Current treatment strategies for inflammatory bowel disease patients at the risk of developing cancer: a comprehensive review

Inflammatory bowel disease (IBD) is a chronic condition that affects the digestive tract and can lead to inflammation and damage to the intestinal lining. IBD patients with cancer encounter difficulties since cancer treatment weakens their immune systems. A multidisciplinary strategy that strikes a balance between the requirement to manage IBD symptoms and the potential effects of treatment on cancer is necessary for effective care of IBD in cancer patients. To reduce inflammation and avoid problems, IBD in cancer patients is often managed by closely monitoring IBD symptoms in conjunction with the necessary medication and surgical intervention. Anti-inflammatory medications, immunomodulators, and biologic therapies may be used for medical care, and surgical options may include resection of the diseased intestine or removal of the entire colon. The current study provides a paradigm for shared decision-making involving the patient, gastroenterologist, and oncologist while considering recent findings on the safety of IBD medicines, cancer, and recurrent cancer risk in individuals with IBD. We hope to summarize the pertinent research in this review and offer useful advice. (AU)

Actinomicosis orofaríngea complicada secundaria al tratamiento farmacológico / Complicated oropharyngeal actinomycosis secondary to pharmacotherapy

Anti-tumor necrosis factor (TNF)-α treatment is an effective therapeutic option in intestinal inflammatory chronic disease in cases of the ineffectiveness of other drugs, but it promotes the development of opportunistic infections in their severe forms, due to the profound suppression of T-cell mediated immunity it produces. Among the most frequent are bacterial granulomatous infections, such as mycobacteria (especially tuberculosis), and fungal infections. Actinomycosis is a rare suppurative granulomatous chronic opportunistic infection, which in states of immunosuppression, such as the one caused after treatment with TNF blockers, is complicated by more severe clinical pictures.We present the clinical case, not previously described, of cervicofacial actinomycosis complicated with pneumonia, secondary to treatment with adalimumab in a patient with Crohn's disease.

El tratamiento con anticuerpos anti-factor de necrosis tumoral (TNF) es una opción terapéutica efectiva en la enfermedad inflamatoria crónica intestinal, en casos de ineficacia a otros fármacos, pero favorece la aparición de infecciones oportunistas en sus formas graves, debido a la gran inmunodepresión de células T que produce. Entre las más frecuentes se encuentran las infecciones granulomatosas bacterianas, como las causadas por micobacterias (en la que se destaca la tuberculosis), y las fúngicas. La actinomicosis es una infección oportunista crónica, granulomatosa, supurativa e infrecuente que, en estados de inmunosupresión, como el provocado tras el tratamiento con anticuerpos monoclonales anti-TNF, puede complicarse con cuadros clínicos más graves. Se presenta el caso clínico, no descrito anteriormente, de actinomicosis cervicofacial complicada con neumonía, secundaria al tratamiento con adalimumab, en una paciente con enfermedad de Crohn.

Analysis on the risk factors and establishment of a prediction model for primary non-response to the treatment of anti-tumor necrosis factor-α monoclonal antibody in Crohn′s disease patients / 中华消化杂志

Objective:To investigate the risk factors and establish a prediction model of primary non-response (PNR) to anti-tumor necrosis factor-α(TNF-α) monoclonal antibody in Crohn′s disease (CD) patients.Methods:From December 1, 2018 to July 31, 2022, 103 patients with CD treated with the anti-TNF-α monoclonal antibody in Renmin Hospital of Wuhan University were enrolled (modeling group), and at the same time, 109 patients with CD treated with anti-TNF-α monoclonal antibody in Zhongnan Hospital of Wuhan University were selected (validation group). The baseline clinical data of all the patients before the first treatment of anti-TNF-α monoclonal antibody were collected, which included C-reactive protein (CRP), the simplified Crohn′s disease activity index (CDAI), and modified multiplier simple endoscopic score for Crohn′s disease (MM-SES-CD), etc. Multivariate logistic regression was used to screen the independent risk factors of PNR in patients with CD treated with the anti-TNF-α monoclonal antibody, and to establish the nomograms prediction model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC), the net reclassification index (NRI), integrated discrimination improvement index (IDI), and decision curve analysis (DCA) were used to evaluate the predictive efficacy and clinical application value of the prediction model. DeLong test was used for statistical analysis.Results:The results of multivariate logistic regression analysis showed that high level of CRP ( OR=1.030, 95% confidence interval (95% CI) 1.002 to 1.059), simplified CDAI ( OR=1.399, 95% CI 1.023 to 1.913), and MM-SES-CD ( OR=1.100, 95% CI 1.025 to 1.181) in baseline were independent risk factors of PNR in patients with CD treated with the anti-TNF-α monoclonal antibody ( P=0.033, 0.036 and 0.008). The results of ROC analysis showed that the AUCs of CRP, simplified CDAI, MM-SES-CD, and the prediction model in the modeling group and the validation group were 0.697(95% CI 0.573 to 0.821), 0.772(95% CI 0.666 to 0.879), 0.819(95% CI 0.725 to 0.912), 0.869 (95% CI 0.786 to 0.951) and 0.856 (95% CI 0.756 to 0.955), respectively. The AUC of the prediction model in the modeling group was greater than those of CRP and simplified CDAI, and the differences were statistically significant ( Z=3.00 and 2.75, P=0.003 and 0.006), while compared with MM-SES-CD and the validation group, the differences were not statistically significant (both P>0.05). However, compared with MM-SES-CD, the NRI and IDI of the prediction model in the modeling group were 0.205(95% CI 0.002 to 0.409, P=0.048) and 0.098(95% CI 0.022 to 0.174, P=0.011), respectively, suggesting that the predictive ability of the prediction model was better than that of MM-SES-CD. The results of DCA indicated that the prediction model had significant clinical benefits in both the modeling group and the validation group. Conclusions:A prediction model was successfully constructed based on the independent risk factors for PNR in patients with CD treated with the anti-TNF-α monoclonal antibody. After verification, the prediction model has good prediction performance and significant clinical benefits.

