Portuguese recommendations for the prevention, diagnosis and management of primary osteoporosis - 2018 update.

BACKGROUND: Advances in osteoporosis (OP)case definition, treatment options, optimal therapy duration and pharmacoeconomic evidence in the national context motivated the Portuguese Society of Rheumatology (SPR) to update the Portuguese recommendations for the diagnosis and management of osteoporosis published in 2007. METHODS: SPR bone diseases' working group organized meetings involving 55 participants (rheumatologists, rheumatology fellows and one OP specialist nurse) to debate and develop the document. First, the working group selected 11 pertinent clinical questions for the diagnosis and management of osteoporosis in standard clinical practice. Then, each question was investigated through literature review and draft recommendations were built through consensus. When insufficient evidence was available, recommendations were based on experts' opinion and on good clinical practice. At two national meetings, the recommendations were discussed and updated. A draft of the recommendations full text was submitted to critical review among the working group and suggestions were incorporated. A final version was circulated among all Portuguese rheumatologists before publication and the level of agreement was anonymously assessed using an online survey. RESULTS: The 2018 SPR recommendations provide comprehensive guidance on osteoporosis prevention, diagnosis, fracture risk assessment, pharmacological treatment initiation, therapy options and duration of treatment, based on the best available evidence. They attained desirable agreement among Portuguese rheumatologists. As more evidence becomes available, periodic revisions will be performed. Target audience and patient population: The target audience for these guidelines includes all clinicians. The target patient population includes adult Portuguese people. Intended use: These recommendations provide general guidance for typical cases. They may not be appropriate in all situations - clinicians are encouraged to consider this information together with updated evidence and their best clinical judgment in individual cases.

Economic considerations and patients' preferences affect treatment selection for patients with rheumatoid arthritis: a discrete choice experiment among European rheumatologists.

OBJECTIVE: To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis. METHODS: In a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists. RESULTS: Responses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients' preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK. CONCLUSIONS: Overall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals.

Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study.

OBJECTIVE: To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). METHODS: Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. RESULTS: In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59-1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. CONCLUSION: Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

Characterization of damage in Portuguese lupus patients: analysis of a national lupus registry.

BACKGROUND: Although the survival rate has considerably improved, many patients with systemic lupus erythematosus (SLE) develop irreversible organ damage. OBJECTIVES: The objectives of this paper are to characterize cumulative damage in SLE patients and identify variables associated with its presence and severity. METHODS: A cross-sectional analysis of SLE patients from the Portuguese Lupus register Reuma.pt/SLE in whom damage assessment using the SLICC/ACR-Disability Index (SDI) was available was performed. Predictor factors for damage, defined as SDI ≥ 1, were determined by logistic regression analyses. A sub-analysis of patients with severe damage (SDI ≥ 3) was also performed. RESULTS: In total, 976 patients were included. SDI was ≥1 in 365 patients, of whom 89 had severe damage. Musculoskeletal (24.4%), neuropsychiatric (24.1%) and ocular (17.2%) domains were the most commonly affected. Older age, longer disease duration, renal involvement, presence of antiphospholipid antibodies and current therapy with steroids were independently associated with SDI ≥ 1. The subpopulation with severe damage had, in addition, a greater interval between the first manifestation attributable to SLE and the clinical diagnosis as well as and more frequently early retirement due to SLE. CONCLUSIONS: This large lupus cohort confirmed that demographic and clinical characteristics as well as medication are independently associated with damage. Additionally, premature retirement occurs more often in patients with SDI ≥ 3. Diagnosis delay might contribute to damage accrual.

Applicability of the EULAR recommendations on the role of the nurse in the management of chronic inflammatory arthritis in Portugal.

