scholarly journals Occurrence of Serious Infection in Patients with Rheumatoid Arthritis Treated with Biologics and Denosumab Observed in a Clinical Setting

2017 ◽  
Vol 45 (2) ◽  
pp. 170-176 ◽  
Author(s):  
Arthur N. Lau ◽  
Matthew Wong-Pack ◽  
Rod Rodjanapiches ◽  
George Ioannidis ◽  
Sally Wade ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Opportunistic Infection ◽  
Opportunistic Infections ◽  
Biologic Agent ◽  
Risk Of Infection ◽  
Group 4 ◽  
Concurrent Use ◽  
Serious Infection ◽  
Increased Risk ◽  
Group 3

Objective.Previous studies combining biologic disease-modifying antirheumatic drugs (bDMARD) to treat rheumatoid arthritis (RA) have shown an increased risk of infection. However, the risk of infection with concurrent use of denosumab, a biologic agent for the treatment of osteoporosis, and a bDMARD remains unclear. Here, we evaluated the incidence of serious and opportunistic infections in patients treated concurrently with denosumab and a bDMARD and patients treated with a bDMARD alone.Methods.A chart review of patients with RA from 2 Canadian rheumatology practices between July 1, 2010, and July 31, 2014, identified 2 groups of patients: those taking denosumab and a bDMARD concurrently (concurrent group) and those taking only a bDMARD (biologic-alone group). Patients were followed from the time of initiation of denosumab, or a matched index date for the biologic-alone group, to the end of the study or loss to followup. Instances of serious or opportunistic infections were recorded.Results.A total of 308 patients (n = 102 for the concurrent group and n = 206 for the biologic-alone group) were evaluated. Within the concurrent group, 3 serious infection events occurred. Within the biologic-alone group, 4 serious infection events and 1 opportunistic infection event occurred. In both groups, all patients with serious or opportunistic infection recovered, and there were no instances of death during the study period.Conclusion.This study demonstrated a low occurrence of serious and opportunistic infections in patients with RA taking bDMARD, including patients with concurrent denosumab use.

Does Anti-Tumor Necrosis Factor-α Therapy Affect Risk of Serious Infection and Cancer in Patients with Rheumatoid Arthritis?: A Review of Longterm Data

2011 ◽  
Vol 38 (8) ◽  
pp. 1552-1562 ◽  
Author(s):  
EDWARD C. KEYSTONE
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Risk Of Infection ◽  
Serious Infection ◽  
Increased Risk ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Given the important role tumor necrosis factor-α (TNF-α) antagonists play in managing rheumatoid arthritis and the concern for safety during longterm therapy, we reviewed the latest evidence regarding longterm risk of infection and malignancy with TNF-α antagonists. Our objective was to provide clinicians with information that can be used to counsel and monitor patients who may be candidates for biologic therapy for rheumatoid arthritis (RA). Risk is examined in the context of background infection and malignancy rates in RA. Randomized controlled trial (RCT) data and observational studies summarizing the risk of infection and/or malignancy in RA and specific risks associated with the use of anti-TNF-α biologic agents (adalimumab, infliximab, and etanercept) were identified through a PubMed search. Overall, patients with RA appear to have an approximately 2-fold increased risk of serious infection compared to the general population and non-RA controls, irrespective of TNF-α antagonist use. Although data on infection rates with TNF-α antagonist use are contradictory, caution is merited. Recent analyses suggest that the risk of infection is highest within the first year. Regarding malignancy risk, RCT and observational data are also conflicting; how ever, caution is warranted regarding lymphoproliferative cancers in children and adolescents.

scholarly journals 1095. Investigation of Risk Factors Associated with Serious Bacterial, Viral and Invasive Fungal Infections in Hematologic Patients on Ibrutinib

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S576-S577
Author(s):  
Thomas Holowka ◽  
Harry Cheung ◽  
Maricar F Malinis ◽  
Sarah Perreault ◽  
Iris Isufi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Fungal Infections ◽  
Antimicrobial Prophylaxis ◽  
Hematologic Malignancy ◽  
Invasive Fungal Infections ◽  
Risk Of Infection ◽  
Factors Associated ◽  
Serious Infection ◽  
Increased Risk ◽  
Serious Infections

