sectional, and retrospective study with analytical scope was carried out in patients diagnosed with rheumatoid arthritis, on biological therapy, under a nationwide insurer, with records in their medical records from 2000 to 2019. Results252 clinical records of users with a rheumatoid arthritis diagnosis and biological therapy were analysed; 62.7% had at least one adverse reaction; nine drugs were evaluated in this study: Tocilizumab, Etanercept, Adalimumab, Abatacept, Certolizumab, Golimumab, Infliximab, Rituximab, and Tofacitinib. Tofacitinib was included in this study at the request of the insurer providing the information. ConclusionsAdverse reactions with biological therapy in patients with rheumatoid arthritis are frequent and were severe in 27.3%. This is a situation previously unknown in Colombia.

Usage of Biological Therapy in Rheumatoid Arthritis Patients with Chronic Renal Failure: A Retrospective Study from a Single Center

Kronik böbrek hastalığı (KBH) olan romatoid artrit (RA) hastalarında, potansiyel toksisiteleri nedeniyle hastalığı modifiye edici antiromatizmal ilaçların (DMARD) çoğunu ve steroid olmayan antiinflamatuar ilaçları (NSAİİ) kullanmak uygun değildir. Biyolojik DMARD'lar RA hastaları için oldukça etkili bir tedavi seçeneği olsa da böbrek fonksiyonları üzerindeki etkisi ve güvenilirliği tam olarak belirlenememiştir. KBH’si olan RA’lı hastalarda biyolojik tedavilerin kullanımına ilişkin veriler kısıtlıdır. 2011-2018 yılları arasında RA tanısı ile takip ettiğimiz, biyolojik ajan kullanan ve düzenli vizitleri bulunan 700 hasta arasından tahmini glomerüler filtrasyon hızı (eGFR) üç aydan uzun süredir

Drug-survival profiling of second-line biologic therapy in rheumatoid arthritis: Choice of another tumour necrosis factor inhibitor or a biologic of different mode of action?

To assess the best choice of second-line therapy between tumour necrosis factor-inhibitor (TNFi) and biologics of different-mode-of-action (BDMA-rituximab/tocilizumab/abatacept) in rheumatoid arthritis (RA) by evaluating drug-survival following discontinuation of the first-line TNFi. This retrospective drug-survival study was performed across two different hospitals by conventional-statistics and machine-learning approach. From a total of 435 patients, 213 (48.9%; TNFi = 122, BDMA = 91) discontinued their second-line biologic {median drug-survival: TNFi, 27 months [95% confidence interval (95%CI) 22-32] vs BDMA, 37 months (95%CI 32-52)}. As a second-line biologic, BDMA was likely to reduce the risk of treatment-discontinuation [hazard-ratio (HR) 0.63, 95%CI 0.48-0.83] compared to TNFi, but only in seropositive-patients (HR 0.52, 95%CI 0.38-0.73), not in seronegative-RA. Drug-survival benefit of BDMA over TNFi was not observed if the seropositive-patients were previously exposed to monoclonal-TNFi (HR 0.77, 95%CI 0.49-1.22) versus soluble-TNFi (etanercept/biosimilars) or if the first-line TNFi was terminated within 23.9 months of initiation (HR 0.97, 95%CI 0.56-1.68). BDMA, as a second-line biologic, is more likely to be sustained in seropositive-patients, particularly without prior exposure to monoclonal-TNFi. The drug-survival benefit of BDMA was not observed in seronegative-patients or if the first-line TNFi was stopped within 2 years.

Obesity and Response to Advanced Therapies in Rheumatoid Arthritis.

We performed a study of tumor necrosis factor inhibitors (TNFi) compared to non-TNFi biologic therapies in rheumatoid arthritis to test whether body mass index (BMI) modified the effect of each therapy. We utilized data from CorEvitas. We studied 3 clinical outcomes based on the Clinical Disease Activity Index (CDAI) at 6 months from therapy initiation: 1) achievement of low disease activity (LDA); 2) a change as large as the minimum clinically important difference (MCID); and 3) the absolute change. We categorized BMI and utilized restricted cubic splines to consider nonlinear associations. We used linear and logistic regression to evaluate associations with response, adjusting for confounders. To determine if comparative effectiveness of therapy varied by BMI, we tested for interactions between BMI and class of therapy. The sample included 2,891 TNFi and 3,010 non-TNFi initiators. Among all initiators, those with severe obesity experienced lower odds of achieving LDA or MCID and less improvement in CDAI score, although associations were attenuated with adjustment. Low BMI was associated with reduced response rates in adjusted models including lower odds of LDA (odds ratio 0.32 [95% confidence interval (95% CI) 0.15, 0.71], P=0.005). Analyses stratified by TNFi and non-TNFi therapies demonstrated no differences in clinical response rates for TNFi versus non-TNFi across BMI categories (all P for interaction >0.05). Estimates for non-TNFi biologics fit within the 95% CI for TNFi. This study observed lower response rates among obese and underweight patients and no evidence of a superior effect of non-TNFi therapy over TNFi therapy in particular BMI categories.

