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1.
Semin Arthritis Rheum ; 64: 152313, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38044241

RESUMEN

OBJECTIVE: To evaluate risk of infections requiring hospitalization and opportunistic infections, including tuberculosis, in patients with rheumatoid arthritis (RA) treated with abatacept versus conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biologic/targeted synthetic (b/ts) DMARDs. METHODS: Five international observational data sources were used: two biologic registries (Sweden, Germany), a disease registry (USA) and two healthcare claims databases (Canada, USA). Crude incidence rates (IRs) per 1000 patient-years, with 95 % CIs, were used to estimate rate ratios (RRs) comparing abatacept versus csDMARDs or other b/tsDMARDs. RRs were adjusted for demographic factors, comorbidities, and other potential confounders and then pooled across data sources using a random effects model (REM). RESULTS: The data sources included 6450 abatacept users, 136,636 csDMARD users and 54,378 other b/tsDMARD users, with a mean follow-up range of 2.2-6.2 years. Across data sources, the IRs for infections requiring hospitalization ranged from 16 to 56 for abatacept, 19-46 for csDMARDs, and 18-40 for other b/tsDMARDs. IRs for opportunistic infections were 0.4-7.8, 0.3-4.3, and 0.5-3.8; IRs for tuberculosis were 0.0-8.4, 0.0-6.0, and 0.0-6.3, respectively. The pooled adjusted RR (95 % CI), only reported for infections requiring hospitalization, was 1.2 (0.6-2.2) for abatacept versus csDMARDs and 0.9 (0.6-1.3) versus other b/tsDMARDs. CONCLUSIONS: Data from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs. IRs for opportunistic infections, including tuberculosis, were low. These data are consistent with the known safety profile of abatacept.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Infecciones Oportunistas , Tuberculosis , Humanos , Abatacept/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/epidemiología , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/epidemiología , Productos Biológicos/efectos adversos , Tuberculosis/inducido químicamente , Tuberculosis/epidemiología , Mercadotecnía
2.
Blood Adv ; 8(4): 878-888, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-37967358

RESUMEN

ABSTRACT: Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicenter observational study evaluating bendamustine toxicity in real-world practice. Patients receiving at least 1 dose of bendamustine with/without rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details, and grade 3 to 5 adverse events (AEs) were analyzed and correlated. In total, 323 patients were enrolled from 9 National Health Service hospitals. Most patients (96%) received bendamustine-R, and 46%, R maintenance. Overall, 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%) and the relative risk highest during maintenance (54%), induction (34%), and follow-up (28%). Toxicity led to permanent treatment discontinuation for 13% of patients, and 2.8% died of bendamustine-related infections (n = 5), myelodysplastic syndrome (n = 3), and cardiac disease (n = 1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor preinduction performance status (PS), poor premaintenance PS, and abnormal preinduction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3 of 10 opportunistic infections occurred despite prophylaxis. In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to those of trial populations of younger, fitter patients. Poor PS, mantle cell histology, and maintenance R were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death, warranting extended antimicrobial prophylaxis and infectious surveillance, especially for maintenance-treated patients.


Asunto(s)
Antiinfecciosos , Linfoma de Células B , Linfoma de Células del Manto , Linfoma no Hodgkin , Infecciones Oportunistas , Humanos , Adulto , Clorhidrato de Bendamustina/efectos adversos , Medicina Estatal , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células B/tratamiento farmacológico , Antiinfecciosos/uso terapéutico , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/tratamiento farmacológico , Reino Unido
3.
BMC Pediatr ; 23(1): 628, 2023 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-38087261

