Tuberculosis in children and adolescents with rheumatic diseases using biologic agents: an integrative review.

OBJECTIVE: To conduct a bibliographic review on tuberculosis (TB) disease in children and adolescents with rheumatic diseases, being managed with biologic therapy. DATA SOURCE: An integrative review with a search in the U.S. National Library of Medicine and the National Institutes of Health (PubMed) using the following descriptors and Boolean operators: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis factor-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), between January 2010 and October 2021. DATA SYNTHESIS: Thirty-seven articles were included, with the total number of 36,198 patients. There were 81 cases of latent tuberculosis infection (LTBI), 80 cases of pulmonary tuberculosis (PTB), and four of extrapulmonary tuberculosis (EPTB). The main rheumatic disease was juvenile idiopathic arthritis. Among LTBI cases, most were diagnosed at screening and none progressed to TB disease during follow-up. Of the TB cases using biologics, most used tumor necrosis factor-alpha inhibitors (anti-TNFα) drugs. There was only one death. CONCLUSIONS: The study revealed a low rate of active TB in pediatric patients using biologic therapy. Screening for LTBI before initiating biologics should be done in all patients, and treatment, in cases of positive screening, plays a critical role in preventing progression to TB disease.

Monocyte to high-density lipoprotein cholesterol ratio decreased in patients with psoriasis treated with ixekizumab.

Background: Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammatory biomarker which has been associated with cardiovascular diseases. Objective: To study MHR in patients with psoriasis treated with biological agents. Methods: Between April 2019 and August 2022, MHR was retrospectively evaluated in patients with psoriasis before and 3 months after treatment with infliximab, adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab in a university hospital in Ankara, Turkey. Results: This study included 128 patients, 53 females and 75 males. 39 (30.5%) patients were treated with infliximab, 26 (20.3%) with adalimumab, 8 (6.3%) with etanercept, 18 (14.1%) with ixekizumab, 12 (9.4%) with secukinumab, and 25 (19.5%) with ustekinumab. The median MHR was 0.0127 (0.0086-0.0165) in females and 0.0146 (0.0119-0.0200) in males (p = 0.011). The median MHR decreased after treatment with adalimumab, ixekizumab, secukinumab, and ustekinumab, whereas it increased after treatment with infliximab and etanercept (p = 0.790, p = 0.015, p = 0.754, p = 0.221, p = 0.276, p = 0.889, respectively). Conclusion: MHR significantly decreased in patients with psoriasis after treatment with ixekizumab. Since high MHR levels have been associated with poor clinical outcomes in patients with cardiovascular diseases, ixekizumab might have a positive impact in the treatment of psoriasis patients who had cardiovascular diseases. We suggest that MHR may be useful both in establishing appropriate biological agent treatment and in the follow-up of patients with psoriasis treated with biological agents.

THE EVALUATION OF INFLIXIMAB TROUGH LEVEL FAVORS MAINTENANCE THERAPY OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases that result from the deregulation of the mucosal immune system of the gastrointestinal tract. The use of biological therapies, including infliximab (IFX), is one of the strategies to treat both CD and UC. The IFX treatment is monitored by complementary tests, namely: fecal calprotectin (FC); C-reactive protein (CRP); and endoscopic and cross-sectional imaging. Besides, serum IFX evaluation and antibody detection are also used. OBJECTIVE: To evaluate trough levels (TL) and antibodies in a population with inflammatory bowel (IBD) disease undergoing treatment with IFX, and the factors that might impact the treatment effectiveness. METHODS: Retrospective, cross-sectional study with patients with IBD that were assessed for TL and antibody (ATI) levels in a southern Brazilian hospital, from June 2014 to July 2016. RESULTS: The study assessed 55 patients (52.7% female) submitted to serum IFX and antibody evaluations (95 blood samples, 55 first test; 30 second test, and 10 as third testing. Forty-five (47.3%) cases were diagnosed with CD (81.8%), and ten with UC (18.2%). Serum levels were adequate in 30 samples (31.57%), subtherapeutic in 41 (43.15%), and supratherapeutic in 24 (25.26%). IFX dosages were optimized for 40 patients (42.10%), maintained for 31 (32.63%), and discontinued for 7 (7.60%). The intervals between infusions were shortened in 17.85% of the cases. In 55 tests (55.79%), the therapeutic approach was exclusively defined according to IFX and/or serum antibody levels. The assessment of patients one year later indicated that: the approach was maintained with IFX for thirty-eight patients (69.09%); the class of biological agent was changed for eight (14.54%); changes using the same class of biological agent occurred for two patients (3.63%); the medication was discontinued and not replaced for three patients (5.45%), and four patients (7.27%) were lost to follow-up. CONCLUSION: There were no differences in TL between groups with or without immunosuppressants, serum albumin (ALB), erythrocyte sedimentation rate (ESR), FC, CRP, and endoscopic and imaging examinations. Current therapeutic approach could be maintained for almost 70% of patients. Thus, serum and antibody levels are a useful tool in the follow-up of patients undergoing maintenance therapy and after treatment induction in patients with inflammatory bowel disease.

