Factors associated with discontinuation of biologics in patients with inflammatory arthritis in remission: data from the BIOBADASER registry

Background: The objectives of this study were to assess the discontinuation of biologic therapy in patients who achieve remission and identify predictors of discontinuation of biologics in patients with inflammatory arthritis in remission. Methods: An observational retrospective study from the BIOBADASER registry comprising adult patients diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) and receiving 1 or 2 biological disease-modifying drugs (bDMARDs) between October 1999 and April 2021. Patients were followed yearly after initiation of therapy or until discontinuation of treatment. Reasons for discontinuation were collected. Patients who discontinued bDMARDs because of remission as defined by the attending clinician were studied. Predictors of discontinuation were explored using multivariable regression models. Results: The study population comprised 3,366 patients taking 1 or 2 bDMARDs. Biologics were discontinued owing to remission by 80 patients (2.4%): 30 with RA (1.7%), 18 with AS (2.4%), and 32 with PsA (3.9%). The factors associated with a higher probability of discontinuation on remission were shorter disease duration (OR: 0.95; 95% CI: 0.91-0.99), no concomitant use of classic DMARDs (OR: 0.56; 95% CI: 0.34-0.92), and shorter usage of the previous bDMARD (before the decision to discontinue biological therapy) (OR: 1.01; 95% CI: 1.01-1.02); in contrast, smoking status (OR: 2.48; 95% CI: 1.21-5.08) was associated with a lower probability. In patients with RA, positive ACPA was associated with a lower probability of discontinuation (OR: 0.11; 95% CI: 0.02-0.53). Conclusions: Discontinuation of bDMARDs in patients who achieve remission is uncommon in routine clinical care. Smoking and positive ACPA in RA patients were associated with a lower probability of treatment discontinuation because of clinical remission.This research is supported by the Research Unit of the Spanish Society of Rheumatology. BIOBADASER is supported by the Spanish Agency of Medicines and Medical Devices (AEMPS), Biogen, Bristol-Myers and Squibb (BMS), Celltrion, Janssen, Lilly, Merck Sharp and Dohme (MSD), Novartis, Pfizer, Regeneron, and Samsung Bioepis.S

Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis

Objective: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. Methods: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. Results: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). Conclusions: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.This research is supported by the Research Unit of the Spanish Society of Rheumatology. BIOBADASER is supported by the Spanish Agency of Drugs and Medical Devices (AEMPS), Biogen, Bristol-Myers and Squibb (BMS), Celltrion, Janssen, Lilly, Merck Sharp and Dohme (MSD), Novartis, Pfizer, Regeneron, and Samsung Bioepis.S

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

Artritis psoriásica: Contribuciones al conocimiento de su patogenia, de sus comorbilidades y al perfil de seguridad de su tratamiento

