Risk Factors For Serious Infections Research Articles

Recovery from rituximab-associated persistent hypogammaglobulinaemia in children with nephrotic syndrome.

There are limited data on the long-term outcomes and risk factors for non-recovery after development of rituximab (RTX)-associated persistent hypogammaglobulinaemia among children with idiopathic nephrotic syndrome (NS). A nationwide Japanese survey was conducted to determine the prognosis of patients with childhood-onset idiopathic NS who developed persistent hypogammaglobulinaemia after RTX administration. Specifically, predictors of IgG level recovery and risk factors for serious infection were examined. The cohort comprised 118 patients (66.1% boys; median age at initial RTX administration, 7.5 years). Among the 121 patients diagnosed with persistent hypogammaglobulinaemia, only 31 (26.3%) recovered within a median observation period of 2.8 years; approximately 70% of patients continued to exhibit persistent hypogammaglobulinaemia. Among the patients who recovered from hypogammaglobulinaemia, the median time to recovery was 14.1 months. Patients with a history of steroid-resistant NS were less likely to recover from persistent hypogammaglobulinaemia (hazard ratio, 0.28; 95% CI, 0.09-0.87). In addition, of the 118 eligible patients, 18 (15.3%) developed serious infections requiring hospitalization, and the main risk factor for infection during hypogammaglobulinaemia was agranulocytosis (a well-known adverse effect of RTX in children). A significant portion of patients with RTX-associated persistent hypogammaglobulinaemia did not exhibit recovery even after 1 year. Moreover, the data indicate that patients with a history of steroid-resistant NS have a significantly lower probability of recovering from this condition. Agranulocytosis under hypogammaglobulinaemia was significantly associated with an elevated risk of serious infections.

Incidence Rates of Infections in Rheumatoid Arthritis Patients Treated with Janus Kinase or Interleukin-6 Inhibitors: Results of a Retrospective, Multicenter Cohort Study.

Objective: This study aimed to compare the incidence rates (IRs) of infections, including herpes zoster (HZ), in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) or interleukin-6 inhibitors (IL-6is). Methods: We retrospectively analyzed 444 RA patients treated using IL-6is (n = 283) or JAKis (n = 161). After adjusting for clinical characteristic imbalances by propensity score matching (PSM), we compared the IRs of infections including HZ between the JAKi and IL-6i groups. Results: Observational period: 1423.93 patient years (PY); median observational period: 2.51 years. After PSM, incidence rate ratios comparing JAKi with IL-6i were 3.45 (95% confidence interval [CI]: 1.48-9.04) for serious infections other than HZ indicating that the JAKi-treated group was more likely to develop serious infection than the IL-6i-treated group. Multivariate Cox regression analyses revealed that the use of prednisolone > 5.0 mg/day, coexisting interstitial lung disease (ILD), and diabetes mellitus (DM) were independent risk factors for serious infections. The crude IR for HZ was significantly higher in the JAKi group, but the difference between groups was not significant (IRR: 2.83, 95% CI: 0.87-10.96) in PSM analysis. Unadjusted and PSM analyses performed in our study showed increased IRs of serious infections in patients with RA treated with JAKis compared with those treated with IL-6is. Conclusions: The presence of ILD or DM and the use of prednisolone were found to be independent risk factors for serious infection in RA patients treated using JAKis. Whereas the IRs for HZ after PSM were not significantly different between the JAKi and IL-6i groups.

Risk factors for serious infections and infection-related mortality in patients with microscopic polyangiitis: Multicentre REVEAL cohort study.

Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections.

Preterm Birth and in Utero Exposure to Corticosteroids Are Associated With Increased Infection Risk in Children of Mothers With IBD.

