Spanish Rheumatology Society Research Articles

Position Paper From the Spanish Society of Rheumatology on Biosimilar Drugs

A biosimilar (BS) is a biological drug that contains a version of the active substance of an already authorised original biological product. The BSs are marketed after patent period of the original drug has ended and once it has been demonstrated that the differences regarding the innovative medicine have no relevant effect on its safety or clinical efficacy. The Spanish Society of Rheumatology, in line with the European Medicines Agency, considers that because of its nature and complexity of production, a BS cannot be considered to be the same as a generic drug. The Spanish Society of Rheumatology expresses an unequivocal commitment to the sustainability of the health system in our country and our steadfast alignment with all measures designed to ensure continuity, without reducing the quality of care. Therefore, we believe that the advent of BSs will likely facilitate access of patients with rheumatic diseases to the biological drugs. This article reviews the European Medicines Agency requirements for authorisation, the Spanish legal framework and controversies on BS and presents the position paper of the Spanish Society of Rheumatology on these drugs.

Actualización 2014 del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide

ObjectiveTo establish recommendations for the management of patients with rheumatoid arthritis (RA) to serve as a reference for all health professionals involved in the care of these patients, and focusing on the role of available synthetic and biologic disease-modifying antirheumatic drugs (DMARDs). MethodsConsensual recommendations were agreed on by a panel of 14 experts selected by the Spanish Society of Rheumatology (SER). The available scientific evidence was collected by updating three systematic reviews (SR) used for the EULAR 2013 recommendations. A new SR was added to answer an additional question. The literature review of the scientific evidence was made by the SER reviewer's group. The level of evidence and the degree of recommendation was classified according to the Oxford Centre for Evidence-Based Medicine system. A Delphi panel was used to evaluate the level of agreement between panellists (strength of recommendation). ResultsThirteen recommendations for the management of adult RA were emitted. The therapeutic objective should be to treat patients in the early phases of the disease with the aim of achieving clinical remission, with methotrexate playing a central role in the therapeutic strategy of RA as the reference synthetic DMARD. Indications for biologic DMARDs were updated and the concept of the optimization of biologicals was introduced. ConclusionsWe present the fifth update of the SER recommendations for the management of RA with synthetic and biologic DMARDs.

Documento de posicionamiento de la Sociedad Española de Reumatología sobre fármacos biosimilares

A biosimilar (BS) is a biological drug that contains a version of the active substance of an already authorized original biological product. The BSs are marketed after patent period of the original drug has ended and once it has been demonstrated that the differences regarding the innovative medicine have no relevant effect on its safety or clinical efficacy. The Spanish Society of Rheumatology, in line with the European Medicines Agency, considers that because of its nature and complexity of production, a BS cannot be considered to be the same as a generic drug. The Spanish Society of Rheumatology expresses an unequivocal commitment to the sustainability of the health system in our country and our steadfast alignment with all measures designed to ensure continuity, without reducing the quality of care. Therefore, we believe that the advent of BSs will likely facilitate access of patients with rheumatic diseases to the biological drugs. This article reviews the European Medicines Agency requirements for authorization, the Spanish legal framework and controversies on BS and presents the position paper of the Spanish Society of Rheumatology on these drugs.

Consensus of the Spanish society of pediatric rheumatology for transition management from pediatric to adult care in rheumatic patients with childhood onset.

To develop recommendations on the transition from pediatric care to adult care in patients with chronic inflammatory rheumatic diseases with childhood onset based. Recommendations were generated following nominal group methodology and Delphi technique. A panel of 16 experts was established. A systematic literature review (on transitional care) and a narrative review were performed and presented to the panel in the first panel meeting to be discussed. A first draft of recommendations was generated and circulated. Focal groups with adolescents, young adults and parents were organized. In a second meeting, the focus group results along with the input from invited psychologist were used to establish definitive recommendations. Then, a Delphi process (two rounds) was carried out. A group of 72 pediatric and adult rheumatologists took part. Recommendations were voted from 1 (total disagreement) to 10 (total agreement). We defined agreement if at least 70% voted ≥7. The level of evidence and grade or recommendation was assessed using the Oxford center for evidence-based medicine levels of evidence. Transition care was defined as a purposeful, planned process that addresses the medical, psychosocial and educational/vocational needs of adolescents and young adults with chronic inflammatory rheumatic diseases with childhood onset as they move from child-centered to adult-oriented healthcare systems. The consensus covers: transition needs, barriers and facilitators, transitional issues (objectives, participants, content, phases, timing, plans, documentation and responsibilities), physicians' and other health professionals' knowledge and skill requirements, models/programs, and strategies and guideline for implementation. Preliminary recommendations and agreement grade are shown in the Table(first Delphi round). These recommendations are intended to provide health professionals, patients, families and other stakeholders with a consensus on the transition process from pediatric to adult care.

Response to "A false dichotomy: RCTs and their contributions to evidence-based public health".

