The role of opioid analgesics in rheumatic disorders: a position paper from the Portuguese Rheumatology Society.

Pain is a common feature of most rheumatic diseases and it is often the main reason for the patient to seek for a clinical appointment. Chronic pain has a major impact on patient's quality of life, being frequently associated with functional incapacity, sleep and mood disorders. This leads to absenteeism and heavy consumption of health resources, both representing huge burdens on national economy. Managing musculoskeletal pain is pivotal but can be challenging. The use of the available pharmaceutical armamentarium should be parsimonious. Opioids are strong analgesic drugs that mostly act through their agonist action on µ-receptors in the central nervous system. Opioid-related side effects are not negligible and are mediated through both central and peripheral opioid receptors. The use of opioids is well established in the treatment of oncologic pain but their role in the management of musculoskeletal pain is still controversial. Inflammatory rheumatic diseases, osteoarthritis, osteoporotic fractures, chronic low back pain and fibromyalgia represent diverse major rheumatic conditions that frequently lead to chronic pain. In order to standardize and optimize management of musculoskeletal chronic pain in these prevalent diseases, the Portuguese Rheumatology Society elaborated this position paper. The objectives were: a) to define the importance of pain assessment and classification; b) to guide patient selection, appropriate choice of opioids, their management, and raise awareness of their adverse effects; c) to review the existent data on possible indications of opioid therapy on rheumatic diseases.

Real-world Longterm Effectiveness of Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis Patients from the Rheumatic Diseases Portuguese Register.

OBJECTIVE: To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017. METHODS: Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months. Baseline predictors of discontinuation and response were studied using Cox and multivariable multinomial/logistic regression models. RESULTS: The 750 patients with PsA showed drug retention of 4.1 ± 3.4 years (followup 5.8 ± 3.8 yrs) for first TNFi. Switching to a second (189 patients) or third (50 patients) TNFi further decreased survival by 1.1 years. Female sex, higher baseline 28-joint count Disease Activity Score, and infliximab were predictors of first TNFi discontinuation. After 6 months of the first TNFi, 48.7% of patients achieved a good EULAR criteria response and 20.9% were in DAPSA remission. There were 11.4% in MDA, and 56.4% had a good ASDAS. Responses to the second TNFi were significantly inferior compared to responses to the first TNFi. Female sex and higher baseline Health Assessment Questionnaire-Disability Index were negatively associated with good EULAR response at 3 months, and obesity decreased the chance of response at 6 months. CONCLUSION: In this study, switching to a second or third TNFi was associated with significantly lower drug survival and response rates for patients with axial and peripheral PsA subtypes. More successful therapeutic approaches will require considering the effect of sex and obesity on TNFi effectiveness.

Prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma - A review.

The prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma patients was reviewed, based on reports cited in two major scientific databases. Data were collected on the following types of antibodies: antinuclear, anti-double-stranded DNA, anticentromere, anti-CENP-A, anti-CENP-B, anti-bicaudal D2, anti-nucleolar, anti-Scl-70 (anti-topoisomerase I), anti-topoisomerase II α, anti-RNP, anti-U1RNP, anti-U3RNP, anti-RNA polymerase III, anti-Th/To, anti-histone, antiphospholipid, anti-PmScl, anti-Sm, anti SSA (anti-Ro),anti SSB (La), anti-Ro52 (TRIM 21), anti-Ku, anti-B23, anti-RuvBL1, anti-RuvBL2, anti-fibrin bound tissue plasminogen activator, anti-endothelial cell, anti-phosphatidylserine-prothrombin complex, anti-endothelin-1 type A receptor, anti-angiotensin II type 1 receptor, anti­carbonic anhydrase II, anti-fibroblast, anti-cyclic citrullinated peptide, anti-4-sulfated N-Acetyl-lactosamine, class I and II anti-human leukocyte antigen. Auto-antibodies were shown by different authors to be associated to this condition, with different prevalence values for each type of auto-antibody. Antinuclear antibodies, anti-centromere antibodies, antiphospholipid antibodies, anti-U3 RNP antibodies and anti-Th/To antibodies would appear to show a particularly important prevalence in scleroderma patients with pulmonary hypertension, appearing in about 8/10 (antinuclear), 1/ 2 (anti-centromere, anti-phospholipid), and 1/4 (anti-U3RNP, anti-Th/To) of patients. The available evidence points in the direction of a strong association between auto-immune mechanisms and pulmonary hypertension in the setting of scleroderma.

Efficacy and Safety of Vaccination in Pediatric Patients with Systemic Inflammatory Rheumatic Diseases: a systematic review of the literature.