[spa] La artritis psoriásica (AP) es una enfermedad articular inflamatoria crónica, seronegativa, asociada a psoriasis. Esta tesis está compuesta por tres artículos publicados en revistas indexadas, sobre diferentes aspectos de la AP. El primer artículo presentado tuvo como objetivo evaluar la prevalencia de psoriasis moderada-grave (P-MG) en pacientes con AP y las relaciones entre la P-MG y otras variables relacionadas con la artritis. La prevalencia de P-MG en la cohorte fue del 31.3% (52 pacientes de 166). La P-MG fue más frecuente en las mujeres (p=0,027). Ciento nueve pacientes (65,7%) tenían onicopatía psoriásica, siendo ésta más frecuente en los pacientes con P-MG (40 (77%) vs 69 (61%), p=0,028). La P-MG se asociaba de manera estadísticamente significativa al patrón articular de afección axial de AP (7 (16%) vs 3 (3%), p=0,014). Los pacientes con P-MG estaban con mayor frecuencia con terapia biológica. No se encontraron diferencias significativas entre la P-MG y la edad de inicio de la psoriasis o de la artritis, la secuencia del diagnóstico de la psoriasis o de la AP, la afección de las IFD, la frecuencia del HLA-B27 ó del FR, la clase funcional o los índices de actividad de la enfermedad. En el segundo artículo presentado se evaluó el estado de la densidad mineral ósea (DMO) y la frecuencia de osteoporosis y de fracturas osteoporóticas clínicas en un grupo de pacientes con AP. Se estudió una cohorte de 155 pacientes con AP periférica. No se encontraron diferencias significativas entre los pacientes con AP de la cohorte y la población general española, ni en la cohorte global, ni en ningún subgrupo. La frecuencia de osteoporosis de la cohorte global fue del 16%, fue mayor en mujeres postmenopáusicas (28%) que en hombres (9%) o en mujeres premenopáusicas (4%). La frecuencia de fracturas clínicas fue del 13% y acontecieron principalmente en mujeres postmenopáusicas. En el tercer trabajo presentado se evaluó la tasa de retención de los antagonistas del TNF-α en pacientes mayores afectos de enfermedades reumáticas y se identificaron variables predictivas de suspensión de este tratamiento por ineficacia ó por efectos adversos. Para realizar este estudio se utilizó la base de datos biobadaser y se incluyeron pacientes diagnosticados de artritis reumatoide (AR) y espondiloartropatías (SpA) (AP y espondilitis anquilosante). Fueron objeto de estudio 4851 pacientes: 2957 con AR, de los cuáles 666 eran mayores de 65 años, y 1894 pacientes con SpA, de los cuáles 99 eran mayores de 65 años. Las curvas de retención fueron estadísticamente diferentes entre los distintos grupos de edad y diagnóstico, y mostraron que el 50% de los pacientes permanecían con el tratamiento como mucho hasta 4 años, salvo los pacientes jóvenes con SpA que permanecían con el tratamiento durante un período de tiempo más largo. Las curvas de incidencia acumulada mostraron que los pacientes jóvenes suspendían el tratamiento por ineficacia con mayor frecuencia que los pacientes mayores, independientemente de si padecían AR o SpA; por otro lado, los pacientes mayores suspendían el tratamiento con mayor frecuencia por efectos adversos que los pacientes jóvenes, especialmente si estaban diagnosticados de AR. Se realizó un análisis por riesgos competitivos que mostró que en los pacientes mayores, la causa más frecuente de suspensión del tratamiento eran los efectos adversos, independientemente del diagnóstico, y en los pacientes jóvenes la causa más frecuente de suspensión del tratamiento fue la ineficacia. Esta tesis incluye un apéndice con dos revisiones. La primera es una revisión sistemática de los estudios publicados sobre seguridad y eficacia de los tratamientos anti-TNF-α en ancianos y la segunda es una revisión sobre tratamientos actuales y en desarrollo para la espondiloartropatía axial.[eng]This thesis is composed of three articles. The aim of the first study was to assess the prevalence of moderate to severe psoriasis (MS-P) in patients with PsA and the relationship between MS-P and other variables related to arthritis. The prevalence of MS-P in the study cohort was 31.3% (52 patients out of 166). MS-P was more prevalent in women (p=0.027). One hundred nine patients (65.7%) had psoriatic nail disease, and MS-P was more frequent in these patients than in non-MS-P patients (40 (77%) vs 69 (61%), p=0.028). Patients with spondyloarthropathy (SpA) were significantly associated with MS-P (7 (16%) vs 3 (3%), p=0.014). No statitiscal association was observed between MS-P and the age of onset of psoriasis or arthritis, the involvement of distal interphalangeal joints, laboratory findings (HLA-B27, RF), functional class, or disease activity indices. The second study focused on the bone mineral density (BMD) and the frequency of osteoporosis and clinical fractures in a cohort of 155 Spanish patients with PsA. No differences in BMD status between the patients and the Spanish general population were found. The frequency of osteoporosis was 16%; it was higher in postmenopausal women (28%) than in men (9%) or premenopausal women (4%). Frequency of clinical fractures was 13%; it accounted specially in postmenopausal women. The aim of the third study was to assess the retention rate of TNF antagonist drugs in elderly patients suffering from chronic arthropathies and to identify predictive variables of discontinuation by efficacy or by adverse events (AE). Retention curves were statistically different between age groups, with the SpA younger group having the largest retention rate. In the older group, AE were the most common reason for discontinuation regardless of the diagnosis of the patient and TNF antagonists drug, whereas in the younger group, the most common cause of discontinuation was inefficacy. The thesis also includes a review on the safety and efficacy of TNF antagonists in elderly people, and a review on current and under development treatments for axial SpA