RESUMEN

INTRODUCTION: AIDS continues to be a serious global public health issue. It targets CD4 cells and immunological cells, which are in charge of the body's resistance against pathogenic pathogens. In situations with limited resources, CD4 cell measurement is essential for assessing treatment responses and clinical judgments in HIV-infected children receiving Anti-Retroviral Therapy (ART). The volatility of CD4 cells during ART follow-up is still largely uncharacterized, and there are few new datasets on CD4 cell changes over time. Therefore, the purpose of this analysis was to identify the factors that were predictive of CD4 cell count changes over time in children who started ART at Mekelle General Hospital in northern Ethiopia. METHODS: A retrospective follow-up study was done. 437 patients in Mekelle general hospital, northern Ethiopia, from 2014-2016 were involved. All patients who have started anti-retrieval treatment (ART) and measured their CD4 cell count at least twice, including the baseline and those who initiated ART treatment, were included in the study population. An exploratory data analysis and linear mixed model analysis were used to explore the predictors of CD4 cell count change in patients and consider variability within and between patients. RESULTS: This study found the correlation variation explained in cells accounted for between patients was 61.3%, and the remaining 38.7% variation existed within. This indicates that there is a substantial change in random slope and intercept between and within patients. WHO clinical stage IV (ß = -1.30, 95% CI: -2.37, -0.23), co-infection HIV/TB (ß = -1.78, 95% CI: -2.58, -0.98), children aged 2-5 (ß = -0.43; 95% CI: -0.82, -0.04), and 6-14 years (ß = -1.02; 95% CI: -1.47, -0.56), non-opportunistic infection (ß = 1.33, 95% CI: 0.51, 2.14), and bedridden functional status (ß = -1.74, 95% CI: -2.81, -0.68) were predictors of cell changes over time. CONCLUSIONS: This study found that patients receiving ART experienced a significant change in CD4 cells over time. Because 61.3% of the variation in CD4 cells explained between patients and the remaining 38.7% within patients, such nested data structures are often strong correlation evidence. Co-infection of HIV/TB, functional status, age category of children, WHO clinical stage, and opportunistic infections are potential predictors of CD4 cells count change. Hence, special guidance and attention is also required, especially for those patients who have an opportunistic infections, higher WHO clinical stages, co-infections with HIV and TB, and bedridden functional status.


Asunto(s)
Fármacos Anti-VIH , Coinfección , Infecciones por VIH , Infecciones Oportunistas , Niño , Humanos , Estudios Retrospectivos , Estudios Longitudinales , Estudios de Seguimiento , Hospitales Generales , Etiopía/epidemiología , Coinfección/epidemiología , Infecciones por VIH/epidemiología , Recuento de Linfocito CD4 , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/complicaciones , Infecciones Oportunistas/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos
4.
Exp Clin Transplant ; 21(10): 801-806, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37965954

RESUMEN

OBJECTIVES: A common complication after transplant is an opportunistic infection, in part due to the necessary immunosuppression regimens that patients are placed on. This study aimed to assess the outcomes and rates of infection in kidney transplant recipients on belatacept compared with kidney transplant recipients on standard immunosuppression therapy. MATERIALS AND METHODS: We conducted a matched-pair case-control retrospective analysis of a prospectively recollected database of all adult kidney transplant patients at the SUNY Upstate Medical Hospital from January 1, 2016, to July 31, 2022. RESULTS: Among study patients, 60.5% of patients in the belatacept group and 47.9% of patients in the standard immunosuppression regimen group were diagnosed with an infectious disease during follow-up, although no significant difference was shown between the 2 groups (P = .21). The most common infection in both groups was urinary tract infection, which was comparable between the groups (41.8% vs 50%; P = .42). No significant difference was shown between patients with early and late conversion to belatacept in terms of infection incident and type. CONCLUSIONS: Kidney transplant recipients who were converted to belatacept because of poor renal function had a similar infection rate compared with patients on standard immunosuppression treatment. Neither conversion to belatacept nor timing of conversion changed the risk of infection after kidney transplant. Our findings suggest that physicians may convert a kidney transplant recipient with poor renal function to belatacept without changing the patient's risk of opportunistic infection.


Asunto(s)
Trasplante de Riñón , Infecciones Oportunistas , Adulto , Humanos , Abatacept/efectos adversos , Trasplante de Riñón/efectos adversos , Inmunosupresores/efectos adversos , Inhibidores de la Calcineurina/efectos adversos , Estudios Retrospectivos , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología , Supervivencia de Injerto , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/inducido químicamente , Receptores de Trasplantes
5.
ARP Rheumatol ; 2(3): 269-274, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37839034

RESUMEN

Cytomegalovirus (CMV) infection is a common and typically benign disease in immunocompetent individuals. However, immunocompromised patients are at a greater risk of reactivation, leading to more severe outcomes. Patients with rheumatic diseases have a particularly high risk of opportunistic infections due to both the inherent immunosuppressive state conveyed by the disease itself and the use of potent immunosuppressant drugs, such as glucocorticoids, cyclophosphamide, and rituximab. Limited data are available regarding prophylactic or preemptive treatment of CMV infection in patients with rheumatic diseases. In this article the authors present two cases of rheumatic conditions complicated by CMV infection. The first case describes a patient with eosinophilic granulomatosis with polyangiitis, previously treated with glucocorticoids and cyclophosphamide, who developed CMV colitis with bowel perforation. The second case involves a woman with systemic lupus erythematosus who was diagnosed with CMV meningitis. Both cases reinforce the importance of establishing guidelines for surveillance and prophylaxis of CMV infection in these patients.


