Contraceptive Recommendations for Women with Immune-Mediated Inflammatory Diseases: A Delphi Consensus.

INTRODUCTION: Immune-mediated inflammatory diseases (IMID) are a group of disorders characterized by chronic inflammation caused by an altered immune regulation in targeted organs or systems. IMID itself could have an implied increased risk of venous thromboembolism (VTE) and this risk varies throughout the course of the disease as well as with some contraceptive methods and treatments. The aim of this study was to present some key considerations in relation to contraception in women with IMID. METHODS: This was an exploratory study conducted in Spain following the online modified Delphi methodology with two rounds of participation. Four questionnaires were designed for each medical specialty: gastroenterology, rheumatology, dermatology, and gynecology. Each questionnaire was divided in three domains: general recommendations about IMID, specific recommendations, and contraceptive methods for patients with IMID. A 5-point Likert scale measured agreement with each statement, with an 80% agreement threshold. Following the first round, the percentage of each response was calculated for every item. Subsequently, a second round was conducted to reach a consensus on the items for which discrepancies were observed. RESULTS: A total of 52 and 50 experts participated in the first and second round, respectively. Participants agreed on the existence of a higher risk of VTE in inflammatory bowel diseases, psoriasis, and rheumatoid arthritis diseases. Regarding recommendations for contraceptive methods in patients with IMID, experts considered the hormonal intrauterine device (IUD) as a first-line contraceptive (80.0%) and low doses of progesterone-only pills if the latter is not recommended (88.0%). Most of the interviewees concurred on the importance of the patients' contraceptive needs during the disease course (98.1%). CONCLUSION: Raising awareness and promoting a multidisciplinary relationship among the physicians involved in the therapeutic decisions by considering all the risk factors when prescribing a contraceptive method is important to prevent VTE in women with IMID.

Real-World Health Care Outcomes and Costs Among Patients With Juvenile Idiopathic Arthritis in Spain.

Background: Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in children. If inflammation is not adequately treated, joint damage, long-term disability, and active disease during adulthood can occur. Identifying and implementing early and adequate therapy are critical for improving clinical outcomes. The burden of JIA on affected children, their families, and the healthcare system in Spain has not been adequately assessed. The greatest contribution to direct costs is medication, but other expenses contribute to the consumption of resources, negatively impacting healthcare cost and the economic conditions of affected families. Objective: To assess the direct healthcare, indirect resource utilization, and associated cost of moderate-to-severe JIA in children in routine clinical practice in Spain. Methods: Children were enrolled in this 24-month observational, multicentric, cross-sectional, retrospective study (N = 107) if they had been treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), had participated in a previous study (ITACA), and continued to be followed up at pediatric rheumatology units at 3 tertiary Spanish hospitals. Direct costs included medication, specialist and primary care visits, hospitalizations, emergency visits or consultations, surgeries, physiotherapy, and tests. Indirect costs included hospital travel expenses and loss of caregiver working hours. Unitary costs were obtained from official sources (€, 2020). Results: Overall, children had inactive disease/low disease activity according to JADAS-71 score and very low functional disability as measured by Childhood Health Assessment Questionnaire score. Up to 94.4% of children received treatment, mainly with bDMARDs as monotherapy (84.5%). Among anti-TNFα treatments, adalimumab (47.4%) and etanercept (40.2%) were used in similar proportions. Annual mean (SD) total JIA cost was €7516.40 (€5627.30). Average cost of pharmacological treatment was €3021.80 (€3956.20), mainly due to biologic therapy €2789.00 (€3399.80). Direct annual cost (excluding treatments) was €3654.60 (€3899.00). Indirect JIA cost per family was €747.20 (€1452.80). Conclusion: JIA causes significant costs to the Spanish healthcare system and affected families. Public costs are partly due to the high cost of biologic treatments, which nevertheless remain an effective long-term treatment, maintaining inactive disease/low disease activity state; a very low functional disability score; and a good quality of life.

Impacto clínico de la capilaroscopia periungueal en la práctica clínica diaria / Clinical impact of nailfold capillaroscopy in daily clinical practice

Introducción: La capilaroscopia periungueal (CP) es útil en la evaluación del fenómeno de Raynaud tanto primario como secundario, y en el seguimiento de los pacientes con esclerosis sistémica. Nuestro estudio evalúa el impacto de la CP en el diagnóstico, en función del motivo de solicitud y el perfil de autoanticuerpos en la práctica clínica diaria. Material y métodos: Se incluyeron todos los pacientes con al menos una CP entre junio de 2012 y diciembre de 2017. Se revisaron las historias clínicas y se determinó de forma dicotómica (sí/no) si la CP contribuyó al diagnóstico realizado en la consulta posterior a la realización de la CP. Se recogieron datos demográficos, clínicos y de laboratorio, motivo de solicitud de la CP y su relación con los patrones CP. Resultados: De 530 pacientes con una primera CP, 266 se realizaron como estudio de un fenómeno de Raynaud. De estos, en 20 pacientes (3,8%) se realizó un diagnóstico de enfermedad del tejido conectivo en la consulta posterior a la CP; 15 fueron diagnosticados de esclerosis sistémica, 4 de conectivopatía indiferenciada y uno de enfermedad mixta. Salvo un paciente diagnosticado de conectivopatía indiferenciada, el resto tenía anticuerpos antinucleares positivos y 11 de ellos, además, anticuerpos específicos (9 anticentrómero, uno anti-Scl70 y otro, anti-RNPC). La positividad de anticuerpos antinucleares se asoció con una mayor probabilidad de presentar una CP de esclerodermia, y ningún paciente diagnosticado de una enfermedad reumática tras la CP tenía un patrón normal. Conclusión: La CP es una técnica útil, pero con impacto limitado en el diagnóstico de enfermedades del tejido conectivo. La positividad de los anticuerpos se relaciona con una mayor probabilidad de presentar patrones patológicos en la CP.(AU)