Abstract Background Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib. Methods We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection. Results A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p < 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p < 0.001), neutropenia (OR 3.6, p < 0.01), lymphopenia (OR 2.4, p < 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p < 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments. Conclusion The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib. Disclosures All Authors: No reported disclosures

scholarly journals Risk of infection associated with targeted therapies for solid organ and hematological malignancies

2021 ◽  
Vol 8 ◽  
pp. 204993612198954
Author(s):  
Isabel Ruiz-Camps ◽  
Juan Aguilar-Company
Keyword(s):  
Hematological Malignancies ◽  
Opportunistic Infections ◽  
Respiratory Infections ◽  
Fungal Infections ◽  
Checkpoint Inhibitors ◽  
Janus Kinase ◽  
Prolonged Treatment ◽  
Solid Organ ◽  
Risk Of Infection ◽  
Increased Risk

Higher risks of infection are associated with some targeted drugs used to treat solid organ and hematological malignancies, and an individual patient’s risk of infection is strongly influenced by underlying diseases and concomitant or prior treatments. This review focuses on risk levels and specific suggestions for management, analyzing groups of agents associated with a significant effect on the risk of infection. Due to limited clinical experience and ongoing advances in these therapies, recommendations may be revised in the near future. Bruton tyrosine kinase (BTK) inhibitors are associated with a higher rate of infections, including invasive fungal infection, especially in the first months of treatment and in patients with advanced, pretreated disease. Phosphatidylinositol 3-kinase (PI3K) inhibitors are associated with an increased risk of Pneumocystis pneumonia and cytomegalovirus (CMV) reactivation. Venetoclax is associated with cytopenias, respiratory infections, and fever and neutropenia. Janus kinase (JAK) inhibitors may predispose patients to opportunistic and fungal infections; need for prophylaxis should be assessed on an individual basis. Mammalian target of rapamycin (mTOR) inhibitors have been linked to a higher risk of general and opportunistic infections. Breakpoint cluster region-Abelson (BCR-ABL) inhibitors are associated with neutropenia, especially over the first months of treatment. Anti-CD20 agents may cause defects in the adaptative immune response, hypogammaglobulinemia, neutropenia, and hepatitis B reactivation. Alemtuzumab is associated with profound and long-lasting immunosuppression; screening is recommended for latent infections and prevention strategies against CMV, herpesvirus, and Pneumocystis infections. Checkpoint inhibitors (CIs) may cause immune-related adverse events for which prolonged treatment with corticosteroids is needed: prophylaxis against Pneumocystis is recommended.

Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study

2019 ◽  
Vol 78 (4) ◽  
pp. 456-464 ◽  
Author(s):  
Ajinkya Pawar ◽  
Rishi J Desai ◽  
Daniel H Solomon ◽  
Adrian J Santiago Ortiz ◽  
Sara Gale ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cohort Study ◽  
Soft Tissue ◽  
Bacterial Infection ◽  
Opportunistic Infection ◽  
Soft Tissue Infections ◽  
Upper Respiratory Tract ◽  
Biologic Drugs ◽  
Increased Risk ◽  
Biologic Drug

ObjectiveTo investigate the rate of serious bacterial, viral or opportunistic infection in patients with rheumatoid arthritis (RA) starting tocilizumab (TCZ) versus tumour necrosis factor inhibitors (TNFi) or abatacept.MethodsUsing claims data from US Medicare from 2010 to 2015, and IMS and MarketScan from 2011 to 2015, we identified adults with RA who initiated TCZ or TNFi (primary comparator)/abatacept (secondary comparator) with prior use of ≥1 different biologic drug or tofacitinib. The primary outcome was hospitalised serious infection (SI), including bacterial, viral or opportunistic infection. To control for >70 confounders, TCZ initiators were propensity score (PS)-matched to TNFi or abatacept initiators. Database-specific HRs were combined by a meta-analysis.ResultsThe primary cohort included 16 074 TCZ PS-matched to 33 109 TNFi initiators. The risk of composite SI was not different between TCZ and TNFi initiators (combined HR 1.05, 95% CI 0.95 to 1.16). However, TCZ was associated with an increased risk of serious bacterial infection (HR 1.19, 95% CI 1.07 to 1.33), skin and soft tissue infections (HR 2.38, 95% CI 1.47 to 3.86), and diverticulitis (HR 2.34, 95% CI 1.64 to 3.34) versus TNFi. An increased risk of composite SI, serious bacterial infection, diverticulitis, pneumonia/upper respiratory tract infection and septicaemia/bacteraemia was observed in TCZ versus abatacept users.ConclusionsThis large multidatabase cohort study found no difference in composite SI risk in patients with RA initiating TCZ versus TNFi after failing ≥1 biologic drug or tofacitinib. However, the risk of serious bacterial infection, skin and soft tissue infections, and diverticulitis was higher in TCZ versus TNFi initiators. The risk of composite SI was higher in TCZ initiators versus abatacept.