INTRODUCTION: Children and adolescents with systemic rheumatic diseases have an increased risk of infections. Although some infections are vaccine-preventable, immunization among patients with juvenile rheumatic diseases is suboptimal, partly due to some doubts that still persist regarding its efficacy and safety in this patient population. OBJECTIVES: To review the available evidence regarding the immunological response and the safety of vaccination in children and adolescents with systemic inflammatory rheumatic diseases (SIRD). METHODS: A systematic review of the current literature until December 2014 using MEDLINE, EMBASE and abstracts from the American College of Rheumatology and European League Against Rheumatism congresses (2011-2014), complemented by hand search was performed. Eligible studies were identified and efficacy (seroprotection and/or seroconversion) and safety (reactions to vaccine and relapse of rheumatic disease) outcomes were extracted and summarized according to the type of vaccine. RESULTS: Twenty-eight articles concerning vaccination in pediatric patients with SIRDs were found, that included almost 2100 children and adolescents, comprising nearly all standard vaccinations of the recommended immunization schedule. Children with SIRDs generally achieved seroprotection and seroconversion; nevertheless, the antibody levels were often lower when compared with healthy children. Glucocorticoids and conventional disease-modifying anti-rheumatic drugs do not seem to significantly hamper the immune responses, whereas TNF inhibitors may reduce antibody production, particularly in response to pneumococcal conjugate, influenza, meningococcal C and hepatitis A vaccine. There were no serious adverse events, nor evidence of a relevant worsening of the underlying rheumatic disease. Concerning live attenuated vaccines, the evidence is scarce, but no episodes of overt disease were reported, even in patients under biological therapy. CONCLUSIONS: Existing literature demonstrates that vaccines are generally well tolerated and effective in stable SIRD patients, yet antibody titers are frequently lower than in healthy controls. There is some evidence that biological therapy could hamper the immune response. Data on safety of live attenuated vaccines is limited. Although the available literature covers most vaccines included in the national immunization plan, there is a need for more information regarding new vaccines and new anti-rheumatic therapies.

[Satisfação com o Internato Médico em Portugal]. / Satisfação com o Internato Médico em Portugal.

INTRODUCTION: In the last years, the global context of medical education and Medical Residency programs in Portugal suffered substantial changes. The primary objective of this study was to evaluate and characterize medical residents ́ satisfaction with medical residency programs in Portugal and to identify features that could be improved. MATERIAL AND METHODS: We utilized as model the survey Postgraduate Hospital Educational Environment Measure that has been developed in the United Kingdom and is speci cally targeted to medical residents. The survey was translated and adapted to the Portuguese reality. The survey was available online during April and May of 2016. RESULTS: A total of 3456 responses were obtained, corresponding to a response rate of 35%. Endocrinology/Nutrition, Cardiology, Anesthesiology, Family Physician and Gastroenterology were the specialties in which the degree of satisfaction was higher, while Forensic Medicine, Medical Oncology, Internal Medicine, General Surgery and Pneumology showed the lowest level of satisfaction. DISCUSSION: This study presented a high response rate when compared to previous studies. Portuguese medical residents presented high levels of satisfaction. Depending on year of medical residency, region, type of specialty and type of hospital marked asymmetries were noticed. CONCLUSION: The survey ́s results should constitute in the future a support tool for the implementation of local and national measures relating to the medical residency. It is advisable to regularly conduct satisfaction surveys to medical residents.

Introdução: Nos últimos anos, o contexto global da formação médica, e em particular do Internato Médico em Portugal, sofreu profundas alterações. O presente estudo teve como objetivo avaliar e caracterizar a satisfação dos médicos internos com a realização do Internato Médico em Portugal e identificar aspetos passíveis de melhoria.Material e Métodos: Foi utilizado como modelo de inquérito o questionário Postgraduate Hospital Educational Environment Measuredesenvolvido no Reino Unido e dirigido a médicos internos, o qual foi traduzido e adaptado à realidade portuguesa. O questionário esteve disponível online durante os meses de abril e maio de 2016.Resultados: Foram obtidas 3456 respostas, correspondendo a uma taxa de resposta de 35%. Endocrinologia/Nutrição, Cardiologia, Anestesiologia, Medicina Geral e Familiar e Gastrenterologia foram as especialidades nas quais o grau de satisfação foi mais elevado,enquanto que Medicina Legal, Oncologia Médica, Medicina Interna, Cirurgia Geral e Pneumologia apresentaram o grau de satisfaçãomais baixo.Discussão: O presente estudo apresenta uma elevada taxa de resposta comparativamente com estudos prévios. A nível nacional, no global, os médicos internos apresentaram níveis elevados de satisfação, destacando-se marcadas assimetrias de acordo com o ano de especialidade, região, tipologia de instituição e de especialidade.Conclusão: Os resultados deste inquérito poderão constituir uma ferramenta de apoio à implementação de medidas de âmbito local enacional relacionadas com o Internato Médico, sendo desejável a realização regular de inquéritos de satisfação aos médico internos.

The Portuguese Society of Rheumatology position paper on the use of biosimilars.

Biotechnological drugs have become a fundamental resource for the treatment of rheumatic patients. Patent expiry of some of these drugs created the opportunity for biopharmaceutical manufacturers to develop biosimilar drugs intended to be as efficacious as the originator product but with a lower cost to healthcare systems. Due to the complex manufacturing process and highly intricate structure of biologicals, a biosimilar can never be an exact copy of its reference product. Consequently, regulatory authorities issued strict preclinical and clinical guidelines to ensure safety and efficacy equivalence and, in September 2013, the biosimilar of infliximab was the first biosimilar monoclonal antibody to be authorized for use in the European Union. The current document is a position statement of the "Sociedade Portuguesa de Reumatologia" (Portuguese Society of Rheumatology) on the use of biosimilar drugs in rheumatic diseases. Two systematic literature reviews were performed, one concerning clinical trials and the other one concerning international position papers on biosimilars. The results were presented and discussed in a national meeting and a final position document was discussed, written and approved by Portuguese rheumatologists. Briefly, this position statement is contrary to automatic substitution of the originator by the biosimilar, defends either a different INN or the prescription by brand name, supports that switching between biosimilars and the originator molecule should be done after at least 6 months of treatment and based on the attending physician decision and after adequate patient information, recommends the registration of all biosimilar treated patients in Reuma.pt for efficacy, safety and immunogenicity surveillance, following the strategy already ongoing for originators, and opposes to extrapolation of indications approved to the originator to completely different diseases and/or age groups without adequate pre-clinical, safety or efficacy data.