Conversión de prueba cutánea de derivado proteico purificado durante el tratamiento con anti-TNF / Skin test conversion of purified protein derivative during treatment with anti-TNF

Introducción: los anti-TNF-α se asocian con mayor riesgo de desarrollar tuberculosis (TB). La prueba del derivado proteico purificado (purified protein derivative, PPD) se emplea para diagnosticar infección de tuberculosis latente (ITL). Se recomienda el cribado para TB previo al inicio de terapia anti-TNF-α y el seguimiento para evaluar la posible conversión de la PPD durante el tratamiento. El tratamiento de la ITL puede reducir el riesgo de desarrollar enfermedad activa en un 90%. Objetivos: actualmente los resultados de conversión de la PPD y su interpretación durante el tratamiento anti-TNF-α son variables, por tal motivo nos propusimos conocer la frecuencia de conversión de la PPD en este grupo de pacientes de nuestro medio. Materiales y métodos: realizamos un estudio descriptivo, observacional y retrospectivo que incluyó pacientes >18 años, diagnosticados con enfermedad reumática, tratados con anti-TNF-α. Resultados: se incluyeron 54 pacientes (46,7 ± a 12 años), de los cuales 36, presentaron diagnóstico de artritis reumatoidea, seis de artritis idiopática juvenil, cinco de espondilitis anquilosante, tres de artritis psoriásica, tres de uveítis y uno de queratitis intersticial. Los tratamientos fueron: 30 adalimumab, 17 certolizumab, siete etanercept, 44 metotrexato, 19 leflunomida, nueve hidroxicloroquina, dos sulfasalazina, dos azatioprina, uno mofetil micofenolato y glucocorticoides (28 de 54); la conversión de la PPD ocurrió en un solo paciente. Conclusiones: en el presente trabajo la seroconversión fue baja en contraste con otras series. La prueba de PPD es un método accesible, ampliamente disponible, adecuado y sensible para diagnosticar ITL.

Introduction: anti-TNF-α are associated with an increased risk of developing tuberculosis (TB). Purified protein derivative (PPD) is used to demonstrate a latent TB infection (LTBI). Screening is recommended for TB prior to the onset of anti-TNF-α and monitoring evaluating possible conversion of PPD during treatment. Treatment of LTBI can reduce the risk of active disease development by up to 90%. Objectives: currently the results of PPD conversion and its interpretation during anti-TNF-α treatment are variable and that is why we set out to know the frequency of conversion of PPD in this group of patients in our environment. Materials and methods: a descriptive, analytical, observational, retrospective study was conducted. Including patients >18 years old, diagnosed with rheumatic disease, treated with anti-TNF-α. Results: 54 patients were included (46.7 ± to 12 years), of which 36 presented a diagnosis of rheumatoid arthritis, 6 juvenile idiopathic arthritis, 5 ankylosing spondylitis, 3 psoriatic arthritis, 3 uveitis, 1 interstitial keratitis. The treatments were: 30 adalimumab, 17 certolizumab, 7 etanercept, 44 methotrexate, 19 leflunomide, 9 hydroxychloroquine, 2 sulfasalazine, 2 azathioprine, 1 mycophenolate mofetil and glucocorticoids (28/54). PPD conversion took place in 1 patient. Conclusions: in the present study, seroconversion was low in contrast to other series. The PPD test is an accessible, widely available, adequate and sensitive method for diagnosing LTBI, which the rheumatologist should use in his daily practice.

Prevalencia de tuberculosis latente determinada mediante la prueba de derivado proteico purificado (PPD) en una población de pacientes adultos con artritis reumatoide llevados a terapia biotecnológica / Prevalence of latent tuberculosis determined using the Purified Protein Derivative (PPD) test in adult patients with rheumatoid arthritis receiving biotechnological therapy

RESUMEN Introducción: Colombia es un país endémico para tuberculosis (TB), con una prevalencia de 26 casos por millón. Sin embargo, no se cuenta con datos recientes y claros respecto a la prevalencia de tuberculosis latente (TBL) en la población con artritis reumatoide (AR) candidata a terapia biotecnológica. Metodología: Estudio de corte transversal con componente analítico para determinar la pre-valencia de TBL en pacientes con AR candidatos a terapia biotecnológica. Resultados: La prevalencia de TBL en pacientes con AR candidatos a terapia biotecnológica es alta, del 18,3% (IC 95% 14,7-21,9), y en los cruces exploratorios se encontró una relación entre TBL y la variable género masculino (p ≤ 0,001), hallazgos anormales en la radiografía de tórax (p = 0,039) y el tabaquismo (p = 0,028). Conclusión: La prevalencia de TBL en pacientes con AR candidatos a terapia biotecnológica es alta. Se requieren estudios prospectivos para evaluar la incidencia de TB en este grupo de pacientes y así corroborar su asociación.

ABSTRACT Introduction: Although tuberculosis (TB) is endemic in Columbia, with a prevalence of 26 cases per million, there are no recent and clear data regarding the prevalence of latent tuberculosis (LBT) in the population with rheumatoid arthritis (RA), candidates for biotechnological therapy. Methodology: A cross-sectional study with an analytical component to determine the prevalence of LBT in patients with RA who are candidates for biotechnological therapy. Results: The prevalence of LTB in RA patients who are candidates for biotechnological therapy is high, 18.3% (95% CI: 14.7-21.9). In the exploratory analysis, a relationship between LBT and male gender was found (P ≤ .001), as well as abnormal findings on chest radiography (P = .039), and smoking (P = .028). Conclusion: The prevalence of LTB in patients with RA who are candidates for biotechnological therapy is high. Prospective studies are needed to evaluate the incidence of TB in this group of patients and corroborate this association.