scholarly journals Comparative risk of malignancies and infections in patients with rheumatoid arthritis initiating abatacept versus other biologics: a multi-database real-world study

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Teresa A. Simon ◽  
Maarten Boers ◽  
Marc Hochberg ◽  
Nicole Baker ◽  
Mary L. Skovron ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rheumatoid Arthritis ◽  
Lung Cancer ◽  
Real World ◽  
Opportunistic Infections ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Malignancy Risk ◽  
Increased Risk ◽  
Meta Analyses

Abstract Background Patients with rheumatoid arthritis (RA) are at an increased risk of developing certain cancers and infections compared with the general population. Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are effective treatment options for RA, but limited evidence is available on the comparative risks among b/tsDMARDs. We assessed the risk of malignancies and infections in patients with RA who initiated abatacept versus other b/tsDMARDs in a real-world setting. Methods This retrospective, observational study used administrative data from three large US healthcare databases (MarketScan, PharMetrics, and Optum) to identify patients treated with abatacept or other b/tsDMARDs. In both groups, age-stratified incidence rates (IRs) with 95% confidence intervals (CIs) were calculated for total malignancy and hospitalized infections; propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs for total malignancy, lung cancer, lymphoma, breast cancer, non-melanoma skin cancer (NMSC), hospitalized infections, opportunistic infections, and tuberculosis (TB), both within individual databases and in meta-analyses across the three databases. Results A rounded total of 19.2, 13.6, and 4.2 thousand patients initiating abatacept and 55.3, 40.8, and 13.8 thousand initiating other b/tsDMARDs were identified in the MarketScan, PharMetrics, and Optum databases, respectively. The IRs for total malignancy and hospitalized infections were similar between the two groups in each age stratum. In meta-analyses, total malignancy risk (HR [95% CI] 1.09 [1.02–1.16]) of abatacept versus other b/tsDMARDs was slightly but statistically significantly increased; small, but not statistically significant, increases were seen for lung cancer (1.10 [0.62–1.96]), lymphoma (1.27 [0.94–1.72]), breast cancer (1.15 [0.92–1.45]), and NMSC (1.10 [0.93–1.30]). No significant increase in hospitalized infections (0.96 [0.84–1.09]) or opportunistic infections (1.06 [0.96–1.17]) was seen. For TB, low event counts precluded meta-analysis. Conclusions In this real-world multi-database study, the risks for specific cancers and infections did not differ significantly between patients in the abatacept and other b/tsDMARDs groups. The slight increase in total malignancy risk associated with abatacept needs further investigation. These results are consistent with the established safety profile of abatacept.

Increased risk of opportunistic infection in early rheumatoid arthritis

2019 ◽  
Vol 22 (7) ◽  
pp. 1239-1246 ◽  
Author(s):  
Hyoungyoung Kim ◽  
Soo‐Kyung Cho ◽  
Jiyoung Lee ◽  
Sang‐Cheol Bae ◽  
Yoon‐Kyoung Sung
Keyword(s):  
Rheumatoid Arthritis ◽  
Opportunistic Infection ◽  
Early Rheumatoid Arthritis ◽  
Increased Risk

Association Between the Number of Comorbidities and the Risk of a Serious Infection in Rheumatoid Arthritis Treated by a First Biologic Agent

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Christopher Banse ◽  
Estelle Houivet ◽  
Aurélien Loison ◽  
Rémi Varin ◽  
Sophie Pouplin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Biologic Agent ◽  
Serious Infection

scholarly journals Cross Talk Between Down Regulation of Steroidogenic Genes Expression, Oxidative and Apoptotic Biomarkers in Testes Induced by Administration of Tramadol and Boldenone and Their Combination in Male Albino Rats

