Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Spanish Validation of the GEPARD Questionnaire for the Detection of Psoriatic Arthritis in Argentinian Patients with Psoriasis.

BACKGROUND/OBJECTIVE: Psoriatic arthritis (PsA) is preceded by psoriasis in approximately 80% of cases. Dermatologists are pivotal for early detection. It is important to have simple tools that allow the detection of PsA in patients with skin psoriasis. The aim of our study was to evaluate the performance of an adapted version of the GEPARD Questionnaire in Spanish in Argentinian patients with psoriasis. METHODS: This is a cross-sectional study. A new Spanish (Argentinian) (GEPARDa) translated version of the original questionnaire (German) was developed and then tested as a diagnostic tool in patients with psoriasis, PsA, osteoarthritis associated to psoriasis, and osteoarthritis, all evaluated by rheumatologists who used the CASPAR criteria. RESULTS: Eighty-three patients were included (55 [66.3%] women with a mean age of 50.7 years [SD 6.3]). Forty-four patients had PsA (29 [34.9%] patients had previous diagnosis of PsA, and 15 [18%] were newly diagnosed after referral by their dermatologists), and 39 patients were without PsA (18 [21.6%] patients had psoriasis without articular involvement, 6 [7.22%] had psoriasis associated with osteoarthritis, and 15 [18%] had osteoarthritis). An area under the curve of 0.9554 (SD 0.01; 95% CI 0.91-0.99) was calculated considering the CASPAR criteria as the gold standard. With a cutoff of ≥6 the questionnaire showed a sensitivity of 88.64%, a specificity of 89.74%, a positive likelihood ratio of 8.6, and a negative likelihood ratio of 0.12. CONCLUSIONS: The GEPARDa version has proven to be a diagnostic tool with excellent performance so that it can be considered a valid tool for the detection of PsA in Argentinian patients.

Reliability of OMERACT ultrasound elementary lesions in gout: results from a multicenter exercise.

The aim of this study was to evaluate the reliability of the outcome measures in rheumatology (OMERACT) definitions for ultrasound (US) elementary lesions in gout through an image reading exercise. Images from patients with gout (static images and videos) were collected. As an initial step, we carried out a image reading exercise within the experts of the Pan-American League of Associations for Rheumatology (PANLAR) US Study Group (n = 16). The following step consisted in a web-based exercise with the participation of larger number of sonographers (n = 63) from different centers. Images were rated evaluating the presence/absence of any US elementary lesion. Inter- and intra-reader reliabilities were analyzed using kappa coefficients. Participants were stratified according to their level of experience. In the first exercise, inter-reader kappa values were 0.45 for aggregates, 0.57 for tophus, 0.69 for erosions, and 0.90 for double contour (DC). Intra-reader kappa values were 0.86, 0.76, 0.80, and 0.90, respectively. The web-based exercise showed inter-reader kappa values for aggregates, tophus, erosions, and DC of 0.42, 0.49, 0.69, and 0.79, respectively. The intra-reader kappa values were 0.62, 0.69, 0.77, and 0.85, respectively. Reliability was not influenced by the sonographer's level of experience. The reliability of the new OMERACT US definitions for elementary lesions in gout ranged from moderate to excellent, depending on the type of lesion.

Prevalence of biologics monotherapy in a cohort of patients with Rheumatoid Arthritis in daily clinical practice.

BACKGROUND: Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy, in spite that combination therapy with Disease Modifying Drugs is more efficacious than monotherapy. The aim of our study was to assess the prevalence of biologics monotherapy in a cohort of patients with RA followed at a single center, and to analyze the reasons for monotherapy, including patients with prescriptions that do not take the medication. METHODS: All patients with Rheumatoid Arthritis, with biologic therapy followed at our Rheumatology Unit were included. Prevalence and reasons for biologics monotherapy was calculated in general, for each biologic course and for each biologic. Prescription data was obtained from the Electronic Medical Record, and drugs acquisition was obtained from the Hospital Administrative database. Drug survival was also calculated and compared between monotherapy and combination therapy. RESULTS: Seventy nine patients with 115 courses of biologic treatments were included. In 40 (35 %, 95 % CI: 26-44 %) of all biologics courses, biologics were initiated as monotherapy. In 27 courses (23 %, 95 % CI: 16-32 %) biologic monotherapy was prescribed by the treating rheumatologists, and in the other 13 (11 %, 95 % CI: 6-18 %) it was initiated as such by decision of the patient regardless of the physician indication. Reasons for prescription of biologic monotherapy by the treating rheumatologists were adverse events with previous DMARDs in 55.5 %, and was not specified in the remaining courses. Only 25 % of biologics' courses were monotherapy from the beginning to the end of the biologic therapy. The overall survival on biologics was 45 % (95 % CI: 35-55 %) at 3 years. There were no statistically differences in biologics survival by modality (monotherapy vs combination) (p = 0.543), course (p = 0.4454), or by biologic drug (p = 0.9612). CONCLUSIONS: Almost 1/3 of patients on biologics use them as monotherapy. This is due to physician's preferences in 60 % of the cases, and to patients not compliance with the indication in around 40 % of the cases. Better communications is needed to assure that physicians and patients agree on the prescribed and used medication.

