Quantifying Physician Preferences for Systemic Atopic Dermatitis Treatments Using a Discrete-Choice Experiment.

INTRODUCTION: As research continues, new drugs will no doubt be added to the current pool of treatments for moderate-to-severe atopic dermatitis (AD). This raises the need for studies to determine prescriber preferences for different pharmacological options and the factors that influence their choice of treatment. Here we aim to explore physician preferences in the systemic treatment of moderate-to-severe AD, identify the sociodemographic characteristics that can influence physician preferences, and evaluate their satisfaction with current AD therapies. METHODS: A discrete-choice experiment (DCE) survey was administered to physicians treating patients with AD in Spain. Results were analyzed using a conditional logit model to estimate the relative importance of each attribute and the maximum risk accepted to achieve therapeutic benefit. RESULTS: A total of 28 respondents completed the DCE survey (67.9% female, mean age 45.9 years). Participants identified objective clinical efficacy and risk of severe adverse events (AEs) as the most important attributes, followed by improvement in sleep and pruritus and faster onset of action from the start of the treatment. Respondents gave less importance to mode of administration and therapeutic benefit in other atopic conditions. Respondents were willing to accept an increased risk of severe AEs and mild-to-moderate AEs leading to treatment discontinuation due to intolerance in order to obtain improvements in efficacy, sleep, and pruritus, and long-term clinical benefit. CONCLUSION: Our findings can help prescribers choose the most appropriate systemic AD therapy.

Comorbidity identification and referral in atopic dermatitis: a consensus document.

BACKGROUND: Atopic dermatitis (AD) is associated with different comorbidities. OBJECTIVE: To develop evidence-based and practical recommendations for comorbidity detection in patients with AD in daily practice. METHODS: We employed a modified RAND/UCLA methodology, including a systematic literature review (SLR). A group of six experts on AD was established. We conducted a comprehensive search strategy on Medline, Embase, and Cochrane Library up to June 2020. The selection criteria included studies with AD patients with any comorbidity reporting data on comorbidity prevalence, burden, and management. The included studies quality was assessed. The SLR results were discussed in a nominal group meeting, and several recommendations were generated. The recommendation agreement grade was tested on additional experts through a Delphi process. RESULTS: The recommendations cover the following issues: (1) Which comorbidities should be investigated at the first and subsequent visits; (2) how and when should comorbidities be investigated (screening); (3) how should patients with specific comorbidities be referred to confirm their diagnosis and initiate management; (4) specific recommendations to ensure an integral care approach for AD patients with any comorbidity. CONCLUSIONS: These recommendations seek to guide dermatologists, patients, and other stakeholders in regard to early comorbidity identification and AD patient referral to improve decision-making.

Efficacy of Tofacitinib in the Treatment of Psoriatic Arthritis: A Systematic Review.

INTRODUCTION: Therapeutic approaches for psoriatic arthritis (PsA) include non-pharmacologic therapies, symptomatic treatments, tumor necrosis factor inhibitors, interleukin inhibitors, cytotoxic T lymphocyte antigen 4 immunoglobulin, and Janus kinase inhibitors. This systematic review aimed to provide complete and up-to-date information on efficacy of tofacitinib in the treatment of PsA, giving special attention to non-skin manifestations (peripheral arthritis, axial disease, enthesitis, and dactylitis). METHODS: A search of studies published between January 2016 and June 2020 was carried out on PubMed and Google Scholar. RESULTS: The number of studies with tofacitinib in PsA is limited and most of them are post hoc analyses from OPAL Broaden and OPAL Beyond. Tofacitinib has been demonstrated to be efficacious for the treatment of all disease manifestations in PsA. Superior effectivity to placebo is achieved at the earliest time point evaluated, and maintained over time. Patients who switch from placebo to tofacitinib show the same improvements; however, the time to initial response is faster in patients who firstly receive tofacitinib, compared with those switching subsequently. Additional data suggest that tofacitinib may be also effective for the treatment of the axial domain. CONCLUSIONS: Tofacitinib has been demonstrated to be efficacious for the treatment of peripheral and axial involvement, enthesitis, and dactylitis manifestation in PsA. Further prospective and long-term studies are required to corroborate and complete the present results. Similarly, real-world evidence is also necessary to complement the information obtained in clinical trials, and thereby to have a better overview of real efficacy and safety of the drug.