Corticosteroids, thiopurines, and biologics may come into play during pregnancy in women with inflammatory bowel disease and potentially impact the developing fetal immune system. We aimed to assess the risk of serious infections in children stratified by in utero exposure to biologics and immunomodulators or concomitant treatment with corticosteroids. All singleton IBD pregnancies between 2008 and 2022 at a tertiary IBD center in Denmark were included. Maternal and offspring demographics, maternal disease activity, antenatal medical treatment, and infant infections resulting in hospital admission were recorded after review of medical records. In 602 live births (99.0%), we registered exposure to antenatal treatment as follows: biological monotherapy (n = 61, 10.2%), thiopurines (n = 110, 17.9%), biologics and concomitant thiopurines (n = 63, 10.3%), and controls (ie, no treatment with biological and/or thiopurines; n = 369, 60.6%). Preterm delivery (<37 gestational weeks) and systemic steroid administration during the third trimester were associated with an increased risk of serious infection in the offspring immediately after birth (relative risk = 17.5; 95% confidence interval, 7.8-39.8; P < .001, and relative risk = 4.8; 95% confidence interval, 1.5-12.7; P = 0.003, respectively).Intra-uterine exposure to biologics or combination treatment were not associated with a statistically significant higher risk of serious infections compared with controls; however, combination treatment showed an inclination towards an increased risk across analyses. Preterm birth and systemic corticosteroid administration late in pregnancy are significant risk factors for serious infections in the offspring of IBD mothers.

Impact of Treatment Response on Risk of Serious Infections in Patients With Crohn’s Disease: Secondary Analysis of the PYRAMID Registry

Traditional risk factors for serious infections with advanced therapies in patients with Crohn's disease (CD) have been assessed at baseline before starting therapy. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry (NCT00524537). We included patients with CD who initiated adalimumab and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs nonresponders (not in steroid-free clinical remission) at 6 months after treatment initiation (landmark). We compared the risk of serious infections between responders vs nonresponders between 6 and 36 months after treatment initiation through stabilized inverse probability of treatment weighting Cox proportional hazards model. Of 1515 adalimumab-treated patients, 763 (50.4%) were classified as responders at 6 months (37 ± 13 y; 56% female; disease duration, 9.5 ± 8.5 y). Compared with nonresponders, responders were less likely to have moderate to severe symptoms (55.6% vs 33%), or require steroids (45.5% vs 17.3%) or opiates (6.6% vs 1.3%) at baseline, without any differences in disease location, perianal disease, and prior CD complications. During follow-up evaluation, using stabilized inverse probability of treatment weighting, responders were 34% less likely to experience serious infections compared with nonresponders (hazard ratio, 0.66; 95% CI, 0.46-0.96). Risk of gastrointestinal and extraintestinal infections was lower in responders vs nonresponders. Patients with CD who respond to adalimumab have a lower risk of developing serious infections compared with nonresponders. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.

Urosepsis Risk in Neuromyelitis Optica Spectrum Disorder Patients Administered Satralizumab.

Objectives The interleukin-6 (IL-6) inhibitor satralizumab is an established treatment for neuromyelitis optica spectrum disorder (NMOSD). Although IL-6 inhibitors are generally well-tolerated, serious infections, including sepsis, can occur. In this study, we compared the sepsis characteristics in NMOSD patients administered satralizumab (NMOSD-satralizumab) to those in rheumatoid arthritis patients administered tocilizumab (RA-tocilizumab), another IL-6 inhibitor. Methods We examined adverse event reports from the Japanese Pharmaceuticals and Medical Devices Agency regarding NMOSD-satralizumab from August 2020 to March 2022 and RA-tocilizumab from April 2008 to November 2019 (term 1) and to March 2022 (term 2). Results We identified 6 sepsis cases in NMOSD-satralizumab, of which 5 (83%) developed from urinary tract infections (UTIs). Although data were unavailable for two patients, three cases had urologic complications in addition to recognized risk factors for serious infections, such as an older age, corticosteroid use, obesity, diabetes mellitus and motor disability. Urosepsis was relatively infrequent in RA-tocilizumab (term 1: 24.2%, term 2: 20.1%). Discussion Safe satralizumab use requires risk factor assessment to minimize the incidence of severe infections. Management of UTIs is also recommended.

Risk Factors and Incidence of Serious Infections in Patients With Systemic Lupus Erythematosus Undergoing Rituximab Therapy.