Derecho de las víctimas

Treball Final de Grau en Criminologia i Seguretat. Codi: CS1044. Curs: 2014/2015Este trabajo se ha realizado para hacer una investigación sobre cuáles son los derechos que asisten a las víctimas y cuál es la verdadera efectividad de los mismos en nuestra sociedad en un momento como en el que nos encontramos, que los delitos están al orden del día y cada vez son más graves. El estudio se centra sobre todo en dos textos legales muy importantes y de conocida existencia últimamente. Estamos hablando de la Directiva 29/2012 y del Estatuto de la víctima del delito. Hemos encontrado que hay una gran variedad de derechos para proteger a los ofendidos o perjudicados, ya que gracias a los dos textos citados en líneas anteriores, estos se han visto aumentados y reforzados. Vemos como tenemos derechos que las víctimas podrán ejercer en el ámbito procesal, llamados derechos procesales, pero que también hay algunos de ellos que se ejercen fuera de este proceso, llamados derechos no procesales. También hemos podido comprobar que aunque los derechos son los mismos para cualquier víctima, en determinados casos se protege más a las víctimas que tienen unas necesidades especiales. Y que no sólo se dan una vez se ha producido el delito y transcurre el proceso, si no que después del mismo también podrán gozar de algunos de ellos. Y finalmente, hemos podido comprobar cómo, a pesar de la gran cantidad de los mismos, y las diferentes vertientes que abarcan, en muchas ocasiones resultan insuficientes o no generan el resultado esperado.This work has been done to do some research on which are the rights granted to the victims and what the real effectiveness of these in our society at a time like where we are, that crimes are the order of the day and they are becoming more serious. The study focuses mainly on two very important and known existence lately legal texts. We are talking of Directive 29/2012 and the draft statute of the crime victim. We have found that there are a variety of rights to protect the offended or harmed, and thanks to the two texts mentioned in previous lines, these have been augmented and strengthened. We see that victims have rights may be exercised at a procedural level, called procedural rights, but there are also some of them which are exercised outside this process, called non-procedural rights. We have also found that although the rights are the same for any victim, in certain cases the victims who have special needs are more protected. And not only occur once the crime has occurred and the process takes place, if not after the same may also enjoy some of them. And finally, as we have seen, despite the large number of them, and covering the different aspects, in many cases insufficient or do not generate the expected result

Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience

There has been a renewed interest in the potential use of psychedelics for the treatment of psychiatric conditions. Nevertheless, little is known about the mechanism of action and molecular pathways influenced by ayahuasca use in humans. Therefore, for the first time, our study aims to investigate the human metabolomics signature after consumption of a psychedelic, ayahuasca, and its connection with both the psychedelic-induced subjective effects and the plasma concentrations of ayahuasca alkaloids. Plasma samples of 23 individuals were collected both before and after ayahuasca consumption. Samples were analysed through targeted metabolomics and further integrated with subjective ratings of the ayahuasca experience (i.e., using the 5-Dimension Altered States of Consciousness Rating Scale [ASC]), and plasma ayahuasca-alkaloids using integrated network analysis. Metabolic pathways enrichment analysis using diffusion algorithms for specific KEGG modules was performed on the metabolic output. Compared to baseline, the consumption of ayahuasca increased N-acyl-ethanolamine endocannabinoids, decreased 2-acyl-glycerol endocannabinoids, and altered several large-neutral amino acids (LNAAs). Integrated network results indicated that most of the LNAAs were inversely associated with 9 out of the 11 subscales of the ASC, except for tryptophan which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with the ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in several pathways involved in neurotransmission such as serotonin and dopamine synthesis. In conclusion, a crosstalk between the circulating LNAAs and the subjective effects is suggested, which is independent of the alkaloid concentrations and provides insights into the specific metabolic fingerprint and mechanism of action underlying ayahuasca experiences

Clinical Outcomes of Golimumab as First, Second or Third Anti-TNF Agent in Patients with Moderate-to-Severe Ulcerative Colitis.

Golimumab efficacy data in ulcerative colitis (UC) are limited to anti-tumor necrosis factor α (TNF)-naive patients. The aim of this study was to assess the short-term and long-term efficacy of golimumab used as first, second, or third anti-TNF in UC in a real-life clinical setting. This retrospective multicenter cohort study included patients with moderate-to-severe UC treated with golimumab. The primary efficacy endpoints were short-term partial Mayo score response, long-term golimumab failure-free survival, and colectomy-free survival. In 142 patients with UC, golimumab was administered as first (40%), second (23%), or third anti-TNF (37%). Ninety-two patients (65%, 95% confidence interval 56.6-73) achieved short-term clinical response. Forty-five patients (32%, 95% confidence interval 23.7-39.7) achieved clinical remission. Response rates for golimumab were 75% as first anti-TNF, 70% as second anti-TNF (ns versus first anti-TNF), and 50% as third anti-TNF (P = 0.007 versus first anti-TNF). After 12 months median follow-up (interquartile range 6-18), 60 patients (42%, 95% confidence interval 34-51) had golimumab failure, and 15 patients (11%) needed colectomy. Thirty-one patients (22%) needed golimumab dose escalation, and 71% of these regained response after escalation. Starting maintenance with 100 mg golimumab doses and short-term nonresponse were independent predictors of golimumab failure. In this real-life cohort of patients with UC, golimumab therapy was effective for inducing and maintaining clinical response. Although anti-TNF-naive patients had better outcomes, golimumab was also effective in anti-TNF-experienced patients. Only the patients given golimumab after previous failure of 2 anti-TNF agents had significantly worse outcomes. Golimumab dose escalation was beneficial and safe

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study

Objective To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies.Patients and methods 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model.Results The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i.Conclusion COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation