Rheumatoid arthritis (RA) is an autoimmune disease, which causes joint inflammation. Different environmental and genetic factors such as smoking, anti-citrullinated protein antibody, rheumatoid factor, and certain MHC-alleles cause RA. It affects mostly women and it is characterised by joint swelling, pain, tiredness, and stiffness. Untreated RA can lead to disability and complications in different organs (brain, lung, heart,). The body develops tolerance against self-antigens using different mechanisms, including Tregs mediated, by increasing the expression of inhibitory receptors and through receptor modification/destruction of self-reactive cells.  Failure in the resistance development mechanism leads to autoimmune diseases. The most important cellular components of RA dependent inflammation are macrophages, T-cells, and B-cells. These cells contribute to the inflammations process by producing antibodies, cytokines, and through antigen presentation or immune cell activation. One of the cytokines, which are released by macrophages and T-cells is Tumour necrosis factor (TNF). It stimulates angiogenesis, activation of osteoclasts and the production of different cytokines by increasing the expression of NF-kB.  The diagnostic process of RA consists of serological, physical, and radiological examinations. These examinations together with other factors are utilized for calculating score (0-10), in order to decide if a patient have RA or not. The treatment of RA depends on disease activity and it is composed of NSAID, steroids, DMARDs, biological DMARDs and non-pharmacological treatment. The interventions can be given as a monotherapy or in combination. The disease activity of RA or the efficacy of a drug which is used to treat RA can be studied by ACR response, DAS-28, HAQ-DI score using joint progression score. The aim of the study was to investigate the efficacy and safety of adalimumab, as well as to compare it with other treatments, which are used to in RA. 5 scientific articles which were obtained from PubMed were used to perform the study. The keywords used to get the materials was” adalimumab rheumatoid arthritis”. It gave 172 results and 5 of the first 20 were selected. ACR 20 response and change in DAS-28 were studied as a primary efficacy endpoint. The result of the studies demonstrated that adalimumab had a moderate-god effect against RA according to the ACR/ EULAR criteria. However, adalimumab was less effective comparing to barcitinib, tocilizumab, sirukumab but it had a similar efficacy as ABP 501 as well as abatacept.   ACR response, change in DAS-28 and remission rate showed better results in patients who treated by sirukumab, tocilizumab or barcitinib. The studies have also proved that adalimumab leads to better outcomes when it is used in combination with methotrexate instead of monotherapy. Regarding safety, all the drugs showed similar patterns and nasopharyngitis as well as lung infections were the most common adverse events. More studies are required in order to find the perfect target molecule and combination therapy so that RA can be treated efficiently and at a lower cost.

<p>Uvod: Reumatoidni artritis (RA) je bolest koja dovodi do ireverzibilnog o&scaron;tećenja zglobova usled čega je neophodno pri postavljanju dijagnoze započeti lečenje. TNF-alfa inhibitori predstavljaju revolucionarno otkriće u lečenju RA, pri čemu su najče&scaron;će kori&scaron;ćeni Etanercept i Adalimumab. Oni nisu efikasni kod svih pacijenata kod kojih se primene, a mehanizmi gubitka odgovora nisu jasni. Cilj rada je odrediti uticaj Etanercepta i Adalimumaba na aktivnost bolesti (merenjem DAS28 SE i DAS28 CRP skora) i funkcionalni status pacijenata (merenjem HAQ-DI upitnika), broj bolnih i otečnih zglobova pre i tokom godinu dana primene ovih lekova, kao i utvrditi povezanost koncentracije Etanercepta i Adalimumaba u krvi sa vrednostima DAS28 SE u momentu odreĎivanja koncentracije leka. Praćena je i učestalost neželjenih efekata kod pacijenata lečenih sa ova dva leka. Ispitan je i uticaj primene Metotreksata na nivoe lekova u krvi, kao i doza Metotreksata pre i 6 meseci nakon uvoĎenja Etanercepta ili Adalimumaba. Metode: Studija je sprovedena u Specijalnoj bolnici za reumatske bolesti i Klinici za nefrologiju i kliničku imunologiju, Kliničkog centra Vojvodine u Novom Sadu i obuhvatila je 88 pacijenata kod kojih je postavljena dijagnoza RA, od kojih je 49 bilo lečeno Etanerceptom, a 39 Adalimumabom. Analizirana je medicinska dokumentacija, a nakon početka primene TNF-alfa inhibitora svim ispitanicima