Granulomatous interstitial nephritis secondary to the use of the anti-TNF adalimumab / Nefritis intersticial granulomatosa secundario al uso del anti TNF adalimumab

Abstract We present the case of a 56-year-old patient with progressive kidney function deterioration whose kidney biopsy reported granulomatous interstitial nephritis. The medical chart was reviewed, and it was noted that the deterioration coincided with the initiation of the medication adalimumab. It was discontinued and steroid plus cytostatic treatment was begun, with improvement. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.2050).

Resumen Se presenta el caso de una paciente de 56 años, quien presenta deterioro progresivo en la función renal, y en quien la biopsia renal reportó nefritis intersticial granulomatosa. Se revisó historia clínica, y se detectó que el deterioro coincidía con el inicio del medicamento adalimumab. Se suspendió, inicio terapia de esteroide más citostático con mejoría. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.2050).

Psoriasis paradójica palmoplantar secundaria al tratamiento de la colitis ulcerosa con adalimumab / Paradoxical psoriasis of the palms and soles due to treatment of ulcerative colitis with adalimumab

Los anticuerpos anti-TNF-a (tumor necrosis factor alpha) se utilizan para tratar tanto la psoriasis como la enfermedad inflamatoria intestinal (EII). Sin embargo, estos fármacos han sido implicados en la ocurrencia de la psoriasis paradójica en los pacientes sin antecedentes de psoriasis que reciben tratamiento por una colitis ulcerosa (CU) y otras enfermedades autoinmunes. Se presenta el caso de un paciente de 29 años, sin antecedentes de dermatosis, que desarrolló una psoriasis palmoplantar paradójica por el uso del adalimumab que recibía por un diagnóstico de CU. El cuadro remitió al suspender el medicamento y recurrió al reiniciarlo, motivo por el cual se rotó al ustekinumab. La CU respondió satisfactoriamente, sin nuevas lesiones dermatológicas.

Anti TNF-a (tumor necrosis factor alpha) antibodies are used to treat both psoriasis and inflammatory bowel disease (IBD). However, these drugs have been implicated in the occurrence of the so-called paradoxical psoriasis in patients with no previous history of psoriasis, who receive treatment for ulcerative colitis and other autoimmune diseases. We present a 29-year-old male patient, with no previous history of dermatosis, who developed paradoxical palmar-plantar psoriasis due to the use of adalimumab that he was receiving for a diagnosis of ulcerative colitis. The condition remitted when the drug was suspended and recurred when it was restarted, and for that reason, treatment was rotated to ustekinumab. Ulcerative colitis responded satisfactorily, with no new dermatological lesions.

Immunogenicity to biological drugs in psoriasis and psoriatic arthritis

Monoclonal antibodies or fusion proteins, defined as biological drugs, have modified the natural history of numerous immune-mediated disorders, allowing the development of therapies aimed at blocking the pathophysiological pathways of the disease, providing greater efficacy and safety than conventional treatment strategies. Virtually all therapeutic proteins elicit an immune response, producing anti-drug antibodies (ADAs) against hypervariable regions of immunoglobulins. Immunogenicity against biological drugs can alter their pharmacokinetic and pharmacodynamic properties, thereby reducing the efficacy of these drugs. In more severe cases, ADAs can neutralize the therapeutic effects of the drug or cause serious adverse effects, mainly hypersensitivity reactions. The prevalence of ADAs varies widely depending on the type of test used, occurrence of false-negative results, and non-specific binding to the drug, making it difficult to accurately assess their clinical impact. Concomitant use of immunosuppressors efficiently reduces the immunogenicity in a dose-dependent manner, either by decreasing the frequency of detectable ADAs or by delaying their appearance, thereby enhancing the effectiveness of biological therapies. Among the new therapeutic strategies for the management of psoriasis, biological agents have gained increasing importance in recent years as they interrupt key inflammation pathways involved in the physiopathology of the disease. Reports regarding ADA in new biologics are still scarce, but the most recent evidence tends to show little impact on the clinical response to the drug, even with prolonged treatment. It is therefore essential to standardize laboratory tests to determine the presence and titles of ADAs to establish their administration and management guidelines that allow the determination of the real clinical impact of these drugs.

Incidencia de tuberculosis en pacientes que reciben fármacos anti-TNF( / Incidence of tuberculosis in patients receiving tumor necrosis factor-( blockers / Incidência de tuberculose em pacientes que recebem fármacos anti-TNF(

Resumen: Introducción: la tuberculosis (TB) es una complicación frecuente del uso de fármacos anti-TNF(. Ocurre por reactivación de una infección latente o por progresión de una infección reciente. Objetivos: conocer la incidencia de TB en la población que recibió fármacos anti- TNF(, analizar las formas de presentación y la realización de pesquisa de infección latente previo al inicio del tratamiento. Método: estudio de cohorte retrospectiva. Se incluyeron los pacientes que recibieron fármacos anti- TNF( entre 2010 y 2016. Los datos se obtuvieron de los sistemas informáticos del Fondo Nacional de Recursos y del Programa Nacional de Tuberculosis. Se calculó la incidencia de TB y se describieron los casos que desarrollaron TB. Resultados: se incluyeron 991 tratamientos para un total de 980 pacientes. Se reportaron nueve casos de TB. La incidencia global fue de 419,9 (IC 95% 191,9-591,2) por 100.000 personas/año. Solo hubo casos de TB en pacientes tratados con adalimumab. El cribado de infección tuberculosa latente (ITBL) previo al inicio del fármaco fue heterogéneo y predominaron las formas de TB diseminadas (6/9) sobre la afectación pulmonar aislada (3/9). En todos los casos se suspendió el anti- TNF( al diagnóstico de TB y en ningún caso se retomó. Conclusiones: la incidencia de TB en la población de pacientes bajo tratamiento con anti- TNF( fue 16,5 veces mayor que en la población general. Predominaron las formas de TB diseminadas y se dieron casos en sujetos que habían recibido tratamiento de ITBL previo al inicio del fármaco, sugiriendo que el riesgo persiste mientras exista exposición a éste.