Pertinence de l'exigence d'un essai préalable avec un immunosuppresseur dans les indications de paiement des médicaments biologiques: gastroentérologie et dermatologie / Relevance of the prerequisite of the use of an immunosuppressant drug for the coverage of biologic agents (gastroenterology and dermatology)

INTRODUCTION: Au cours des dernières années, les médicaments biologiques se sont ajoutés à l'arsenal thérapeutique des maladies inflammatoires chroniques. Afin d'assurer un usage responsable de ces agents coûteux, leur paiement est actuellement autorisé suivant l'essai préalable de certains traitements conventionnels, notamment des immunosuppresseurs, à moins d'intolérances ou de contre-indications. Toutefois, des associations médicales en gastroentérologie et en dermatologie font état d'un décalage entre les indications de paiement des médicaments biologiques et les meilleures pratiques cliniques. Actuellement, lorsque l'utilisation des médicaments biologiques sans l'essai préalable des immunosuppresseurs est requise, une assistance par un programme de soutien aux patients et aux patientes pourrait être offerte par les fabricants des médicaments biologiques, selon certaines conditions. Dans le traitement des maladies inflammatoires de l'intestin, l'utilisation précoce des médicaments biologiques par le biais de ces programmes de soutien semble être une pratique bien établie et largement répandue depuis plusieurs années. Avec l'entrée en vigueur en avril 2021 de l'article 80.2 de la Loi sur l'assurance médicaments, lequel interdit le paiement ou le remboursement d'un médicament ou d'une fourniture dont le paiement est couvert par le régime général d'assurance médicaments, des associations médicales ont partagé des préoccupations quant à l'accès des médicaments biologiques sans l'essai préalable des immunosuppresseurs au ministère de la Santé et des Services Sociaux (MSSS). Notons que les médicaments biologiques, qu'ils soient de référence ou biosimilaires, font actuellement partie des exceptions prévues au règlement. Afin d'évaluer la pertinence des préalables de traitement dans les indications de paiement des médicaments biologiques, le MSSS a demandé à l'Institut national d'excellence en santé et en services sociaux (INESSS) de mobiliser les savoirs quant à la place des immunosuppresseurs et des médicaments biologiques dans les domaines de la gastroentérologie et de la dermatologie. MÉTHODOLOGIE: Tout d'abord, les indications de paiement des médicaments biologiques inscrits sur les listes de médicaments du Québec (ou dont la décision du ministre est en attente) ont été comparées à celles des autres provinces canadiennes. Ensuite, une revue rapide de la littérature a été réalisée pour répertorier notamment les recommandations des guides de pratique clinique (GPC) concernant la place des médicaments biologiques et des immunosuppresseurs dans la prise en charge de la maladie de Crohn chez l'adulte et l'enfant, de la colite ulcéreuse chez l'adulte et du psoriasis en plaques chez l'adulte. Finalement, les savoirs expérientiels et contextuels ont été recueillis par l'intermédiaire d'une invitation à recevoir des commentaires sur le plan de travail de l'INESSS et d'une consultation d'experts comprenant des gastroentérologues et des dermatologues. RÉSULTATS: Les GPC retenus dans les travaux relatent le manque d'étude de bonne qualité évaluant le moment optimal pour l'introduction des médicaments biologiques dans le traitement. Néanmoins, selon les données disponibles et le degré de valorisation de plusieurs autres facteurs, y compris les risques de complications, la gravité de la maladie, la réponse aux traitements antérieurs et les coûts, les sociétés savantes ont émis des recommandations concernant diverses séquences de traitement avec les médicaments biologiques, autant avant que suivant un traitement par les immunosuppresseurs. Pour le traitement des maladies inflammatoires de l'intestin, la plupart des GPC sélectionnés présentent des recommandations au sujet de l'utilisation des médicaments biologiques suivant un traitement conventionnel, lequel inclut l'acide 5-aminosalicylique (5-ASA) et (ou) les corticostéroïdes et (ou) les immunosuppresseurs. Plusieurs GPC font toutefois également état d'un changement de paradigme vers l'utilisation des médicaments biologiques en première intention de traitement, particulièrement chez les personnes qui ont des facteurs de risque de mauvais pronostic, afin de prévenir les complications, l'hospitalisation et le recours à la chirurgie. Très peu d'essais ont comparé l'efficacité des médicaments biologiques par rapport à celle des immunosuppresseurs, et ceux répertoriés ne sont pas représentatifs de la pratique clinique actuelle avec les médicaments biologiques. Les immunosuppresseurs sont généralement