je u toku godinu dana svaka tri meseca raĎena kontrola koja je podrazumevala anamnezu i fizički pregled, analizu biohemijskih nalaza krvi, merena je aktivnost bolesti merenjem indeksa aktivnosti bolesti DAS28 SE i DAS28 CRP i raĎena procena funkcionalnog statusa tako &scaron;to je pacijent popunjavao HAQ-DI upitnik. Rezultati: Aktivnost RA merena DAS28 SE i DAS28 CRP indeksima, funkcionalni status meren HAQ-DI upitnikom, broj bolnih i otečenih zglobova i vrednosti reaktanata akutne faze značajno su veći pre početka terapije Etanerceptom i Adalimumabom i smanjuje se tokom prvih 6 meseci lečenja ovim lekovima i potom se taj efekat terapije održava do kraja perioda praćenja. Nema statistički značajne razlike u poreĎenju Etanercepta i Adalimumaba u odnosu na učestalost neželjenih dejstava. Doza Metotreksata je statistički značajno manja 6 meseci nakon upotrebe biolo&scaron;kog leka Etanercept i Adalimumab. Pacijenti lečeni Metotreksatom uz Adalimumab imali su statistički značajno veće nivoe leka, nego oni koji ga nisu koristili. Zaključak: TNF-alfa inhibitori ne dovode do zaustavljanja bolesti kod svih pacijenata kod kojih se primene. Mehanizam gubitka odgovora na terapiju TNF-alfa inhibitorima nije jasan. Kako bi se donela najbolja odluka za pacijenta, neophodno je odrediti nivo leka u krvi, kao i nivo antitela na lek prilikom svake promene stanja pacijenta. Za sada nema dovoljno studija koje ukazuju da li postoji veza izmeĎu ekspresije TNF-alfa gena i nivoa TNF-alfa u krvi, te da li bi se merenjem TNF-alfa u krvi mogla korigovati terapija i doza TNF-alfa inhibitora &scaron;to će verovatno biti predmet budućih istraživanja.</p> / <p>Rheumatoid Arthritis (RA) is a disease that leads to irreversible joint damage, which makes necessary to start treatment when the diagnosis is set. TNF-alpha inhibitors represent a revolutionary discovery in the treatment of RA, and the most commonly used are Etanercept and Adalimumab. They are not effective in all patients, and the mechanisms of loss of response are not clear. The aim of this study is to determine the effect of Etanercept and Adalimumab on disease activity (by measuring DAS28 SE and DAS28 CRP score) and the functional status of patients (by measuring the HAQ-DI questionnaire), the number of painful and swollen joints before and during the first year of administration of these drugs. Also, it was determined a correlation between the concentration of Etanercept and Adalimumab in blood and the values of DAS28 SE at the moment of drug concentration measurement. The incidence of adverse effects in patients treated with these two drugs was also observed. It was examined the effect of Methotrexate on drug levels in the blood as well as the dose of Methotrexate before and 6 months after the introduction of Etanercept or Adalimumab. Methods: The study was conducted at the Special Hospital for Rheumatic Diseases and the Clinic of Nephrology and Clinical Immunology, Clinical Center of Vojvodina in Novi Sad. It included 88 patients with RA, 49 were treated with Etanercept and 39 with Adalimumab. Medical documentation was analyzed, and during the first year of TNF-alpha inhibitor administration, every three months were done anamnesis and physical examination, analysis of blood biochemical findings, measurements of the disease activity with DAS28 SE and DAS28 CRP score and a functional status assessment with the HAQ-DI questionnaire. Results: Disease activity measured by DAS28 SE and DAS28 CRP scores, functional status measured with HAQ-DI questionnaire, number of painful and swollen joints and acute phase reactant values are significantly higher before Etanercept and Adalimumab therapy and decreased during the first 6 months of treatment with these drugs and then this effect of therapy is maintained until the end of the monitoring period. There is no statistically significant difference in the comparison of Etanercept and Adalimumab with respect to the frequency of adverse events. The dose of Methotrexate was statistically significantly lower for 6 months after the use of Etanercept and Adalimumab. Patients treated with Methotrexate and Adalimumab had statistically significantly higher drug levels than those who did not use it. Conclusion: TNF-alpha inhibitors are not effective in all patients who used them. The mechanism of loss of response to TNF-alpha inhibitors is not clear. In order to make the best decision for the patient, it is necessary to determine the drug level in the blood as well as the level of antibodies to the drug in each change in the patient&#39;s condition. For now, there are not enough studies to indicate whether there is a link between expression of the TNF-alpha gene and the level of TNF-alpha in the blood, and whether the measurement of the TNF-alpha in blood could be used for therapy correction and change of dose of TNF-alpha inhibitor, which is likely to be the subject of the future research.</p>