Summary: Introduction: tuberculosis (TB) is a frequent complication in patients receiving tumor necrosis factor-alpha (TNF-() blockers. It occurs upon the reactivation of a latent infection or the progression of a recent infection. Objective: to learn about the incidence of TB in a population receiving tumor necrosis factor-alpha (TNF-() blockers, to analyze the presentation of this condition and to conduct a latent infection research prior to the initiation of therapy. Method: retrospective cohort study. Patients receiving tumor necrosis factor-alpha (TNF-() blockers between 2010 and 2016 were included in the study. Data were obtained from the IT systems of the National Resources Fund and the National Tuberculosis Program. The incidence of TB was calculated and the cases developing TB were described. Results: 991 treatments were included for 980 patients in total. 9 cases of TB were reported. Global incidence was 419.9 (IC 95% 191.9-591.2) out of 100,000 people per year. Cases of TB were only seen in patients treated with adalimumab. Screening for LTBI upon initiation of the drug was heterogeneous and the disseminated forms of TB prevailed (6/9) over isolated pulmonary affectation (3/9). In all cases anti- TNF( was suspended when TB was diagnosed, and it was not reinitiated. Conclusions: the incidence of TB in patients receiving tumor necrosis factor-alpha (TNF-() blockers was 16.5 times greater than in the general population. Disseminated forms of TB prevailed, and some cases occurred in individuals who had received LTBI therapy prior to the initiation of the drug, suggesting the risk persists as long as there is exposure to the drug.

Resumo: Introdução: a tuberculose (TB) é uma complicação frequente do uso de fármacos anti- TNF(. É causada pela reativação de uma infecção latente ou pela evolução de uma infecção recente. Objetivos: conhecer a incidência de TB na população que recebeu fármacos anti- TNF(, analisar as formas de apresentação e a realização de pesquisa de infecção latente prévia ao início do tratamento. Método: estudo de coorte retrospectivo. Foram incluídos todos os pacientes que receberam fármacos anti- TNF( no período 2010-2016. Os dados foram obtidos dos registros informatizados do Fondo Nacional de Recursos e do Programa Nacional de Tuberculosis. A incidência de TB foi calculada e foram descritos os casos que desenvolveram esta patologia. Resultados: foram incluídos 991 tratamentos para um total de 980 pacientes. Nove casos de TB foram registrados. A incidência global foi de 419,9 (IC 95% 191,9-591,2) por 100.000 pessoas/ano. Somente foram registrados casos de TB em pacientes tratados com adalimumab. A triagem de infecção tuberculosa latente (ITBL) prévia ao início do fármaco foi heterogênea e predominaram as formas de TB disseminadas (6/9) sobre a pulmonar isolada (3/9). Em todos os casos o uso de anti- TNF( foi suspenso definitivamente quando o diagnóstico de TB foi realizado. Conclusões: a incidência de TB na população de pacientes em tratamento com anti- TNF( foi 16,5 vezes maior que na população em geral. Predominaram as formas disseminadas de TB e foram registrados casos em pacientes que haviam recebido tratamento para ITBL prévio ao início do fármaco, sugerindo que o risco persiste enquanto houver exposição a este.

Incidence of tuberculosis infection in spondyloarthritis patients treated with biological and conventional disease-modifying anti-rheumatic drugs in an endemic area

Introduction: Registries of spondyloarthritis (SpA) patients' follow-up provided evidence that tumor necrosis factor inhibitors (TNFi) increase the incidence of active tuberculosis infection (TB). However, most of these registries are from low burden TB areas. Few studies evaluated the safety of biologic agents in TB endemic areas. This study compares the TB incidence rate (TB IR) in anti-TNF-naïve and anti-TNF-experienced subjects with SpA in a high TB incidence setting.Methods: In this retrospective cohort study, medical records from patients attending a SpA clinic during 13 years (2004 to 2016) in a university hospital were reviewed. The TB IR was calculated and expressed as number of events per 105 patients/year; the incidence rate ratio (IRR) associated with the use of TNFi was calculated.Results: A total of 277 patients, 173 anti-TNF-naïve and 104 anti-TNF-experienced subjects, were evaluated; 35.7% (N = 35) of patients who were prescribed an anti-TNF drug were diagnosed with latent tuberculosis infection (LTBI). Total follow-up time (person-years) was 1667.8 for anti-TNF-naïve and 394.9 for anti-TNF-experienced patients. TB IR (95% CI) was 299.8 (37.4-562.2) for anti-TNF naïve and 1012.9 (25.3-2000.5) for anti-TNF experienced subjects. The IRR associated with the use of TNFi was 10.4 (2.3- 47.9).Conclusions: In this high TB incidence setting, SpA patients exposed to anti-TNF therapy had a higher incidence of TB compared to anti-TNF-naïve subjects, although the TB incidence in the control group was significant.(AU)

Latent tuberculosis infection in patients with rheumatic diseases / Infecção latente por tuberculose em pacientes com doenças reumatológicas

ABSTRACT Most people infected by Mycobacterium tuberculosis (Mtb) do not have any signs or disease symptoms, a condition known as latent tuberculosis infection (LTBI). The introduction of biological agents, mainly tumor necrosis factor (TNF) inhibitors, for the treatment of immune-mediated diseases such as Rheumatoid Arthritis (RA) and other rheumatic diseases, increased the risk of reactivation of LTBI, leading to development of active TB. Thus, this review will approach the aspects related to LTBI in patients with rheumatologic diseases, especially those using iTNF drugs. For this purpose it will be considered the definition and prevalence of LTBI, mechanisms associated with diseases and medications in use, criteria for screening, diagnosis and treatment. Considering that reactivation of LTBI accounts for a large proportion of the incidence of active TB, adequate diagnosis and treatment are crucial, especially in high-risk groups such as patients with rheumatologic diseases.

