Objectives
A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety.
Methods
Literature searches ...were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn’s disease, and ulcerative colitis.
Results
Of >21,000 screened publications, 443 were included. Anti-drug antibody (ADAb) rates varied widely among biologics across diseases (and are not directly comparable because of immunoassay heterogeneity); the highest overall rates were reported with infliximab (0–83%), adalimumab (0–54%), and infliximab biosimilar CT-P13 (21–52%), and the lowest with secukinumab (0–1%), ustekinumab (1–11%), etanercept (0–13%), and golimumab (0–19%). Most ADAbs were neutralizing, except those to abatacept and etanercept. ADAb+ versus ADAb− patients had lower rates of clinical response to adalimumab (RA, PsA, JIA, AS, Ps), golimumab (RA), infliximab (RA, PsA, AS, Ps), rituximab (RA), ustekinumab (Ps), and CT-P13 (RA, AS). Higher rates of infusion-related reactions were reported in infliximab- and CT-P13-treated ADAb+ patients. Background immunosuppressives/anti-proliferatives reduced biologic immunogenicity across diseases.
Conclusions
Based on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab. As ADAb formation in biologic-/biosimilar-treated patients may increase the risk of lost response, the immunogenicity of these agents is an important (albeit not the only) consideration in the treatment decision-making process.
Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients ...experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians.
This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure.
This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients).
A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS < 1.2 after 6 months of the first bDMARD (OR 11.12; 95% CI 3.34-26.82) were independently associated with being MR-patients to bDMARDs.
In our cohort, 10% of patients with RA were observed to have multi-refractoriness to bDMARDs. This study supports the contention that younger patients with erosive disease and especially the early absence of clinical response to the first bDMARDs are predictors of multi-refractoriness to consecutive biologics. Hence, patients with these characteristics should be monitored more closely and may benefit from personalized treatments.
The initial management of rheumatoid arthritis (RA) has a high impact on disease prognosis. Therefore, we need to select the most appropriate treatment as soon as possible. This goal requires ...biomarkers of disease severity and prognosis. One such biomarker may be the presence of anti-carbamylated protein antibodies (ACarPA) because it is associated with adverse long term outcomes as radiographic damage and mortality. Here, we have assessed the ACarPA as short-term prognostic biomarkers. The study was conducted in 978 prospective early arthritis (EA) patients that were followed for two years. Our results show the association of ACarPA with increased levels of all the disease activity measures in the first visit after arthritis onset. However, the associations were more significant with the high levels in local measures of inflammation and physician assessment than with the increases in systemic inflammation and patient-reported outcomes. More notably, disease activity was persistently increased in the ACarPA positive patients during the two years of follow-up. These differences were significant even after accounting for the presence of other RA autoantibodies. Therefore, the ACarPA could be considered short-term prognostic biomarkers of increased disease activity in the EA patients.
Abstract
Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell ...activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum B-cell activating factor (BAFF) with immunogenicity after 6 months of TNFi treatment. A total of 127 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association. At 6 months, 31 patients (24%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value = 5.30; p = 0.02); therefore, subsequent results were stratified according to mean age (≤ / > 55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR = 1.51; 95% CI 1.03–2.21). Baseline serum BAFF ≥ 1034 pg/mL predicted the presence of ADA at 6 months (AUC = 0.81; 95% confidence interval (CI) 0.69–0.93; p = 0.001; positive likelihood ratio = 3.7). In conclusion, our results suggest that the association of BAFF concentration and immunogenicity depends on the patient’s age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.
Methotrexate (MTX) is a remarkable drug with a key role in the management of rheumatoid arthritis (RA) at every stage of its evolution. Its attributes include good overall efficacy for signs and ...symptoms, inhibition of structural damage and preservation of function with acceptable and manageable safety, a large dose-titratable range, options for either an oral or parenteral route of administration, and currently unrivalled cost-effectiveness. It has a place as a monotherapy and also as an anchor drug that can be safely used in combination with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or used concomitantly with biological DMARDs or targeted synthetic DMARDs. MTX is not without potential issues regarding toxicity, notably hepatotoxicity and bone marrow toxicity, as well as tolerability problems for some, but not all, patients. But many of these issues can be mitigated or managed. In the face of a welcome expansion in available targeted therapies for the treatment of RA, MTX looks set to remain at the foundation of pharmacotherapy for the majority of people living with RA and other inflammatory rheumatic diseases. In this article, we provide an evidence-based discussion as to how to achieve the best outcomes with this versatile drug in the context of a treat-to-target strategy for the management of RA.