L’utilisation d’agents anti-TNF a grandement amélioré la prise en charge de certaines maladies inflammatoires chroniques comme la polyarthrite rhumatoïde (PR) ou les maladies inflammatoires chroniques de l’intestin (MICI). Cependant, le quart des patients environ ne vont pas répondre au traitement ou présenteront une perte de réponse secondaire. Des marqueurs prédictifs de réponse sont nécessaires afin limiter les effets secondaires et les coûts inutiles en ciblant les patients qui pourraient être améliorés par les anti-TNF. Ces travaux de recherche se sont dans un premier temps concentrés sur l’importance de l’immunogénicité de ces traitements. Des anticorps anti-médicaments (ADAs) étaient bien associés à un taux bas d’anti-TNF avec des conséquences cliniques en termes de perte de réponse clinique et d’absence de cicatrisation muqueuse dans les MICI. Des seuils cliniques d’interprétation des tests biologiques pour la détection du médicament et de ses anticorps ont pu être définis et correspondent à 4.9 μg/ml pour l’infliximab et 200 ng/ml pour les ADAs. Ces résultats obtenus par ELISA sont bien corrélés avec les tests fonctionnels réalisés en parallèle et confirment l’intérêt de cette technique dans ce dépistage. Les ADAs étaient diminués par traitement immunosuppresseur concomitant. Ensuite, la persistance d’une infection chronique mise en évidence par des anticorps anti-bactériens a été évaluée en tant que marqueur prédictif de réponse aux anti-TNF. Aucun résultat statistiquement significatif n’a pu être relevé sur ces premières données, que ça soit pour les anticorps dirigés contre la flore intestinale pour les MICI ou contre le microbiote oral dans la PR. Seul un taux élevé de MMP-3 à l’initiation de l’infliximab chez les patients PR prédisait d’une bonne réponse clinique selon les critères de l’EULAR par la suite / The use of anti-TNF agents has greatly improved the management of chronic inflammatory diseases such as rheumatoid arthritis (RA), or chronic inflammatory bowel disease (IBD). However, about a quarter of patients will not respond to treatment or will present a secondary loss of response. Predictive biomarkers of response are needed to reduce side effects and unnecessary costs by targeting patients that could be improved by anti-TNF. This research work was initially focused on the importance of immunogenicity of these treatments. Anti-drug antibodies (ADAs) were well associated with low levels of anti-TNF with clinical consequences in terms of loss of clinical response and absence of mucosal healing in IBD. Clinical thresholds for drug and ADAs have been defined and correspond to 4.9 μg/ml for infliximab and 200 ng/ml for ADAS. These results obtained by ELISA correlate well with functional tests done in parallel, and confirm the value of this technique for screening. The ADAs were decreased with concomitant immunosuppressive therapy. Then, the persistence of chronic infection as evidenced by anti-bacterial antibody was evaluated as a predictive marker for response to anti-TNF. No statistically significant results could be raised on these first data, for antibodies against the intestinal flora in IBD or against the oral microbiota in RA. Only high levels of MMP-3 at the initiation of infliximab in RA patients predicted a good clinical response according to the EULAR criteria

O adalimumabe (Humira®, Abbott) é um antagonista do Fator de Necrose Tumoral- alpha (TNF-alfa ). É aprovado para o tratamento de artrite reumatoide, espondilite anquilosante, doença de Crohn, psoríase crônica e artrite reumatoide juvenil. É um anticorpo monoclonal que contém apenas sequências humanas de peptídeos contra a molécula do Fator de Necrose Tumoral-alfa. Na literatura, relatos e série de casos sugerem que os antagonistas do Fator de Necrose Tumoral-alfa são úteis no tratamento da inflamação ocular, edema macular cistoide e secundário à uveíte e degeneração macular relacionada à idade. Entretanto, a administração sistêmica do adalimumabe pode gerar efeitos adversos graves. A fim de diminuir esses efeitos adversos e aumentar a concentração da medicação no segmento posterior do olho, uma possível opção é a injeção intravítrea. O objetivo do