recommandés pour le maintien de la rémission et pourraient constituer une option de traitement acceptable suivant l'atteinte d'une rémission par les corticostéroïdes, mais leur utilisation suscite des préoccupations liées à leur innocuité, notamment le risque de lymphome T hépatosplénique associé aux thiopurines, telles l'azathioprine et la mercaptopurine. Pour le traitement du psoriasis en plaques, les recommandations issues des GPC sélectionnés concernant la place des médicaments biologiques dans le traitement sont peu nombreuses. Néanmoins, tous les GPC retenus s'accordent pour recommander l'utilisation des médicaments biologiques suivant un traitement par les agents de rémission systémiques conventionnels, lesquels incluent les immunosuppresseurs (principalement la cyclosporine et le méthotrexate) et l'acitrétine. Un GPC suggère également l'introduction précoce des médicaments biologiques dans des situations particulières. L'efficacité différentielle entre les médicaments biologiques et les agents de rémission systémiques conventionnels relève principalement de comparaisons indirectes. Une méta-analyse en réseau réalisée par le groupe Cochrane rapporte que la plupart des médicaments biologiques serait plus efficace que les agents de rémission systémiques conventionnels pour atteindre une réduction d'au moins 90 % sur le Psoriasis Area and Severity Index (PASI90). Par ailleurs, des enjeux d'innocuité sont liés aux agents de rémission systémiques conventionnels : le traitement continu par la cyclosporine n'est pas recommandé en pratique au-delà d'un an en raison des risques de néphrotoxicité, l'acitrétine pouvant causer des effets muco-cutanés et le méthotrexate, entraîner une hépatotoxicité. PERSPECTIVE DES EXPERTS ET AUTRES PARTIES PRENANTES: Pour le traitement des maladies inflammatoires de l'intestin, malgré l'absence de données de bonne qualité entre les immunosuppresseurs et les médicaments biologiques, les experts consultés estiment, selon leur expérience clinique, que les médicaments biologiques présentent une efficacité supérieure et un profil d'innocuité favorable par rapport aux immunosuppresseurs. Dans ce contexte, ils considèrent que l'essai des immunosuppresseurs avant l'autorisation des médicaments biologiques expose les patients à des risques de toxicité, de progression de la maladie et de complications. Afin d'éviter ces risques aux personnes qui en font usage, les cliniciens rapportent que l'utilisation des médicaments biologiques sans l'essai préalable des immunosuppresseurs par l'intermédiaire des programmes de soutien aux patients financés par les fabricants est une pratique bien établie au Québec depuis plusieurs années. En dermatologie, les cliniciens rapportent que les préalables de traitement dans les indications de paiement des médicaments biologiques pour le traitement du psoriasis en plaques pourraient forcer le choix d'options thérapeutiques souvent inappropriées pour les patients. Ils mentionnent que seul le méthotrexate dispose d'une réelle place dans le traitement du psoriasis en plaques modéré à grave. Les cliniciens reconnaissent que les délais engendrés par l'essai préalable d'au moins deux agents de rémission systémiques conventionnels, tel que requis actuellement dans les indications de paiement des médicaments biologiques, n'influencent pas le pronostic vital des patients. Toutefois, ils jugent important d'adapter le traitement à la condition particulière des personnes qui en font usage afin de réduire les plaques de psoriasis tout en limitant la survenue d'effets indésirables. CONCLUSIONS: Le moment optimal pour l'introduction des médicaments biologiques par rapport aux immunosuppresseurs dans les domaines de la gastroentérologie et de la dermatologie n'a pas été évalué dans des études de bonne qualité. Ainsi, les présents travaux démontrent une inadéquation entre la pratique clinique actuelle en gastroentérologie et les données probantes de bonne qualité disponibles. À ce propos, l'expérience clinique acquise au cours des dernières années avec les médicaments biologiques dans le traitement des maladies inflammatoires de l'intestin a mené les gastroentérologues à préconiser leur utilisation sans l'essai préalable des immunosuppresseurs. Les cliniciens estiment que l'exigence d'un traitement antérieur par les immunosuppresseurs dans les indications de paiement des médicaments biologiques pour le traitement des maladies inflammatoires de l'intestin devrait être retirée, principalement puisque les immunosuppresseurs retarderaient la guérison et exposeraient les patients à des risques de toxicité et de complications non négligeables, selon eux. Bien que la situation soit quelque peu différente en dermatologie, les cliniciens consultés soutiennent également le retrait de cette exigence pour le psoriasis en plaques.