To evaluate the risk and protective factors of serious infection (SI) in patients with systemic lupus erythematosus (SLE) within 180 days of rituximab (RTX) treatment. Patients with SLE treated with RTX were analyzed. SI was defined as any infectious disease requiring hospitalization. The clinical characteristics, laboratory profiles, medications, and incidence rate (IR) are presented. Multivariate Cox proportional hazards models and Kaplan-Meier analysis for risk factors of SI were performed. A total of 174 patients with SLE receiving RTX treatment were enrolled. The overall IR of SIs was 51.0/100 patient-years (PYs). Pneumonia (30.4/100 PYs), followed by soft tissue infections, intra-abdominal infections, and Pneumocystis jiroveci pneumonia (all 6.1/100 PYs) were the leading types of SIs. Twelve patients died during the 180-day follow-up (crude mortality rate: 14.6/100 PYs). Chronic kidney disease (CKD), defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 (hazard ratio [HR] 2.88, 95% CI 1.30-6.38), and a background prednisolone (PSL) equivalent dosage ≥ 15 mg/day (HR 3.50, 95% CI 1.57-7.78) were risk factors for SIs among all patients with SLE. Kaplan-Meier analysis confirmed the risk of SI for patients with SLE with CKD and a background PSL equivalent dosage ≥ 15 mg/day (log-rank P = 0.001 and 0.02, respectively). Hydroxychloroquine (HCQ) reduced the risk of SIs in patients with SLE (HR 0.35, 95% CI 0.15-0.82; log-rank P = 0.003). SI was prevalent in patients with SLE after RTX treatment. Patients with SLE with CKD and high-dose glucocorticoid use required constant vigilance. HCQ may reduce the risk of SI among patients with SLE administered RTX.

Infectious complications among patients receiving ibrutinib for the treatment of hematological malignancies.

Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat multiple hematologic malignancies and graft-versus-host disease. Though less myelosuppressive than cytotoxic chemotherapy, increased infections, including invasive fungal infections (IFIs), have been reported with ibrutinib use. This study aimed to determine the characteristics and risk factors for infection associated with ibrutinib at our institution. Patients who received ibrutinib between June 2014 and August 2019 were included. Primary endpoints were the incidence of any infection and the incidence of serious infection (defined as hospitalization, parenteral antimicrobial therapy, or pneumonia regardless of hospitalization). Infection risk factors were assessed using logistic regression. One hundred thirty-two patients were identified (78% male; median age, 71 years). The most common indications for ibrutinib were chronic lymphocytic leukemia (67%) and mantle cell lymphoma (12%). Infection and serious infection occurred in 94 (71%) and 47 (36%) patients, respectively; when pneumonia was excluded as a criterion for serious infection, the serious infection rate was 27%. The median time from ibrutinib initiation to first infection was 125 days. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) (odds ratio [OR], 4.60; 95% CI, 1.22-17.4) and corticosteroid use (OR, 5.55; 95% CI, 1.52-20.3) were significant risk factors for serious infection. IFIs were diagnosed in 7 patients (5%): 5 had Pneumocystis jirovecii pneumonia and 2 were infected with invasive molds. Serious infection and IFI rates are high but similar to those previously described. Risk factors for serious infection included allo-HSCT and corticosteroid use. Targeted antimicrobial prophylaxis should be evaluated in prospective studies in patients on ibrutinib to reduce serious infections and IFI.

Six-month safety andeffectiveness oftofacitinib inpatients with rheumatoid arthritis inJapan: Interim analysis ofpost-marketing surveillance.

We evaluated the real-world safety/effectiveness of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), in patients with RA in Japan registered in a post-marketing surveillance study. This interim analysis included data from July 2013 to December 2018. Adverse events (AEs), serious AEs (SAEs), Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] scores, and rates of SDAI/CDAI/DAS28-4(ESR)-defined remission and low disease activity were analysed using 6 months of data. Risk factors for serious infections were assessed by multivariable analyses. Safety and disease activity were evaluated in 6866 and 6649 patients, respectively. Overall, 32.73%/7.37% of patients reported AEs/SAEs. Clinically important AEs with tofacitinib included serious infections/infestations [3.13% of patients; incidence rate (IR; patients with events) 6.91/100 patient-years (PY)], herpes zoster (3.63%; IR 8.02/100 PY), and malignancies (0.68%; IR 1.45/100 PY). SDAI/CDAI/DAS28-4(ESR) scores and remission/low disease activity rates improved over 6 months. Male sex, older age, Steinbrocker's stage IV, history of infection, and diabetes mellitus at baseline were independent risk factors for serious infection. In patients with RA receiving tofacitinib in Japan, safety was consistent with the reported profile, and disease activity improved over 6 months. NCT01932372.