"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.

Manifestaciones trombóticas en el síndrome SAPHO. Revisión de la literatura / Thrombotic manifestations in SAPHO syndrome. Review of the literature

El síndrome SAPHO (sinovitis, acné, pustulosis, hiperostosis y osteítis) comprende un conjunto de manifestaciones cutáneo-osteoarticulares. Se han descrito algunas complicaciones graves que pueden aparecer durante la evolución de la enfermedad, como la trombosis venosa, principalmente en pacientes que desarrollan afectación inflamatoria grave de la pared torácica anterior. El objetivo de la presente revisión fue analizar los casos descritos en la literatura médica relacionados con la presencia de complicaciones trombóticas en pacientes diagnosticados de síndrome SAPHO e intentar establecer los probables factores de riesgo y su posible mecanismo patogénico. Se analizaron 11 artículos publicados de casos clínicos aislados o series de casos, con un total de 144 pacientes, que describen en total 15 casos de trombosis venosa. Se exponen las características clínicas de estos pacientes, se evalúa si cumplen los criterios de clasificación ASAS para espondiloatritis axial y periférica, y se resalta la necesidad de realizar un diagnóstico y tratamiento precoces (AU)

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a cluster of osteo-cutaneous manifestations that can lead to serious complications such as thrombosis of the subclavian vein or superior vena cava, mainly in patients with significant inflammatory involvement of the anterior-chest-wall. The objective of this study was to review the cases published in the medical literature related with the presence of thrombotic complications in patients diagnosed with SAPHO syndrome and to try to determine their possible pathogenic mechanism and risk factors. We analyzed 11 published reports of isolated clinical cases or case series, a total of 144 patients, which described a total of 15 cases of venous thrombosis. The clinical characteristics of these patients, evaluated to determine whether they meet the ASAS criteria for axial and peripheral spondyloarthritis, is analyzed the need for early diagnosis and treatment is highlighted (AU)

Thrombotic manifestations in SAPHO syndrome. Review of the literature.

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a cluster of osteo-cutaneous manifestations that can lead to serious complications such as thrombosis of the subclavian vein or superior vena cava, mainly in patients with significant inflammatory involvement of the anterior-chest-wall. The objective of this study was to review the cases published in the medical literature related with the presence of thrombotic complications in patients diagnosed with SAPHO syndrome and to try to determine their possible pathogenic mechanism and risk factors. We analyzed 11 published reports of isolated clinical cases or case series, a total of 144 patients, which described a total of 15 cases of venous thrombosis. The clinical characteristics of these patients, evaluated to determine whether they meet the ASAS criteria for axial and peripheral spondyloarthritis, is analyzed the need for early diagnosis and treatment is highlighted.

[New therapeutic targets in psoriatic arthritis]. / Nuevas dianas terapéuticas en artritis psoriásica.

Registries estimate that one third of patients with psoriatic arthritis (PsA) are "resistant" to of TNF-alpha blockers. Therefore, the search for new approaches to treatment of this disease may be justified. Currently the treatment options that have proven effective are associated with inhibition of the T cell costimulatory pathway (abatacept and alefacept) and blocking the P40 fraction of IL-12 and IL-23 (ustekinumab). A novel pathway inhibition, which deserves special attention is offered by apremilast. This molecule inhibits phosphodiesterase IV, responsible for hydrolyzing cyclic adenosine monophosphate to adenosine monophosphate, which causes an increase in cAMP. This metabolite is associated with decreased TNF-alpha. It has a modest efficacy (ACR 20 response of 43%), and subsequent studies have shown an improvement in visual analog scale and the SF36 compared to placebo. Currently there are five clinical trials in phase III to assess its effectiveness in parameters of inflammation and radiographic progression. The spectrum of possibilities before treatment failure with anti-TNF alpha, is augmented by the appearance of several reports that show efficacy with the individual use of CD20 inhibitors and IL-1. In patients with rheumatoid arthritis (RA) the effectiveness of molecules that inhibit signal transduction of cytokines (Anti-JAK) has been proven, so it is possible that in the future they may be used in patients with PsA.