INTRODUCTION: Over the past few years, biologic agents have been included in the therapeutic arsenal for treating chronic inflammatory diseases. To ensure responsible use of these costly drugs, their payment is currently only authorized following the use of conventional treatments (notably immunosuppressants), except in the presence of intolerances or contraindications. However, medical associations in gastroenterology and dermatology report a disconnect between coverage information for biologic agents and best clinical practices. At present, when biologic agents must be used without any prior trials of immunosuppressants, patients can, under certain conditions, receive assistance from biologic drug manufacturers for access through a patient support program. In the treatment of inflammatory bowel diseases, the early use of biologic agents through such support programs appears to be an established and widespread practice for several years. With the coming into force of section 80.2 of the Act respecting prescription drug insurance in April 2021, which prohibits the payment or reimbursement of a medication or supply covered by the Public Prescription Drug Insurance Plan, medical associations shared their concerns regarding access to biologic agents without any prior trials of immunosuppressants with the Ministère de la Santé et des Services sociaux (department of health issues and social services) (MSSS). It bears noting that biologic agents, whether they are reference products or biosimilars, are included in the exceptions provided for under the regulation. To assess the relevance of the prerequisite of the use of an immunosuppressant for the coverage of biologic agents, the MSSS asked the Institut national d'excellence en santé et en services sociaux (INESSS) to draw on the existing knowledge regarding the role of immunosuppressants and biologic agents in gastroenterology and dermatology. METHODOLOGY: First, coverage information for biologic agents listed on Québec drug formulary (or for which the Minister's decision is pending) was compared with that in other Canadian provinces. Then, a rapid review of the literature was performed to identify CPG (Clinical practice guidelines) recommendations regarding the place of biologic agents and immunosuppressants in the treatment algorithm of Crohn's disease in adults and children, ulcerative colitis in adults and plaque psoriasis in adults. Lastly, experiencebased and contextual knowledge was gathered through an invitation to receive feedback on the INESSS' work plan and from a consultation panel including gastroenterologists and dermatologists. RESULTS: The CPGs selected report a lack of quality studies on the best timing for incorporating biologic agents into a treatment plan. However, according to available data and the importance of several other factors, including the risk of complications, the severity of the illness, the response to previous treatments and the associated costs, learned societies made recommendations regarding various sequences of treatment with biologic agents, both before and after a treatment with immunosuppressants. For the treatment of inflammatory bowel diseases, most of the CPGs selected comprise recommendations as to the use of biologic agents following a conventional treatment that includes 5-ASA (aminosalicylic acids) and/or corticosteroids and/or immunosuppressants. Numerous CPGs, however, report a paradigm shift towards the use of biologic drugs as the front-line treatment, especially for persons at risk of a poor prognosis, to prevent complications, hospitalization and the need for surgery. Very few clinical trials have compared the efficacy of biologic agents and immunosuppressants, and the ones reported are not representative of current clinical practices with biologic agents. Immunosuppressants are generally recommended to maintain complete remission and could prove an acceptable treatment option once remission is achieved with corticosteroids; however, concerns associated with their safety have been raised, notably regarding the risk of hepatosplenic T-cell lymphoma due to thiopurines, such as azathioprine and mercatopurine. There are few recommendations in the selected CPGs