The factors predicting development of serious infections in ANCA-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease usually involving small vessels and progressing with necrotizing inflammation. Treatment requires long-term use of immunosuppressive agents to inhibit disease activity. Serious infections (SIs) are a common complication in AAV. The aim of this study was to identify the risk factors for serious infections which required hospitalization in patients with AAV. In this retrospective cohort study., we included 84 patients admitted to the Ankara University Faculty of Medicine in the last 10 years with a diagnosis of AAV. In 42 (50%) of 84 patients followed up with the diagnosis of AAV, an infection requiring hospitalization was identified. The patients' total corticosteroid dose, use of pulse steroids, induction regimen, levels of C-reactive protein (CRP) and the presence of pulmonary and renopulmonary involvement were found to be associated with the frequency of infection (p=0.015, p=0.016, p=0.010, p=0.03, p= 0.026 and p=0.029, respectively). In multivariable analysis, it was found that renopulmonary involvement (p=0.002, HR=4.95, 95% CI= 1.804-13.605), age of over 65 (p=0.049, HR=3.37, 95% CI=1.004-11.369) and high CRP levels (p=0.043, HR=1.006, 95% CI=1.000-1.011) constituted independent predictors of serious infection risk. The frequency of infection is known to be increased in ANCA-associated vasculitis. Our study showed that renopulmonary involvement, age and elevated CRP levels on admission are independent risk factors of infection.

Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study.

Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002·7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117·7 (95% CI 98·3-141·0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1·68 [0·60-4·68]) and belimumab groups (1·01 [0·21-4·80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg; 2·38 [95%CI 1·47-3·84]), hypogammaglobulinaemia (<6 g/L; 2·16 [1·38-3·37]), and multimorbidity (1·45 [1·17-1·80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0·60 [0·41-0·90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. None.

Rates and Predictors of Serious Infections in MS and NMOSD Patients treated with Anti-CD20 Therapy (P7-3.008)

<h3>Objective:</h3> To evaluate the rates and predictors of serious infections in MS and NMOSD patients treated with anti-CD20 agents. <h3>Background:</h3> Chronic immunosuppression with anti-CD20 therapy can increase the risk of serious infections including complicated COVID19. <h3>Design/Methods:</h3> MS and NMOSD patients treated with ocrelizumab or rituximab at University Hospitals Cleveland Medical Center were evaluated. Patients hospitalized for any infection during their anti-CD20 therapy were identified and compared to those without infection-related hospitalizations. Significant differences were evaluated in a multivariate logistic regression model to identify predictors of serious infection. <h3>Results:</h3> There were 184 patients treated with anti-CD20 therapy (average age 48+/−13 years, 67% females, 84% MS). Of those, 21 (11%) patients had one or more serious infection during therapy including 16 MS patients treated with ocrelizumab and 5 NMOSD patients treated with rituximab. The most common serious infections were complicated COVID19 (9), bacterial skin infections (5), bacterial pneumonia (3), urosepsis (3), ocular infection (1), and disseminated shingles (1). Compared to those without serious infections, patients with serious infections had a higher average time on anti-CD20 therapy (1087.57±5 days vs 796.28±35 t= −2.61, P=0.005) and were more likely to have total lymphopenia (80% vs 40%; p=.004). There was a trend towards higher rates of hypogammaglobulinemia in patients with serious infections (24% vs 10%; P=.07). Logistic regression identified total lymphopenia (&lt;1.0×109/L) as an independent predictor of serious infection in patients treated with anti-CD20 therapy. <h3>Conclusions:</h3> Serious infections are rare in MS and NMOSD patients treated with anti-CD20 therapies. Those with serious infections were exposed to treatment longer and more frequently had lymphopenia and hypogammglobulinemia. Total lymphopenia during therapy is an independent risk factor for serious infections. <b>Disclosure:</b> Dr. Abboud has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Abboud has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech . Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Abboud has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Abboud has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS. Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion . Dr. Abboud has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Horizon. The institution of Dr. Abboud has received research support from Genentech . The institution of Dr. Abboud has received research support from Novartis. The institution of Dr. Abboud has received research support from BMS. The institution of Dr. Abboud has received research support from Sanofi-Genzyme. Dr. Mears has nothing to disclose. Dr. Jakubecz has nothing to disclose. Dr. Serra has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen Idec. Dr. Serra has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb.

Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD.

Ocrelizumab and rituximab are monoclonal antibodies targeting the CD20 marker on B lymphocytes. The enhanced efficacy of B lymphocyte depleting therapies poses a greater risk of decreased immunoglobulin (Ig) levels. The rate and risk factors of hypogammaglobulinemia in MS and NMOSD patients treated with anti-CD20 therapies are unknown. A retrospective study was conducted among patients who received anti-CD20 therapy for the treatment of MS, NMOSD, and other related neurological disorders. The goal was to determine the incidence and risk factors of hypogammaglobulinemia and serious infections in patients receiving ocrelizumab versus rituximab. The secondary goals were to determine the rates of lymphopenia, neutropenia, and early B cell repopulation among patients on anti-CD20 therapy. Overall, 184 patients (mean age 48.4±13.7, 66.8% female) met inclusion criteria; 152 patients received ocrelizumab and 32 patients received rituximab. A total of 22 patients (12%) developed hypogammaglobulinemia. Patients who developed hypogammaglobulinemia were more likely to have been ≥50years of age (p=.0275) with lower baseline IgG (p=.001) and IgA (p=.0038) levels. Serious infections were observed in 21 patients (11%) and seen more commonly in those that developed total lymphopenia (<1.0×109/L) and had longer duration of B-cell therapy. Multivariate analysis identified age≥50years, white race, and rituximab as independent predictors of hypogammaglobulinemia, and absolute lymphopenia as an independent risk factor for serious infections. Among patients receiving anti-CD20 therapy, 12% of patients experienced hypogammaglobulinemia which was seen more commonly in white patients, at least 50years old, with lower baseline IgG and IgA levels and in those treated with rituximab. Serious infections were seen more commonly in patients with total lymphopenia and longer exposure to anti-CD20 therapy.

Risk factors for serious infections in ANCA-associated vasculitis

ObjectivesSevere infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus...

Clinical Features of Infection in Newly Diagnosed Patients with Myelodysplastic Syndrome and Its Correlation with Curative Effect

To explore the characteristics of infection in patients with myelodysplastic syndromes (MDS), risk factors of serious infection, and their correlation with curative effect. The clinical data of 92 newly diagnosed MDS patients with nosocomial infection from January 2016 to June 2020 in our hospital were retrospectively analyzed. A total of 306 courses of treatment were completed in 92 newly diagnosed MDS patients. The infection rate was the highest in the first course of treatment (84.8%, 78/92), and then decreased gradually. The top three infection sites were lung, upper respiratory tract, and gastrointestinal tract. A total of 90 strains of pathogenic bacteria were detected, of which 33.4% (30/90) were gram-negative bacilli, 23.3% (21/90) were gram-positive cocci, 23.3% (21/90) were fungi, and 20.0% (18/90) were viruses. The serious infection rate among 92 patients with MDS was 22.8% (21/92). Multivariate analysis showed that neutrophil deficiency>7 days (OR=10.875, 95%CI: 2.747-43.051, P=0.001) was an independent risk factor for serious infection in MDS patients. Compared with non-severe infection group, the total effective rate of severe infection group was lower (90.9% vs 63.6%, χ2=4.393, P<0.05). The infection rate of MDS patients is high in the first course of treatment, and the most common infection site is the lung. Gram-negative bacteria is the most common pathogen. MDS patients with neutrophil deficiency>7 days have a high risk of serious infection and poor efficacy.

Risk factors for serious infections in inpatients with systemic lupus erythematosus.