<h3>Background</h3> Since the description of the efficacy of rituximab (RTX) in treating patients with rheumatoid arthritis (RA), the use of this drug has been extended. The recommendation in fact sheet is the administration of two infusions of 1 g in each cycle but some studies have used two infusions of 500 mg. Currently the most suitable pattern for its use is not established. <h3>Objectives</h3> To systematically review the published evidence to date regarding on the difference in efficacy in the treatment of RA with RTX when used at a dose of 2 x 500 mg (1 g) or 2 x 1000 mg (2 g) per cycle. <h3>Methods</h3> A sensitive search of all published studies on the difference in the efficacy of RTX in RA patients used at a dose of 1 and 2 g per cycle was performed in Medline, Embase and Cochrane Central databases since its inception until July 2013. We selected all studies involving adult patients with RA treated with RTX in which intervention was described as treatment with RTX at a dose of 1 g per cycle and comparator as the administration of RTX at a dose of 2 g per cycle. Any standardized measure of efficacy in RA was considered as outcome measure at two years of follow-up. Although meta analysis, systematic reviews, clinical trials and cohorts well designed were preferably selected, finally we also included open studies and all studies that showed a methodologically correct subanalysis related to the question even if it had not been his main objective. After removing duplicates, an initial selection by reading titles, a second selection after reading abstracts and, finally, full reading of selected studies, assessing the methodological quality by levels of the Oxford Centre for Evidence Based Medicine Evidence (2001 update) where applicable, was carried out. A manual search of the references of included studies was also performed. <h3>Results</h3> A total of 451 citations about the treatment of RA patients with RTX used at a dose of 1 and 2 g per cycle were identified, which were reduced to 46 after removing duplicates and selection by reading titles and abstracts. Of the 46 articles selected, finally 14 were included in the review, 3 reviews, 2 of them systematic and one not systematic, 5 corresponding to 4 clinical trials, 3 open studies and 3 abstracts, two of them about the same retrospective cohort and, the third one, an open study previously included as a publication. Although published outside the period included in this review, an article about a systematic review and meta-analysis was included because it provides valuable information for the same. <h3>Conclusions</h3> RTX shows an equivalent overall clinical efficacy administered at doses of 1 and 2 g per cycle in the treatment of RA patients (level of evidence 1a, grade of recommendation A). However, there may be differences in extreme efficacy parameters with trend, not statistically significant, to a more ACR70 response or EULAR good response at the dose of 2 g per cycle. <h3>Acknowledgements</h3> This work has been funded by the Spanish Society of Rheumatology. <h3>Disclosure of Interest</h3> A. M. Ortiz Grant/research support: Spanish Society of Rheumatology, M. Rosario Lozano: None declared, C. Martínez Fernández: None declared, I. González-Άlvaro Grant/research support: Spanish Society of Rheumatology <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4004

Juvenile idiopathic arthritis: cross-sectional study of incidence and prevalence observed in a tertiary center of spain

Juvenile Idiopathic Arthritis (JIA) is the most chronic musculoskeletal disease of pediatric population. Its incidence and prevalence vary considerably throught the world. The Spanish Society of Rheumatology has estimated a incidence and prevalence of 8-22/100.000 and 0.7-40/100.000 respectively.

FRI0408 Analysis of Disease Activity and Response to Treatment in A Large Cohort from the Spanish Society of Rheumatology Registry of Patients with Systemic Lupus Erythematosus (RELESSER)

ObjectivesTo analyze activity and response to therapies in a large multicenter sample of patients with systemic lupus erythematosus (SLE).MethodsStudy design: national, multicenter, cross-sectional. Patients: SLE patients according to ACR criteria....

SAT0225 Is There A Difference in the Effectiveness in the Treatment of Rheumatoid Arthritis with Rituximab When Using A Dose of 1 or 2 Grams per Cycle? A Systematic Review

BackgroundSince the description of the efficacy of rituximab (RTX) in treating patients with rheumatoid arthritis (RA), the use of this drug has been extended. The recommendation in fact sheet is...

AB0558 What is the Prevalence of NON Criteria Antiphospholipid Antibodies in Patients with Antiphospholipid Syndrome?

BackgroundIncreasing interest has focussed upon assays which are not currently included in the Antiphospholipid syndrome (APS) classification criteria to detect antibodies directed against other phospholipids (PL), PL binding proteins and/or...

AB0418 Is There A Difference in the Effectiveness in the Treatment of Rheumatoid Arthritis with Rituximab When IT is Used with A Fixed Pattern Every Six Months or On-Demand? A Systematic Review

BackgroundSince the description of the efficacy of rituximab (RTX) in treating patients with rheumatoid arthritis (RA), the use of this drug has been extended. Nevertheless, there are not clearly established...

FRI0296 Is There A Difference in the Effectiveness in the Treatment of Rheumatoid Arthritis with Rituximab in Patients with Rheumatoid Factor Positive and Negative? A Systematic Review

BackgroundSince the description of the efficacy of rituximab (RTX) in treating patients with rheumatoid arthritis (RA), the use of this drug has been extended. However it is not clearly established...