regarding the role of biologic drugs in the treatment of plaque psoriasis. However, all of the CPGs selected agree in recommending the use of biologic drugs following a treatment with conventional systemic agents, which include immunosuppressants (primarily cyclosporine and methotrexate) and acitretin. One CPG also suggests resorting to the early use of biologic agents in special situations. The differential efficacy of biologic drugs and conventional systemic agents was mainly established through indirect comparisons. A network meta-analysis performed by Cochrane reports that most biologic drugs would be more effective than conventional systemic agents at achieving a decrease of at least 90% on the Psoriasis Area and Severity Index (PASI90). In addition, conventional systemic agents have certain safety issues: ongoing treatment with cyclosporine is not recommended beyond one year given the risks of nephrotoxicity, acitretin can cause mucocutaneous effects and methotrexate can induce hepatotoxicity. OPINIONS OF EXPERTS AND OTHER STAKEHOLDERS: For the treatment of inflammatory bowel diseases, despite the lack of quality data on immunosuppressants and biologic agents, the experts consulted believe, based on their clinical experience, that biologic agents offer a superior efficacy and a more favourable safety profile compared to immunosuppressants. Given this, they also consider that requiring a trial with an immunosuppressant before allowing the use of a biologic agent exposes patients to risks, among them toxicity, disease progression and complications. To avoid such risks, clinicians report that the use of biologic agents without the prior use of immunosuppressants through manufacturer-funded patient support programs is a wellestablished practice in Québec since many years. Clinicians in the field of dermatology report that the inclusion of preliminary treatments for the coverage of biologic agents in plaque psoriasis could result in patients being inappropriately treated. They mention that among the systemic drugs listed as prerequisite (acitretin, cyclosporin and methotrexate), methotrexate is the preferred agent for treating moderate to severe plaque psoriasis. The clinicians acknowledge that the delays resulting from the trial of at least two traditional systemic agents, as currently required in the coverage information for biologic agents, is not life-threatening for patients. However, they do believe that the treatment should be tailored based on the specific condition of the persons who benefit from it, to reduce psoriatic plaques while limiting the occurrence of adverse effects. CONCLUSIONS: The optimal timing for the introduction of biologics agents versus immunosuppressants in the field of gastroenterology and dermatology has not been assessed in good quality studies. Current research illustrates a discrepancy between actual clinical practices in gastroenterology and the quality evidence-based data available. The clinical experience using biologic drugs to treat inflammatory bowel diseases acquired over the past few years has led gastroenterologists to favour their use without a preliminary treatment with immunosuppressants. Clinicians consider that requiring such a prior treatment with immunosuppressants in the payment indications of biologic drugs for inflammatory bowel diseases should be ceased, mainly because immunosuppressants delay healing and expose patients to risks that include toxicity and non-negligeable complications. And while the circumstances are somewhat different in the field of dermatology, the clinicians consulted also support the removal of this requirement from payment indications of biologic drugs in the case of plaque psoriasis. Given a lack of data, this work did not evaluate the economic impact of withdrawing the requirement regarding prior treatment with immunosuppressants from the coverage information for biologic agents. This would likely generate a significant increase in costs, but the amounts involved should be compared to the cost of complications and other avoidable consequences. It should also be noted that a large portion of these costs are currently borne by the manufacturers, through patient support programs.