Bridging disconnected networks of first and second lines of biologic therapies in rheumatoid arthritis with registry data: bayesian evidence synthesis with target trial emulation

ObjectivesWe aim to use real-world data in evidence synthesis to optimize an evidence base for the effectiveness of biologic therapies in rheumatoid arthritis to allow for evidence on first-line therapies to inform second-line effectiveness estimates. Study Design and SettingWe use data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis to supplement randomized controlled trials evidence obtained from the literature, by emulating target trials of treatment sequences to estimate treatment effects in each line of therapy. Treatment effects estimates from the target trials inform a bivariate network meta-analysis (NMA) of first-line and second-line treatments. ResultsSummary data were obtained from 21 trials of biologic therapies including two for second-line treatment and results from six emulated target trials of both treatment lines. Bivariate NMA resulted in a decrease in uncertainty around the effectiveness estimates of the second-line therapies, when compared to the results of univariate NMA, and allowed for predictions of treatment effects not evaluated in second-line randomized controlled trials. ConclusionBivariate NMA provides effectiveness estimates for all treatments in first and second line, including predicted effects in second line where these estimates did not exist in the data. This novel methodology may have further applications; for example, for bridging networks of trials in children and adults.

Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: optimising treatment outcomes.

Anti-tumour necrosis factors (anti-TNFs) are established as first-line biological therapy for rheumatoid arthritis (RA) with over two decades of accumulated clinical experience. Anti-TNFs have well established efficacy/safety profiles along with additional benefits on various comorbidities. However, up to 40% of patients may respond inadequately to an initial anti-TNF treatment because of primary non-response, loss of response, or intolerance. Following inadequate response (IR) to anti-TNF treatment, clinicians can consider switching to an alternative anti-TNF (cycling) or to another class of targeted drug with a different mechanism of action, such as Janus kinase inhibitors, interleukin-6 receptor blockers, B-cell depletion agents, and co-stimulation inhibitors (swapping). While European League Against Rheumatism recommendations for pharmacotherapeutic management of RA, published in 2020, are widely regarded as helpful guides to clinical practice, they do not provide any clear recommendations on therapeutic choices following an IR to first-line anti-TNF. This suggests that both cycling and swapping treatment strategies are of equal value, but that the treating physician must take the patient’s individual characteristics into account. This article considers which patient characteristics influence clinical decision-making processes, including the reason for treatment failure, previous therapies, comorbidities, extra-articular manifestations, pregnancy, patient preference and cost-effectiveness, and what evidence is available to support decisions made by the physician.

Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass index and adipose tissue cytokines.

To analyse the role of body mass index (BMI) in the clinical response to biologic dis-ease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). To per-form an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment. This study involved 105 patients with RA starting tumour necrosis factor inhibitors (TNFi) or tocilizumab (TCZ). Patients were classified ac-cording to BMI as normal-weight and overweight/obesity. The clinical response to treatment was as-sessed by Clinical Disease Activity Index (CDAI) 6 months after initiation of bDMARDs. Serum adi-pokines (leptin and adiponectin) were determined using a commercial immunoassay kit in samples ob-tained before initiation of bDMARDs and after 6 months of treatment. A correlation was observed between BMI and disease activity and between BMI and serum adipokines. Sixty percent of patients achieved low disease activity (LDA)/remission: 45 patients in TNFi group (64.2%) and 18 (51.4%) in TCZ group. In TNFi group, patients who did not attain LDA/remission had a higher BMI (kg/m2) ([28.7±5.1] vs. [24.5±4.6], p=0.001) and baseline CDAI (26.3 [17.4-33.9] vs. 19.8 [14.0-28.8], p<0.03). However, no differences in BMI or baseline CDAI were observed between patients who achieved LDA after 6 months in TCZ group. Obesity influences the extent of LDA/remission in patients treated with TNFi, but not in patients treated with TCZ, probably because of underlying pathophysiological mechanisms intrinsic to the production of proinflammatory adi-pokines. Therefore, therapeutic strategies with a mechanism of action other than TNF inhibition would be more suitable for obese patients.