Introduction: Nailfold capillaroscopy (NC) is useful in the evaluation of Raynaud's phenomenon, associated with some connective tissue diseases and in the follow-up of patients with systemic sclerosis. Our study evaluates the impact of NC in the diagnosis, according to the reason for the request and profile of autoantibodies in daily clinical practice. Material and methods: All patients that undergone at least one NC between June 2012 and December 2017 were included. Clinical records were reviewed and analysed in a dichotomous way (yes/no), to see whether the NC contributed to a change of diagnosis in subsequent consultations. In addition, demographic, clinical and laboratory data were collected, and the relationship with NC patterns evaluated. Results: Of the 530 patients who had undergone at least one NC, 266 had Raynaud's phenomenon as primary indication for the technique. Of those, 20 patients (3.8%) had a diagnostic change in the post-NC consultation; 15 were diagnosed with systemic sclerosis, 4 with undifferentiated connective tissue disease and one with mixed connective tissue disease. All patients had, except for one patient diagnosed with undifferentiated connective tissue disease, positive antinuclear antibodies titres, 11 of them had disease specific antibodies (9 anti-centromere, one anti-Scl70 and other anti-RNPC). The positivity of antinuclear antibodies titres was associated with a higher probability of presenting a scleroderma pattern in the NC, and all patients with a specific rheumatological diagnosis had an abnormal NC. Conclusion: NC is a useful technique, but with limited impact in the diagnosis of connective tissue diseases. Autoantibody positivity is associated with a greater likelihood of presenting pathological NC patterns.(AU)

Clinical impact of nailfold capillaroscopy in daily clinical practice. / Impacto clínico de la capilaroscopia periungueal en la práctica clínica diaria.

INTRODUCTION: Nailfold capillaroscopy (NC) is useful in the evaluation of Raynaud's phenomenon, associated with some connective tissue diseases and in the follow-up of patients with systemic sclerosis. Our study evaluates the impact of NC in the diagnosis, according to the reason for the request and profile of autoantibodies in daily clinical practice. MATERIAL AND METHODS: All patients that undergone at least one NC between June 2012 and December 2017 were included. Clinical records were reviewed and analysed in a dichotomous way (yes/no), to see whether the NC contributed to a change of diagnosis in subsequent consultations. In addition, demographic, clinical and laboratory data were collected, and the relationship with NC patterns evaluated. RESULTS: Of the 530 patients who had undergone at least one NC, 266 had Raynaud's phenomenon as primary indication for the technique. Of those, 20 patients (3.8%) had a diagnostic change in the post-NC consultation; 15 were diagnosed with systemic sclerosis, 4 with undifferentiated connective tissue disease and one with mixed connective tissue disease. All patients had, except for one patient diagnosed with undifferentiated connective tissue disease, positive antinuclear antibodies titres, 11 of them had disease specific antibodies (9 anti-centromere, one anti-Scl70 and other anti-RNPC). The positivity of antinuclear antibodies titres was associated with a higher probability of presenting a scleroderma pattern in the NC, and all patients with a specific rheumatological diagnosis had an abnormal NC. CONCLUSION: NC is a useful technique, but with limited impact in the diagnosis of connective tissue diseases. Autoantibody positivity is associated with a greater likelihood of presenting pathological NC patterns.

"There is something you must see": breaking down the remission concept in rheumatoid arthritis from a rheumatologist's perspective.

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and the implications of the existing definitions when applied to clinical practice among rheumatologists with different profiles. METHODS: A qualitative study through focus groups was conducted. Three focus groups were organised from February to March 2016. Each group was composed of rheumatologists with extensive clinical experience with different profiles; experts in basic research (RBR), experts in imaging techniques research (RIR), and experts in clinical research (RCR). The data was collected with audio recording. Verbatim transcriptions of the audio files were made, and a subsequent reflexive thematic analysis assisted by ATLAS.ti (GmbH, Berlin, v. 7) software was performed. RESULTS: From the reflexive thematic analysis, three main themes were generated: (1) remission limitations, (2) instruments or measures to assess remission, and (3) a new definition of remission. Rheumatologists mentioned frequently that the following variables should be considered when developing a new remission definition: inflammatory activity, calprotectin, psychological variables, sex, disease stage, and sociocultural factors. Contrary to what could be expected, all groups acknowledged that their research field could contribute with domains for a gold standard remission instrument, but not in a hierarchical arrangement of importance. The dissonance existing in the entire remission evaluation process was outlined: remission in clinical practice versus remission in clinical trials, remission following the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean versus Musculoskeletal Ultrasound (US) remission, and remission from the rheumatologist's point of view versus the patient's point of view. CONCLUSIONS: Currently, rheumatologists would not accept a domain as more important than others in remission. Our suggestion is, not to generate a universal definition of remission - one that could cover all aspects - but rather to develop definitions of remission for the different settings that could be pondered by the patient's perspective.