Not the same, but is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social.

INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non- medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9 years, ranging from 16 to 84 years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12 months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12 months after the switch (P > .05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS 28 after 12 months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non- biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.

Lipid nanoparticles with improved biopharmaceutical attributes for tuberculosis treatment.

Tuberculosis is a topic of relevance worldwide because of the social and biological factors that triggered the disease and the economic burden on the health-care systems that imply its therapeutic treatment. Challenges to handle these issues include, among others, research on technological breakthroughs modifying the drug regimens to facilitate therapy adherence, avoid mycobacterium drug resistance, and minimize toxic side-effects. Lipid nanoparticles arise as a promising strategy in this respect as deduced from the reported scientific data. They are prepared from biodegradable and biocompatible starting materials and compared to the use of the free drugs, the entrapment of active molecules into the carriers might lead to both dose reduction and controlled delivery. Moreover, the target to the lung, the organ mainly affected by the disease, could be possible if the particle surface is modified. Although conclusive statements cannot be made considering the limited number of available research works, looking into what has been achieved up to now definitively encourages to continue investigations in this regard.

PRESUMED TUBERCULOUS MULTIFOCAL RETINITIS IN PATIENTS UNDER TREATMENT WITH BIOLOGIC AGENTS.

PURPOSE: To report unique retinal fundus lesions and treatment outcomes of intraocular tuberculosis in patients under anti-tumor necrosis factor treatment. METHODS: Retrospective review of two patients with laboratorial evidence of tuberculosis who had bilateral ocular signs and symptoms not attributable to other diseases. Multimodal imaging was analyzed at the time of presentation and after the treatment initiation. The study patients underwent standard treatment for tuberculosis. RESULTS: Clinical and laboratory findings were consistent with the diagnosis of presumed tuberculosis. Color fundus photograph revealed the presence of multifocal yellowish retinal spots in the study eyes. On fluorescein angiography, the retinal lesions seen on color fundus photograph showed early hypofluorescence with progressive staining of its edges. Occlusive vasculitis with peripheral nonperfusion was also observed in both cases. Spectral domain optical coherence tomography demonstrated increased reflectivity and thickness on the topography of retinitis lesions. After specific antibiotic treatment for tuberculosis, there was complete disappearance of the retinal lesions in all study eyes. CONCLUSION: We report two unique cases of bilateral presumed intraocular tuberculosis presenting as multifocal retinitis in patients under biologic agent treatment. Anti-tumor necrosis factor agents may be related to unusual fundus manifestations of tuberculosis.

Expert recommendations for biological treatment in patients with psoriasis.

In recent years, the introduction of a series of biological drugs for the treatment of psoriasis has considerably increased the therapeutic armamentarium of doctors, and thus a strongly positive impact on the control of this condition has been achieved. With the purpose to provide the best recommendations for the use of these biological agents in patients with psoriasis, the Mexican group of psoriasis experts, PSOMEX, has developed recommendations in order to improve the understanding and therapeutic positioning of this type of medications.

En los últimos años, la introducción de diversos medicamentos biológicos para el tratamiento de la psoriasis ha aumentado considerablemente el arsenal terapéutico del médico, con lo cual se ha logrado un fuerte impacto positivo en el control de la enfermedad. Con el fin de proveer de las mejores recomendaciones para el uso de estos biológicos en los pacientes afectados de psoriasis, el grupo mexicano de expertos en psoriasis PSOMEX ha formulado recomendaciones para mejorar la comprensión y el posicionamiento terapéutico de este tipo de medicamentos.

Recomendaciones de expertos para el tratamiento biológico en pacientes con psoriasis / Expert recommendations for biological treatment in patients with psoriasis

Resumen En los últimos años, la introducción de diversos medicamentos biológicos para el tratamiento de la psoriasis ha aumentado considerablemente el arsenal terapéutico del médico, con lo cual se ha logrado un fuerte impacto positivo en el control de la enfermedad. Con el fin de proveer de las mejores recomendaciones para el uso de estos biológicos en los pacientes afectados de psoriasis, el grupo mexicano de expertos en psoriasis PSOMEX ha formulado recomendaciones para mejorar la comprensión y el posicionamiento terapéutico de este tipo de medicamentos.

Abstract In recent years, the introduction of a series of biological drugs for the treatment of psoriasis has considerably increased the therapeutic armamentarium of doctors, and thus a strongly positive impact on the control of this condition has been achieved. With the purpose to provide the best recommendations for the use of these biological agents in patients with psoriasis, the Mexican group of psoriasis experts, PSOMEX, has developed recommendations in order to improve the understanding and therapeutic positioning of this type of medications.

Emerging Therapies in Neovascular Age-Related Macular Degeneration in 2020.