Clinical phenotype with high risk for initiation of biologic therapy in rheumatoid arthritis: a data-driven cluster analysis.

The clinical manifestations and treatment outcome in patients with rheumatoid arthritis (RA) are heterogeneous. We classified RA patients into subgroups with distinct phenotypes through unsupervised clustering and evaluated the utility of this subclassification for evaluation of clinical outcome. A total of 1,103 patients with RA were clustered in an unbiased manner using a k-means clustering method, based on their clinical and phenotypic profiles. Initiation of biological disease-modifying anti-rheumatic drugs (bDMARDs) was evaluated in the segregated clusters to investigate the differential clinical course of each cluster. Patients with RA were classified into four clusters, each with distinct phenotypes. The key features for subclassification were sex, smoking, hypertension, and dyslipidaemia. Cluster 1 consisted of male smokers, who were most likely to initiate bDMARDs by 30 months (p=0.04). Multivariate analysis revealed that overweight, smoking, erythrocyte sedimentation rate, autoantibodies of high titre, and disease activity were the independent predictors of bDMARD initiation at 30 months. Cluster 1 was the highest or the second highest for these independent predictors, suggesting that cluster 1 contained a high-risk group for early initiation of bDMARDs. The unsupervised clustering of RA patients demonstrated the feasibility of the novel subclassification with respect to predicting clinical outcome. Identifying high-risk patients by a combination of clinical parameters may be useful for the management of RA.

One-year direct costs of biological therapy in rheumatoid arthritis and its predictive factors: data from the Moroccan RBSMR registry.

The aim of the study was to estimate the annual direct costs of biological therapies in rheumatoid arthritis (RA), and to establish possible factors associated with those costs. The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR Registry). We included patients with available 1-year data. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Differences in costs across groups were tested by Mann-Whitney and Kruskal-Wallis tests. Correlations analysis was performed in search of factors associated with high costs. We included 197 rheumatoid arthritis patients. The mean age was 52.3 ± 11years, with female predominance 86.8%. Receiving one of the following therapies: rituximab (n = 132), tocilizumab (n = 37), or TNF-blockers (n = 28). Median one-year direct costs per patient were €1665 [€1472-€9879]. The total annual direct costs were € 978,494. Rituximab, constituted 25.7% of the total annual budget. TNF-blockers and tocilizumab represented 27.3% and 47% of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. A positive correlation was found between the annual direct cost and body mass index (r = 0.15, p = 0.04). In Morocco, a developing country, the annual direct costs of biological therapy are high. Our results may contribute to the development of strategies for better governance of these costs.

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.

