Dataset Information

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.

ABSTRACT:

Importance

Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood.

Objective

To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs.

Design, setting, and participants

This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included.

Exposures

Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy.

Main outcomes and measures

The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations.

Results

A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone.

Conclusions and relevance

In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.

SUBMITTER: Izadi Z

PROVIDER: S-EPMC8524310 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.

Izadi Zara Z Brenner Erica J EJ Mahil Satveer K SK Dand Nick N Yiu Zenas Z N ZZN Yates Mark M Ungaro Ryan C RC Zhang Xian X Agrawal Manasi M Colombel Jean-Frederic JF Gianfrancesco Milena A MA Hyrich Kimme L KL Strangfeld Anja A Carmona Loreto L Mateus Elsa F EF Lawson-Tovey Saskia S Klingberg Eva E Cuomo Giovanna G Caprioli Marta M Cruz-Machado Ana Rita AR Mazeda Pereira Ana Carolina AC Hasseli Rebecca R Pfeil Alexander A Lorenz Hanns-Martin HM Hoyer Bimba Franziska BF Trupin Laura L Rush Stephanie S Katz Patricia P Schmajuk Gabriela G Jacobsohn Lindsay L Seet Andrea M AM Al Emadi Samar S Wise Leanna L Gilbert Emily L EL Duarte-García Alí A Valenzuela-Almada Maria O MO Isnardi Carolina A CA Quintana Rosana R Soriano Enrique R ER Hsu Tiffany Y-T TY D'Silva Kristin M KM Sparks Jeffrey A JA Patel Naomi J NJ Xavier Ricardo Machado RM Marques Claudia Diniz Lopes CDL Kakehasi Adriana Maria AM Flipo René-Marc RM Claudepierre Pascal P Cantagrel Alain A Goupille Philippe P Wallace Zachary S ZS Bhana Suleman S Costello Wendy W Grainger Rebecca R Hausmann Jonathan S JS Liew Jean W JW Sirotich Emily E Sufka Paul P Robinson Philip C PC Machado Pedro M PM Griffiths Christopher E M CEM Barker Jonathan N JN Smith Catherine H CH Yazdany Jinoos J Kappelman Michael D MD

JAMA network open 20211001 10

<h4>Importance</h4>Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood.<h4>Objective</h4>To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared wit ...[more]

PMID: 34661663

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Project description:ImportanceTumor necrosis factor (TNF) inhibitors are common therapies for certain autoimmune diseases, such as rheumatoid arthritis. An association between TNF inhibitor exposure and inflammatory central nervous system (CNS) events has been postulated but is poorly understood.ObjectiveTo evaluate whether TNF inhibitor exposure is associated with inflammatory demyelinating and nondemyelinating CNS events in patients with an indication for TNF inhibitor use and to describe the spectrum of those CNS events.Design, setting, and participantsA nested case-control study was conducted using the medical records of patients with autoimmune diseases treated at 3 Mayo Clinic locations (Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida) between January 1, 2003, and February 20, 2019. Patients were included if their records reported International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnostic codes for US Food and Drug Administration-approved autoimmune disease indication for TNF inhibitor use (ie, rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, Crohn disease, and ulcerative colitis) and diagnostic codes for inflammatory CNS events of interest. Patients were matched 1:1 with control participants by year of birth, type of autoimmune disease, and sex.ExposuresTNF inhibitor exposure data were derived from the medical records along with type of TNF inhibitor, cumulative duration of exposure, and time of exposure.Main outcomes and measuresThe main outcome was either inflammatory demyelinating (multiple sclerosis and other diseases such as optic neuritis) or nondemyelinating (meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis) CNS event. Association with TNF inhibitor was evaluated with conditional logistic regression and adjusted for disease duration to determine the odds ratios (ORs) and 95% CIs. Secondary analyses included stratification of outcome by inflammatory demyelinating and nondemyelinating CNS events and by autoimmune disease (rheumatoid arthritis and non-rheumatoid arthritis).ResultsA total of 212 individuals were included: 106 patients with inflammatory CNS events and 106 control participants without such events. Of this total, 136 were female (64%); the median (interquartile range) age at disease onset for patients was 52 (43-62) years. Exposure to TNF inhibitors occurred in 64 patients (60%) and 42 control participants (40%) and was associated with an increased risk of any inflammatory CNS event (adjusted OR, 3.01; 95% CI, 1.55-5.82; P = .001). These results were similar when the outcome was stratified by demyelinating and nondemyelinating CNS events. Secondary analyses found the association was predominantly observed in patients with rheumatoid arthritis (adjusted OR, 4.82; 95% CI, 1.62-14.36; P = .005).Conclusions and relevanceThis study found that exposure to TNF inhibitors in patients with autoimmune diseases appeared to be associated with increased risk for inflammatory CNS events. Whether this association represents de novo or exacerbated inflammatory pathways requires further research.

Project description:ImportanceInflammatory bowel disease (IBD) is commonly treated with corticosteroids and anti-tumor necrosis factor (TNF) drugs; however, medications have well-described adverse effects. Prior work suggests that anti-TNF therapy may reduce all-cause mortality compared with prolonged corticosteroid use among Medicare and Medicaid beneficiaries with IBD.ObjectiveTo examine the association between use of anti-TNF or corticosteroids and all-cause mortality in a national cohort of veterans with IBD.Design, setting, and participantsThis cohort study used a well-established Veteran's Health Administration cohort of 2997 patients with IBD treated with prolonged corticosteroids (≥3000-mg prednisone equivalent and/or ≥600 mg of budesonide within a 12-month period) and/or new anti-TNF therapy from January 1, 2006, to October 1, 2015. Data were analyzed between July 1, 2019, and December 31, 2020.ExposuresUse of corticosteroids or anti-TNF.Main outcomes and measuresThe primary end point was all-cause mortality as defined by the Veterans Health Administration vital status file. Marginal structural modeling was used to compare associations between anti-TNF therapy or corticosteroid use and all-cause mortality.ResultsA total of 2997 patients (2725 men [90.9%]; mean [SD] age, 50.0 [17.4] years) were included in the final analysis, 1734 (57.9%) with Crohn disease (CD) and 1263 (42.1%) with ulcerative colitis (UC). All-cause mortality was 8.5% (n = 256) over a mean (SD) of 3.9 (2.3) years' follow-up. At cohort entry, 1836 patients were new anti-TNF therapy users, and 1161 were prolonged corticosteroid users. Anti-TNF therapy use was associated with a lower likelihood of mortality for CD (odds ratio [OR], 0.54; 95% CI, 0.31-0.93) but not for UC (OR, 0.33; 95% CI, 0.10-1.10). In a sensitivity analysis adjusting prolonged corticosteroid users to include patients receiving corticosteroids within 90 to 270 days after initiation of anti-TNF therapy, the OR for UC was statistically significant, at 0.33 (95% CI, 0.13-0.84), and the OR for CD was 0.55 (95% CI, 0.33-0.92).Conclusions and relevanceThis study suggests that anti-TNF therapy may be associated with reduced mortality compared with long-term corticosteroid use among veterans with CD, and potentially among those with UC.

Dataset Information

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Conclusions and relevance

Publications

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.

Similar Datasets

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