presente estudo foi avaliar a toxicidade do adalimumabe intravítreo nas diferentes doses para a retina de coelhos por meio de avaliação clínica (biomicroscopia e oftalmoscopia indireta), funcional (eletrorretinograma) e histopatológica (microscopia óptica e eletrônica). Foram utilizados 30 coelhos albinos da raça Nova Zelândia divididos em cinco grupos de seis coelhos. Injeções intravítreas foram realizadas nas seguintes concentrações de adalimumabe: 0,5mg/0,1ml, 1mg/0,1ml, 2,5mg/0,1ml, 5,0mg/0,1ml e 10mg/0,2ml e 0,1ml de solução salina balanceada (BSS) foi injetada nos olhos esquerdos dos grupos 1 e 2 para constituir o grupo controle. Foram realizadas biomicroscopia e fundoscopia e sinais de inflamação, infecção ou toxicidade foram observados durante duas semanas. O eletrorretinograma foi realizado antes do tratamento e após 14 dias da injeção intravítrea. Os animais foram sacrificados, foi feita a enucleação dos olhos, e o tecido para a avaliação histopatológica foi preparado. A injeção intravítrea de adalimumabe (Humira®) nas doses estudadas até 5mg (0,5mg, 1,0mg, 2,5mg, 5mg) não apresentou sinais clínicos, eletrorretinográficos e histopatológicos de toxicidade para a retina de coelhos a curto prazo. No grupo de 10mg, foram observados sinais inflamatórios leves em três dos seis olhos e houve diminuição da amplitude da onda a na resposta fotópica do ERG, não foram observadas alterações na microscopia óptica / Adalimumab is a fully human anti-TNF alpha monoclonal antibody consisting of 100% human sequences developed using phage display technology. It is currently FDA approved for the treatment of rheumatoid arthritis, ankylosing spondylitis, Crohns disease, moderate to severe chronic psoriasis, and juvenile idiopathic arthritis. Anti-TNF alpha drugs may be an effective therapy for cystoid macular edema associated with uveitis. Significant improvements in chronic diabetic macular edema and regression of CNV from AMD have also been documented in small published series after systemic treatment with TNF-alpha antagonists. However the systemic administration of these drugs can have serious side effects. Intravitreous injection would assure delivery of high concentrations of medication at the posterior segment with minimum side effects.The aim of this study was to evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira®) in the rabbit eye. Thirty New Zealand albino rabbits received intravitreous injections of 0.1ml of adalimumab 0.5 mg (6 eyes), 1mg (6 eyes), 2.5mg (6 eyes), 5mg (6 eyes) and 0.2ml was injected in the10mg (6 eyes) group. BSS (0,1ml) was injected in the left eye of the rabbits from the groups 1 and 2 to serve as control group. Slit lamp biomicroscopy, fundoscopy were carried out at baseline, day 7 and 14 following intravitreous injection while electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14 and histopathological examination of the eyes was performed. The tested doses of intravitreous adalimumab up to 5mg (0.5mg, 1.0mg, 2.5mg, 5mg) had no associated ocular short-term toxicity in rabbit eyes. The 10mg group showed mild inflammatory reaction in 3 out of 6 eyes and showed decrease in the a wave amplitude in the photopic response, light microscopy was normal

O adalimumabe (Humira®, Abbott) é um antagonista do Fator de Necrose Tumoral- alpha (TNF-alfa ). É aprovado para o tratamento de artrite reumatoide, espondilite anquilosante, doença de Crohn, psoríase crônica e artrite reumatoide juvenil. É um anticorpo monoclonal que contém apenas sequências humanas de peptídeos contra a molécula do Fator de Necrose Tumoral-alfa. Na literatura, relatos e série de casos sugerem que os antagonistas do Fator de Necrose Tumoral-alfa são úteis no tratamento da inflamação ocular, edema macular cistoide e secundário à uveíte e degeneração macular relacionada à idade. Entretanto, a administração sistêmica do adalimumabe pode gerar efeitos adversos graves. A fim de diminuir esses efeitos adversos e aumentar a concentração da medicação no segmento posterior do olho, uma possível opção é a injeção intravítrea. O objetivo do presente estudo foi avaliar a toxicidade do adalimumabe intravítreo nas diferentes doses para a retina de coelhos por meio de avaliação clínica (biomicroscopia e oftalmoscopia indireta), funcional (eletrorretinograma) e histopatológica (microscopia óptica e eletrônica). Foram utilizados 30 coelhos albinos da raça Nova Zelândia divididos em cinco grupos de seis coelhos. Injeções intravítreas foram realizadas nas seguintes concentrações de adalimumabe: 0,5mg/0,1ml, 1mg/0,1ml, 