Age-related macular degeneration (AMD) is one of the most common causes of vision loss. Advanced forms of AMD are seen in primarily 2 types-neovascular AMD (nAMD) with the presence of choroid neovascularization and nonneovascular AMD (nnAMD) with geographic atrophy. Although there are 4 anti-vascular endothelial growth factor drugs either widely used or approved for the former, there are no current treatments for the latter. This review will highlight upcoming treatments for AMD currently in clinical trials. For nAMD: Abicipar pegol, an intravitreal anti-vascular endothelial growth factor based on designed ankyrin repeat proteins (DARP) in protein, is currently pending approval. Conbercept and Faricimab, 2 intravitreal anti-growth factors, are currently in phase 3. Nine other upcoming agents have at least produced results in the 2A phase including intravitreal injections (KSI-301, OPT-302, RGX-314, ICON-1, and DE-122), depot (GB-102), drug reservoir (PDS), topical drops (PAN-90806), and oral formulations (AKST4290). We summarize all the newer molecules.

Artritis psoriásica: La elección del fármaco antirreumático biológico en la Ley Ricarte Soto / Choosing biological agents for the treatment of psoriatic arthritis

The financial coverage granted by law in Chile for patients with psoriatic arthritis who require biological treatment is of paramount importance and a great advance. However physicians must be knowledgeable about the advantages and limitations of this therapy. The challenge of clinicians is to choose the drug with the greater odds of achieving therapeutic success, with less adverse events and lower costs for our health system. This article aims to help doctors to select the best biological treatment for a specific patient, trying to optimize its effectiveness, minimizing adverse effects, always looking for an efficient use of resources.

[Choosing biological agents for the treatment of psoriatic arthritis]. / Artritis psoriásica: La elección del fármaco antirreumático biológico en la Ley Ricarte Soto.

The financial coverage granted by law in Chile for patients with psoriatic arthritis who require biological treatment is of paramount importance and a great advance. However physicians must be knowledgeable about the advantages and limitations of this therapy. The challenge of clinicians is to choose the drug with the greater odds of achieving therapeutic success, with less adverse events and lower costs for our health system. This article aims to help doctors to select the best biological treatment for a specific patient, trying to optimize its effectiveness, minimizing adverse effects, always looking for an efficient use of resources.

Optimizando el manejo de la uveítis con agentes biológicos en Chile del 2020 / Optimizing uveitis management with biological agents in Chile in 2020

Los agentes biológicos han irrumpido como una alternativa eficaz en el tratamiento de las uveítis no-infecciosas, especialmente en cuadros refractarios a inmunosupresores convencionales, con buena tolerancia y rápido efecto. Hay patologías como la enfermedad de Behçet en que incluso pueden estar indicados como tratamiento de primera línea. Este artículo ayudará a reconocer las patologías específicas donde presentan mayor eficacia, entrega herramientas para escoger el agente más adecuado para cada paciente y sugiere estrategias para evitar la pérdida de control de la enfermedad en el largo plazo.

Biological therapies have emerged as an effective option for the treatment of non-infectious uveitis, especially in refractive cases to conventional immunosup-pressive drugs. They are fast-acting, well tolerated, and can be considered as first-line agents for the treatment of certain uveitis like in Behçet ́s disease. This article will aid in identifying the uveitis syndromes where biological therapy is more effective, help choosing the most appropriate agent for a particular case and offer suggestions on how to keep long-term disease control.

World Workshop on Oral Medicine VII: Immunobiologics for salivary gland disease in Sjögren's syndrome: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of immunobiologics for the management of oral disease in Sjögren's syndrome (SS). MATERIALS AND METHODS: MEDLINE® , Embase, Scopus, and the Cochrane Library were searched for evidence on the use of immunobiologics for management of glandular disease in SS. Primary outcomes were xerostomia and salivary gland dysfunction, assessed via visual analogue scales, disease-specific scales for SS, measurement of salivary flow, ultrasound data, and quality of life measures. RESULTS: Seventeen studies (11 randomized controlled trials and 6 observational studies) met inclusion criteria. Rituximab showed efficacy in improving salivary gland function but not xerostomia. Abatacept showed promise in improving both xerostomia and salivary flow. Belimumab exhibited long-term improvement of salivary flow and subjective measures. The novel agent CFZ533 improved both disease activity and patient-reported indexes. CONCLUSIONS: There is strong evidence pointing to the efficacy of rituximab in the management of oral disease in SS. Future controlled trials may elucidate the efficacy of belimumab and abatacept. The new drug CFZ533 is a promising alternative for the management of SS and its salivary gland involvement. In considering these agents, the promise of efficacy must be balanced against the harmful effects associated with biologic agents.

