Consensus statement on a framework for the management of comorbidity and extra-articular manifestations in rheumatoid arthritis.

The objective of the study was to develop evidence-based and practical recommendations for the detection and management of comorbidity in patients with rheumatoid arthritis (RA) in daily practice. We used a modified RAND/UCLA methodology and systematic review (SR). The process map and specific recommendations, based on the SR, were established in discussion groups. A two round Delphi survey permitted (1) to prioritize the recommendations, (2) to refine them, and (3) to evaluate their agreement by a large group of users. The recommendations cover: (1) which comorbidities should be investigated in clinical practice at the first and following visits (including treatments, risk factors and patient's features that might interfere with RA management); (2) how and when should comorbidities and risk factors be investigated; (3) how to manage specific comorbidities, related or non-related to RA, including major adverse events of RA treatment, and to promote health (general and musculoskeletal health); and (4) specific recommendations to assure an integral care approach for RA patients with any comorbidity, such as health care models for chronic inflammatory patients, early arthritis units, relationships with primary care, specialized nursing care, and self-management. These recommendations are intended to guide rheumatologists, patients, and other stakeholders, on the early diagnosis and management of comorbidity in RA, in order to improve disease outcomes.

Positron Emission Computed Tomography Spectrum of Large Vessel Vasculitis in a Tertiary Center: Differences in 18F-fluorodeoxyglucose Uptake between Large Vessel Vasculitis with Predominant Cranial and Extracranial Giant Cell Arteritis Phenotypes.

(1) Objective:To assess the spectrum of PET-CT-related large vessel vasculitis (LVV) in a Spanish tertiary center and to determine whether FDG uptake by PET-CT differs between giant cell arteritis (GCA) with predominant cranial or extracranial phenotypes. (2) Methods: The spectrum of patients diagnosed with LVV by PET-CT in a tertiary referral hospital that cares for 450,000 people over a period of two years was reviewed. Moreover, differences in FDG uptake between LVV-GCA with predominantly cranial and extracranial phenotype were analyzed. (3) Results: Eighty patients were diagnosed with LVV by PET-CT. Most were due to systemic vasculitis (n = 64; 80%), especially GCA (n = 54; 67.5%). Other conditions included the presence of rheumatic diseases (n = 4; 3.2%), tumors (n = 9; 7.2%) and infections (n = 3; 2.4%). LVV-GCA patients with predominant extracranial GCA phenotype were younger (mean ± SD: 68.07 ± 9.91 vs. 75.46 ± 7.64 years; p = 0.017) and had a longer delay to the diagnosis (median [interquartile range] 12 [4-18] vs. 4 [3-8]; p = 0.006), but had polymyalgia rheumatica symptoms more frequently than those with predominantly cranial GCA phenotype (46.3% vs. 15.4%, p = 0.057). When FDG uptake was compared according to the two different disease patterns, no statistically significant differences were observed. However, patients with extracranial LVV-GCA showed a non-significantly higher frequency of vasculitic involvement of lower-extremity arteries. (4) Conclusions: Regardless of the predominant phenotype, LVV identified by PET-CT is more commonly due to GCA in the Spanish population. In these GCA patients, younger age, PMR, and a higher frequency of lower-extremity artery vasculitis suggest the presence of LVV.

18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Findings of Polymyalgia Rheumatica in Patients with Giant Cell Arteritis.

