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Résumé: Les patientes avec une maladie inflammatoire chronique de l'intestin (MICI) sont habituellement préoccupées par l'exposition aux médicaments pendant la grossesse et leurs effets sur le fœtus. La gestion des biothérapies avant, pendant et après la grossesse évolue rapidement, c'est pourquoi les médecins qui s'occupent de cette population de patientes doivent être bien informés et se sentir à l'aise pour conseiller leurs patientes afin d'obtenir le meilleur déroulement de la grossesse possible. Il est particulièrement important de comprendre les implications de l'utilisation des biothérapies dans les périodes précédant la conception, la grossesse et le post-partum. Nous souhaitons ici informer le clinicien sur l'impact d'une inflammation non contrôlée pendant la grossesse, les mécanismes de transport des produits biologiques à travers le placenta, les effets des biothérapies tant au niveau maternel que néonatal et d'autres considérations du post-partum telles que l'allaitement et la sécurité vaccinale. Les connaissances apportées par les précédentes recherches en termes de sécurité des biothérapies pendant la grossesse sont rassurantes. Avec l'arrivée de nouvelles biothérapies ayant des mécanismes différents d'action mais une structure protéique similaire, c'est-à-dire des anticorps IgG1, on peut s'attendre à ce que la recommandation de poursuivre la thérapie pendant la grossesse soit maintenue. Women with Inflammatory Bowel Disease (IBD) are preoccupied about their medication exposure during pregnancy and their effects on the fetus. The management of biologics before, during and after pregnancy is quickly changing, that is why the doctors who take care for this patient population should be well informed and feel comfortable counselling their patients for the best possible pregnancy outcome. It is of particular importance to understand the implications of use of biologics in preconception, pregnancy and postpartum timeframes. Herein, we aim to inform the clinician about the impact of uncontrolled inflammation during pregnancy, the mechanisms of biologic transport through the placenta, the effects of biologics in maternal and neonatal outcomes and additional postpartum considerations such as breastfeeding and vaccination safety. The knowledge provided by previous researches on the safety of biologics during pregnancy is reassuring. With the advent of new biologics with different mechanisms of action but similar protein structure, IgG1 antibodies, it is expected that the recommendation of continuation of therapy throughout pregnancy will be sustained. [ABSTRACT FROM AUTHOR]

The paper reviews the new European League Against Rheumatism (EULAR) guidelines covering a wide range of rheumatology issues discussed at the 2018 EULAR Congress.

Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR'97), 2012 Systemic Lupus International Collaborating Clinics (SLICC'12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR'19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC'12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR'19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work. [ABSTRACT FROM AUTHOR]

Prof Josef Smolen opened the symposium and briefly described the aims of the meeting. Co-host Prof Constantino Pitzalis first discussed the pathophysiology of rheumatoid arthritis (RA), identifying the pro-inflammatory cytokines involved and explaining why specific drugs only work in certain conditions. Prof Simon Jones followed with a discussion on comorbidities and adverse events associated with interleukin (IL)-6 intervention in rheumatic disease. Dr Frank McKenna presented on the psychological impact of RA, including mood changes and development of depressive disorders, and Prof Smolen described the upcoming therapeutic approaches for the condition while also comparing and contrasting existing treatment options. The symposium concluded with a question and answer session.

Prof Peter Taylor opened the symposium focussed on optimisation of treatment for rheumatoid arthritis (RA) at each stage of the patient’s journey. Prof Ronald van Vollenhoven reviewed the evidence for first- line biologics in the ‘exceptional patient’ and explored which patients may be suitable for such treatments. Prof Taylor then expanded on how use of such treatments could be optimised and when to introduce biologic therapy for the so-called ‘standard’ patient. Finally, Prof Daniel Aletaha discussed treatment options and targets for patients who have failed on a biologic as ‘the rule’ in the treatment of RA.

Three biosimilar products are now licensed for the treatment of rheumatic diseases in Europe. The European Medicines Agency (EMA) requires that similarity between a biosimilar and its reference product is demonstrated using a rigorous, stepwise process that includes extensive physicochemical and biological analytical testing, non-clinical pharmacology, clinical evaluations, and pharmacovigilance plans. Each step is highly sensitive to any differences between products and progressively reduces any uncertainty over similarity; all steps must be satisfied to demonstrate biosimilarity. The US Food and Drug Administration (FDA) requires a similar stringent biosimilar development process. The etanercept biosimilar SB4 (Benepali®), recently approved for the treatment of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis (ankylosing spondylitis, non-radiographic axial spondyloarthritis), and plaque psoriasis, is herein used to demonstrate the detailed analytical characterisation and clinical testing that are required by the EMA before biosimilars are approved for use. A comprehensive characterisation study involving >55 physiochemical and >25 biological assays demonstrated that SB4 has highly similar structural, physicochemical, and biological quality attributes to reference etanercept. A Phase I study demonstrated pharmacokinetic equivalence between SB4 and reference etanercept in healthy male subjects. Furthermore, a Phase III, randomised, controlled trial performed in patients with moderate-to-severe rheumatoid arthritis despite treatment with methotrexate (MTX) showed that SB4 was equivalent to etanercept in terms of efficacy, safety, and immunogenicity. In conclusion, the biosimilar development process performed according to EMA or FDA guidelines is highly rigorous and comprehensive. Biosimilars such as SB4 are now available in clinical practice and are likely to improve access, reduce costs, and ultimately, improve health outcomes.