Nuevas dianas terapéuticas en artritis psoriásica / New therapeutic targets in psoriatic arthritis

Los registros estiman que un tercio de los pacientes con artritis psoriásica (Aps) son «resistentes» a los bloqueantes del TNF-alfa. Por ello, la búsqueda de nuevos abordajes terapéuticos de la enfermedad es un objetivo que se puede considerar justificado. Actualmente las opciones terapéuticas que han probado su eficacia, son las vinculadas a la inhibición de la vía coestimuladora del linfocito T (abatacept y alefacept) y el bloqueo de la fracción P40 de la IL-12 e IL-23 (ustekinumab). Una novedosa vía de inhibición, que merece especial atención, es la que ofrece Apremilast. Esta molécula inhibe la fosfodiesterasa IV encargada de hidrolizar la adenosina monofosfato cíclica a adenosina monofosfato, lo que provoca un aumento de la cAMP. Este metabolito se relaciona con una disminución del TNF alfa. Capaz de provocar una modesta eficacia (respuesta ACR 20 del 43%), estudios posteriores han demostrado una mejoría en la escala visual analógica y en el SF36 respecto al grupo placebo. Actualmente hay en marcha 5 ensayos clínicos en fase III que evaluarán su eficacia en parámetros de inflamación y de progresión radiográfica. El espectro de posibilidades, ante el fracaso terapéutico con anti-TNF alfa, se amplía con la aparición de diversos reportes donde se ha mostrado eficacia en la utilización individual con agentes inhibidores del CD20 y de la IL-1. Se está demostrando en pacientes con artritis reumatoide (AR) la eficacia de las moléculas que inhiben la transducción de las señales de las citocinas (Anti-JAK), por lo que es posible que en un futuro sean utilizadas en pacientes con Aps (AU)

Registries estimate that one third of patients with psoriatic arthritis (PsA) are "resistant" to of TNF-alpha blockers. Therefore, the search for new approaches to treatment of this disease may be justified. Currently the treatment options that have proven effective are associated with inhibition of the T cell costimulatory pathway (abatacept and alefacept) and blocking the P40 fraction of IL-12 and IL-23 (ustekinumab). A novel pathway inhibition, which deserves special attention is offered by apremilast. This molecule inhibits phosphodiesterase IV, responsible for hydrolyzing cyclic adenosine monophosphate to adenosine monophosphate, which causes an increase in cAMP. This metabolite is associated with decreased TNF-alpha. It has a modest efficacy (ACR 20 response of 43%), and subsequent studies have shown an improvement in visual analog scale and the SF36 compared to placebo. Currently there are five clinical trials in phase III to assess its effectiveness in parameters of inflammation and radiographic progression. The spectrum of possibilities before treatment failure with anti-TNF alpha, is augmented by the appearance of several reports that show efficacy with the individual use of CD20 inhibitors and IL-1. In patients with rheumatoid arthritis (RA) the effectiveness of molecules that inhibit signal transduction of cytokines (Anti-JAK) has been proven, so it is possible that in the future they may be used in patients with PsA (AU)

[Physiopathologic relationship between interstitial cystitis and rheumatic, autoimmune, and chronic inflammatory diseases]. / Relación fisiopatológica de la cistopatía intersticial con enfermedades reumáticas, autoinmunes e inflamatorias crónicas.