2021 ◽  
Author(s):  
Gihan F. Asaad ◽  
Noha Mowaad ◽  
Marwa E.A. El-Shamarka ◽  
Sahar Khalil
Keyword(s):  
Control Group ◽  
Albino Rats ◽  
Group 4 ◽  
Vital Functions ◽  
Concurrent Use ◽  
Genes Expression ◽  
Group 3 ◽  
Group 2 ◽  
Oxidative Biomarkers ◽  
Reproductive Gland

Abstract BackgroundThe testis is the male reproductive gland or gonad having two vital functions - to produce both sperm and androgens, primarily testosterone.PurposeThe study aimed to investigate the effect of tramadol and boldenone injected alone or in combinatio for 2 months in rats on testicular function.MethodsGroup 1; normal control, Group 2; tramadol Hcl (TRAM) (20 mg/kg bwt.) (i.p). Group 3; boldenone undecylenate (BOLD) (5 mg/kg bwt) (i.m). Group 4; combination of TRAM (20 mg/kg bwt.) and BOLD (5 mg/kg), respectively for 2 months.ResultsTRAM and BOLD alone and in combination rats showed deteriorated testicular functions, lowered serum steroid levels (FSH, LH and testesterone), elevation in oxidative biomarkers (MDA & NO) and reduction in GSH and SOD, downregulation of StaR and HSD17B3 as well as assessment of testicular histopathological using H&E staining, PAS stain for histochemical assessment of polysaccharides and glycoproteins in the testes and Masson trichrome stain to assess the changes in the collagen fibers.ConclusionThe study illuminated the hazard of administration of these drugs for a long period as well as the prominent deleterious effects reported on concurrent use of both drugs.

scholarly journals Infections in baricitinib clinical trials for patients with active rheumatoid arthritis

2020 ◽  
Vol 79 (10) ◽  
pp. 1290-1297 ◽  
Author(s):  
Kevin L Winthrop ◽  
Masayoshi Harigai ◽  
Mark C Genovese ◽  
Stephen Lindsey ◽  
Tsutomu Takeuchi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Active Rheumatoid Arthritis ◽  
Opportunistic Infections ◽  
Response Assessment ◽  
Janus Kinase ◽  
Jak2 Inhibitor ◽  
Serious Infection ◽  
Adjusted Incidence Rate ◽  
Over Time

ObjectivesTo evaluate the incidence of infection in patients with active rheumatoid arthritis (RA) treated with baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor.MethodsInfections are summarised from an integrated database (8 phase 3/2/1b clinical trials and 1 long-term extension (LTE)) with data to 1 April 2017. The ‘all-bari-RA’ analysis set included patients who received any baricitinib dose. Placebo comparison was based on six studies with 4 mg and placebo to week 24, including four trials with 2 mg (placebo-controlled set). Dose–response assessment was based on four studies with 2 mg and 4 mg, including LTE data (2–4 mg extended set).ResultsThere were 3492 patients who received baricitinib for 7860 patient-years (PY) of exposure (median 2.6 years, maximum 6.1 years). Treatment-emergent infections were higher for baricitinib versus placebo (exposure-adjusted incidence rate (IR)/100 PY: placebo 75.9, 2 mg 84.0 (p not significant), 4 mg 88.4 (p≤0.001)). The IR of serious infection was similar for baricitinib versus placebo and stable over time (all-bari-RA IR 3.0/100 PY). There were 11 cases of tuberculosis (all-bari-RA IR 0.1/100 PY); all occurred with 4 mg in endemic regions. Herpes zoster (HZ) IR/100 PY was higher for baricitinib versus placebo (placebo 1.0, 2 mg 3.1 (p not significant), 4 mg 4.3 (p≤0.01)); rates remained elevated and stable over time (all-bari-RA 3.3). Opportunistic infections, including multidermatomal HZ, were infrequent in the baricitinib programme (all-bari-RA IR 0.5/100 PY).ConclusionsIncreased rates of treatment-emergent infections including HZ were observed in patients with RA treated with baricitinib, consistent with baricitinib’s immunomodulatory mode of action.

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