Rheumatoid Arthritis: Santos MJ

Canhão H, Santos MJ, Costa L, Bogas M, Mourão AF, Machado P, Fonseca JE, Silva JA, Anonymous00048. · Serviço de Reumatologia, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisboa. · Acta Reumatol Port. · Pubmed #19377402 No free full text.

Abstract: OBJECTIVES: To develop Portuguese evidence-based recommendations for the use of methotrexate (MTX) in daily clinical practice in rheumatic disorders. METHODS: The Portuguese project was integrated in the multinational 3E Initiative (Evidence, Expertise, Exchange) 2007-2008 where a total of 751 rheumatologists from 17 countries have participated. Ten clinical questions concerning the use of MTX in rheumatic diseases were formulated and the Portuguese group added three more questions. A systematic literature search in Medline, Embase, Cochrane Library and 2005-2007 ACR/EULAR meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford Levels of Evidence. In Portugal, a national meeting was held in Obidos on February 15th and 16th, 2008, involving 50 rheumatologists who discussed and voted by Dephi method the recommendations. Finally, the agreement among the rheumatologists and the potential impact on their clinical practice was assessed. RESULTS: Thirteen national key recommendations on the use of MTX were formulated: work-up before starting MTX, optimal dosage and route of administration, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy, management in the peri-operative period, during infections, before/during pregnancy and after clinical remission, screening and treatment of tuberculosis and the role of MTX as a steroid-sparing agent in rheumatic diseases. DISCUSSION: The Portuguese recommendations for the use of MTX in daily clinical practice were developed, which are evidence-based and supported by a panel of 50 rheumatologists, enhancing their validity and practical use. This project was integrated in a multinational initiative that led to the recent publication of ten multinational recommendations which differ from ours in some specific aspects.

Santos MJ, Fonseca JE, Canhão H, Conde M, José Vieira M, Costa L, Costa M, Salgado M, Melo Gomes JA, Anonymous00046. · Sociedade Portuguesa de Reumatologia, Lisboa. · Acta Reumatol Port. · Pubmed #17450764 links to  free full text

Abstract: The Pediatric RheumatologyWorking Group of the Portuguese Society of Rheumatology recommends the use of biological treatments in children with polyarticular course Juvenile Idiopathic Arthritis (JIA) with active disease (5 or more active joints) refractory to subcutaneous or intramuscular methotrexate (MTX) 15 mg/m(2)/week during 3 to 6 months. If toxicity occurs, or if there is contraindication for the use of MTX in this optimum dose, biological treatment can be started, as a first option, or the use of other conventional Disease ModifyingAnti Rheumatic Drug (DMARD) either alone or in combination with MTX might be considered. Prior to starting treatment, children should be screened for latent tuberculosis through clinical evaluation, chest X ray and PPD skin test. The suspension of the biological treatment should be considered if the American College of Rheumatology (ACR) definition of improvement in JIA is not fulfilled in two consecutive visits 3 months apart. Etanercept is the only biological agent currently approved for JIA in Portugal. In refractory cases the use of infliximab is accepted, in accordance with preliminary published evidence. In case of systemic manifestations of JIA refractory to conventional treatment, anakinra can be considered.

Fonseca JE, Lucas H, Canhão H, Duarte R, Santos MJ, Villar M, Faustino A, Raymundo E, Anonymous00188, Anonymous00189. · Grupo de Estudos de Artrite Reumatóide, Sociedade Portuguesa de Reumatologia, Rua D. Estefânia 177, 1 D1000-154 Lisbon. · Rev Port Pneumol. · Pubmed #17117328 No free full text.

Abstract: The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-a) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-a therapy. When TB (LTBI or AT) treatment is indicated, it should be performed before the beginning of anti-TNF-a therapy. If the IJD activity requires urgent anti-TNF-a therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. If TST is performed in immunosuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNF-a therapy, even in the presence of a negative test.

Fonseca JE, Lucas H, Canhão H, Duarte R, Santos MJ, Villar M, Faustino A, Raymundo E, Anonymous00298, Anonymous00299. · Grupo de Estudos de Artrite Reumatóide da Sociedade Portuguesa de Reumatologia. · Acta Reumatol Port. · Pubmed #17094335 links to  free full text

Abstract: The Portuguese Society of Rheumatology (SPR) and the Portuguese Society of Pulmonology (SPP) have developed guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (AT) in patients with inflammatory joint diseases (IJD), namely rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with tumour necrosis factor alpha (TNF-alpha) antagonists. Due to the high risk of tuberculosis (TB) in patients with IJD, LTBI and AT screening should be performed as soon as possible, ideally at the moment of IJD diagnosis. Even if TB screening was performed at the beginning of the disease, the evaluation should be repeated before starting anti-TNF-alpha therapy. When TB (LTBI orAT) treatment is indicated, it should be performed before the beginning of anti-TNF-alpha therapy. If the IJD activity requires urgent anti-TNF-alpha therapy, these drugs can be started after two months of antituberculosis therapy in AT cases, or after one month in LTBI cases. Chest X-ray is mandatory for all patients. If abnormal, e.g. Gohn complex, the patient should be treated as LTBI; residual lesions require the exclusion of AT and patients with history of untreated or incomplete TB treatment should be treated as LTBI. In cases of suspected active lesions, AT diagnosis should be confirmed and adequate therapy initiated. Tuberculin skin test (TST), with two units of RT23, should be performed in all patients. If induration is less than 5 mm, the test should be repeated after 1 to 2 weeks, on the opposite forearm, and should be considered negative if the result is again inferior to 5 mm. Positive TST implicates LTBI treatment. IfTST is performed in immunosupressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test.