Knee effusion: ultrasound as a useful tool for the detection of calcium pyrophosphate crystals.

The objective of this study was to evaluate the sensitivity and specificity of ultrasound (US) and conventional radiography (CR) for the detection of calcium pyrophosphate (CPP) crystals in patients with knee effusion. Consecutive patients ≥50 years old with knee effusion were included. All patients underwent arthrocentesis with aspiration of synovial fluid (SF) and subsequent analysis of CPP crystals using plain light and polarizing light microscopy. US and CR of the involved knee were performed immediately after arthrocentesis. CR results were read by an experienced rheumatologist, searching for chondrocalcinosis. US examinations were carried out by an experienced rheumatologist blinded to all clinical and imaging data. The following US abnormal findings were considered indicative of CPP crystals deposition (CPPD): (1) hyperechoic bands within the femoral hyaline cartilage layer, and (2) hyperechoic sparkling spots in meniscal fibrocartilage. A total of 75 knees were evaluated in the same number of patients. Analysis of SF revealed CPP crystals in 15 out of 75 (20 %) knees: all (10) patients with previous diagnosis of CPPD, 3 patients with previous diagnosis of primary knee osteoarthritis (OA) and 2 patients without previous definitive diagnosis of a rheumatic condition. Using SF analysis as reference method, sensitivity and specificity for US findings was 60 and 96.7 %, respectively, while CR showed a sensitivity of 40 % and a specificity of 83.3 %. US results showed high specificity with acceptable sensitivity to detect CPP crystals in patients with knee effusion. Compared with CR, US results had better specificity and sensitivity. US may be used in daily rheumatologic practice when CPPD is suspected.

Cost of rheumatoid arthritis in a selected population from Argentina in the prebiologic therapy era.

BACKGROUND: The present study aimed to estimate the cost of rheumatoid arthritis and its components in a university hospital-based health management organization in Argentina, during the prebiologic era. METHODS: A one-year (2002) observational prevalence, cost-of illness study of patients with rheumatoid arthritis from the societal perspective was performed in a hospital-based health management organization population. Direct medical costs were obtained using administrative databases. Direct nonmedical and indirect costs were obtained from a semistructured questionnaire. Indirect costs included work absenteeism, permanent work disability, and housework lost for housewives, using the human capital approach. Costs are expressed in 2002 US dollars per patient per year. RESULTS: A total of 165 patients (84% females), of mean age 61 ± 15 years and with a mean disease duration of 8.5 ± 8.3 years were included. Mean total direct medical costs were US$1862 (95% confidence interval [CI] 828-2899). Mean direct nonmedical costs were US$222 (95% CI 149-294). Mean indirect costs were US$1008 (95% CI 606-1412). The annual mean total cost was US$3093 without biologics. Hospitalizations represented 73% of total direct medical costs while drugs and outpatient procedures represented 16% and 8% of total direct medical costs, respectively. Sixty percent of the total costs were related to direct medical costs, while indirect costs represented 33% of total costs. CONCLUSION: In our population, annual mean total costs in the prebiologic therapy era were mainly driven by direct medical costs. Even without the use of biologic agents, rheumatoid arthritis represents an important burden for society in developing countries.

[Aldosterone/renin ratio in the diagnosis of primary aldosteronism]. / Utilidad de la relación aldosterona y actividad renina plasmática en el diagnóstico de hiper- aldosteronismo primario.