OBJECTIVES: To evaluate the level of agreement and applicability of the EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis in Portugal. METHODS: Nurses from all Portuguese rheumatology centers were invited to fill-in a questionnaire addressing the level of agreement (1=strongly disagree to 5=strongly agree) and the level of confidence (1=no confidence to 5=complete confidence) in the applicability of each of the recommendations. Comparisons were established between subgroups of nurses. RESULTS: A total of 75 nurses (85% female; mean (SD) of 3.9 (4.1) years of practice, 32% with some type of training in rheumatology) participated in the study. The mean level of agreement with the recommendations was 4.8 (SD 0.3). The level of confidence in their full applicability was 3.6 (SD 0.8). Significantly more nurses with rheumatology training totally agreed with recommendations 7 (88% vs 73%, p=0.03) and 3 (96% vs 65% p=0.04) and were fully confident in the applicability of recommendations 2, 3, 7, 9 and 10, comparing with those without specific training. CONCLUSIONS: The overall level of agreement with EULAR recommendations among Portuguese nurses is high, although rheumatology does not exist as a nursing specialty. Agreement and confidence in the applicability of these recommendations is higher among nurses with specific training, underlining the importance of continuous education for future commitment.

[Rheumatic expression of secondary syphilis]. / Manifestações reumáticas da Sífilis Secundária.

Syphilis is a disease caused by Treponema pallidum infection with protean clinical manifestations. Musculoskeletal complaints are however uncommon and most of the time mild. Occasionally they can dominate the clinical picture and simulate a variety of rheumatic diseases. The authors present the clinical case of a 33-year-old woman who developed a lupus-like syndrome in the postpartum, characterized by polyarthritis, elevated acute phase reactants and positive antinuclear antibodies (ANA). Physical examination revealed a macular non-pruriginous skin rash involving the trunk, upper limbs and palms. The Rapid Plasma Reagin (RPR) and Treponema Pallidum Hemaglutination (TPHA) tests gave a positive result and the patient was diagnosed as secondary syphilis and medicated with 2.4 MU of benzathine penicillin intramuscular weekly for 3 weeks, with complete resolution of clinical signs and ANA negativation. The association of rash and arthritis may occur in several rheumatic diseases but in the presence of palmoplantar involvement, the possibility of syphilis infection should not be overlooked.

[Mixed cryoglobulinemia]. / Crioglobulinémia mista.

The authors describe two clinical cases of cryoglobulinemia. A 70 years old woman, having skin ulcers on lower limbs, arthralgias, paresthesias and constitutional symptoms, for about 10 months. Exams revealed mild anemia, elevation of the biological parameters of inflammation and aminotransferases, positive cryoglobulin and rheumatoid factor in serum, and a severe reduction in C4 complement fraction. Hepatitis C virus (HCV) serology was negative. Idiopathic mixed cryoglobulinemia was diagnosed and corticosteroid therapy started. Given the lack of response, cyclophosphamide and plasmapheresis were added. Two weeks later the patient died in septic shock. The second case refers to a 41 years old female, with untreated hepatitis C who developed over a 6 month period petechiae and livedoid lesions on the lower limbs, peripheral neuropathy, and constitutional symptoms and was admitted with intestinal necrosis. Exams were consistent with the diagnosis of mixed cryoglobulinemia associated, with HCV. She started therapy with ribavirin and pegylated interferon-alpha, with improvement.

Biologicals and switch in rheumatoid arthritis throughout time - are we being more aggressive?