To investigate the risk factors for serious infections among hospitalized systemic lupus erythematosus (SLE) patients, and to provide the advice for preventing serious infections in SLE patients. Information of SLE patients hospitalized from March 2017 to February 2019 at the Department of Rheumatology and Immunology, Xiangya Hospital, Central South University was obtained. The patients were assigned into a serious infection group and a non-serious infection group. The risk factors for serious infections among SLE inpatients were identified by comparison between the 2 groups and multivariate logistic regression analysis. There were 463 SLE inpatients in total, and 144 were in the serious infection group and 319 in the non-serious infection group. Multivariate logistic regression analysis showed that age ≥54.50 years old (OR=4.958, P<0.001), cardiovascular involvement (OR=6.287, P<0.001), hematologic involvement (OR=2.643, P=0.003), serum albumin <20 g/L (OR=2.340, P=0.036), C-reaction protein (CRP)/erythrocyte sedimentation rate (ESR)≥0.12 (OR=2.430, P=0.002), glucocorticoid dose ≥8.75 mg/d prednisone-equivalent (OR=2.465, P=0.002), and the combined use of immunosuppressive agents (OR=2.847, P=0.037) were the risk factors for serious infections in SLE inpatients. SLE patients with older age, cardiovascular involvement, hematologic involvement, low serum albumin are prone to suffering serious infections. Increased CRP/ESR ratio indicates serious infections in SLE inpatients. High-dose glucocorticoid and the combined use of immunosuppressive agents can increase the risk of serious infections in SLE inpatients.

1087. Evaluation of Risk Factors for Infection among Patients Receiving Ibrutinib

BackgroundIbrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK) approved for various B-cell malignancies and cGVHD. Rates of serious infection—defined as requiring hospitalization or parenteral antimicrobials— and invasive fungal infection (IFI) in patients on ibrutinib are as high as 11.4% and 4.2% respectively (Varughese T, et al. Clin Infect Dis 2018;67(5):687-92), which may be related to off-target inhibition of interleukin-2-inducible T-cell kinase or macrophage function.MethodsWe retrospectively reviewed infection complications in patients receiving ibrutinib at our institution between 06/01/2014 and 08/31/2019, including patients who received single-agent or combination ibrutinib. In this study, serious infection was defined as above, or a diagnosis of pneumonia regardless of hospitalization or parenteral antimicrobial therapy. Logistic regression was used to identify risk factors.ResultsBaseline characteristics of 134 included patients are in Table 1. Infection and serious infection occurred in 96 (72%) and 48 (36%) patients, respectively. When pneumonia was not included as a criterion for serious infection, the serious infection rate was 22%. Prior allogeneic stem cell transplant (allo-HSCT) (OR 4.50; 95% CI 1.19 – 17.00) and corticosteroid use (OR 5.42; 95% CI 1.49 – 19.82) were significant risk factors for serious infection without pneumonia (Table 2).Of 37 patients (28%) who received primary HSV/VZV prophylaxis with acyclovir, there was one case of suspected herpes zoster infection (3%). IFI developed in 7 patients (5%): 5 with Pneumocystis jirovecii pneumonia (PJP), 1 with invasive aspergillosis, and 1 with a filamentous fungus, species unknown. Other identified organisms are detailed in Figure 1. Classical risk factors for IFI, including diabetes, allo-HSCT, and concurrent corticosteroid use, were not significant predictors in this group.Table 1. Baseline Characteristics Table 2. Risk Factor Analysis Figure 1. Identified Organisms in Serious Infection ConclusionSerious infections developed at a higher rate than previously reported in the literature, with IFI rates similar to those previously described. Prior allo-HSCT and steroid use were found to be risk factors for serious infection without pneumonia. Treating physicians should have a high index of suspicion for pneumonia, IFI, and PJP in this population.Disclosures All Authors: No reported disclosures

Elevation of cytomegalovirus antigenemia predicts serious infection and death in patients receiving immunosuppressive therapies for autoimmune diseases.

We examined the relationship between cytomegalovirus (CMV) reactivation and serious infections. We conducted a single-center retrospective chart review study with 43 autoimmune disease patients experiencing CMV reactivation. We investigated the risk factors for serious infections among the patients using logistic regression analysis. We identified that the maximum count of CMV antigenemia during the course of infection (CMV Ag MAX) was significantly associated with serious infection by multivariate analysis (adjusted odds ratio: 1.509; 95% confidence interval: 1.071-2.125). The receiver operating characteristic curve of CMV Ag MAX count showed a predictive value for serious infections (76.9% in sensitivity and 93.3% in specificity) and death (83.3% in sensitivity and 91.9% in specificity), and the cut-off count of serious infections and death was 6 and 10 per 105 white blood cell count, respectively. We suggest that the counts of CMV Ag MAX can reflect the extent of compromise in the immune system, and can be a predictive marker for serious infections and death.