OBJECTIVES: To evaluate the current knowledge about interstitial cystitis pathophysiology and its relationship with rheumatic, autoimmune and chronic inflammatory diseases. METHODS: Literature search under "interstitial cystitis pathophysiology" either clinical or experimental trials and reports, in Medline, PubMed, Digital Urology Journal and Doctor's Guide, in addition to our own clinical research experience results. RESULTS: Both human and experimental trials show resemblances between interstitial cystitis and rheumatic, autoimmune, and chronic inflammatory diseases on clinical presentations, pathophysiology. Some interstitial cystitis patients show the bladder infiltrated with specific mononuclear cells, high incidence of circulating antinuclear antibodies, good response to anti-inflammatory and/or immunosuppressive therapies. Interstitial cystitis in association with rheumatic, autoimmune and chronic inflammatory diseases is very common. Many patients with systemic lupus erythematosus, Sjögren syndrome and fibromyalgia syndrome show antibodies against urothelium and/or muscle cells and/or other connective tissue components of urinary bladder. Systemic lupus erythematosus and Sjögren syndrome are the autoimmune diseases which bear strongest similarity with interstitial cystitis. Moreover, rheumatoid arthritis, chronic pelvic pain syndrome, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, Evan's syndrome and atopic dermatitis share some pathogenic characteristics. CONCLUSIONS: Nowadays, interstitial cystitis pathophysiology is unknown. Based on clinical presentations, epidemiology, pathology and laboratory findings and treatment response, there is an important correlation among interstitial cystitis and rheumatic, autoimmune and chronic inflammatory diseases. These disorders may share some pathophysiologic mechanisms. Rigorous studies of pathophysiology of these group of diseases are needed to confirm consistently this approach for such conditions.

Relación fisiopatológica de la cistopatía intersticial con enfermedades reumáticas, autoinmunes e inflamatorias crónicas / Physiopathologic relationship between interstitial cystitis and rheumatic, autoimmune, and chronic inflammatory diseases

OBJETIVOS: Estado actual del conocimiento de la fisiopatología de la cistopatía intersticial y surelación con las enfermedades reumáticas, autoinmunes e inflamatorias crónicas. MÉTODOS: Identificación y análisis crítico de los estudios sobre la fisiopatología de la cistopatía intersticial publicados, clínicos y experimentales, mediante búsqueda en Medline, PubMed, Digital Urology Journal, Doctor's Guide, además aportación personal de los estudios y resultados en nuestra práctica clínica. RESULTADOS: Existen similitudes clínicas, fisiopatológicas, y en hallazgos de laboratorio, tanto en estudios humanos como experimentales, entre las enfermedades de naturaleza reumática, autoinmune e inflamatoria crónica y la cistopatía intersticial (CI). Algunos pacientes con CI tienen infiltrado mononuclear organo específico, responden al tratamiento con esteroides y otros inmunosupresores, alta prevalencia de anticuerpos antinucleares y asociación con otros síndromes autoinmunes. Muchos pacientes con lupu seritematoso sistémico (LES), fibromialgia y síndrome de Sjögren (SS), presentan anticuerpos contra la mucosa vesical y/o contra las células musculares y/o contra otros componentes del tejido conectivo de la vejiga. El LES y el SS son las enfermedades autoinmunes con más similitudes clínicas y fisiopatológicas con la CI. Así mismo, existen rasgos patogénicos comunes con la artritis reumatoide, el síndrome de dolor pelviano crónico, intestino irritable, fibromialgia, síndrome de fatiga crónica, síndrome de Evans y dermatitis atópica, entre otros. CONCLUSIONES: La fisiopatología precisa de la cistopatía intersticial se desconoce. Existen similitudes clínicas, epidemiológicas, patológicas, hallazgos de laboratorio, y respuesta al tratamiento, entre la cistopatía intersticial, y enfermedades reumáticas, autoinmunes e inflamatorias crónicas. Los mecanismos fisiopatológicos aparecen relacionados y son semejantes en muchos aspectos en este conjunto de enfermedades. Se precisan más estudios que confirmen estos hallazgos consecuentemente (AU)