Fonseca JE, Lucas H, Canhão H, Duarte R, Santos MJ, Villar M, Faustino A, Raymundo E. · Rheumatoid Arthritis Study Group (Grupo de Estudos de Artrite Reumatoide-GEAR) of the Portuguese Society of Rheumatology (Sociedade Portuguesa de Reumatologia-SPR), Lisbon, Portugal. · Acta Reumatol Port. · Pubmed #18344925 links to  free full text

Abstract: The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology have updated the guidelines for the diagnosis and treatment of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with inflammatory joint diseases (IJD) that are candidates to therapy with tumour necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of tuberculosis (TB) reactivation and the incidence of new infections, TB screening is recommended to be done as soon as possible, ideally at the moment of IJD diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy. Treatment for ATB and LTBI must be done under the care of a TB specialist. When TB treatment is indicated, it should be completed prior to starting anti-TNFalpha therapy. If the IJD activity justifies the need for immediate treatment, anti-TNFalpha therapy can be started two months after antituberculous therapy has been initiated, in the case of ATB, and one month after in the case of LTBI. Chest X-ray is mandatory for all patients. If Gohn s complex is present, the patient should be treated for LTBI; healed lesions require the exclusion of ATB. In cases of suspected active lesions ATB should be excluded/confirmed and adequate therapy initiated. Tuberculin skin test, with two units of RT23, should be performed in all patients. If the induration is <5 mm, the test should be repeated within 1 to 2 weeks, on the opposite forearm, and will be considered negative only if the result is again <5 mm. Positive TST implicates LTBI treatment, unless previous proper treatment was provided. If TST is performed in immunossuppressed IJD patients, LTBI treatment should be offered to the patient before starting anti-TNFalpha therapy, even in the presence of a negative test, after risk/benefit assessment.

Mourão AF, Caetano-Lopes J, Costa P, Canhão H, Santos MJ, Pinto P, Brito I, Nicola P, Cavaleiro J, Teles J, Sousa A, Gomes JM, Branco J, da Costa JT, Pedro JG, de Queiroz MV, Fonseca JE. · Rheumatology Research Unit, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal. · J Rheumatol. · Pubmed #19208590 No free full text.

Abstract: OBJECTIVE: Considering the relevance of tumor necrosis factor-alpha (TNF-alpha) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-alpha serum concentrations were associated with TNF-alpha -308 genotypes. METHODS: Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-alpha gene promoter polymorphisms at position -308 by restriction fragment-length polymorphism. RESULTS: One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the -308 GA/AA genotypes and 76% the -308 GG genotype, similar to findings in controls. Patients with the -308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-alpha levels compared to those with the -308 GG genotype. CONCLUSION: TNF-alpha -308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.

Fonseca JE, Santos MJ, Canhão H, Choy E. · Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. · Autoimmun Rev. · Pubmed #19189867 No free full text.

Abstract: Interleukin-6 (IL-6) is a cytokine that can facilitate autoimmune phenomena, amplify acute inflammation and promote the evolution into a chronic inflammatory state. In addition, it is a major promoter of bone resorption in pathological conditions. In particular, IL-6 has a pivotal role in synovitis, bone erosions and in the systemic features of inflammation. This cytokine specifically binds to IL-6 receptor (IL-6R), forming the IL-6/IL-6R complex that binds to gp130, a membrane-bound protein, which is involved in non-ligand-binding signal transduction. Targeting IL-6R in both animal models of arthritis and in rheumatoid arthritis patients with a humanized anti IL-6R monoclonal antibody (tocilizumab) effectively controls local and systemic inflammatory manifestations and blocks cartilage and bone destruction. Given the pleiotropic function of IL-6 it can be anticipated that other inflammatory diseases and bone metabolic conditions might benefit from selective IL-6 signaling inhibition.