2,5mg/0,1ml, 5,0mg/0,1ml e 10mg/0,2ml e 0,1ml de solução salina balanceada (BSS) foi injetada nos olhos esquerdos dos grupos 1 e 2 para constituir o grupo controle. Foram realizadas biomicroscopia e fundoscopia e sinais de inflamação, infecção ou toxicidade foram observados durante duas semanas. O eletrorretinograma foi realizado antes do tratamento e após 14 dias da injeção intravítrea. Os animais foram sacrificados, foi feita a enucleação dos olhos, e o tecido para a avaliação histopatológica foi preparado. A injeção intravítrea de adalimumabe (Humira®) nas doses estudadas até 5mg (0,5mg, 1,0mg, 2,5mg, 5mg) não apresentou sinais clínicos, eletrorretinográficos e histopatológicos de toxicidade para a retina de coelhos a curto prazo. No grupo de 10mg, foram observados sinais inflamatórios leves em três dos seis olhos e houve diminuição da amplitude da onda a na resposta fotópica do ERG, não foram observadas alterações na microscopia óptica / Adalimumab is a fully human anti-TNF alpha monoclonal antibody consisting of 100% human sequences developed using phage display technology. It is currently FDA approved for the treatment of rheumatoid arthritis, ankylosing spondylitis, Crohns disease, moderate to severe chronic psoriasis, and juvenile idiopathic arthritis. Anti-TNF alpha drugs may be an effective therapy for cystoid macular edema associated with uveitis. Significant improvements in chronic diabetic macular edema and regression of CNV from AMD have also been documented in small published series after systemic treatment with TNF-alpha antagonists. However the systemic administration of these drugs can have serious side effects. Intravitreous injection would assure delivery of high concentrations of medication at the posterior segment with minimum side effects.The aim of this study was to evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira®) in the rabbit eye. Thirty New Zealand albino rabbits received intravitreous injections of 0.1ml of adalimumab 0.5 mg (6 eyes), 1mg (6 eyes), 2.5mg (6 eyes), 5mg (6 eyes) and 0.2ml was injected in the10mg (6 eyes) group. BSS (0,1ml) was injected in the left eye of the rabbits from the groups 1 and 2 to serve as control group. Slit lamp biomicroscopy, fundoscopy were carried out at baseline, day 7 and 14 following intravitreous injection while electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14 and histopathological examination of the eyes was performed. The tested doses of intravitreous adalimumab up to 5mg (0.5mg, 1.0mg, 2.5mg, 5mg) had no associated ocular short-term toxicity in rabbit eyes. The 10mg group showed mild inflammatory reaction in 3 out of 6 eyes and showed decrease in the a wave amplitude in the photopic response, light microscopy was normal

Inflammation is often a protective reaction against harmful foreign agents. However, in many disease conditions, the mechanisms behind the inflammatory response are poorly understood. Often times, the inflammation causes adverse effects, such as joint pain, abdominal pain, fever, fatigue, and loss of appetite. Thus, many treatments aim to inhibit the inflammatory response in order to control adverse symptoms. Such treatments include TNFα inhibitors. However, a major risk associated with drugs inhibiting tumor necrosis factor alpha (TNFα) is serious infection, including tuberculosis (TB). Anti-TNFα therapy is used to treat patients with Crohn’s disease, for which the risk of tuberculosis may be even more concerning. Recent literature suggests Crohn’s might involve Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular TB-like bacterium. This study seeks to investigate the risk of developing TB in patients with Crohn’s disease treated with TNFα inhibitors. A meta-analysis synthesized existing evidence. Evidence came from published randomized, double-masked, placebo-controlled trials of TNFα inhibitors for treatment of adult Crohn’s disease. Twenty-three trials were identified, including 5,669 patients. The risk of tuberculosis was significantly increased in anti-TNFα treated patients, with a risk difference of 0.028 (95% confidence interval [CI], 0.0011-0.055). The odds ratio was 4.85 (95% CI, 1.02-22.99) when all studies were included and 5.85 (95% CI, 1.13-30.38) when studies reporting zero tuberculosis cases were excluded. The risk of tuberculosis is increased in patients with Crohn’s disease treated with TNFα inhibitors. The medical community should be alerted about this risk and the potential for TNFα inhibitor usage favoring granulomatous infections and worsening the patient condition.