This educational symposium was opened by Prof Ernest Choy, who introduced the concept of precision medicine and highlighted the importance of integrating current research with clinical experience to guide treatment decisions. He also highlighted the growing recognition of precision medicine within rheumatology. Prof Eric Ruderman then explored current medical views around the use of glucocorticoids (GCs) in rheumatoid arthritis (RA), revealing how uncertainty over the true risk/benefit ratio of these agents means that their impact as part of patient care must be further studied. Next, Prof Cem Gabay reviewed the evidence from clinical trials, registries, and real-world studies supporting biologic monotherapy as a treatment strategy in patients for whom methotrexate (MTX) is inappropriate. Prof Georg Schett then considered how current biomarker research might influence patient care in the future, especially with respect to assessing disease course and treatment responses in RA. Finally, Prof Choy presented a series of patient case studies, featuring practical issues faced by rheumatologists in the clinic, and drew upon the themes of the preceding presentations to highlight the value of a precision medicine approach to RA. Following closing remarks from Prof Choy, a lively discussion session enabled the audience to ask the expert panel about the wider clinical implications of their views. The pivotal role of IL-6 in RA5 was explored in a video at the beginning of the session, which highlighted the importance of further research in this area (available to view here)

Targeted biologics have revolutionised the treatment and outlook of patients with inflammatory joint diseases. The combination of high-cost long-term therapy straining healthcare systems with impending expiry of key biologics patents has led to heightened interest in the development of biosimilars. The expanding landscape of biosimilars has triggered, in healthcare providers, the need to explore the option to non-medically switch stable patients from costly reference products to less expensive alternatives. Currently, there are many unknowns surrounding the effects of non-medical switching on patient outcomes and cost-effectiveness. Prof Edward Keystone opened the symposium by discussing the constantly evolving landscape of biologics, highlighting that their high cost is becoming an increasing challenge and has created the issue of non-medical switching. Dr Leigh Revers provided a background to the structural and functional relationships of biologic therapies, stressing the need for careful control of the manufacturing processes of these large and complex molecules. Prof Keystone presented the long-term data currently available for anti-tumour necrosis factor (anti-TNF) agents and examined how sustainability of response can be influenced by multiple factors. Prof Thomas Dörner concluded the symposium by stressing the importance of the prescribing doctor being in control of which biologics their patients receive to ensure effective pharmacovigilance. The challenge of non-medical switching was discussed along with the potential trial designs that could help to determine if biologics and biosimilars could be interchangeable.

Prof Philip Mease introduced psoriatic arthritis (PsA) with a particular emphasis on disease symptoms and an update on the status of current disease management. Erik Lubberts described the interleukin (IL)-17 pathway and its role in the pathogenesis of PsA. Prof Iain McInnes reviewed the clinical evidence for the efficacy of IL-17 inhibition in PsA. Prof Désirée van der Heijde brought the symposium to a close with a presentation on the clinical impact of joint structural damage and strategies for its prevention in PsA.

The meeting was opened by Prof Atul Deodhar who introduced the prevalence, epidemiology, and clinical features of axial spondyloarthritis (axSpA), and discussed the ongoing unmet needs in the management of axSpA. Prof Dirk Elewaut described the role of the interleukin-17 (IL-17) pathway in the pathogenesis of axSpA. Prof Dominique Baeten reviewed the latest clinical data from existing and emerging therapies for axSpA. Finally, Prof Xenofon Baraliakos discussed recent advances in the assessment of bone inflammation and structural damage in axSpA. Each discussion was followed by questions and answers. The meeting was concluded with an interactive final discussion between the panellists and the audience, with concluding remarks by Prof Atul Deodhar.