Background:
Despite advances in the treatment of rheumatoid arthritis (RA) and the wide range of therapies available, there is a percentage of patients whose treatment presents a challenge for ...clinicians due to lack of response to multiple biologic and target-specific disease-modifying antirheumatic drugs (b/tsDMARDs).
Objective:
To develop and validate an algorithm to predict multiple failure to biological therapy in patients with RA.
Design:
Observational retrospective study involving subjects from a cohort of patients with RA receiving b/tsDMARDs.
Methods:
Based on the number of prior failures to b/tsDMARDs, patients were classified as either multi-refractory (MR) or non-refractory (NR). Patient characteristics were considered in the statistical analysis to design the predictive model, selecting those variables with a predictive capability. A decision algorithm known as ‘classification and regression tree’ (CART) was developed to create a prediction model of multi-drug resistance. Performance of the prediction algorithm was evaluated in an external independent cohort using area under the curve (AUC).
Results:
A total of 136 patients were included: 51 MR and 85 NR. The CART model was able to predict multiple failures to b/tsDMARDs using disease activity score-28 (DAS-28) values at 6 months after the start time of the initial b/tsDMARD, as well as DAS-28 improvement in the first 6 months and baseline DAS-28. The CART model showed a capability to correctly classify 94.1% NR and 87.5% MR patients with a sensitivity = 0.88, a specificity = 0.94, and an AUC = 0.89 (95% CI: 0.74–1.00). In the external validation cohort, 35 MR and 47 NR patients were included. The AUC value for the CART model in this cohort was 0.82 (95% CI: 0.73–0.9).
Conclusion:
Our model correctly classified NR and MR patients based on simple measurements available in routine clinical practice, which provides the possibility to characterize and individualize patient treatments during early stages.
This article presents a review of the current approach to diagnostic and therapeutic conditions of septic arthritis. Acute septic arthritis is an uncommon, but potentially fatal, emergency. Early ...diagnosis as well as prompt and effective treatment are essential to avoid either irreversible joint destruction or even death. The clinical features of this condition are different in neonates, children and adults. The definitive diagnosis of septic arthritis requires the direct demonstration of bacteria in synovial fluid or on positive culture of the pathogen. A combination of antibiotics and the prompt removal of purulent material from the affected joint constitutes the mainstay of successful treatment. In addition, this article discusses, in particular, prosthetic joint infection and gonococcal arthritis.
Comorbidities in patients with rheumatoid arthritis (RA) are often associated with poor health outcomes and increased mortality. Treatment decisions should take into account these comorbidities due ...to known or suspected associations with certain drug classes. In clinical practice, it is critical to balance potential treatment benefit against the possible risks for comorbidities as well as the articular manifestations of RA. This review summarises the current literature relating to prevalence and risk factors for the important comorbidities of cardiovascular disease, infections, lymphomas and nonmelanoma skin cancers in patients with RA. The impact on patient outcomes and the interplay between these comorbidities and the therapeutic options currently available, including tumour necrosis factor inhibitors and newer biological therapies, are also explored. As newer RA therapies are developed, and patients gain wider and earlier access to advanced therapies, in part due to the emergence of biosimilars, it is important to consider the prevention or treatment of comorbidities as part of the overall management of RA.
The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria. These criteria ...involve stratification on antibody levels, which limits reproducibility, and underperform in the RA patients without RF and anti-CCP. Here, we have explored if two anti-acetylated peptide antibodies (AAPA), anti-acetylated lysine (AcLys) and anti-acetylated ornithine (AcOrn), could improve the performance of the current criteria. The analysis was done in 1062 prospectively-followed early arthritis (EA) patients. The anti-AcOrn were more informative than the anti-AcLys, the conventional RA antibodies and the anti-carbamylated protein antibodies. The anti-AcOrn produced a classification that did not require antibody levels and showed improved specificity (77.6% vs. 72.6%, p = 0.003) and accuracy (79.0% vs. 75.8%, p = 0.002) over the current criteria. These improvements were obtained with a scoring system that values concordance between anti-AcOrn, RF and anti-CCP. No significant gain was obtained in sensitivity (80.2% vs. 78.8%, p = 0.25) or in improving the classification of the RA patients lacking RF and anti-CCP, although the anti-AcOrn ranked first among the analysed new antibodies. Therefore, the anti-AcOrn antibodies could contribute to the improvement of RA classification criteria by exploiting antibody concordance.