Introdução: O fragmento amino-terminal do pró-peptídeo natriurético do tipo B (NT-proBNP) é um forte marcador de doença cardiovascular com evidências recentes de que a inflamação também pode influenciar seus valores. A diferenciação dessa variável de confusão é de particular interesse nas doenças reumáticas. Objetivos: Avaliar o comportamento dos valores de NT-proBNP em pacientes com espondilite anquilosante (EA) pré e pós uso de bloqueadores de TNF para determinar a possível associação entre os valores de NT-proBNP e os parâmetros inflamatórios. Métodos: Quarenta e cinco pacientes consecutivos com EA sem evidência prévia ou atual de doença cardiovascular ou disfunção miocárdica sistólica e que eram elegíveis para terapia anti-TNF foram incluídos prospectivamente. Todos os pacientes receberam bloqueadores de TNF e foram avaliados para concentrações circulantes de NT-proBNP, parâmetros clínicos e laboratoriais de atividade de doença, fatores de risco cardiovasculares tradicionais e ecodopplercardiografia convencional e tecidual no momento da inclusão e após seis meses de tratamento. Resultados: No momento da inclusão, todos os pacientes tinham EA ativa, os valores de NT-proBNP tinham uma mediana de 36 (20-72) pg/mL e 11% dos valores estavam altos mesmo na ausência de alteração miocárdica sistólica. A análise de regressão linear múltipla revelou que esse peptídeo estava independentemente correlacionado com o VHS (p < 0,001), com a idade dos pacientes (p = 0,01) e com a pressão de pulso (p = 0,01) no momento da inclusão. Após seis meses, todos os parâmetros relacionados a doença de base melhoraram e os valores de NT-proBNP se reduziram significativamente [24 (16-47) pg/mL, p = 0,037] quando comparados com os valores do momento da inclusão. As mudanças nos valores de NT-proBNP correlacionaram-se positivamente com as mudanças nos valores do VHS (r = 0,41, p = 0.006). Os fatores de risco cardiovasculares avaliados permaneceram estáveis durante o seguimento. Conclusão: As elevações nos valores de NT-proBNP devem ser interpretadas com cuidado nos pacientes com EA ativa e sem evidência de doença cardiovascular. A redução no curto prazo dos valores de NT-proBNP nesses pacientes recebendo terapia anti-TNF parece refletir uma melhora do estado inflamatório / Introduction: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong marker of cardiovascular disease with recent evidence that inflammation may also influence its levels; discrimination of this confounding variable is of particular interest in rheumatic diseases. Objectives: to evaluate NT-proBNP in ankylosing spondylitis (AS) patients pre- and post-TNF blocker to determine the possible association between NT-proBNP levels and inflammatory parameters. Methods: Forty-five consecutive AS patients without previous/current cardiovascular disease or systolic myocardial dysfunction, who were eligible to anti-TNF therapy, were prospectively enrolled. All patients received TNF blockers and they were evaluated for circulating NT-proBNP levels, clinical and laboratory parameters of disease activity, traditional cardiovascular risk factors, and conventional and tissue Doppler imaging echocardiography at baseline (BL) and six months after (6M) treatment. Results: At BL, all patients had active AS, NT-proBNP levels had a median of 36 (20-72) pg/mL and 11% were high in spite of no systolic alteration. Multiple linear regression analysis revealed that this peptide, at BL, was independently correlated with ESR (p < 0.001), age (p = 0.01) and pulse pressure (p = 0.01). After 6M, all disease parameters improved and NT-proBNP levels were significantly reduced [24 (16-47) pg/mL, p = 0.037] compared to BL. Changes in NT-proBNP were positively correlated with ESR changes (r = 0.41, p = 0.006). Cardiovascular risk factors remained stable during follow-up. Conclusion: our data suggests that elevations of NT-proBNP should be interpreted with caution in active AS patients with no other evidence of cardiovascular disease. The short-term reduction of NT-proBNP levels in these patients receiving anti-TNF therapy appears to reflect an improvement in inflammatory status