RESUMO A maioria das pessoas infectadas por Mycobacterium tuberculosis (Mtb) não possui sinais ou sintomas da doença, quadro conhecido como infecção latente por tuberculose (ILTB). A introdução de agentes biológicos, sobretudo inibidores do fator de necrose tumoral (iTNF), para o tratamento de doenças imunomediadas, como artrite reumatoide (AR) e outras doenças reumatológicas, aumentou o risco de reativação de ILTB, levando ao desenvolvimento de tuberculose (TB) ativa. Assim, esta revisão abordará os aspectos relacionados à ILTB em pacientes com doenças reumatológicas, especialmente naqueles em uso de medicamentos iTNF. Para tanto, serão considerados a definição e a prevalência de ILTB, os mecanismos associados às doenças e às medicações em uso, bem como os critérios para rastreamento, diagnóstico e tratamento da ILTB. Como a reativação da ILTB é responsável pela grande proporção de casos de TB ativa, o diagnóstico e o tratamento adequados são cruciais, principalmente em grupos de alto risco, como os pacientes com doenças reumatológicas.

Electrocardiographic changes in spondyloarthritis and use of anti-TNF-α drugs: a retrospective study with 100 patients / Alterações eletrocardiográficas em espondiloartrites e uso de anti-TNF-α: estudo retrospectivo em 100 pacientes

ABSTRACT Objective To investigate the prevalence of electrocardiographic changes in patients with spondyloarthritis and to correlate these changes with use of anti-tumor necrosis factor-alpha (TNF-α) drugs and HLA-B27 positivity. Methods Retrospective study including 100 patients diagnosed with spondyloarthritis according to Assessment of SpondyloArthritis International Society (ASAS) criteria and 50 controls. Epidemiological and clinical features, results of inflammatory activity tests, HLA-B27 positivity, and medication use data were extracted from medical records. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). All participants were submitted to electrocardiogram performed using a 12-lead device; rhythm, heart rate, conduction disorders and QT interval corrected using the Bazett formula were analyzed. Results Of 100 patients with spondyloarthritis, 51 were on anti-TNF-α drugs and 49 were not. HLA-B27 was detected in 53.1% of patients in the sample. Patients with spondyloarthritis had lower heart rate (p=0.06), longer QT interval (p<0.0001) and higher prevalence of right bundle branch block (p=0.014) compared to controls. Duration of disease was weakly correlated with heart rate (Rho=0.26; 95%CI: 0.06-0.44; p=0.008). The prevalence of right bundle branch block was positively correlated with HLA-B27 positivity. Use of Anti-TNF-α drugs did not interfere with electrocardiographic parameters. Conclusion Patients with spondyloarthritis had lower heart rate, longer QT interval and a higher prevalence of right bundle branch block compared to controls. HLA-B27 positivity was associated with the prevalence of right bundle branch block. Anti-TNF-α drugs had no impact on electrocardiographic findings.

RESUMO Objetivo Avaliar a prevalência de alterações eletrocardiográficas em pacientes com espondiloartrites, correlacionando-as com o uso de medicações antifator de necrose tumoral alfa (TNF-α) e presença do HLA-B27. Métodos Estudo retrospectivo com 100 pacientes com diagnóstico de espondiloartrites pelo critério Assessment of SpondyloArthritis International Society (ASAS) e 50 controles. Foram coletados nos prontuários dos pacientes, dados epidemiológicos, clínicos, exames de atividade inflamatória, presença do HLA-B27, e uso de medicamentos. A atividade de doença foi avaliada pelo Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Todos foram submetidos a eletrocardiograma realizado com aparelho de 12 derivações, sendo analisados ritmo, frequência cardíaca, distúrbios de condução e intervalo QT corrigido pela fórmula de Bazett. Resultados Dos 100 pacientes com espondiloartrites, 49 não usavam anti-TNF-α e 51 utilizavam este medicamento. O HLA-B27 estava presente em 53,1% da amostra. A frequência cardíaca foi mais baixa (p=0,06), o intervalo QT foi mais prolongado (p<0,0001) e existia mais perturbação de condução do ramo direito (p=0,014) nos pacientes com espondiloartrites do que nos controles. Uma modesta correlação de tempo de doença com frequência cardíaca foi encontrada (Rho=0,26; IC95%: 0,06-0,44; p=0,008). A presença do HLA-B27 aumentou a prevalência de perturbação de condução do ramo direito. Nenhum dos parâmetros eletrocardiográficos analisados alterou-se com uso de anti-TNF-α. Conclusão Pacientes com espondiloartrites tiveram frequência cardíaca menor, maior intervalo QT e prevalência maior de perturbação de condução do ramo direito do que controles. O HLA-B27 influi no aparecimento de perturbação de condução do ramo direito. O uso de anti-TNF-α não influiu nos achados eletrocardiográficos.