OBJECTIVES: To investigate the switches performed in patients with rheumatoid arthritis under biological therapy and specifically comparing the switches from earlier days with more recent switches. PATIENTS AND METHODS: Patients with rheumatoid arthritis under biological therapy followed at Hospital Garcia de Orta, Almada, and included in the Rheumatic Diseases Portuguese Register (Reuma.Pt) were included in this study. Switches occurring before and after January 2007 were compared with respect to patients' demographic and clinical characteristics, such as disease activity and duration of biological therapy. The survival of the first biological agent was compared between patients starting biological therapy before and after 2007. EULAR response and remission rate at the last evaluation were calculated. Comparisons between groups were established using a t-test or chi--square, as appropriate. Survival curves of the first biological were compared through the logrank test. RESULTS: In total, 123 patients were included in the analysis (mean age 57.0 ± 13.1 years and mean disease duration 11.7 ± 8.0 years). A total of 85 switches were documented, 20% of which took place before 2007. Comparing the switches before and after 2007, the latter were registered among older patients (recent switches 56.2 ± 12.9 years vs older switches 48.9 ± 11.0 years, p=0.04) and with a shorter duration of the first biological agent (recent switches 461.9 ± 293.2 days vs older switches 773.7 ± 475.8 days, p=0.03). No further significant differences were found, including the disease activity. The survival of the first biological was shorter in patients starting biological therapy after 2007 (2949 days for biological onset before 2007 and 818 days for onset after 2007, p <0.001). A good EULAR response was achieved by 19% and 30% of the patients, before and after 2007, respectively (p = 0.23). Remission was achieved by 14% and 22% of the patients, before and after 2007, respectively (p = 0.30). CONCLUSIONS: Switches were more frequently performed in more recent years, in older patients and with a shorter duration of biological therapy. A trend towards a better and more targeted control of the disease could be discussed in light of our results. Although switches were more frequently performed in more recent years, in older patients and with a shorter duration of biological therapy, there is still room for improvement when aiming at remission, for example by applying a tighter therapy strategy like the "treat to target model".

Body composition phenotypes in systemic lupus erythematosus and rheumatoid arthritis: a comparative study of Caucasian female patients.

OBJECTIVES: The amount and distribution of fat and lean mass have important implications for health and systemic inflammation may represent a risk for altered body composition. The aim of this study was to analyse whether changes in body composition are similarly associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), two inflammatory conditions of different pathogenesis. METHODS: Body mass index (BMI), waist circumference, fat mass (FM) and fat-free mass (FFM) were measured in 92 women with SLE, 89 with RA and 107 controls. Results were compared among the 3 groups and correlations of FM percentage were explored within SLE and RA. RESULTS: Abnormal body composition was more frequent in women with SLE and RA than in non-inflammatory controls, despite having a similar BMI. RA diagnosis was significantly associated with overfat (OR=2.782, 95%CI 1.470-5.264; p=0.002) and central obesity (OR=2.998, 95%CI 1.016-8.841; p=0.04), while sarcopenia was more common among SLE (OR=3.003; 95%CI 1.178-7.676; p=0.01). Sarcopenic obesity, i.e. the coexistence of overfat with sarcopenia, was present in 6.5% of SLE and 5.6% of RA women, but no controls. Independent correlations of FM percentage in women with SLE included smoking, disease activity and CRP. In RA, education, disease activity and cumulative corticosteroid dose were identified as independent predictors of FM percentage. CONCLUSIONS: Women with SLE or RA diagnosis are more likely to have abnormal body composition phenotype, with some differences existing between these two conditions. Changes in body composition are partly explained by the inflammatory burden of disease and its treatment.

[Myalgia of the girdle in the elderly: an uncommon etiology]. / Mialgias das cinturas no idoso: uma etiologia pouco frequente.

We describe the clinical case of 80 years, caucasian woman, with personal history of osteoporosis and chronic normochromic normocytic anemia (NN). She had a three month history of myalgias of the girdle, stiffness in the morning, exceeding 1 hour, associated with inflammatory arthralgia of the small joints of hands and feet. Complementary exams showed normocytic normochromic anemia with Hg 9.8 g/dL; ESR 44 mm/h; CRP 7 mg/dL. Given the profile suggestive of Polymyalgia Rheumatica started prednisolone 10 mg/day with favorable clinical response. Four months after treatment she started paresthesias of right hand and foot, polaquiuria, petequial lesions in lower limbs and inability to walk; there was worsening of anemia and elevation of the biological parameters of inflammation, beginning of renal insufficiency with creatinine clearance 22 ml/min, proteinuria and eritrocituria. Renal biopsy was compatible with Wegener's granulomatosis/microscopic poliangeite. Vasculitis is a rare disease of the elderly and its clinical presentation is varied. The arteritis of giant cells and Polymyalgia Rheumatica are more common in the elderly. It is not often Polymyalgia-like presentation in cases of Wegener's granulomatosis/microscopic polyangitis.