Primary aldosteronism (PA) is a possible cause of endocrine hypertension. Recent studies have suggested a prevalence ranging between 5% and 15% of all hypertensive patients, and 20% in patients with refractory hypertension.The objective of this transversal study was to establish the prevalence of PA in a hypertensive population using the aldosterone / plasma renin ratio (ARR) as a screening method, considering that the prevalence rates for PA among hypertensive people present a wide range and that there are only few reports in Argentina. This ratio was then related with the degree of hypertension and with the presence or absence of hypokalemia. Serum aldosterone and plasma renin activity levels were measured in 123 hypertensive patients after discontinuing all medications that could interfere with the hormonal tests. Patients with an aldosterone/plasma renin activity ratio > 25 were submitted to the saline suppression test (SST) to confirm the diagnosis of PA, followed by computed tomography (CT) of the abdomen. Twenty patients presented an ARR > 25 (16.4%). Eighteen were submitted to the SST, eight had a diagnosis of PA confirmed with positive SST (6.5%). Of 8 patients who underwent an abdominal CT, two showed adenoma, and six normal adrenal anatomy. All the eight patients with a PA diagnosis belonged to group II and III of hypertension according to Joint National Committee VI (JNC VI), and only 4 (50%) were normokalemic. We found a 6.5% prevalence of PA, associated with grade II and III hypertension, and normal potassium values in half of the patients with PA.

Utilidad de la relación aldosterona y actividad renina plasmática en el diagnóstico de hiperaldosteronismo primario / Aldosterone/renin ratio in the diagnosis of primary aldosteronism

El hiperaldosteronismo primario (HP) es la forma más común de hipertensión arterial (HTA) secundaria. Recientemente varios estudios sugieren que la prevalencia de esta enfermedad varía entre 5% y 15% entre la población hipertensa, y 20% para hipertensión arterial refractaria. El objetivo de este estudio fue, ante la gran variabilidad de prevalencias sobre HP según las publicaciones internacionales y pocos datos en la Argentina, aportar la prevalencia de HP en un hospital general del interior del país, relacionándolo con el grado de HTA y presencia de normokalemia. En este estudio transversal se realizó dosaje de A/ARP en 123 pacientes hipertensos, suspendiendo toda medicación que interfiriera en los dosajes hormonales; se utilizó como método confirmatorio el test de solución salina (SS) para el diagnóstico de HP y la tomografía computarizada (TC) de abdomen para el diagnóstico etiológico del HP. Se detectó una relación A/ARP elevada en 20 (16.4%) pacientes. En 18 se realizó el test de SS, confirmando el diagnóstico de aldosteronismo en 8 (6.5% del total). En la TC, dos presentaron adenomas, y seis glándulas suprarrenales normales. Todos los pacientes con HP pertenecían al grupo II y III de HTA según el VI Joint National Committee (VI JNC) y el 50% fue normokalémico. Encontramos una prevalencia de 6.5% de HP, asociado a grado II y III de hipertensión, y valores de potasio normal en la mitad de los pacientes.

Primary aldosteronism (PA) is a possible cause of endocrine hypertension. Recent studies have suggested a prevalence ranging between 5% and 15% of all hypertensive patients, and 20% in patients with refractory hypertension.The objective of this transversal study was to establish the prevalence of PA in a hypertensive population using the aldosterone / plasma renin ratio (ARR) as a screening method, considering that the prevalence rates for PA among hypertensive people present a wide range and that there are only few reports in Argentina. This ratio was then related with the degree of hypertension and with the presence or absence of hypokalemia. Serum aldosterone and plasma renin activity levels were measured in 123 hypertensive patients after discontinuing all medications that could interfere with the hormonal tests. Patients with an aldosterone/plasma renin activity ratio > 25 were submitted to the saline suppression test (SST) to confirm the diagnosis of PA, followed by computed tomography (CT) of the abdomen. Twenty patients presented an ARR > 25 (16.4%). Eighteen were submitted to the SST, eight had a diagnosis of PA confirmed with positive SST (6.5%). Of 8 patients who underwent an abdominal CT, two showed adenoma, and six normal adrenal anatomy. All the eight patients with a PA diagnosis belonged to group II and III of hypertension according to Joint National Committee VI (JNC VI), and only 4 (50%) were normokalemic. We found a 6.5% prevalence of PA, associated with grade II and III hypertension, and normal potassium values in half of the patients with PA.