Asunto(s)
Síndrome de Churg-Strauss , Infecciones por Citomegalovirus , Granulomatosis con Poliangitis , Infecciones Oportunistas , Enfermedades Reumáticas , Femenino , Humanos , Síndrome de Churg-Strauss/inducido químicamente , Ciclofosfamida/uso terapéutico , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/complicaciones , Glucocorticoides/uso terapéutico , Granulomatosis con Poliangitis/inducido químicamente , Inmunosupresores/efectos adversos , Infecciones Oportunistas/inducido químicamente , Enfermedades Reumáticas/complicaciones
6.
Arthritis Res Ther ; 25(1): 129, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37495973

RESUMEN

BACKGROUND: To compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea. METHODS: Using 2009-2019 Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users. RESULTS: We included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00-2.80) for HZ, 1.04 (0.71-1.52) for SBI, and 0.25 (0.09-0.73) for OI. CONCLUSIONS: This population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Herpes Zóster , Inhibidores de las Cinasas Janus , Infecciones Oportunistas , Humanos , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/complicaciones , Estudios de Cohortes , Herpes Zóster/inducido químicamente , Herpes Zóster/epidemiología , Herpesvirus Humano 3 , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/uso terapéutico , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/epidemiología , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa
7.
N Engl J Med ; 388(26): 2444-2455, 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37379135

RESUMEN

BACKGROUND: Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial. METHODS: We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis. In the induction trial, patients were randomly assigned in a 3:1 ratio to receive mirikizumab (300 mg) or placebo, administered intravenously, every 4 weeks for 12 weeks. In the maintenance trial, patients with a response to mirikizumab induction therapy were randomly assigned in a 2:1 ratio to receive mirikizumab (200 mg) or placebo, administered subcutaneously, every 4 weeks for 40 weeks. The primary end points were clinical remission at week 12 in the induction trial and at week 40 (at 52 weeks overall) in the maintenance trial. Major secondary end points included clinical response, endoscopic remission, and improvement in bowel-movement urgency. Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as extended induction. Safety was also assessed. RESULTS: A total of 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial. Significantly higher percentages of patients in the mirikizumab group than in the placebo group had clinical remission at week 12 of the induction trial (24.2% vs. 13.3%, P<0.001) and at week 40 of the maintenance trial (49.9% vs. 25.1%, P<0.001). The criteria for all the major secondary end points were met in both trials. Adverse events of nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1217 patients treated with mirikizumab during the controlled and uncontrolled periods (including the open-label extension and maintenance periods) in the two trials, 15 had an opportunistic infection (including 6 with herpes zoster infection) and 8 had cancer (including 3 with colorectal cancer). Among the patients who received placebo in the induction trial, 1 had herpes zoster infection and none had cancer. CONCLUSIONS: Mirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis. Opportunistic infection or cancer occurred in a small number of patients treated with mirikizumab. (Funded by Eli Lilly; LUCENT-1 and LUCENT-2 ClinicalTrials.gov numbers, NCT03518086 and NCT03524092, respectively.).


Asunto(s)
Antiinflamatorios no Esteroideos , Colitis Ulcerosa , Adulto , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Método Doble Ciego , Herpes Zóster/inducido químicamente , Herpes Zóster/etiología , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/métodos , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/métodos , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/etiología , Inducción de Remisión , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/inmunología , Antiinflamatorios no Esteroideos/uso terapéutico , Administración Intravenosa , Absorción Subcutánea
8.
BMJ Case Rep ; 16(2)2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36805876

RESUMEN

Trastuzumab-deruxtecan (T-DXd) is a novel antibody drug conjugate that has improved treatment outcomes in patients with ERBB2-positive cancer, including locally advanced or metastatic gastric and gastro-oesophageal junction adenocarcinoma. One of the reported side effects of this medication is drug-induced pneumonitis. We present in this case report, a diagnostic dilemma of a patient presenting with clinical and radiographical features of drug-induced pneumonitis but was found to have pneumocystis jirovecii pneumonia (PJP). Our case is the first of PJP in a patient treated with T-DXd, highlighting the increasing incidence of this opportunistic infection in patients with solid malignancy. It also highlights the clinical and radiographical similarities between the PJP and drug-induced pneumonitis.