OBJECTIVE: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are often overlapping conditions. We studied whether 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is useful in identifying PMR in the setting of large vessel (LV) GCA. METHODS: LV-GCA patients diagnosed by PET-CT at a tertiary care center for a population of 450,000 people over a two-year period were reviewed. Scoring was performed based on potential significant FDG uptake at up to 16 sites in nine different extravascular areas (SCORE 16). Differences in extravascular sites of significant FDG uptake were evaluated between LV-GCA with a clinical diagnosis of PMR or not. RESULTS: Fifty-four patients were diagnosed with LV-GCA by 18F-FDG-PET-CT. Of them, 21 (38.8%) were clinically diagnosed with PMR. Significant extravascular FDG uptake was more frequently observed in those with a clinical diagnosis of PMR. In this sense, the SCORE 16 was higher in those with clinical PMR (5.10 ± 4.05 versus 1.73 ± 2.31 in those without a clinical diagnosis of PMR; p < 0.001). A SCORE 16 involving more than four sites of significant FDG uptake yielded a sensitivity of 52% and a specificity of 91% for establishing a clinical diagnosis of PMR associated with LV-GCA. The best areas of significant FDG uptake to clinically identify PMR in patients with LV-GCA were the shoulder, the greater trochanter, and the lumbar interspinous regions, with an area under the ROC curve of 0.810 (0.691-0.930). CONCLUSIONS: Significant extravascular 18F-FDG-PET-CT uptake may help establish a clinical diagnosis of PMR in patients with LV-GCA. These patients are more commonly diagnosed with PMR if they have significant FDG uptake in the shoulder, greater trochanter, and lumbar interspinous areas.

Efficacy and safety of DMARDs in psoriatic arthritis: a systematic review.

OBJECTIVES: Disease-modifying antirheumatic drugs (DMARDs) are frequently prescribed as a first step therapy in active psoriatic arthritis (PsA). However, evidence is sparse and scattered. The objective of this study is to evaluate the efficacy and safety of DMARDs in PsA. METHODS: We performed a systematic review based on electronic searches through Medline, Cochrane Central and Embase (from July 1980-2010) for randomised control trials (RCTs) in PsA. Outcome measures were those included in the core-set from Outcome Measures in Rheumatology Clinical Trials (OMERACT) and adverse effects. RESULTS: A preliminary search identified 3781 potentially relevant RCTs, while only 11 fulfilled inclusion criteria. Ten studies had a parallel design and, one was a cross-over trial. Quality reached a Jadad score over 3 in 6/11 (54.6%). We observed evidence of a moderate improvement of pain and reduction of ESR with DMARDs. The global risk of withdrawals due to adverse events was 2.41 [95% confidence interval (CI) 1.53, 3.82]. The risk of GI adverse effects (nausea, vomiting, abdominal pain, diarrhoea and/or oral ulcers) was 2.02 [95% CI 1.34, 3.03] and of headache was 2.34[95% CI 1.05, 5.19]. There were no significant differences in the rate of increase of flu-like symptoms, rash, or liver enzymes. CONCLUSIONS: The evidence of DMARD efficacy in PsA is certainly limited, basically due to the small number of studies, dissimilar outcomes being evaluated, high withdrawal rates, and absence of new published studies. With regard to adverse effects, only GI events and headaches were significant compared to placebo.

Calcium supplementation and kidney stone risk in osteoporosis: a systematic literature review.

OBJECTIVES: This paper aims to examine the risk of nephrolithiasis in patients with osteoporosis and calcium supplementation. METHODS: This work is based on the systematic review of studies retrieved by a sensitive search strategy in Medline and Embase (1991-2010), and the Cochrane Central register of Controlled Trials (CENTRAL) up to 2010. The abstracts of the annual scientific meetings of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) (2008-2010) were also examined. The selection criteria were the following: patients with osteoporosis, on calcium supplementation alone or associated with other treatments for osteoporosis. We measured the likelihood of developing kidney stones, renal colic, changes in urinary sediment and serum parameters. We selected systematic literature reviews, randomised clinical trials (RCT) and cohort studies. RESULTS: We included 10 studies, 8 RCT and 2 cohort studies of moderate quality. All patients had osteoporosis (>8.000 patients), they were mostly women with a mean age of 50-70 years. Daily calcium doses varied from 120 mg up to 1.500 mg, and treatment duration from 3 days to 3 years. Changes in urinary sediment were found, but in general they were not clinically relevant. No cases of nephrolitiasis were found in more than a half of the included studies. In total there were 3 cases of kidney stone, 2 urinary tract calcifications, 16 cases of nephrolithiasis or urolithiasis, 4 of haematuria and 5 patients reporting kidney pain. CONCLUSIONS: According to our results, calcium supplements in the treatment of osteoporosis alone or in combination with another type of treatment does not significantly increase the risk of nephrolithiasis or renal colic.