The symposium, co-chaired by Prof Johanne Martel-Pelletier and Prof Antonello Pietrangelo, opened with a discussion of metabolic syndrome-associated osteoarthritis (OA) and a brief overview of treatment options by Prof Francis Berenbaum. Prof Jean-Pierre Pelletier then discussed the use of symptomatic slow-acting drugs for OA (SYSADOA) for knee OA within the context of the new European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommendations. Finally, Dr Burkhard Leeb concluded the session by discussing the indications, contraindications, and side-effect management of diacerein.

As awareness of the risk of vaccine-preventable diseases for children with rheumatic diseases has increased, vaccination has become an important clinical consideration and focus of research in paediatric rheumatology. Conflicting reports in the literature and differing advice from national bodies regarding the safety of different vaccines for this patient population have led to confusion in the minds of many rheumatologists as to what is appropriate. This article will provide an overview of crucial aspects of the recently published European League Against Rheumatism recommendations regarding vaccination of paediatric patients with rheumatic disease, and will review advances in this field since their publication. [ABSTRACT FROM AUTHOR]

Introduction: The American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, and European League Against Rheumatism (EULAR)/ACR 2019 SLE criteria are often used to classify patients with adult-onset and childhood-onset systemic lupus erythematosus (SLE) in clinical practice because there are currently no diagnostic criteria for SLE. However, there is scarce evidence regarding which criteria are best for diagnosing patients with adult-onset and childhood-onset SLE., Methods: We searched Medline and Scopus databases for English-language articles from inception through October 2021. Data were extracted from the included publications by two independent reviewers. We performed bivariate meta-analysis with a random-effects model to pool diagnostic parameters. Meta-regression and subgroup analyses were performed to explore heterogeneity sources. We used network meta-analysis to compare diagnosis performance among the three criteria and ranked them in descending order. Publication bias was assessed using Deeks' funnel plot., Results: We included 29 studies for systematic review and meta-analysis. Of these, 18 studies involved adult-onset SLE and 11 studies involved childhood-onset SLE. The pooled sensitivities of the three criteria for diagnosis of adult-onset SLE were comparable between SLICC 2012 and EULAR/ACR 2019 [95.86, 95% confidence interval (CI) 92.28-97.81 vs. 94.79, 95% CI 92.03-96.63]; pooled specificity was highest in ACR 1997 (92.24, 95% CI 87.06-95.46). In childhood-onset SLE, pooled sensitivity was highest in SLICC 2012 (93.76, 95% CI 89.45-96.39), and pooled specificity was highest in ACR 1997 (95.89, 95% CI 91.73-98.00). In network meta-analysis, the pooled diagnostic odds ratio ranked highest for EULAR/ACR 2019 (131.570, 95% CI 61.50-281.47) in adult-onset SLE and ranked highest for SLICC 2012 (191.07, 95% CI 76.06-480.01) in childhood-onset SLE. Deeks' funnel plot showed no publication bias., Conclusion: We found that the diagnostic performance of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria differed between adult-onset and childhood-onset SLE. EULAR/ACR 2019 performed best for adult-onset SLE and SLICC 2012 was best for childhood-onset SLE in classifying patients with SLE., Systematic Review Registration: [www.ClinicalTrials.gov], identifier [CRD420 21281586]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lerkvaleekul, Chobchai, Rattanasiri and Vilaiyuk.)

Objectivos: Identificar os tratamentos farmacológicos e não farmacológicos mais recomendados na abordagem da fibromialgia, com base no nível de evidência científica. Fontes de dados e métodos de revisão: Revisão bibliográfica na Medline, via plataformas PubMed e Medscape, consulta de livros de texto especializados e textos de apoio fornecidos em congresso, entre 2005 e 2008. Resultados: Foram seleccionados, com base nos critérios de inclusão, duas normas de orientação clínica, dois artigos de revisão sistemática e 3 artigos de revisão baseada na evidência. O crescente aparecimento de estudos resultou em novas evidências científicas na abordagem terapêutica desta patologia. As guidelines da «American Pain Society» - 2005, privilegiam a confirmação diagnóstica, a educação do doente, a avaliação e tratamento de co-morbilidades. As guidelines da «European League against Rheumatism» - 2007, acrescentam que as co-morbilidades, o tipo e intensidade dos sintomas são importantes na selecção do tratamento inicial. Os americanos preconizam, como primeira linha, a utilização de antidepressivos tricíclicos e da ciclobenzaprina. Contudo, estudos mais recentes, comprovam a maior eficácia dos inibidores selectivos da recaptação da serotonina e norepinefrina, bem como dos alfa-2-delta ligandos-pre-gabalina, estes nos doentes com predomínio de distúrbios do sono e ansiedade. Na ausência de resposta clínica à monoterapia, a associação destas duas abordagens é uma hipótese. Ambas as guidelines consideram como fármacos de segunda linha os analgésicos e anti-inflamatórios. Quanto à terapêutica não farmacológica, ambas recomendam o exercício físico e a terapia cognitivo-comportamental. É consensual que a combinação da terapêutica farmacológica e não farmacológica, numa abordagem multidisciplinar, deverá ser a primeira opção, ainda que de uma forma individualizada. Conclusão: A fibromialgia implica um elevado consumo de recursos de saúde, devendo ser abordada perspectivando o indivíduo, enquanto unidade bio-psico-social, e encarada como uma realidade, à luz dos estudos recentes. Novos estudos deverão ser realizados na tentativa de melhor compreender a fisiopatologia e, assim, desenvolver novas e mais adequadas abordagens terapêuticas.