Risk factors for postoperative complications in Crohn disease: analysis of 173 patients / Fatores de risco para complicações pós-operatórias na Doença de Crohn: análise de 173 pacientes

ABSTRACT Background and objectives: Surgery for Crohn disease has a wide range of factors that are being studied as possible risk factors for postoperative complications. The later are a major problem in those patients and are associated with longer hospital stays and increased mortality and morbidity. Despite the debate regarding the influence of patients' characteristics, preoperative and operative details, the risk factors are not fully identified. The debate has been focused on the new medical therapy and the time of surgery. Our goal was to help identify and confirm risk factors for postoperative complications. Materials and methods: A retrospective cohort study including all patients operated due to Crohn disease in São João Hospital Center from 2010 to 2015. We analyzed patient, preoperative and surgical characteristics. For postoperative complications data only those occurring within 30 days were included. Results: Neither age at diagnosis or previous corticotherapy/anti-TNF/ustekinumab was significantly associated with an increased risk in postoperative complications. Only age at surgery >40 years (Montreal Classification A1 + A2 vs. A3; OR = 4.12; p < 0.05) and the group others (occlusion vs. others [combination of intestinal perforation, mesenteric ischemia and postoperative complications] vs. fistula/abscess as indication for surgery; OR = 4.12; p < 0.05) remained as independent risk factors after multivariable regression analysis. Conclusions: We described clear associations between age at surgery >40 years and the group others (intestinal perforation, mesenteric ischemia and postoperative complications) and overall postoperative complications in Crohn disease. These results may suggest that surgery does not need to be delayed and, in some cases, should be anticipated.

RESUMO Introdução e objetivos: Vários fatores têm sido estudados como possíveis fatores de risco para complicações pós-operatórias na doença de Crohn. Estas complicações estão associadas a estadias mais prolongadas no hospital e a um aumento da mortalidade. Apesar do debate relativo à influência das características dos pacientes, pré-operatórias e operatórias, os fatores de risco ainda não estão completamente identificados. Atualmente, o debate centra-se nos avanços da terapia médica e no melhor momento para realizar a operação. O objetivo era identificar os fatores de risco para complicações pós- operatórias. Materiais e métodos: Realizamos um estudo retrospectivo incluindo todos os pacientes operados devido à doença de Crohn no Hospital São João desde 2010 até 2015. Analisamos as características dos doentes, as pré e as pós-operatórias. Apenas foram incluídos os dados relativos a complicações no período de 30 dias após a cirurgia. Resultados: A idade ao diagnóstico e o uso prévio de corticoterapia/anti-TNF/ustekinumab não foram associados a um aumento no risco de complicações pós-operatórias. Apenas a idade na cirurgia superior aos 40 anos (Classificação de Montreal A1 + A2 vs. A3; OR = 4.12; p < 0.05) e o grupo 'outros' (oclusão vs. outros [combinação de perfuração intestinal, isquemia mesentérica e complicações pós-operatórias] vs. fistula/abscesso como indicação para cirurgia; OR = 4.12; p < 0.05) são fatores de risco independentes. Conclusões: Descrevemos uma associação clara entre a idade na cirurgia superior aos 40 anos e o grupo 'outros' e a existência de complicações pós-operatórias na doença de Crohn. A cirurgia não deve ser adiada e, em alguns casos, seria benéfico antecipá-la.

Análise da frequência de uveítes em pacientes com espondiloartrites, suas complicações e associação com parâmetros clínicos da doença / Analysis of the frequency of uveitis in spondyloarthritis patients and associations with clinical parameters of the disease

Resumo Objetivo: A uveíte anterior aguda é a principal manifestação extra-articular na espondiloartrite. O objetivo deste estudo foi analisar se a presença da uveíte se associa com diferentes manifestações clínicas, laboratoriais, radiológicas e a terapêutica nos pacientes com espondiloartrite. Métodos: Estudo observacional retrospectivo realizado com 153 pacientes portadores de espondiloartrite atendidos no período de 1997 a 2017 na Grande Florianópolis, Brasil. Foram analisados dados demográficos, laboratoriais, clínicos e do tratamento de pacientes com espondiloartrite em relação a presença ou não de uveíte. Resultados: A uveíte foi encontrada em 26,8% dos pacientes. A presença de complicações foi rara, ocorrendo catarata em somente quatro pacientes e glaucoma em dois deles. Foi observada uma tendência a maior frequência de uveíte anterior aguda no sexo masculino (p=0,06), nos pacientes com história familiar (p=0,19) e HLA-B27 positivos (p=0,14). Pacientes com espondiloartrite e uveíte mais frequentemente usavam anti-TNF (p=0,04) e apresentavam sacroiliite em exames de imagem (p=0,02). Não observou-se associação entre a uveíte e o acometimento cardiovascular (p=0,44), cutâneo (p=0,13) ou gastrointestinal (p=0,10). Conclusão: A uveíte que ocorre em pacientes com espondiloartrite é comum, tem predomínio no sexo masculino e é mais frequente em pacientes com HLA-B27 positivo. O uso de imunobiológicos como o anti-TNF é frequente nos pacientes com uveíte.

Abstract Objective: Acute anterior uveitis (AAU) is the most common extra-articular manifestation of spondyloarthritis. The aim of this study is to analyze if the presence of uveitis is associated with a diferent clinical manifestation, laboratorial, radiological and therapetiuc among spondyloarthritis patients. Methods: This was a observational retrospective study with 153 patients with spondyloarthritis attended in the period from 1997 to 2017 in Florianopolis, Brazil. It was analyzed demografical, laboratorial, clinical and therapeutic data in spondyloarthritis patients with or without uveitis. Results: 26,8% of the patients with spondyloarthritis presented uveitis. The presence of complications was rare, with cataract occurring in only four patients and glaucoma in two of them. A higher frequency of acute anterior uveitis in males (p = 0.06) was observed in patients with a family history (p = 0.19) and HLA-B27 positive (p = 0.14). Patients with spondyloarthritis and uveitis more frequently used anti-TNF (p = 0.04) and presented sacroiliitis on imaging tests (p = 0.02). There was no association between uveitis and cardiovascular (p = 0.44), cutaneous (p = 0.13) or gastrointestinal involvement (p = 0.10). Conclusion: Uveitis in patients with spondylarthritis is common, predominantly in males, and more frequently in HLA-B27 positive patients. The use of immunobiological agents such as anti-TNF is common in patients with uveitis.