Importance of family planning in patients with immune-mediated inflammatory diseases: A multidisciplinary approach.

BACKGROUND AND OBJECTIVES: Family planning in women with immune-mediated inflammatory diseases is a challenge for healthcare teams, highlighting the need for standardized available evidence to provide patients with objective and agreed information. This study reflects the work performed by a multidisciplinary team in reviewing available scientific evidence, and the strategy agreed for family planning, pregnancy, postpartum, and breastfeeding in patients with immune-mediated inflammatory diseases. METHODS: A literature search was conducted, information was structured across the different stages (preconception, pregnancy, postpartum and breastfeeding), and an on-site meeting was convened, in which patients and healthcare providers participated. RESULTS: Specific materials, which are included in this work, were developed to guide clinical decisions to be agreed upon by patients and healthcare providers. CONCLUSION: These materials meet the need for validated and updated information on the approach and use of indicated drugs for professionals responsible for the management of immune-mediated inflammatory diseases.

Multidisciplinary models for pregnancy care in patients with rheumatic diseases: Clinical experiences and experts opinion.

OBJECTIVES: To describe different models of multidisciplinary pregnancy care for patients with inflammatory and autoimmune rheumatic diseases, and the steps to follow concerning their implementation. METHODS: A qualitative study was conducted including: (1) a comprehensive literature search in PUBMED focused on multidisciplinary care models; (2) structured interviews with seven rheumatologists from multidisciplinary pregnancy clinics for patients with inflammatory and autoimmune rheumatic diseases. Data were collected related to the hospitals, medical departments, populations cared for, and multidisciplinary care models (type, material, and human resources, professional requirements, objectives, referral criteria, agendas, protocols, responsibilities, decision-making, research and educational activities, multidisciplinary clinical sessions, initiation/start, planning, advantages/disadvantages, and barriers/facilitators for implementation); (3) a nominal meeting group in which the results of searches and interviews were analyzed and the recommendations for the implementation of the multidisciplinary care models defined. RESULTS: We analyzed seven models of multidisciplinary care in pregnancy, implemented 3-10 years ago, which can all be summarized by two different subtypes: parallel (patients are assessed the same day in the involved medical services) and preferential (patients are assessed on different days in the involved medical services) circuits. The implementation of a specific model results rather from an adaptation to the hospital's and professionals' circumstances. Correct planning and good harmony among professionals are key points to implementing a model. CONCLUSION: Different multidisciplinary care models have been implemented for patients with inflammatory and autoimmune rheumatic diseases during pregnancy. They pretend to improve care, system efficiency, and collaboration among specialists and should be carefully implemented.

Importance of family planning in patients with immune-mediated inflammatory diseases: a multidisciplinary approach. / Importancia de la planificación familiar en pacientes con enfermedades inflamatorias inmunomediadas: un abordaje multidisciplinar.

BACKGROUND AND OBJECTIVES: Family planning in women with immune-mediated inflammatory diseases is a challenge for healthcare teams, highlighting the need for standardized available evidence to provide patients with objective and agreed information. This study reflects the work performed by a multidisciplinary team in reviewing available scientific evidence, and the strategy agreed for family planning, pregnancy, postpartum, and breastfeeding in patients with immune-mediated inflammatory diseases. METHODS: A literature search was conducted, information was structured across the different stages (preconception, pregnancy, postpartum and breastfeeding), and an on-site meeting was convened, in which patients and healthcare providers participated. RESULTS: Specific materials, which are included in this work, were developed to guide clinical decisions to be agreed upon by patients and healthcare providers. CONCLUSION: These materials meet the need for validated and updated information on the approach and use of indicated drugs for professionals responsible for the management of immune-mediated inflammatory diseases.

Pregnancy control in patients with systemic lupus erythematosus/antiphospholipid syndrome. Part 2: Pregnancy follow-up. / Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. parte 2: seguimiento del embarazo.