FRI0293 Characteristics of Patients with Rheumatoid Arthritis Treated with Biologic Therapy as Monotherapy

BackgroundThe treatment for Rheumatoid Arthritis (RA) is based mainly on the use of synthetic or biological DMARDs. Most current guidelines recommend the use of biologics in combination with MTX as...

Capacidad funcional, características del dolor y tratamiento farmacológico en pacientes con artrosis de rodilla

IntroductionOur objective was to assess the characteristics of pain, functional capacity, and pharmacological treatment in patients with knee osteoarthritis attending primary care centers and the factors associated with these characteristics. Material and methodsA cross-sectional study was performed in which patients over 50 years old consulting for knee pain and meeting diagnostic criteria for knee osteoarthritis (Spanish Rheumatology Society) were selected by consecutive sampling from February to November 2011. The following variables were recorded using a specifically designed protocol: sociodemographic and clinical variables, the WOMAC and Lequesne questionnaires, visual analog pain scale, radiographs of the knees, and drug use. ResultsWe included 86 patients, of whom 70.9% were women. Age ranged from 52 to 93 years (mean: 73.7) and 96.5% had other chronic diseases. Eighty three patients took analgesics regularly and 87.9% (95% CI: 80.3-95.6%) were in the first step of the World Health Organization (WHO) analgesic ladder. Patients in steps 2 and 3 scored significantly higher on the visual analog scale than those in stage 1 or not taking analgesics (mean: 7.9 vs 5.9, p=.01). The WOMAC scale showed significant differences in only two items: all those taking opioids had difficulty getting out of the bed (p=.001), and 90% had difficulty in rising from the toilet (p=.005). The Lequesne index showed a mean value of 13.1 (SD: 4.1; range 3-21). ConclusionsMost patients with knee osteoarthritis attending primary care essentially have pain on movement, severely limiting their functional capacity. Analgesics are used to a limited extent, leaving a wide therapeutic margin in these patients.

Safe Prescription Recommendations for Non Steroidal Anti-inflammatory Drugs: Consensus Document Elaborated by Nominated Experts of Three Scientific Associations (SER-SEC-AEG)

This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations.

Recomendaciones para una prescripción segura de antiinflamatorios no esteroideos: documento de consenso elaborado por expertos nominados por 3 sociedades científicas (SER-SEC-AEG)

This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations

Recomendaciones para una prescripción segura de antiinflamatorios no esteroideos: documento de consenso elaborado por expertos nominados por 3 sociedades científicas (SER-SEC-AEG)

This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations

Quality of Care Standards for Nursing Clinics in Rheumatology

BackgroundNursing clinics in rheumatology (NCR) are organizational models in the field of nursing care. There are various NCR models, but there is no consensus on its operational definition. Our objective is to develop quality standards to define and characterize a NCR. MethodTwo-round Delphi method. The panel consisted of 67 experts: rheumatologists and nurses of the nursing working group of the Spanish Society of Rheumatology (SSR). The Delphi questionnaire was developed after a literature and experience review from previous SSR projects. The questionnaire consists of 7 sections: general considerations, standards of structure, process, treatment and monitoring, health education, training and research and quality of care. Each item was scored from 1 (least important) to 9 (most important) or by assigning a number (e.g. waiting days). The degree of agreement among the experts was categorized according to the coefficient of variation (CoV) between very high (CoV≤25%) and very low (CoV>100%). ResultsThe second round questionnaire (182 items) was answered by 46 panelists (34 rheumatologists and 12 nurses). A very important agreement was reached on the general standards of structure, process, treatment and monitoring, health education and quality of care. Less agreement was observed on standards related to training time, number of recommended nurses’ research projects and publications. ConclusionThe standards developed in this study would be useful for establishing desirable quality standards of structure and process, and criteria for clinical work, research and teaching that can be used to develop and evaluate the NCRs.

THU0101 Secondary loss of efficacy of rituximab in patients with rheumatoid arthritis: How often does it occur and what does it mean?

BackgroundSecondary loss of efficacy to individual treatments in patients with rheumatoid arthritis (RA) is well described. It is not clear whether pharmacokinetic or pharmacodynamic changes have taken place or whether...

AB0639 Usefulness of musculoskeletal high resolution ultrasonography (hru) in routine clinical evaluation of “real world” patients with gout

BackgroundThe identification of urate monosodium crystals in aspirated joint fluid or tophi is the “gold standard” for its diagnosis, however clinical features helps in the assessment of typical cases. Ultrasound...

FRI0391 Musculoskeletal high resolution ultrasonography assessment in real life outpatients with GOUT

BackgroundThe musculoskeletal high resolution ultrasonography (HRU) is useful in the gout diagnosis, the assessment of UMS deposits extension and following up the response to urate lowering therapy.Therefore we consider that...