Clinical Pharmacology Aspects in Patients Treated with TNF Inhibitors During SARS-Cov-2 Pandemic

In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and golimumab have been used for over 20 years in severe cases of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease or ankylosing spondylitis. Due to their mechanism of action they reduce inflammation and can stop the progression of the disease by inhibiting a key factor of inflammation such as Tumor Necrosis Factor (TNF). In this article we want to examine the possible correlation between therapy with TNF inhibitors and the increased risk of SARS-CoV-2 infection, and the possible paradoxical therapeutic efficacy in patients with ongoing infection, especially in phase two and three. We express our opinion on this very complex and sensitive topic which is the subject of discussion among physicians and experts, based on current knowledge of the literature.

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Factors associated with sepsis risk in immune-mediated inflammatory diseases receiving tumor necrosis factor inhibitors: a nationwide study

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x20929208 ◽

2020 ◽

Vol 12 ◽

pp. 1759720X2092920

Author(s):

Wen-Cheng Chao ◽

Chen-Yu Wang ◽

Bo-Chueh Hsu ◽

Ching-Heng Lin ◽

Wen-Nan Huang ◽

...

Keyword(s):

Risk Factors ◽

Socioeconomic Status ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Inflammatory Diseases ◽

Research Database ◽

Cox Regression Analysis ◽

Immune Mediated ◽

Increased Risk ◽

Necrosis Factor

Background: Risk factors for sepsis have not been assessed in patients receiving tumor necrosis factor-alpha inhibitors (TNFi) for immune-mediated inflammatory diseases (IMIDs) who are vulnerable to serious/hospitalized infections. Methods: Data from 2003–2017 were obtained from Taiwan’s National Health Insurance Research Database to identify patients receiving TNFi, including etanercept, adalimumab, and golimumab, for IMIDs including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis (PsO), psoriatic arthritis (PsA), Crohn’s disease (CD), and ulcerative colitis (UC). To investigate risk factors for sepsis, we used the Sepsis-3 definition and calculated hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression analysis. Results: There were 17,764 patients (mean age 49.3 ± 14.3 years; females, 57.6%) receiving TNFi for IMIDs, including RA (58.6%), AS (19.1%), PsO (15.1%), PsA (2.5%), CD (3.0%), and UC (1.7%). The overall incidence rate of sepsis was 1088 per 100,000 person-years. After adjustment for potential confounders, recent sepsis within 3 months before TNFi initiation (HR, 2.35; 95% CI, 1.73–3.20), CD (HR, 3.36; 95% CI 2.11–5.34; reference group: AS) and glucocorticoid use (prednisolone-equivalent dose, mg/day HR, 1.05; 95% CI, 1.05–1.06) were associated with the risk of sepsis. Intriguingly, golimumab users appeared to have a lower risk of sepsis compared with etanercept users (HR, 0.56; 95% CI, 0.38–0.83). In addition, socioeconomic status, including urbanization level and insured amount, was associated with sepsis in a dose-response manner. Conclusions: Recent sepsis, CD, concomitant glucocorticoid use, and low socioeconomic status, which were associated with an increased risk of sepsis, are crucial for individualized risk management plans.

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Severe Extraarticular Manifestations in a Community-based Cohort of Patients with Rheumatoid Arthritis: Risk Factors and Incidence in Relation to Treatment with Tumor Necrosis Factor Inhibitors

The Journal of Rheumatology ◽

10.3899/jrheum.161103 ◽

2017 ◽

Vol 44 (7) ◽

pp. 981-987 ◽

Cited By ~ 11

Author(s):

Lisa Theander ◽

Britt-Marie Nyhäll-Wåhlin ◽

Jan-Åke Nilsson ◽

Minna Willim ◽

Lennart T.H. Jacobsson ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tnf Inhibitors ◽