Introdução: O fragmento amino-terminal do pró-peptídeo natriurético do tipo B (NT-proBNP) é um forte marcador de doença cardiovascular com evidências recentes de que a inflamação também pode influenciar seus valores. A diferenciação dessa variável de confusão é de particular interesse nas doenças reumáticas. Objetivos: Avaliar o comportamento dos valores de NT-proBNP em pacientes com espondilite anquilosante (EA) pré e pós uso de bloqueadores de TNF para determinar a possível associação entre os valores de NT-proBNP e os parâmetros inflamatórios. Métodos: Quarenta e cinco pacientes consecutivos com EA sem evidência prévia ou atual de doença cardiovascular ou disfunção miocárdica sistólica e que eram elegíveis para terapia anti-TNF foram incluídos prospectivamente. Todos os pacientes receberam bloqueadores de TNF e foram avaliados para concentrações circulantes de NT-proBNP, parâmetros clínicos e laboratoriais de atividade de doença, fatores de risco cardiovasculares tradicionais e ecodopplercardiografia convencional e tecidual no momento da inclusão e após seis meses de tratamento. Resultados: No momento da inclusão, todos os pacientes tinham EA ativa, os valores de NT-proBNP tinham uma mediana de 36 (20-72) pg/mL e 11% dos valores estavam altos mesmo na ausência de alteração miocárdica sistólica. A análise de regressão linear múltipla revelou que esse peptídeo estava independentemente correlacionado com o VHS (p < 0,001), com a idade dos pacientes (p = 0,01) e com a pressão de pulso (p = 0,01) no momento da inclusão. Após seis meses, todos os parâmetros relacionados a doença de base melhoraram e os valores de NT-proBNP se reduziram significativamente [24 (16-47) pg/mL, p = 0,037] quando comparados com os valores do momento da inclusão. As mudanças nos valores de NT-proBNP correlacionaram-se positivamente com as mudanças nos valores do VHS (r = 0,41, p = 0.006). Os fatores de risco cardiovasculares avaliados permaneceram estáveis durante o seguimento. Conclusão: As elevações nos valores de NT-proBNP devem ser interpretadas com cuidado nos pacientes com EA ativa e sem evidência de doença cardiovascular. A redução no curto prazo dos valores de NT-proBNP nesses pacientes recebendo terapia anti-TNF parece refletir uma melhora do estado inflamatório / Introduction: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong marker of cardiovascular disease with recent evidence that inflammation may also influence its levels; discrimination of this confounding variable is of particular interest in rheumatic diseases. Objectives: to evaluate NT-proBNP in ankylosing spondylitis (AS) patients pre- and post-TNF blocker to determine the possible association between NT-proBNP levels and inflammatory parameters. Methods: Forty-five consecutive AS patients without previous/current cardiovascular disease or systolic myocardial dysfunction, who were eligible to anti-TNF therapy, were prospectively enrolled. All patients received TNF blockers and they were evaluated for circulating NT-proBNP levels, clinical and laboratory parameters of disease activity, traditional cardiovascular risk factors, and conventional and tissue Doppler imaging echocardiography at baseline (BL) and six months after (6M) treatment. Results: At BL, all patients had active AS, NT-proBNP levels had a median of 36 (20-72) pg/mL and 11% were high in spite of no systolic alteration. Multiple linear regression analysis revealed that this peptide, at BL, was independently correlated with ESR (p < 0.001), age (p = 0.01) and pulse pressure (p = 0.01). After 6M, all disease parameters improved and NT-proBNP levels were significantly reduced [24 (16-47) pg/mL, p = 0.037] compared to BL. Changes in NT-proBNP were positively correlated with ESR changes (r = 0.41, p = 0.006). Cardiovascular risk factors remained stable during follow-up. Conclusion: our data suggests that elevations of NT-proBNP should be interpreted with caution in active AS patients with no other evidence of cardiovascular disease. The short-term reduction of NT-proBNP levels in these patients receiving anti-TNF therapy appears to reflect an improvement in inflammatory status