OBJECTIVE: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology set up a working group for the preparation of three consensus documents. METHODS: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. RESULTS: This second document contains the recommendations regarding the management of pregnancy in women with SLE and APS, including complications such as lupus activity, congenital heart block, thrombotic and obstetric manifestations of APS and placental vascular disease. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Pregnancy Control in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Part 1: Infertility, Ovarian Preservation and Preconception Assessment. Consensus Document of the Spanish Society of Gynaecology and Obstetrics (SEGO), the Spanish Society of Internal Medicine (SEMI) and the Spanish Society of Rheumatology (SER). / Control del embarazo en pacientes con lupus eritematoso sistémico y síndrome antifosfolípido. Parte 1: Infertilidad, preservación ovárica y valoración preconcepcional. Documento de consenso de la Sociedad Española de Ginecología y Obstetricia (SEGO), Sociedad Española de Medicina Interna (SEMI) y Sociedad Española de Reumatología (SER).

OBJECTIVE: Pregnancy and puerperium are considered a risk situation in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Therefore, specialized assessment is essential both preconception and during pregnancy and the puerperium. Likewise, it is very important that different specialists in autoimmune diseases and high-risk pregnancies participate in the follow-up of these patients in a coordinated manner. The Spanish Society of Gynaecology and Obstetrics, the Spanish Society of Internal Medicine, and the Spanish Society of Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: The stages of the work were: distribution of work in three groups corresponding to the three periods related to pregnancy (preconception, during pregnancy and childbirth and puerperium), identification of key areas, exhaustive review of the literature and formulation of recommendations. RESULTS: This first document includes the 48 recommendations that address aspects related to infertility, the need for and treatments for gonadal preservation and preconception assessment. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with SLE/APS during pregnancy.

Pregnancy control in Patients with Systemic Lupus Erythematosus/Antiphospholipid Syndrome. Part 3: Childbirth. Puerperium. Breastfeeding Contraception. Newborn. / Control del embarazo en pacientes con lupus eritematoso sistémico/síndrome antifosfolípido. Parte 3. Parto. Puerperio. Lactancia. Anticoncepción. Recién nacido.

OBJECTIVE: In order to agree on the fundamental aspects related to the management of pregnancy in patients with systemic lupus erythematosus and antiphospholipid syndrome, the Spanish Societies of Gynaecology and Obstetrics, Internal Medicine and Rheumatology have set up a working group for the preparation of three consensus documents. METHODS: Each of the Scientific Societies involved proposed five representatives based on their experience in the field of pregnancy control in patients with autoimmune diseases. The recommendations were developed following the Delphi methodology. RESULTS: This third document contains the recommendations regarding the management of delivery, puerperium and lactation, including medication use during these periods and the care of the newborn. In addition, a section on contraception is included. CONCLUSIONS: These multidisciplinary recommendations are considered decision-making tools for clinicians involved in the care of patients with systemic lupus erythematosus/antiphospholipid syndrome during pregnancy.

Recommendations for the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding. / Recomendaciones sobre actuaciones a seguir durante la edad fértil, el embarazo, posparto y lactancia en pacientes con enfermedades reumáticas inflamatorias y autoinmunes.

OBJECTIVE: To develop recommendations on the evaluation and management of patients with rheumatic autoimmune and inflammatory diseases during the reproductive age, pregnancy, post-partum and breastfeeding based on the best evidence and experience. METHODS: Recommendations were generated using nominal group and Delphi techniques. An expert panel of 12 rheumatologists was established. A systematic literature review and a narrative review (websites, clinical guidelines and other relevant documentation) were performed and presented to the panel in its 1st meeting to be discussed and to help define recommendations. A first draft of recommendations was generated and circulated for comments and wording refinement. A national survey analyzing different aspects of this topic was undertaken separately, followed by a Delphi process (2 rounds). Agreement with each recommendation was ranked on a scale of 1 (total disagreement) to 10 (total agreement), and was considered to be achieved if at least 70% voted≥7. The level of evidence and grade of recommendation were assessed using the Oxford Centre for Evidence-based Medicine Levels of Evidence. RESULTS: A total of 14 recommendations were generated for the preconception period (oral and hormonal contraception, reproductive techniques), pregnancy (planning, treatment and follow-up), and breastfeeding (treatment and follow-up). High-risk situations such as lupus or antiphospholipid syndrome were included. A consensus>90% was reached for all but one recommendation. CONCLUSIONS: These recommendations are intended to provide rheumatologists, patients, families and other stakeholders with a consensus on the evaluation and management of patients with autoimmune and inflammatory diseases during the reproductive age, pregnancy, postpartum and breastfeeding.