Time Dependent ◽

Community Based ◽

Rheumatoid Arthritis Risk ◽

Increased Risk ◽

Clinical Records ◽

Necrosis Factor

Objective.The aims of this study were to evaluate whether treatment with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) affects the risk of developing severe extraarticular rheumatoid arthritis (ExRA) manifestations and to investigate potential predictors for developing ExRA.Methods.A dynamic community-based cohort of patients with RA was studied (n = 1977). Clinical records were reviewed and cases of severe ExRA were identified. Information on exposure to TNF inhibitors was obtained from a regional register. Exposure to TNF inhibitors was analyzed in a time-dependent fashion and the incidence of severe ExRA in exposed patients was compared with the incidence in unexposed patients. Cox regression models were used to assess potential predictors of severe ExRA.Results.During treatment with TNF inhibitors, there were 17 patients with new onset of severe ExRA in 2400 person-years at risk (PY; 0.71/100 PY, 95% CI 0.41–1.13) compared with 104 in 15,599 PY (0.67/100 PY, 95% CI 0.54–0.81) in patients without TNF inhibitors. This corresponded to an incidence rate ratio of 1.06 (95% CI 0.60–1.78). The age- and sex-adjusted HR for ExRA in anti-TNF–treated patients was 1.21 (95% CI 1.02–1.43), with similar findings in models adjusted for time-dependent Health Assessment Questionnaire and propensity for anti-TNF treatment. Male sex, positive rheumatoid factor (RF), long disease duration, and greater disability were predictors for ExRA.Conclusion.This study suggests that patients treated with TNF inhibitors are at a slightly increased risk of developing severe ExRA. RF-positive patients with disabling disease of long duration were more likely to develop severe ExRA.

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A common polymorphism of tumor necrosis factor receptor-associated factor 6 (TRAF6) is associated with an increased risk for spontaneous bacterial peritonitis

Zeitschrift für Gastroenterologie ◽

10.1055/s-0034-1397095 ◽

2015 ◽

Vol 53 (01) ◽

Author(s):

M Mai ◽

S Stengel ◽

E Al-Herwi ◽

P Reuken ◽

A Stallmach ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Spontaneous Bacterial Peritonitis ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Associated Factor ◽

Bacterial Peritonitis ◽

Common Polymorphism ◽

Increased Risk ◽

Necrosis Factor

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Anti-tumor necrosis factor-induced lupus in patients with inflammatory bowel disease: a hospital-based cohort study from Korea

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284821997794 ◽

2021 ◽

Vol 14 ◽

pp. 175628482199779

Author(s):

Su Jin Choi ◽

Soo Min Ahn ◽

Ji Seon Oh ◽

Seokchan Hong ◽

Chang-Keun Lee ◽

...

Keyword(s):

Risk Factors ◽

Inflammatory Bowel Disease ◽

Tumor Necrosis Factor ◽

Bowel Disease ◽

Tumor Necrosis ◽

Cox Regression ◽

Cox Regression Analysis ◽

Inflammatory Bowel ◽

Necrosis Factor ◽

Mucocutaneous Symptoms

Background: Anti-tumor necrosis factor (TNF) agents are increasingly used for rheumatic diseases and inflammatory bowel disease (IBD), but are associated with the development of anti-TNF-induced lupus (ATIL). Nonetheless, few ATIL studies on non-Caucasian IBD patients exist. Here, we investigated the incidence, clinical features, and risk factors of ATIL in Korea. Methods: We retrospectively reviewed the medical records of IBD patients undergoing anti-TNF therapy at our tertiary IBD center between 2008 and 2020. ATIL was diagnosed as a temporal association between symptoms and anti-TNF agents, and the presence of at least one serologic and non-serologic American College of Rheumatology criterion. The risk factors for ATIL occurrence were assessed using multivariate Cox regression analysis. Results: Of 1362 IBD patients treated with anti-TNF agents, 50 (3.7%) ATIL cases were suspected, of which 14 (1.0%) received a definitive diagnosis. Arthritis and mucocutaneous symptoms were observed in 13 and 4 patients, respectively. All ATIL cases were positive for anti-nuclear and anti-dsDNA antibodies. Four patients (30.8%) improved while continuing anti-TNF therapy. At the final follow up, the ATIL group ( n = 14) had a lower IBD remission rate (30.8% versus 68.8%, p = 0.019) than the non-ATIL group ( n = 36). Ulcerative colitis and longer disease duration were associated with ATIL occurrence, with hazard ratios of 7.017 ( p = 0.005) and 1.118 ( p = 0.002), respectively. Conclusion: Although rare, ATIL is associated with poor treatment response to IBD in Korean patients. ATIL should be considered if arthritis and mucocutaneous symptoms develop during anti-TNF therapy for IBD.