Exploring the remission concept in rheumatoid arthritis with patients and rheumatologists: time for a new approach?

OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and to compare remission definitions and related concepts between rheumatologists and patients with the purpose of identifying similarities and disparities to comprehend the different perspectives of the disease. METHODS: This was a qualitative study of discourse and content analysis through focus groups, conducted from February to March 2016. Four focus groups were set up, each one with different interests: rheumatologists involved in basic research (BR), rheumatologists with high specialisation in imaging techniques (IR), clinical rheumatologists (CR), and patients (PA). RESULTS: There is no consensus in a remission definition in RA; differences exist between-groups, rheumatologists and patients value remission differently, and there are discrepancies within the group of rheumatologists. Rheumatologists highlight quantifiable objective parameters, in contrast, patients did not consider objective measures as the best instruments, and they prefer subjective measures of remission. The data confirmed the existence of two sources of knowledge of the disease, technical (physicians) and experiential (patients). These sources of knowledge should concur in order to establish new remission criteria well-adjusted to reality. CONCLUSIONS: The lack of consensus between key groups implicated in defining remission and remission criteria suggests a new strategy for its operational definition. Our group proposes that subjects with a balance between experiential and technical knowledge, should be the ones in charge of this assignment.

Relation of Doppler ultrasound synovitis versus clinical synovitis with changes in native complement component levels in rheumatoid arthritis patients treated with biologic disease-modifying anti-rheumatic drugs.

OBJECTIVES: The complement system plays a fundamental role in mediating the activity of rheumatoid arthritis (RA). Biologic therapy can reduce native complement component levels and its activation. We aimed to study the relation of Doppler ultrasound (US) synovitis versus clinical synovitis with changes in native complement component levels in RA patients on biologic therapy. METHODS: This was a cross-sectional study. Ninety-seven consecutive patients with RA on biologic therapy for at least 3 months were recruited. Clinical, laboratory and Doppler US assessments were performed. The Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI) and a 12-joint US assessment were carried out. Synovitis was semiquantitatively scored in B-mode and power Doppler (PD) mode. RESULTS: A significant decrease in native complement (i.e. C3 and C4) and C-reactive protein (CRP) levels was observed. This was highly significant for C3 decrease (p<0.0005), and C4 decrease (p<0.0005). Synovitis detected by PD US showed significant negative association with C3 change (p<0.008), where patients with higher C3 change were more likely to have PD US inactive status on assessment. CONCLUSIONS: Our results suggested that disease inactive status determined by PD US but not by clinical assessment can be related with decrease in complement in RA patients treated with biologic therapy.

Effectiveness and safety of abatacept in moderate to severe rheumatoid arthritis.

PURPOSE: Abatacept was approved in our hospital by the Pharmacy and Therapeutics Committee for treatment of moderate to severe rheumatoid arthritis (RA) in adult patients with inadequate response or intolerance to disease modifying antirheumatic drugs (DMARDs), including at least one anti-tumour necrosis factor (anti-TNF). The objectives of this study were to analyze compliance with our protocol and to evaluate effectiveness and safety of abatacept in our patients. METHODS: We performed a descriptive longitudinal study of patients with RA treated with abatacept between August 2008 and May 2010 in our day care unit. We reviewed clinical records and recorded the following data: sex, age, weight, year of diagnosis, previous antirheumatic treatments and reasons for withdrawal of anti-TNFs, indication for abatacept, dose and date of administration, Disease Activity Score (DAS28) and adverse events. Effectiveness was evaluated using the European League Against Rheumatism (EULAR) criteria. RESULTS: We recruited 16 patients. Mean follow-up time was 10.4 (SD: 6.1) months. All patients had been previously treated with DMARDs, including at least one anti-TNF, and the mean dose of abatacept was 9.4 (SD: 1.4) mg/kg. During the first 6 months of treatment, 11/16 of patients experienced a decrease in their DAS28 value, but only 5/16 achieved a satisfactory response. Dyspnea was the most frequent adverse event (7/16), followed by fatigue and asthenia (6/16) and dry skin (5/16). CONCLUSIONS: The indication for abatacept in our hospital complied with the protocol approved by the Pharmacy and Therapeutics Committee. Only 5/16 of patients achieved a satisfactory response; however, it should be noted that these patients had moderate to severe RA that was refractory to other treatments. Adverse reactions were consistent with those described in the summary of product characteristics. Further studies with larger cohorts are needed to analyze the long-term safety and effectiveness profile in clinical practice.