Multimodality Management of Complex Periorbital Venolymphatic Malformations.

PURPOSE: To review a representative case series and share a stepwise approach to the diagnosis and treatment of periorbital venolymphatic malformations. METHODS: A case series of 9 patients with representative periorbital venolymphatic malformations. All patients managed at the University of California, Los Angeles Orbital Center for a vascular malformation over the last 5 years were reviewed. Cases representative of the varied pathologic findings and techniques were selected. The clinical, radiologic, and intraoperative findings are presented and a survey of techniques composed. RESULTS: Venolymphatic malformations can have protean manifestations. Characteristics vital to the understanding and management of these lesions are the classification and vascular composition of the lesion, internal flow and drainage patterns, anatomic localization and association with distant components. Options for treatment include sclerotherapy, biologic therapy, embolization, surgical excision, or some combination thereof. CONCLUSIONS: A comprehensive understanding of each patient's unique lesion is critical to a rational treatment approach. Teamwork and creativity are key to effectively managing these lesions.

Bioactive food and exercise in chronic kidney disease: Targeting the mitochondria.

Chronic kidney disease (CKD), which affects 10%-15% of the population, associates with a range of complications-such as cardiovascular disease, frailty, infections, muscle and bone disorders and premature ageing-that could be related to alterations of mitochondrial number, distribution, structure and function. As mitochondrial biogenesis, bioenergetics and the dynamic mitochondrial networks directly or indirectly regulate numerous intra- and extracellular functions, the mitochondria have emerged as an important target for interventions aiming at preventing or improving the treatment of complications in CKD. In this review, we discuss the possible role of bioactive food compounds and exercise in the modulation of the disturbed mitochondrial function in a uraemic milieu.

High rate of serious infection in juvenile idiopathic arthritis patients under biologic therapy in a real-life setting.

OBJECTIVES: To assess the rate of serious and/or opportunistic infections in juvenile idiopathic arthritis (JIA) patients from a single tertiary center under biologic therapy and to identify possible risk factors associated to these complications. METHODS: A total of 107 JIA patients followed at the biologic therapy center of our tertiary university hospital using a standardized electronic database protocol including demographic data, clinical and laboratorial findings and treatment at baseline and at the moment of infection. Opportunistic infections included tuberculosis, herpes zoster and systemic mycosis. RESULTS: A total of 398 patient-yrs(py) were included. The median time of biologic exposure was 3.0 years (0.15-11.5). We observed 35 serious/opportunistic infectious events in 27 (25%) patients: 31(88.6%) were serious infections and four (11.4%) opportunistic infections. Serious/opportunistic infections rates were 10.6/100py for ETN, 10.9/100py for ADA, 2.6/100py for ABA and 14.8/100py for TCZ. Comparison of 27 patients with and 80 without infection showed a higher frequency of systemic-onset JIA, lower age at biologic therapy initiation and a history of previous serious infection (p < .05) in the former group. CONCLUSIONS: This study demonstrated a high rate of serious infections in JIA patients under biologic therapy in a real-life setting. Systemic-onset JIA, lower age at biologic therapy start and history of previous serious infections were important risk factors for these complications. Also, higher rates of severe infections comparing to the former studies was possibly due to elevated MTX doses in our patients.

Immunogenicity in Protein and Peptide Based-Therapeutics: An Overview.

Currently it is well known that all biological drugs, including those with a fully human structure, are capable of inducing a host immune response known as immunogenicity [1]. The presence of ADAs can condition the drug´s level and action, thus modifying the therapeutic effect and even the safety profile by its mechanism of action - neutralizing or non-neutralizing - and / or an increase in its clearance. Immunogenicity is a dynamic factor to be taken into account in biological therapy, especially in long-term treatments, and as a relevant aspect in the assessment of secondary response loss [2]. With the above, not only the knowledge but also the management of the immunogenicity of the different biological treatments, represent a useful instrument for optimization of the strategies of use for each drug, and in the design of predictive models of response, which finally permits a significant improvement in the efficacy and safety profile, aiming to a personalization of the therapies, especially in patients with autoimmune diseases, genetic disorders and cancer [3]. This review summarizes the events of immunogenicity that produce the biological drug, the factor that influence to immunogenicity and the assessment of immunogenicity.