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Lipopolysaccharide-induced production of tumor necrosis factor activity in rats with and without risk factors for stroke

Brain Research ◽

10.1016/0006-8993(91)91083-d ◽

1991 ◽

Vol 541 (1) ◽

pp. 115-120 ◽

Cited By ~ 41

Author(s):

John M. Hallenbeck ◽

Andrew J. Dutka ◽

Stefanie N. Vogel ◽

Eliahu Heldman ◽

David A. Doron ◽

...

Keyword(s):

Risk Factors ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Factor Activity ◽

Necrosis Factor

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Tumor necrosis factor- α is associated with cardiovascular disease risk factors among overweight and obese adolescents

Journal of Nutrition & Intermediary Metabolism ◽

10.1016/j.jnim.2017.04.024 ◽

2017 ◽

Vol 8 ◽

pp. 67-68

Author(s):

D.C. Sulistyoningrum ◽

E. Huriyati ◽

R. Susilowati ◽

W. Ni Putu Diah ◽

H.F.L. Muhammad ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Cardiovascular Disease Risk Factors ◽

Factor Α ◽

Necrosis Factor

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Two Cases of Paradoxical Hidradenitis Suppurativa while on Adalimumab

Case Reports in Gastroenterology ◽

10.1159/000444442 ◽

2016 ◽

Vol 10 (1) ◽

pp. 92-98 ◽

Cited By ~ 3

Author(s):

Glenn Harvin ◽

George Kasarala

Keyword(s):

Tumor Necrosis Factor ◽

Skin Disease ◽

Hidradenitis Suppurativa ◽

Tumor Necrosis ◽

Tnf Inhibitors ◽

Tnf Inhibitor ◽

Inflammatory Skin Disease ◽

Inflammatory Skin ◽

Necrosis Factor ◽

Inhibitor Treatment

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by recurring abscesses, nodules, and fistulas predominantly in the groin and axillae. The association between HS and Crohn’s disease (CD) has been well documented. Tumor necrosis factor (TNF) inhibitors have shown to be effective in treating both HS and CD. We report 2 patients who developed HS while on TNF inhibitor treatment for CD.

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Changing Patterns of Tumor Necrosis Factor Inhibitor Use in 9074 Patients with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.080592 ◽

2009 ◽

Vol 36 (5) ◽

pp. 907-913 ◽

Cited By ~ 44

Author(s):

YUSUF YAZICI ◽

SVETLANA KRASNOKUTSKY ◽

JAIME P. BARNES ◽

PATRICIA L. HINES ◽

JASON WANG ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Tumor Necrosis Factor ◽

Dose Escalation ◽

Tumor Necrosis ◽

Randomized Clinical Trials ◽

Tnf Inhibitors ◽

Tnf Inhibitor ◽

Insurance Claims ◽

Claims Database ◽

Necrosis Factor

Objective.Patients with rheumatoid arthritis (RA) commonly switch between tumor necrosis factor (TNF) inhibitors after failing to control disease activity. Much of the clinical data that support switching to a second TNF agent when one agent fails to work has come from small, short-term studies. We utilized a US insurance claims database to determine patterns of use such as dose escalation, time to discontinuation, and switching between TNF inhibitors in patients with RA.Methods.A retrospective analysis was performed using an insurance claims database in the US from 2000 to 2005. TNF inhibitor use, time to switch, dose escalation, and continuation times were analyzed in patients with RA.Results.Nine thousand seventy-four patients with RA started TNF inhibitors during the period 2000 to 2005. Etanercept was the most commonly used TNF inhibitor; infliximab had the highest duration of continuation, about 50% at 2 years. In addition, infliximab showed higher rates of dose escalation compared to etanercept and adalimumab. For all TNF inhibitors, time to switching decreased from 2000 to 2005.Conclusion.TNF inhibitor use patterns changed from 2000 to 2005, with more frequent changes among the different TNF inhibitors and a shorter duration of treatment before the change. Only about 50% of TNF inhibitors are still continued at 2 years, reflecting the difference between randomized clinical trials and real-world experience.

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