Lemos A, Ramos MP, Furtado MJ, Carvalho C, Santos MJ, Silva JC, Ventura H. · Laboratório de Imunologia, Serviço de Patologia Clinica. · Acta Reumatol Port. · Pubmed #18159201 links to  free full text

Abstract: The presence of IgM class rheumatoid factor RF-M in the serum is one of the ACR criteria for the classification of rheumatoid arthritis RA . OBJECTIVES: To compare the sensitivity and specificity of two diagnostic markers for RA in Portuguese patients the 2nd generation anti-cyclic citrullinated peptide antibodies anti-CCP2 and the RF-M. METHODS: Serum samples from 56 patients with established RA 44 women and 12 men mean disease duration 9 5 -8 5 years were evaluated for the presence of anti-CCP2 and RF-M. Results were compared with 93 samples from a control group with identical demographic characteristics 43 from patients with spondylarthropaties and 50 from healthy blood donors . The determination of anti-CCP2 antibodies was performed by enzymatic fluroimunoassay and RF-M was measured by microElisa. RESULTS: Anti-CCP2 antibodies were positive in 40 patients with RA 71 4 at a mean antibody concentration of 350 5 UA ml range 11-1670 UA ml and negative in all controls. The RF-M was positive in 34 patients with RA 60 7 in 4 patients with spondylarthropaties 9 3 and in one blood donor 2 . The sensitivity specificity positive predictive value and negative predictive value for RF-M was 60 7 90 7 89 5 and 63 9 and for anti-CCP2 was 71 4 100 100 and 72 9 respectively. CONCLUSIONS: The anti-CCP2 assay showed an excellent specificity and a global performance superior to that of the RF-M test in this population with established RA.

Canhão H, Fonseca JE, Santos MJ, Gomes JA. · Serviço de Reumatologia, Hospital de Santa Maria, Lisbon. · Acta Reumatol Port. · Pubmed #17928788 links to  free full text

Abstract: The development of new and more efficacious therapeutic agents, though expensive and potentially toxic, helped to implement objective measures to quantify the improvement and to monitor the evolution of inflammatory rheumatic diseases. The aim of our protocol (PMAIJ) is to supply rheumatologists and paediatricians with a useful tool for follow-up of juvenile arthritis patients using validated instruments for the evaluation of activity, functional capacity and response to treatment. PMAIJ has 2 pages. The first page is filled only at the initial evaluation; the second page is filled at first and in all the appointments after that. The application of this protocol would contribute to the standardization of procedures in different Paediatric Rheumatology Centres and would help to obtain useful information on the clinical evolution of JIA patients followed in Portugal.

Fonseca JE, Canhão H, Silva C, Miguel C, Mediavilla MJ, Teixeira A, Castelão W, Nero P, Bernardes M, Bernardo A, Mariz E, Godinho F, Santos MJ, Bogas M, Oliveira M, Saavedra MJ, Barcelos A, Cruz M, Santos RA, Maurício L, Rodrigues M, Figueiredo G, Quintal A, Patto JV, Malcata A, da Silva JC, Araújo D, Ventura F, Branco J, Queiroz MV, Anonymous00300. · Serviço de Reumatologia, Hospital de Santa Maria. · Acta Reumatol Port. · Pubmed #17094336 links to  free full text

Abstract: In Portugal, 13 cases of tuberculosis (TB) were reported, in the period between 1999 and 2005, in 960 patients exposed to anti-TNFalpha treatment (1.35%), 8 females and 5 males. Mean age was 46.7 +/- 13.8 years. 9 patients had rheumatoid arthritis (RA), in 639 exposed patients (1.4%), 3 had ankylosing spondylitis (AS), in 200 exposed patients (1.5%) and 1 had psoriatic arthritis (PA), in 101 exposed patients (1%). The anti-TNFa used was in 8 cases infliximab (in 456 patients exposed, 1.5%), in 4 adalimumab (in 171 patients exposed, 2.3%) and in 1 etanercept (in 333 exposed, 0.3%). Treatment with a biological agent was started 11.1 +/- 8.7 months (min 3 and max 50) before TB onset. Tuberculin skin test (TST) was performed in 9 out of the 13 patients (the other 4 had started biological therapy before 2002). In 3 cases the TST response was 0 mm, in 3 less than 10 mm, in one was 14 mm and in two 20 mm. In the 3 cases with a TST response superior to 10 mm, isoniazid treatment 300 mg/d was prescribed, during 9 months. The time between first symptoms and TB diagnosis was 2.6 +/- 2.9 months. TB involvement was pulmonary in 6 patients, lymph node disease in 2, peritoneal and pulmonary in 2, osteoarticular in one case, lymph node disease and splenic in another and miliar TB in the last case. One death was reported; all of the other cases had a good outcome after anti-TB treatment. In two cases (one treated with adalimumab and the other with infliximab), paradoxical response to treatment occurred. None of the patients has restarted biological therapy after TB treatment.

Melo-Gomes JA, Ruperto N, Canhao H, Fonseca JE, Quintal A, Salgado M, Santos MJ, Anonymous00079. · Infantile, Adolescent and Young Adult Rheumatology Unit-Instituto Português de Reumatologia, Lisbon, Portugal. · Clin Exp Rheumatol. · Pubmed #11510315 No free full text.

Abstract: We report herein the results of the cross-cultural adaptation and validation into the Portuguese language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well being of children independently from the underlying disease. The Portuguese CHAQ CHQ were fully validated with 3 forward and 3 backward translations. A total of 130 subjects were enrolled: 69 patients with JIA (32% systemic onset, 19% polyarticular onset, 26% extended oligoarticular subtype, and 23% persistent oligoarticular subtype) and 61 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well being when compared to their healthy peers. In conclusion the Portuguese version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.