Asunto(s)
Adenocarcinoma , Inmunoconjugados , Infecciones Oportunistas , Neumonía por Pneumocystis , Humanos , Neumonía por Pneumocystis/inducido químicamente , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/tratamiento farmacológico , Trastuzumab/efectos adversos , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico
9.
Biochem Pharmacol ; 209: 115417, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36682388

RESUMEN

Opioids are excellent analgesics for the clinical treatment of various types of acute and chronic pain, particularly cancer-related pain. Nevertheless, it is well known that opioids have some nasty side effects, including immunosuppression, which is commonly overlooked. As a result, the incidence of opportunistic bacterial and viral infections increases in patients with long-term opioid use. Nowadays, there are no effective medications to alleviate opioid-induced immunosuppression. Understanding the underlying molecular mechanism of opioids in immunosuppression can enable researchers to devise effective therapeutic interventions. This review comprehensively summarized the exogenous opioids-induced immunosuppressive effects and their underlying mechanisms, the regulatory roles of endogenous opioids on the immune system, the potential link between opioid immunosuppressive effect and the function of the central nervous system (CNS), and the future perspectives in this field.


Asunto(s)
Inmunidad Adaptativa , Analgésicos Opioides , Sistema Nervioso Central , Tolerancia Inmunológica , Inmunidad Innata , Péptidos Opioides , Infecciones Oportunistas , Analgésicos Opioides/efectos adversos , Inmunidad Innata/efectos de los fármacos , Inmunidad Adaptativa/efectos de los fármacos , Humanos , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/inmunología , Incidencia , Sistema Inmunológico , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/inmunología , Péptidos Opioides/metabolismo
10.
Semin Arthritis Rheum ; 58: 152120, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36347212

RESUMEN

BACKGROUND: The availability of Janus kinase (JAK) inhibitors has transformed the management of rheumatoid arthritis (RA), helping patients achieve clinical remission. However, the emergence of opportunistic infections (OIs) associated with the use of JAK inhibitors has been reported. This structured literature review was conducted to summarize reports of OIs associated with JAK inhibitor treatment for RA in clinical trials. METHODS: Structured searches were performed in MEDLINE® and Embase® to identify relevant clinical trial data through March 2021. Bibliographic searches of recent reviews were also conducted, and gray literature searches were used to supplement key gap areas. Publications were screened, extracted, and quality assessed. Data were narratively synthesized. RESULTS: Following screening, 105 publications describing 62 unique clinical trials reporting the rates of OIs in RA patients treated with JAK inhibitors were included. Overall, the highest exposure-adjusted incidence rate was reported for herpes zoster (HZ) infection (any form), followed by OI (any) and tuberculosis based on limited data from clinical trials with approved doses of JAK inhibitors. Lack of head-to-head trials and differences in trial design preclude direct comparison across JAK inhibitors. Higher rates of OIs were noted in the Asian and Australian populations compared with the global population. Higher rates of OIs were also noted with increasing dose of JAK inhibitors in most clinical trial data. CONCLUSIONS: HZ was the most common OI reported among RA patients using all currently approved JAK inhibitors in clinical trials, although tuberculosis and other OIs were also reported. More long-term safety studies in the real-world setting are needed to compare the risk of OIs between various JAK inhibitors.


Asunto(s)
Artritis Reumatoide , Herpes Zóster , Inhibidores de las Cinasas Janus , Infecciones Oportunistas , Tuberculosis , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inducido químicamente , Australia , Herpes Zóster/inducido químicamente , Herpes Zóster/epidemiología , Inhibidores de las Cinasas Janus/efectos adversos , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/epidemiología , Tuberculosis/inducido químicamente , Ensayos Clínicos como Asunto
11.
Thorax ; 77(3): 304-311, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34607905

RESUMEN

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.