Paradoxical skin reaction with infliximab treatment / Reação cutânea paradoxal com tratamento com infliximabe

Considering the increased utilization of anti-TNF medications in the treatment of inflammatory and autoimmune diseases, dermatologists should be aware of the possible adverse skin reactions. We describe a case of inverted psoriasis due to the use of infliximab used in the treatment of inflammatory bowel disease. (AU)

Com o aumento do uso de anti-TNF no tratamento de doenças inflamatórias e auto-imunes, os dermatologistas devem estar conscientes da possibilidade de reações cutâneas adversas. Apresentamos um caso de psoríase invertida devido ao uso de infliximab utilizado no tratamento da doença inflamatória intestinal. (AU)

Three cases of anti-TNF induced myositis and literature review / Três casos de miosite induzida pelo anti-TNF e revisão da literatura

Abstract Anti-tumor necrosis factor drugs are frequently preferred in the treatment of rheumatologic diseases and other inflammatory diseases. The development of myositis after using anti-tumor necrosis factor drugs is a rare clinical condition. Here we aimed to report cases who developed myositis after using anti-tumor necrosis factor drugs and review the current literature. We report two cases of rheumatoid arthritis and a case of ankylosing spondylitis developed idiopathic inflammatory myopathy following anti-tumor necrosis factor therapy. In conclusion, myositis could develop during anti-tumor necrosis factor therapy, so these patients should be evaluated carefully initially for myositis and should be closely monitored due to the potential for developing myositis in treatment process.

Resumo Os fármacos antifator de necrose tumoral (anti-TNF) são frequentemente preferidos no tratamento de doenças reumatológicas e outras doenças inflamatórias. O desenvolvimento de miosite após o uso de anti-FNT é uma condição clínica rara. Este estudo objetivou descrever casos de pacientes que desenvolveram miosite após o uso de anti-TNF e fazer uma revisão da literatura atual. Descrevem-se dois casos de artrite reumatoide (AR) e um caso de espondilite anquilosante (EA) que desenvolveram miopatia inflamatória idiopática após o tratamento com anti-TNF. Em conclusão, pode haver desenvolvimento de miosite durante o tratamento com anti-TNF, de modo que esses pacientes devem ser cuidadosamente avaliados inicialmente à procura de miosite e devem ser cuidadosamente monitorados em razão do potencial de desenvolvimento de miosite no processo de tratamento

Latent tuberculosis infection screening in juvenile idiopathic arthritis patients preceding anti-TNF therapy in a tuberculosis high-risk country / Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti-TNF em um país de alto risco para tuberculose

Abstract Objectives: To evaluate, in an endemic country, the long-term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers. Methods: This was a retrospective cohort that included JIA patients eligible to anti-TNF therapy. Patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history of exposure to TB. Subjects were regularly followed at 2-month intervals. Results: Sixty-nine JIA patients with current age of 17.4 ± 5.8 years, mean disease duration of 5.0 ± 4.9 years were included. Forty-seven patients received a single anti-TNF, while 22 patients switched to another anti-TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST-positive and history of TB exposure and two had solely TST-positive. No active TB was diagnosed during the study period (median of follow-up was 3.8 years). Conclusion: Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment was effective in a high-risk country and TST was the most sensitive parameter to identify these patients.

Resumo Objetivo: Avaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF. Métodos: Trata-se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti-TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti-TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses. Resultados: Incluíram-se 69 pacientes com AIJ com idade atual de 17,4 ± 5,8 anos, com média de duração da doença de 5 ± 4,9 anos; 47 pacientes receberam um único anti-TNF, enquanto 22 foram transferidos para outro anti-TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos). Conclusão: A avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti-TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.

Infecciones severas en pacientes con artritis reumatoide tratados con fármacos antagonistas del factor de necrosis tumor alfa / Serious infections in patients with rheumatoid arthritis treated with tumor necrosis factor alpha antagonist therapy

ResumenJustificación y objetivos:el uso de fármacos antagonistas del factor de necrosis tumoral alfa se asocia a infecciones severas en artritis reumatoide, con una alta morbi-mortalidad en la práctica clínica. No existe casuística publicada respecto al tema en nuestro país. Se pretende aportar información relacionada con la epidemiología local de las infecciones severas e identificar factores de riesgo asociados.Métodos:estudio observacional retrospectivo, que incluyó 50 pacientes tratados al menos un año en el periodo 2006-2012. Se evaluaron las características demográficas, así como las clínicas y epidemiológicas de la(s) infección(es) severa(s) desarrollada(s) y los factores de riesgo asociados.Resultados:la mayor parte de los pacientes fueron mujeres en edad media. Solo se documentó una infección severa, que correspondió a una infección de piel y tejido blando que resolvió con terapia antibiótica intravenosa. Se registraron factores de riesgo, especialmente en uso de terapia inmunosupresora esteroidal y el antecedente quirúrgico reciente, con una baja prevalencia de comorbilidades.Conclusiones:el perfil demográfico, así como el perfil clínico de las infecciones severas es similar a otras poblaciones, la baja incidencia de éstas en la cohorte podría relacionarse a una menor prevalencia de comorbilidades, no obstante se requiere investigaciones futuras para corroborar o descartar dicha observación.