E. COLI PNEUMONIA WITH PNEUMATOCELE, EMPYEMA NECESSITANS, AND BRONCHOPLEURAL FISTULA IN A PATIENT WITH SEVERE COVID-19

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Tocilizumab, an interleukin-6 inhibitor used in rheumatologic disease and cytokine release syndrome, is one of many investigational drugs used for coronavirus disease-19 pneumonia (COVID). While the safety profile has been well studied, there is little known about its effect on opportunistic infections (OI) risk in patients with COVID. We present a 43-year-old man with COVID who received tocilizumab and subsequently developed cavitating lung lesions suspicious for invasive aspergillosis. CASE PRESENTATION: A 43-year-old man with diabetes mellitus was admitted for hypoxemic respiratory failure (HRF). Nasopharyngeal swab polymerase chain reaction was positive for COVID. He was placed on high-flow nasal cannula (HFNC), and on day 10 he was intubated for worsening HRF. He was treated with ceftriaxone, azithromycin, methylprednisolone, convalescent plasma, and tocilizumab. Antibiotics later included ertapenem due to E. coli with extended-spectrum beta lactamase (ESBL) found in sputum culture. He was extubated on day 15 and oxygen requirements were weaned to HFNC. However, bronchial aspirate cultures from day 14 grew mold and subsequent serologies were positive for Aspergillus. Chest computerized tomography (CT) was notable for the development of multiple new cavitary lesions concerning for invasive pulmonary aspergillosis. The patient was initially treated with voriconazole and later with amphotericin B due to liver enzyme elevation. The patient’s oxygen requirements initially decreased, however on day 30 the patient suffered an aspiration event and was reintubated. Subsequent CT was concerning for worsening of cavitary lung disease. Bronchoalveolar lavage was collected, which tested positive for Aspergillus galactomannan. On hospital day 31, the patient suffered a left-sided tension pneumothorax requiring tube thoracostomy. At the time of submission the patient remains critically ill. DISCUSSION: Influenza-associated pulmonary aspergillosis (IAPA) is a known complication of severe influenza.1,2 Similarly, COVID-associated pulmonary aspergillosis (CAPA) may become an emerging problem given the overwhelming inflammation and use of experimental immunosuppressive therapies in COVID.1,2 While tocilizumab has not been shown to increase risk of Aspergillus infection in rheumatologic disease, it has not been studied in COVID and the risk of OI in an already-susceptible group may outweigh the benefits of using this drug in patients with COVID.3 If CAPA is similar to IAPA, BAL galactomannan is the gold standard for diagnosis.2 CONCLUSIONS: As the medical community searches for COVID treatments, these patients’ potentially inherent vulnerability to OI may be under-appreciated. When using immunosuppressive agents to curtail the inflammatory cascade, the risk of OI must be considered and agents like tocilizumab must be further studied in this context. Reference #1: Koehler P, Cornely OA, Böttiger BW, et al. COVID-19 associated pulmonary aspergillosis. Mycoses. 2020;63(6):528-534. Reference #2: van Arkel ALE, Rijpstra TA, Belderbos HNA, van Wijngaarden P, Verweij PE, Bentvelsen RG. COVID-19 associated pulmonary aspergillosis. Am J Respir Crit Care Med. 2020;online May 2020. Reference #3: Kourbeti IS, Ziakas PD, Mylonakis E. Biologic therapies in rheumatoid arthritis and the risk of opportunistic infections: a meta-analysis. Clin Infect Dis. 2014;58(12):1649-57. DISCLOSURES: No relevant relationships by Michael Kahn, source=Web Response No relevant relationships by Nader Kamangar, source=Web Response No relevant relationships by Jay Thetford, source=Web Response No relevant relationships by Richard Watson, source=Web Response

Biologic therapies for systemic lupus erythematosus: where are we now?

Conventional approaches using hydroxychloroquine, corticosteroids and immunosuppressives have improved the prognosis for systemic lupus erythematosus (SLE) patients. Unfortunately, they have reached the limits of what they can achieve and patients still die prematurely and/or find their quality of life greatly impaired. Here, we discuss the problems of assessing activity in SLE, optimizing clinical trial design and more recent biologic approaches. The success of B-cell depletion using Rituximab in open clinical studies, the approval of Belimumab (blocks the B-cell activating factor BAFF) and improvements in clinical trial design, gives cause for hope. Approaches including the use of fully humanized anti-CD20 and CD19 monoclonals, blocking interferons, inhibiting Bruton's tyrosine kinase (BTK), blocking the CD40 ligand (CD40L), utilizing an analogue of the Fc[Latin Small Letter Gamma]RIIB and an IL12-23 blocker and targeting the JAK-STAT pathway have met end points in phase II and III trials. For 20 years, we hoped that the successes of the biologic therapies in rheumatoid arthritis and psoriatic arthritis would be replicated in SLE but we have been generally disappointed. However, the encouraging recent results with monoclonals that block interferon and fully humanized anti-CD20 in particular, offer the prospect of a real revolution in the treatment of SLE.

Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.

Author(s): Gianfrancesco, Milena A; Hyrich, Kimme L; Gossec, Laure; Strangfeld, Anja; Carmona, Loreto; Mateus, Elsa F; Sufka, Paul; Grainger, Rebecca; Wallace, Zachary; Bhana, Suleman; Sirotich, Emily; Liew, Jean; Hausmann, Jonathan S; Costello, Wendy; Robinson, Philip; Machado, Pedro M; Yazdany, Jinoos; COVID-19 Global Rheumatology Alliance Steering Committee

Low but Long-lasting Risk of Reversal of Seroconversion in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy

In patients who have resolved hepatitis B virus (HBV) infection, treatment of rheumatoid arthritis (RA) can result in reappearance of hepatitis B surface antigen (HBsAg), called reverse seroconversion. We investigated clinical features and outcomes of reverse seroconversion in patients who received immunosuppressant or biologic therapy for RA. We identified 1494 patients with RA (925 who resolved HBV infection) and available data on levels of antibody to HB core antigen and HBsAg who had attended Taipei Veterans General Hospital from January 2007 through December 2017. We identified 17 cases (median age, 66 years) who were negative for HBsAg before treatment of RA and reverse seroconversion (HBsAg reappearance) after glucocorticoid treatment (n = 13) and/or biologic therapy (adalimumab, n= 2; etanercept, n = 1; rituximab, n = 9; or abatacept, n = 4). Four patients were positive for antibodies against HBsAg (seroconverted) before the immunosuppressive treatment. The median time from immunosuppressive treatment to reverse seroconversion was 120 months (range, 20-264 months), whereas the time from biologic therapy treatment to reverse seroconversion was 66 months (range, 10-105 months). After reverse seroconversion, 8 individuals (47.1%) were positive for HB e antigen; 9 cases (52.9%) did not have a flare of alanine transaminase. However, 3 patients (17.6%) developed liver decompensation. In patients who resolved HBV infection and received immunosuppressant treatment of RA, risk of reversal of seroconversion is low but persists for up to 10 years. Patients with RA who previously resolved HBV infections should be monitored for levels of HBsAg and HBV DNA once immunosuppressive treatment of RA begins.

Predictors of presenteeism, absenteeism and job loss in patients commencing methotrexate or biologic therapy for rheumatoid arthritis.

ObjectivesWork is an important health outcome. This study aimed to identify predictors of work loss, absenteeism and presenteeism over 1 year in RA patients commencing treatment with MTX or biologics.MethodsPatients aged 18–65 years in full/part-time employment from two UK prospective cohorts were included: MTX-starters = Rheumatoid Arthritis Medication Study; and biologic-starters = Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate. Presenteeism and absenteeism were assessed using the RA-specific Work Productivity Survey at baseline, and 6 and 12 months. Potential predictors including baseline age, gender, clinical measures (e.g. disability, pain, fatigue), psychological distress, occupation and EULAR response from baseline to 6 months were investigated.ResultsA total of 51/463 MTX-starters and 30/260 biologic-starters left work over 12 months. Higher baseline psychological distress in MTX-starters [odds ratio (OR) 1.1 (95% CI: 1.0, 1.1)] and higher disability in biologic-starters [OR 3.5 (95% CI: 1.4, 8.6)] predicted work loss. Some 16.1% of patients reported sick-leave, which was predicted by disability [OR (95% CI): MTX-starters: 1.5 (0.9, 2.3); biologic-starters: 2.4 (1.1, 5.2)]. Median presenteeism scores were very low (minimal interference) in both cohorts. Higher fatigue for MTX starters [incidence rate ratio 1.2 (95% CI: 1.0, 1.4)] and higher disability in biologic-starters (incidence rate ratio 1.4 (95% CI: 1.1, 1.7)] predicted presenteeism. Good EULAR response was associated with lower absenteeism and presenteeism in both cohorts.ConclusionPatients with RA still face significant limitations regarding their ability to work. Disability and EULAR response were the main predictors of work outcomes, emphasizing the need to control the disease and the importance of function in enabling work participation.

Biologic monotherapy in the biologic na\xefve patient with rheumatoid arthritis (RA): results from an observational study

Approximately one-third of patients on biologic therapy for rheumatoid arthritis (RA) receive them as monotherapy. There are few head-to-head randomised control trials comparing biologics as monotherapy. Our aim was to compare the efficacy and persistence of multimodal biologic agents as monotherapy in biologic naïve patients with RA in the real-world setting. A multicentre retrospective observational study was carried out comparing TNF inhibitors (TNFi), IL6 receptor inhibitor (IL6Ri) and CTLA-4 inhibitor (CTLA-4i) monotherapy in biologic naïve RA patients. The primary study outcome was DAS28 score at 6, 12, and 18 months. 126 patients were enrolled; 98 patients (78%) were taking TNFi, 19 patients (15%) IL6Ri and 10 (8%) CTLA-4i with similar baseline characteristics of sex and age across groups. Patients in the CTLA-4i group were more often seropositive and had greater numbers of comorbidities. At 6 and 12 months, patients in the IL6Ri group had a lower DAS28 score compared to TNFi monotherapy. Those on CTLA-4i monotherapy also had a lower DAS28 score at 6 months than the TNFi group, although differences were lost by 12 months. Drug retention at 18 months was highest in the IL6Ri arm (68%) and CTLA-4i arm (80%) compared with only 55% in the TNFi group. Our findings support current guidance that IL6Ri should be considered in biologic naïve patients requiring biologic monotherapy, but also indicated that CTLA-4i could be an option.

Surgical Treatment of Fracture during Biologic Therapy for Rheumatoid Arthritis : Report of Three Cases

Surgical Treatment of Fracture during Biologic Therapy for Rheumatoid Arthritis : Report of Three Cases