Abstract Introduction From Occupational Therapy, social participation is considered one of the areas of vital importance in the lives of people with schizophrenia. Therefore, when there is a ...limitation in participation in this occupational area, it is necessary to generate intervention strategies that favor and enable access to them. Objectives Know the effectiveness of different interventions in the occupational area "social participation" in users with schizophrenia. Method A bibliographic search was carried out in three databases in the health and social field: Pubmed, Scopus and Web of Science. The inclusion criteria for the selection of articles were: People between 18 and 65 years old with a diagnosis of schizophrenia, published in the last 10 years in English, Spanish and Portuguese, excluding opinion articles and articles with less than 10 participants in the intervention. A total of 13 studies were selected. All papers were evaluated according to a cheklist. Results The most effective intervention has been the ACT, with results of; improvement in symptomatic remission of 43.98 pints, comparing with control group; in terms of hospital readmissions, 19.05%; Regarding social functionality, it has had an improvement of 11.36 points; Finally, regarding the quality of life, there has been an improvement of 1.40 points. Conclusions Social participation is essential in the psychosocial rehabilitation process of a user with schizophrenia. Assertive Community Treatment (ACT) has shown significantly better results compared to Community-Based Rehabilitation (CBR). We must take the results obtained with caution due to the study’s limitations, where the little scientific evidence available on this subject stands out.
Resumo Introdução A participação social é considerada uma das áreas ocupacionais de vital importância na vida das pessoas com esquizofrenia. Por isso, quando há uma limitação nessa área ocupacional, é necessário gerar estratégias de intervenção que favoreçam e possibilitem o acesso a elas. Objetivos Conhecer a eficácia de diferentes intervenções de participação social em usuários com esquizofrenia. Método Foi realizada uma pesquisa bibliográfica em três bases de dados no âmbito das ciências sociais e de saúde: Pubmed, Scopus e Web of Science. Os critérios de inclusão foram: adultos com diagnóstico de esquizofrenia, estudos experimentais publicados nos últimos 10 anos em inglês, espanhol e português, excluindo artigos de opinião e aqueles realizados com menos de 10 participantes. Um total de 13 estudos foi selecionado. Todos os trabalhos foram avaliados de acordo com um checklist. Resultados A intervenção mais eficaz tem sido o Assertive Community Treatment (ACT), com resultados de melhora na remissão sintomática de 43,98 pontos em comparação quanto ao grupo controle; enquanto as reinternações hospitalares, 19,05%; quanto à funcionalidade social, teve uma melhora de 11,36 pontos. Por fim, em relação à qualidade de vida, houve uma melhora de 1,40 pontos. Conclusões A participação social é essencial no processo de reabilitação psicossocial de um usuário com esquizofrenia. O ACT mostrou resultados significativamente melhores em comparação com o Community-Based Rehabilitation (CBR). Devemos tomar os resultados obtidos com cautela devido às limitações deste estudo, onde se destaca a pouca evidência científica disponível sobre o assunto.
Resumen Introducción La participación social es considerada una de las áreas ocupacionales de vital importancia en las vidas de las personas con esquizofrenia. Por ello, cuando existe una limitación en esta área ocupacional es necesario generar estrategias de intervención que favorezcan y posibiliten el acceso a las mismas. Objetivos Conocer la efectividad de diferentes intervenciones en la participación social en usuarios con esquizofrenia. Método Se realizó una búsqueda bibliográfica en tres bases de datos de ámbito sanitario y social: Pubmed, Scopus y Web of Science Los criterios de inclusión fueron: adultos diagnosticados de esquizofrenia, estudios experimentales publicados en los últimos 10 años en inglés, castellano y portugués excluyendo los artículos de opinión y con menos de 10 participantes. Se seleccionaron un total de 13 estudios. Todos los trabajos fueron evaluados de acuerdo a un checklist. Resultados La intervención más efectiva ha sido la Assertive Community Treatment (ACT), con unos resultados de: mejora en la remisión sintomatológica de 43,98 puntos en comparación el grupo control; en cuanto a los reingresos hospitalarios 19,05%; respecto a la funcionalidad social, ha tenido una mejora de 11,36 puntos; por último, respecto a la calidad de vida ha habido una mejora de 1,40 puntos. Conclusiones La participación social es fundamental en el proceso de rehabilitación psicosocial, de un usuario con esquizofrenia. La ACT ha mostrado mejores resultados de forma significativa frente a la Community-Based Rehabilitation (CBR). Debemos tomar con cautela los resultados obtenidos debido a las limitaciones de este estudio, donde resalta la poca evidencia científica disponible sobre esta temática.
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