AbstractAim and objetives:the use of tumour necrosis factor alpha therapy antagonist leads to an increased risk of serious infections in rheumatoid arthritis, with a high morbi-mortality in clinical practice. There are no published data in our country. This study pretends to provide knowledge about the local epidemiology of serious infections and to identify associated risk factors.Methods:An observational and retrospective study, included 50 patients treated at least for one year between 2006-2012. Demographic characteristics, clinical and epidemiological characteristics of serious infections and risk factors associated with serious infections were described.Results:A predominant female population in middle age was detected. Just one serious infection was described, corresponding to serious skin and soft tissue infection that resolved with intravenous antibiotics. Risk factors were described including inmunosuppresive therapy with steroids and prior surgery.Conclusions:Demographic profile of analized population and their clinic profile of serious infectios are similar to others populations. Low incidence of serious infections in this cohort could be related with less comorbilities than others populations, although, this topic needs further investigations to corroborate or discard this observation.

Physicians Should Provide Shared Decision-Making for Anti-TNF Therapy to Inflammatory Bowel Disease Patients

Shared decision-making may increase the effectiveness of inflammatory bowel disease (IBD) treatment, as different anti-tumor necrosis factor (anti-TNF) administrations may have different effects on the quality of life (QOL). Patient preference is integral to the selection of anti-TNFs and their routes of administration, however, previous studies on the patient preference to anti-TNFs are inconsistent and limited. We evaluated the predictive factors for preferences to anti-TNF administrations in IBD patients between March and August in 2015. Consecutive adult IBD patients who received care at one of four university hospitals in Korea were invited to participate in this study. Patients were administered questionnaires about their preferences regarding anti-TNF therapy and QOL. During the study period, 322 IBD patients completed the questionnaires. IBD patients preferred intravenous anti-TNFs to subcutaneous anti-TNFs (2.4:1), and 58.4% of patients preferred shared decision-making. When comparing subcutaneous anti-TNF therapy with intravenous anti-TNF therapy, patients with higher income levels, patients who experienced adverse events with prior medication and patients with a longer disease duration preferred subcutaneous anti-TNF therapy over intravenous anti-TNF therapy (P = 0.043, P = 0.000, and P = 0.029, respectively). In a logistic regression analysis, high income level (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.1–3.5; P = 0.026) and an adverse event with prior medication (OR 4.0; 95% CI 2.2–7.2; P = 0.000) and were found to be independent predictors for preference to subcutaneous anti-TNF therapy. Therefore, physicians should share decision-making with their IBD patients regarding the mode of anti-TNF administration.

El papel de los biosimilares en la enfermedad inflamatoria intestinal: una realidad en nuestro país / The Role of Biosimilars in Inflammatory Bowel Disease: A Reality in our Country

Resumen La enfermedad inflamatoria intestinal (EII) es un término con el que se conocen varias entidades, las 2 más importantes son: la colitis ulcerativa idiopática (CUI) y la enfermedad de Crohn (EC), cuyo origen es multifactorial y se caracterizan por un fenómeno inflamatorio, crónico, recurrente con diferentes grados de severidad del tubo digestivo; pero además con afectación potencial de otros órganos. En la última década ha habido un renovado interés en dichas entidades, debido a una incidencia creciente de estas, pero también debido al desarrollo de medicamentos que por primera vez están cambiando la historia natural de estas enfermedades: son los medicamentos llamados biológicos, que son aquellos producidos o derivados de organismos vivos y representan el sector de mayor crecimiento en la industria farmacéutica mundial. Debido al interés comercial, se han desarrollado y sometido a las autoridades reguladoras productos no originadores; similares, pero no idénticos a los productos de referencia. La Agencia Europea de Medicamentos (EMA) aprobó el primer biosimilar del infliximab para todas las indicaciones en las cuales este estaba aprobado, incluidas: colitis ulcerativa moderada a severa en todas las edades, EC moderada a severa en todas las edades, al igual que EC fistulizante, artritis psoriásica (AP), psoriasis, espondilitis anquilosante (EA) y artritis reumatoide (AR) (1). En esta revisión nos proponemos definir lo que son estos productos al igual que algunos conceptos relacionados (extrapolación, sustitución e intercambiabilidad), además hacer una revisión histórica de su desarrollo, sus indicaciones actuales, las posiciones de las diferentes asociaciones científicas al respecto y, lo más importante, brindar datos de la vida real en cuanto a su efectividad, seguridad y costos en los diferentes países donde se han estado usando.

Abstract The term Inflammatory Bowel Disease (IBD) is used to identify several entities, the two most important of which are Idiopathic Ulcerative Colitis (IUC) and Crohn's Disease (EC). Both are multifactorial in origin, are chronic and recurrent, are characterized by inflammation, have varying degrees of severity, and potentially involve other organs. In the last decade there has been renewed interest in these entities due to growing incidence and to the development of drugs called biologicals. For the first time, these drugs have changed the natural history of these diseases. They are produced or derived from living organisms and represent the fastest growing sector in the global pharmaceutical industry. Due to commercial interest, products similar but not identical to the original products have been developed and submitted to regulatory authorities. The European Medicines Agency has approved the first biosimilar for infliximab for all indications for which it has been approved. These include moderate to severe ulcerative colitis (UC) at all ages, moderate to severe Crohn's disease (CD) at all ages, fistulizing Crohn's disease, Psoriasic arthritis, Psoriasis, Ankylosing Spondylitis, and Rheumatoid Arthritis. 1 In this review, we define what these products are, as well as some concepts coined for their usage including extrapolation, substitution and interchangeability. We also make a historical review of their development, current indications, the positions of various scientific associations with respect to them, and - most importantly - provide real-life data regarding their effectiveness, safety and costs in countries where they have been used.