Asunto(s)
Neoplasias , Infecciones Oportunistas , Humanos , Inhibidores de Puntos de Control Inmunológico , Inmunosupresores/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/tratamiento farmacológico , Infecciones Oportunistas/inducido químicamente
12.
Expert Opin Drug Saf ; 20(10): 1237-1246, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34310251

RESUMEN

OBJECTIVE: We aimed to systematically assess the pooled prevalence of infective complications in randomized controlled trials (RCTs) and real-world studies (RWSs) investigating alemtuzumab treatment in multiple sclerosis (MS), also looking at selected infections and their severity. METHODS: We included in the analysis RCTs and RWSs investigating the use of alemtuzumab in MS in which infective complications were reported, as well as case reports of rare infections. We conducted a meta-analysis of proportions and a random effect model meta-regression to investigate heterogeneity. RESULTS: The pooled prevalence of infective complications in alemtuzumab treated MS patients is 24%. The most common reported infections are respiratory tract infections (47%) and the most part of the infections are mild-to-moderate (85%). Severe infections account for 6% of the total estimate. We found first-time-reported cases of invasive aspergillosis, hepatitis E virus infection, EBV hepatitis, and cerebral toxoplasmosis. The prevalence of infections is higher in studies conducted before 2009, and in studies with higher proportion of male participants. CONCLUSIONS: Clinicians should be aware that the prevalence of serious infections during alemtuzumab can be higher than expected from RCTs. Peculiar opportunistic infections should be considered when evaluating a patient treated with alemtuzumab who develops signs of infection.


Asunto(s)
Alemtuzumab/efectos adversos , Infecciones Oportunistas/inducido químicamente , Alemtuzumab/administración & dosificación , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/microbiología , Prevalencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad
13.
Rheumatol Int ; 41(4): 751-762, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33590331

RESUMEN

To examine whether treatment with interleukin (IL)-1-, IL-6-, tumour necrosis factor α (TNFα)-inhibitors or Abatacept is associated with an increased risk of common infections, infections requiring hospitalization (SAE) or opportunistic infections among real-world juvenile idiopathic arthritis (JIA) patients. Furthermore, the influence of other patient-related covariates on the occurrence of infections was investigated. Patients diagnosed with JIA and treated with biologics were selected from the German BIKER registry. Incidence rates (IR) of infections per 100 person years were calculated and compared between the different cohorts. Using multivariate logistic regression, odds ratios with 95% confidence intervals (CI) were determined for the influence of patient-related covariates (age, diagnosis, laboratory data, concomitant medication, JIA activity, comorbidities, and premedication) on the occurrence of infections. 3258 patients entered the analysis. A total of 3654 treatment episodes were distributed among TNFα- (Etanercept, Adalimumab, Golimumab, Infliximab, n = 3044), IL-1- (Anakinra, Canakinumab, n = 105), IL-6- (Tocilizumab, n = 400) and T-cell activation inhibitors (Abatacept, n = 105). 813 (22.2%) patients had at least one infection, 103 (2.8%) patients suffered from an SAE infection. Both common and SAE infections were significantly more frequent in IL-1 (IR 17.3, 95% CI 12.5/24 and IR 4.3, 95% CI 2.3/8.3) and IL-6 cohort (IR 16.7, 95% CI 13.9/20 and IR 2.8, 95% CI 1.8/4.4) compared to TNFα-inhibitor cohort (IR 8.7, 95% CI 8.1/9.4 and IR 1, 95% CI 0.8/1.3). When comparing the influencing factors for various infectious diseases, the use of corticosteroids, younger age, cardiac comorbidities and higher JIA-activity are the most striking risk factors. Relative to TNFα inhibitors and Abatacept, IL-1 and IL-6 inhibitors were associated with an increased risk of common and SAE infections. The influencing covariates identified may be helpful for the choice of a suitable biologic to treat JIA.