S0707 The Use of Combination Vedolizumab and Ustekinumab in Crohn's Disease: A Retrospective Cohort Study

INTRODUCTION: There is limited data on the use of more than one biologic in the treatment of patients with inflammatory bowel disease (IBD). The aim of our study was to determine the effectiveness and safety of combining vedolizumab (VDZ) and ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: We collected data on 30 patients with CD who received treatment with a combination of VDZ and UST from 2015 to 2019 for persistent disease activity or concomitant rheumatologic or dermatologic disease. Clinical scoring and laboratory markers (ESR, CRP, albumin, and vitamin D) were collected at baseline (prior to starting combination therapy) and at follow up (after at least two months on combination therapy). Endoscopic data was collected within 6 months prior to initiation of combination therapy and at follow up (after at least two months on combination therapy). Adverse events were documented. The primary outcome was effectiveness defined by improvement in laboratory parameters, clinical, and endoscopic scoring; the secondary outcome was safety. RESULTS: The mean age was 37 (+/-12.2) years, 63% were female, 73% Caucasian, with a disease duration of 14 (+/-10.6) years. Patients had failed therapy with a median of 2 (2–3) previous biologic medications. The mean ESR decreased, 42.8 vs 27.3, P = 0.04, and mean albumin improved, 3.4 vs 4.0, P = 0.0005. The median HBI score improved from 7 to 5, P = 0.004 at follow up. There was no significant improvement in endoscopic score at follow up, however 50% of the group did not yet have follow up available. There were 5 serious adverse events (SAE), and no deaths. On multivariate analysis, immunomodulator use, longer disease duration, increasing age, and albumin were found to be risk factors for serious infection. CONCLUSION: Combination biologic therapy with VDZ and UST may be an effective option for CD patients with refractory disease or concomitant autoimmune disease inadequately controlled by biologic monotherapy. There appears to be an increased risk of serious infection compared to biologic monotherapy, however this risk might be minimized by discontinuing immunomodulators prior to the initiation of combination therapy. Larger prospective studies are needed to confirm these findings.Table 1Table 2

Opportunistic and Serious Infections in Patients with Neuroendocrine Tumors Treated with Everolimus: A Multicenter Study of Real-World Patients

Introduction: The incidence of infections is poorly studied in patients with neuroendocrine tumors (NET) treated with everolimus outside of clinical trials. We aimed to evaluate the frequency of and risk factors for opportunistic infections (Opl) or any serious infection in eligible patients. Methods: This was a retrospective multicenter study of a Latin American cohort of consecutive patients with advanced NET treated with everolimus. Duration of everolimus, comorbidities, Charlson comorbidity score, type of prior treatment, institution, and concurrent immunosuppressive conditions were tested for possible associations with serious (grade 3–5) infections in univariate and multivariable logistic regression models. Results: One hundred eleven patients from 5 centers were included. The median duration of everolimus was 8.9 months. After a median follow-up of 32.9 months, 34 patients (30.6%; 95% CI 22.2–40.1) experienced infections of any grade, with 24 (21.6%; 95% CI 14.8–30.4) having a serious infection and 7 (6.3%; 95% CI 2.6–12.6) having at least 1 OpI (Candida sp., Toxoplasma gondi, Pneumocystis sp., Herpes sp., and Cryptococcus sp.). Four patients (3.6%) died from infections, but only 2 deaths (1.8%) were deemed to be related to everolimus. The multivariable analysis identified everolimus duration (every 6-month increase; OR = 1.28; 95% CI 1.02–1.60; p = 0.03) as an independent risk factor for serious infection. Conclusion: Infections are more frequent in NET patients using everolimus than previously reported in clinical trials. Patients on everolimus should be closely monitored for infections, especially those receiving it for several months.