Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program.

INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from Latin America (LATAM) versus the rest of the world (RoW). METHODS: Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were analyzed. RESULTS: Overall, 3209 patients received upadacitinib 15 mg QD for 7024 patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 1518 PY. Baseline characteristics were generally similar between LATAM and RoW populations. AE rates (including serious/opportunistic infections, tuberculosis, and herpes zoster) and deaths were comparable between populations. LATAM patients had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of cardiovascular events were low (≤ 0.5 E/100 PY) and similar between populations. Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were similar between populations, with decreases in hemoglobin, lymphocyte, and neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. Mean change from baseline in low- and high-density lipoprotein cholesterol was generally comparable between LATAM and RoW populations. CONCLUSION: Upadacitinib 15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient populations, with no new safety risks observed. TRIAL REGISTRATION NUMBERS: SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, NCT03086343.

Burden of rheumatoid arthritis on patients' work productivity and quality of life.

BACKGROUND: To determine the burden of Rheumatoid Arthritis (RA) on patients' work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. METHODS: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. RESULTS: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. CONCLUSIONS: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control.

Burden of rheumatoid arthritis on patients' work productivity and quality of life

Abstract Background: To determine the burden of Rheumatoid Arthritis (RA) on patients' work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. Methods: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. Results: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. Conclusions: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control.

Pressure sores among malnourished necropsied adults: preliminary data

Pressure sores are common among bedridden, elderly, or malnourished patients, and may occur in terminal ill patients because of impaired mobility, fecal or urinary incontinence, and decreased healing capacity. The aim of this study was to compare frequency of pressure sores between malnourished and non-malnourished necropsied adults. METHOD: All (n = 201) adults (age > or = 18 years) autopsied between 1986 and 1996 at the Teaching Hospital of Triangulo Mineiro Medical School (Uberaba) were eligible for the study. Gender, race, weight, height and main diagnoses were recorded. Ninety-six cases were excluded because of probable body water retention (congestive heart failure, hepatic insufficiency, nephrotic syndrome) or pressure sores secondary to peripheral vascular ischemia. Body mass index (BMI) was used to define malnourished (BMI < 18.5 kg/m2) and non-malnourished (BMI > 18.5kg/m2) groups. RESULTS: Except for weight (42.5kg; range: 28-57 vs. 60; 36-134.5kg) and BMI (16.9; range: 12.4-18.5 vs. 22.7; range: 18.5-54.6kg/m2), respectively, there were no statistical differences among 43 malnourished and 62 non-malnourished cases in relation to age (54.9 +/- 20.4 vs. 52.9 +/- 17.9 years), percentage of white persons (74.4 vs. 64.5 percent), male gender (76.7 vs. 69.3 percent) and main diagnoses. Five malnourished (11.6 percent) and 7 (11.5 percent) non-malnourished cases had pressure sores (p=0.89). CONCLUSION: Pressure sores were equally common findings in necropsied persons with protein-energy malnutrition, as assessed by body mass index

Pneumopatia intersticial secundária à proliferaçäo difusa idiopática de células neuroendócrinas ("tumorlets carcinoids") / Interstitial lung disease after idiopathic diffuse proliferation of neuroendocrine cells (tumorlets carcinoids)

Relata-se o caso de uma paciente de 35 anos, da raça negra, sem doenças pulmonares prévias, apresentando há um ano tosse seca e dispnéia a esforços usuais, com exames de imagem normais e espirometria mostrando padräo restritivo de intensidade leve. A biópsia pulmonar aberta foi indicada pela sintomatologia persistente em acompanhamentos ambulatoriais, sem melhora clínica, em uso de sintomáticos. O relatório anatomopatológico demonstrou difusas proliferaçöes de células neuroendócrinas peribronquiolares. Enfatiza-se a importância dessa entidade, apesar de rara e pouco conhecida, como causa de pneumopatia intersticial e sua fisiopatologia.