Asunto(s)
Artritis Juvenil/tratamiento farmacológico , Factores Biológicos/efectos adversos , Factores Biológicos/uso terapéutico , Productos Biológicos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Infecciones/epidemiología , Infecciones Oportunistas/epidemiología , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Abatacept/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/sangre , Artritis Juvenil/complicaciones , Femenino , Alemania/epidemiología , Humanos , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/uso terapéutico , Incidencia , Interleucina-1/uso terapéutico , Interleucina-6/uso terapéutico , Masculino , Infecciones Oportunistas/inducido químicamente , Sistema de Registros , Factor de Necrosis Tumoral alfa
14.
Rheumatol Int ; 41(4): 819-825, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33576887

RESUMEN

Interleukin-6 receptor antagonist tocilizumab is a biologic drug used for treating patients with active rheumatoid arthritis (RA) who failed to respond to synthetic or other biologic disease-modifying antirheumatic drugs or where they were contraindicated. Interleukin-6 receptor blockade results in a decrease of disease activity but has some potential adverse effects, the most common being infections. We present a case of a 75-year-old female patient with long-lasting RA, several comorbidities and multiple prior therapies, who developed back pain and general malaise during tocilizumab intravenous treatment. The laboratory findings were typical of toxemia, and the imaging findings revealed large psoas muscle abscess. Surgical and antibiotic treatment was performed with a good outcome. To our knowledge, this has been the first case of a psoas abscess in a patient with RA treated with tocilizumab described in the literature so far. We also present a review of the literature regarding infection, and particularly abscess formation in patients treated with biological disease-modifying antirheumatic drugs, tocilizumab included.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Absceso del Psoas/diagnóstico por imagen , Receptores de Interleucina-6/antagonistas & inhibidores , Administración Intravenosa , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Vértebras Cervicales/diagnóstico por imagen , Femenino , Humanos , Inyecciones Intravenosas , Imagen por Resonancia Magnética , Infecciones Oportunistas/inducido químicamente , Psoriasis/tratamiento farmacológico , Resultado del Tratamiento
15.
Diagn Microbiol Infect Dis ; 99(4): 115272, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33388572

RESUMEN

Tocilizumab, an interleukin-6 receptor antagonist, has been used to treat critically ill patients with coronavirus disease-2019. We present the case of a previously immunocompetent man with coronavirus disease-2019 who developed invasive pulmonary aspergillosis after treatment with tocilizumab, illustrating the importance of considering opportunistic infections when providing immune modulating therapy.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antivirales/efectos adversos , Tratamiento Farmacológico de COVID-19 , Aspergilosis Pulmonar Invasiva/diagnóstico , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Aspergillus/aislamiento & purificación , Humanos , Inmunomodulación , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Masculino , Micafungina/uso terapéutico , Infecciones Oportunistas/inducido químicamente , Receptores de Interleucina-6/antagonistas & inhibidores , SARS-CoV-2/efectos de los fármacos , Voriconazol/uso terapéutico
16.
Folia Med (Plovdiv) ; 63(4): 586-590, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-35851163

RESUMEN

Patients with HIV-infection diagnosed at late stages usually have significant immunosuppression and demand simultaneous antiretroviral therapy and treatment of opportunistic infections. The presence of HCV coinfection makes treatment even more challenging because of possible adverse effects and drug-drug interactions. HCV cure in such clinical situations not only prevents fibrosis progression, but can also enhance virologic and/or immunologic response to antiretrovirals and thus effective treatment of opportunistic infections. Thorough consideration of all existing diseases and drug interactions of the combined therapy makes simultaneous treatment of HIV, chronic hepatitis C, and opportunistic infections not only possible but the best way to improve outcomes in a complex clinical situation.


Asunto(s)
Infecciones por VIH , Hepatitis C , Infección por Mycobacterium avium-intracellulare , Infecciones Oportunistas , Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Humanos , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/complicaciones , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/tratamiento farmacológico
17.
J Am Acad Dermatol ; 84(2): 300-311, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33038471

RESUMEN

BACKGROUND: Dupilumab is an effective treatment for moderate to severe atopic dermatitis (AD) with limited safety data in clinical practice. OBJECTIVE: To assess the 6-month risk of conjunctivitis and serious infections in patients with AD who initiated dupilumab. METHODS: In a cohort study using US claims data, we compared the risk of conjunctivitis and serious infections in patients with AD who initiated either dupilumab, methotrexate (MTX), cyclosporine, or mycophenolate. Relative risks (RRs) were computed after 1:1 propensity score matching. RESULTS: We identified 1775 dupilumab, 1034 MTX, 186 cyclosporine, and 257 mycophenolate users. The 6-month risk for any conjunctivitis was 6.5% for dupilumab, 3.3% for MTX, 4.8% for cyclosporine, and 1.2% for mycophenolate initiators. After PS matching, the RR of any conjunctivitis was increased in dupilumab users versus MTX (RR, 2.45; 95% confidence interval [CI], 1.47-4.08), versus cyclosporine (RR, 1.56; 95% CI, 0.69-3.50), and versus mycophenolate (RR, 7.00; 95% CI, 2.12-23.2). The risk of serious infection was 0.6% in dupilumab and 1.0% in MTX initiators (RR, 0.90; 95% CI, 0.37-2.20). LIMITATIONS: Analyses were based on few events, and differential surveillance is a concern. CONCLUSIONS: Although dupilumab shows a low risk of serious infections, it is associated with a clinically meaningful increase in conjunctivitis that needs to be managed in practice.


Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Infecciones Bacterianas/epidemiología , Conjuntivitis/epidemiología , Dermatitis Atópica/tratamiento farmacológico , Infecciones Oportunistas/epidemiología , Adolescente , Adulto , Anciano , Infecciones Bacterianas/inducido químicamente , Infecciones Bacterianas/inmunología , Conjuntivitis/inducido químicamente , Conjuntivitis/inmunología , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/inmunología , Puntaje de Propensión , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiología , Adulto Joven
18.
Transplant Proc ; 53(3): 1058-1063, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32921434

RESUMEN

BACKGROUND: Antibody induction immunosuppression is commonly used in kidney transplantation to decrease the risk of early acute rejection. However, infectious complications may arise in patients treated with higher intensity induction immunosuppression. In this study, we compared the rate of opportunistic infections during the 3 years after kidney transplantation in recipients who received either alemtuzumab or basiliximab for induction therapy. METHODS: All renal transplant recipients from our center who received induction with alemtuzumab between 2011 and 2016 were included and matched 1:2 (by age and date of transplant) to renal transplant recipients who received basiliximab. The primary outcome was the rate of opportunistic infections. RESULTS: Twenty-seven patients received alemtuzumab (mean age = 50.8 years; SD ±12), and 54 received basiliximab (mean age = 50.8 years; SD ±11.8). Infections within 3 years posttransplant were not different between groups: BK viremia (P = .99), BK nephritis (P = .48), cytomegalovirus infection (P = .13), varicella zoster virus (P = .22), and all infections (P = .87). Time to infection (P = .67), patient survival (P = .21), and time to rejection (P = .098) were similar in both groups. There were also no group differences in delayed graft function (P = .76), graft loss (P = .97), or rejection (P = .2). CONCLUSION: The rate of infection was not significantly increased in recipients receiving lymphocyte-depleting alemtuzumab compared to recipients receiving basiliximab induction therapy, despite receiving similar maintenance immunosuppression. Although the immunologic risks differed between the 2 groups, there was no observable difference in clinical outcomes.


Asunto(s)
Alemtuzumab/efectos adversos , Basiliximab/efectos adversos , Terapia de Inmunosupresión/efectos adversos , Inmunosupresores/efectos adversos , Infecciones Oportunistas/inducido químicamente , Complicaciones Posoperatorias/inducido químicamente , Adulto , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Trasplante de Riñón/efectos adversos , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/inmunología , Complicaciones Posoperatorias/inmunología , Resultado del Tratamiento
19.
Br J Haematol ; 193(2): 316-324, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33058237

RESUMEN

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib.


Asunto(s)
Adenina/análogos & derivados , Trastornos Linfoproliferativos/tratamiento farmacológico , Terapia Molecular Dirigida/efectos adversos , Infecciones Oportunistas/inducido químicamente , Piperidinas/efectos adversos , Purinas/efectos adversos , Quinazolinonas/efectos adversos , Adenina/administración & dosificación , Adenina/efectos adversos , Adenina/uso terapéutico , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/inducido químicamente , Infecciones Bacterianas/epidemiología , Estudios de Casos y Controles , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Infecciones Fúngicas Invasoras/inducido químicamente , Infecciones Fúngicas Invasoras/epidemiología , Italia/epidemiología , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/microbiología , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/estadística & datos numéricos , Piperidinas/administración & dosificación , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Purinas/administración & dosificación , Purinas/uso terapéutico , Quinazolinonas/administración & dosificación , Quinazolinonas/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Virosis/inducido químicamente , Virosis/epidemiología
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