Denosumab for the treatment of osteoporosis: a systematic literature review.

PURPOSE: To determine the efficacy and safety of denosumab in osteoporosis. METHODS: A systematic search was performed in MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (1950 to July 2010), meeting abstracts (2009-2010), trial registries, and reference lists. The selection criteria were as follows: (population) osteoporosis patients of any age; (intervention) treatment with denosumab; (outcome) efficacy and safety; (study design) randomized clinical trials (RCTs); no language restrictions. Two reviewers independently screened titles and abstracts and subsequently extracted data from the selected studies including quality items, and on outcomes of interest. A meta-analysis was performed for safety issues. RESULTS: A total of 25 studies were included. Denosumab reduces the risk of new radiographic vertebral fracture in a 68% compared with placebo (p<0.001) and increases bone mineral density (BMD) at lumbar spine, total hip, and one-third radius more than alendronate and placebo. A single subcutaneous dose of denosumab resulted in a dose-dependent, rapid, profound, and sustained decrease bone turnover markers (BTMs). Denosumab was in general well tolerated. A meta-analysis has shown an increase in the incidence of urinary infections (p=0.012) and eczema (p<0.001) in the patients treated with denosumab. Meta-analysis of efficacy was complicated due to the study features. CONCLUSIONS: Denosumab given subcutaneously twice yearly is associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. Denosumab is associated with greater and sustained increases in BMD and reductions in BTMs compared with placebo and/or alendronate and with a risk of urinary infections and eczema.

[Update of the Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in rheumatoid arthritis]. / Actualización del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide.

OBJECTIVE: To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. RESULTS: We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. CONCLUSIONS: We present an update on the SER recommendations for the use of biologic therapy in patients with RA.

[Systematic review: is the use of NSAIDs safe during pregnancy in women with rheumatic disease?]. / Revisión sistemática: ¿es seguro el uso de AINE durante el embarazo en mujeres con afección reumática?

OBJECTIVE: To analyze the security of non-steroidal anti-inflammatory drugs (NSAID) in rheumatic disease patients during pregnancy. METHODS: We performed a systematic review using a sensitive search strategy. All studies published in MEDLINE (since 1961), EMBASE (since 1961) and Cochrane Library (up to January 2008) were selected. We defined the population (pregnant women 16 years or above with a musculoskeletal disease), the intervention (use of NSAID), and the outcomes related to safety (number of live births, stillbirths, length of gestation and of labour, birth-weight, number and type of congenital malformations). The titles and abstracts of articles retrieved from the search were reviewed and high quality cohorts and case-control studies were included. RESULTS: Of a total of 149 references retrieved, only 8 were analyzed in detail, and 3 were finally included. More than 2600 pregnant patients were analyzed. There are many different NSAIDs as well as many different outcomes. Different NSAID were included as well as different outcomes. There was no increased risk of congenital malformations in two of the studies. In the third one there was an increased risk for cardiac malformations (OR=1.86; 95% CI, 1.32-2.62) and orofacial clefts (OR=2.61; 95% CI, 1.01-6.78). CONCLUSIONS: There is not enough information to support the negative effects of NSAIDs during pregnancy. On the other hand there is one study suggesting that the use of NSAIDs could increase the risk of cardiac and orofacial malformations in newborns, therefore these drugs should be used with caution.