Increasing evidence suggests low disease activity or remission is achievable in rheumatoid arthritis (RA). Using a treat to target strategy (T2T) has been shown to achieve these targets of remission or low disease activity in RA. In order to successfully treat to target, rheumatologists need reliable measures of disease activity to switch and/or escalate therapy to achieve or maintain therapeutic targets. Multiple disease-activity measures have been developed for both research and clinical practice. For clinical practice, the American College of Rheumatology (ACR) has recommended the PAS, PAS II, RAPID 3, CDAI, DAS 28, and SDAI for measuring disease activity in rheumatoid arthritis. Each of these measures has strengths and limitations, but they all accurately reflect disease activity, discriminate well between disease states, and are feasible to perform in the clinical setting. Implementation in the clinical setting can be optimized through leveraging technology and systems redesign. Tools such as web-based and smartphone applications have been developed to increase the ease with which these measures can be deployed. Disease-activity measurement in rheumatoid arthritis is included in the rheumatoid arthritis quality measures group in the Centers for Medicare and Medicaid Services' incentive-based Physician Quality Reporting System. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is used widely as a first-line drug for the treatment of rheumatoid arthritis (RA) worldwide. There are large interindividual differences in the therapeutic response to MTX, but it is not known which factors influence them. We therefore investigated predictive factors associated with the therapeutic response to MTX in a hospital-based cohort study. Japanese adult RA outpatients prescribed MTX were enrolled and their characteristics were collected from the electronic medical records. The European League Against Rheumatism (EULAR) response criteria were used as the response to MTX therapy. The observation period was 1 year after beginning MTX administration. Sixteen types of single-nucleotide polymorphisms were investigated using the real-time PCR method. Associations between the MTX response and patient characteristics were evaluated using the multivariate logistic regression model. Among 70 Japanese adult RA outpatients, 52 were classified as MTX responders. In multivariate analysis, patients with the solute carrier family 19 member 1 (SLC19A1) 80G>A A/A genotype had a better response than those with the A/G or G/G genotype, and patients with the C allele of γ-glutamyl hydrolase (GGH) 16T>C had a better response than those with the T/T genotype.This study showed that the therapeutic response to MTX in Japanese RA patients was associated with the genetic polymorphisms of SLC19A1 80G>A and GGH 16T>C in actual clinical practice.

Objectives: This study aims to evaluate the effects of passive smoking on disease activity in female patients with rheumatoid arthritis (RA)., Patients and Methods: Among a total of 191 female patients with RA (mean age 59.1±12.5 years; range 21 to 87 years) consecutively recruited, 100 female patients (mean age 56.1±13.4 years; range 21 to 87 years) completed the study with mean 17.3 months of follow-up. Patients were classified according to smoking status: current, never, passive, or ex-smoker. Clinical response between never and passive smokers was assessed by disease- activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (DAS28-ESR and DAS28-CRP) and by the European League Against Rheumatism response criteria., Results: Among the 100 female RA patients analyzed, the distribution of smoking status was as follows: current (n=3), never (n=55), passive (n=34), and ex-smokers (n=8). There was no difference of DAS28-ESR and DAS28-CRP between never and passive smokers at baseline. At the time of follow-up, the values of DAS28-ESR and DAS28-CRP in never smokers were significantly decreased than those in passive smokers (p=0.019 and p=0.023, respectively). Patients who never smoked showed a trend to have good or moderate European League Against Rheumatism response without statistical significance, compared to passive smokers (52.7% vs. 32.4%, respectively; p=0.060)., Conclusion: This preliminary study implicates that passive smoking might be responsible for higher disease activity in female RA patients and never smoking might induce good clinical response in RA., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. In this review, we provide the latest views on additional roles of the BAFF system in health and diseases, as well as an update on BAFF and autoimmunity, with particular focus on current clinical trials., (Copyright © 2013 Elsevier Ltd. All rights reserved.)