tetano
Editor, Senior Moderator
JAMA Netw Open
. 2021 Oct 1;4(10):e2129639.
doi: 10.1001/jamanetworkopen.2021.29639.
Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
Zara Izadi[SUP] 1 2 [/SUP], Erica J Brenner[SUP] 3 [/SUP], Satveer K Mahil[SUP] 4 5 [/SUP], Nick Dand[SUP] 6 7 [/SUP], Zenas Z N Yiu[SUP] 8 9 [/SUP], Mark Yates[SUP] 10 [/SUP], Ryan C Ungaro[SUP] 11 [/SUP], Xian Zhang[SUP] 12 [/SUP], Manasi Agrawal[SUP] 11 [/SUP], Jean-Frederic Colombel[SUP] 11 [/SUP], Milena A Gianfrancesco[SUP] 2 [/SUP], Kimme L Hyrich[SUP] 13 14 15 [/SUP], Anja Strangfeld[SUP] 16 [/SUP], Loreto Carmona[SUP] 17 [/SUP], Elsa F Mateus[SUP] 18 19 [/SUP], Saskia Lawson-Tovey[SUP] 14 15 20 [/SUP], Eva Klingberg[SUP] 21 [/SUP], Giovanna Cuomo[SUP] 22 [/SUP], Marta Caprioli[SUP] 23 [/SUP], Ana Rita Cruz-Machado[SUP] 24 25 [/SUP], Ana Carolina Mazeda Pereira[SUP] 26 [/SUP], Rebecca Hasseli[SUP] 27 [/SUP], Alexander Pfeil[SUP] 28 [/SUP], Hanns-Martin Lorenz[SUP] 29 [/SUP], Bimba Franziska Hoyer[SUP] 30 31 [/SUP], Laura Trupin[SUP] 2 [/SUP], Stephanie Rush[SUP] 2 [/SUP], Patricia Katz[SUP] 2 [/SUP], Gabriela Schmajuk[SUP] 2 32 [/SUP], Lindsay Jacobsohn[SUP] 2 [/SUP], Andrea M Seet[SUP] 2 [/SUP], Samar Al Emadi[SUP] 33 [/SUP], Leanna Wise[SUP] 34 [/SUP], Emily L Gilbert[SUP] 35 [/SUP], Alí Duarte-García[SUP] 36 37 [/SUP], Maria O Valenzuela-Almada[SUP] 36 [/SUP], Carolina A Isnardi[SUP] 38 [/SUP], Rosana Quintana[SUP] 38 [/SUP], Enrique R Soriano[SUP] 39 [/SUP], Tiffany Y-T Hsu[SUP] 40 41 [/SUP], Kristin M D'Silva[SUP] 41 42 [/SUP], Jeffrey A Sparks[SUP] 40 41 [/SUP], Naomi J Patel[SUP] 41 43 [/SUP], Ricardo Machado Xavier[SUP] 44 [/SUP], Claudia Diniz Lopes Marques[SUP] 45 [/SUP], Adriana Maria Kakehasi[SUP] 46 [/SUP], René-Marc Flipo[SUP] 47 [/SUP], Pascal Claudepierre[SUP] 48 49 [/SUP], Alain Cantagrel[SUP] 50 [/SUP], Philippe Goupille[SUP] 51 52 [/SUP], Zachary S Wallace[SUP] 41 42 [/SUP], Suleman Bhana[SUP] 53 [/SUP], Wendy Costello[SUP] 54 [/SUP], Rebecca Grainger[SUP] 55 [/SUP], Jonathan S Hausmann[SUP] 56 57 [/SUP], Jean W Liew[SUP] 58 [/SUP], Emily Sirotich[SUP] 59 60 [/SUP], Paul Sufka[SUP] 61 [/SUP], Philip C Robinson[SUP] 62 63 [/SUP], Pedro M Machado[SUP] 64 65 66 [/SUP], Christopher E M Griffiths[SUP] 8 9 [/SUP], Jonathan N Barker[SUP] 67 [/SUP], Catherine H Smith[SUP] 4 5 [/SUP], Jinoos Yazdany[SUP] 2 [/SUP], Michael D Kappelman[SUP] 3 [/SUP], Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Allianc; Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Alliance (GRA)
Collaborators, Affiliations
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.
. 2021 Oct 1;4(10):e2129639.
doi: 10.1001/jamanetworkopen.2021.29639.
Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
Zara Izadi[SUP] 1 2 [/SUP], Erica J Brenner[SUP] 3 [/SUP], Satveer K Mahil[SUP] 4 5 [/SUP], Nick Dand[SUP] 6 7 [/SUP], Zenas Z N Yiu[SUP] 8 9 [/SUP], Mark Yates[SUP] 10 [/SUP], Ryan C Ungaro[SUP] 11 [/SUP], Xian Zhang[SUP] 12 [/SUP], Manasi Agrawal[SUP] 11 [/SUP], Jean-Frederic Colombel[SUP] 11 [/SUP], Milena A Gianfrancesco[SUP] 2 [/SUP], Kimme L Hyrich[SUP] 13 14 15 [/SUP], Anja Strangfeld[SUP] 16 [/SUP], Loreto Carmona[SUP] 17 [/SUP], Elsa F Mateus[SUP] 18 19 [/SUP], Saskia Lawson-Tovey[SUP] 14 15 20 [/SUP], Eva Klingberg[SUP] 21 [/SUP], Giovanna Cuomo[SUP] 22 [/SUP], Marta Caprioli[SUP] 23 [/SUP], Ana Rita Cruz-Machado[SUP] 24 25 [/SUP], Ana Carolina Mazeda Pereira[SUP] 26 [/SUP], Rebecca Hasseli[SUP] 27 [/SUP], Alexander Pfeil[SUP] 28 [/SUP], Hanns-Martin Lorenz[SUP] 29 [/SUP], Bimba Franziska Hoyer[SUP] 30 31 [/SUP], Laura Trupin[SUP] 2 [/SUP], Stephanie Rush[SUP] 2 [/SUP], Patricia Katz[SUP] 2 [/SUP], Gabriela Schmajuk[SUP] 2 32 [/SUP], Lindsay Jacobsohn[SUP] 2 [/SUP], Andrea M Seet[SUP] 2 [/SUP], Samar Al Emadi[SUP] 33 [/SUP], Leanna Wise[SUP] 34 [/SUP], Emily L Gilbert[SUP] 35 [/SUP], Alí Duarte-García[SUP] 36 37 [/SUP], Maria O Valenzuela-Almada[SUP] 36 [/SUP], Carolina A Isnardi[SUP] 38 [/SUP], Rosana Quintana[SUP] 38 [/SUP], Enrique R Soriano[SUP] 39 [/SUP], Tiffany Y-T Hsu[SUP] 40 41 [/SUP], Kristin M D'Silva[SUP] 41 42 [/SUP], Jeffrey A Sparks[SUP] 40 41 [/SUP], Naomi J Patel[SUP] 41 43 [/SUP], Ricardo Machado Xavier[SUP] 44 [/SUP], Claudia Diniz Lopes Marques[SUP] 45 [/SUP], Adriana Maria Kakehasi[SUP] 46 [/SUP], René-Marc Flipo[SUP] 47 [/SUP], Pascal Claudepierre[SUP] 48 49 [/SUP], Alain Cantagrel[SUP] 50 [/SUP], Philippe Goupille[SUP] 51 52 [/SUP], Zachary S Wallace[SUP] 41 42 [/SUP], Suleman Bhana[SUP] 53 [/SUP], Wendy Costello[SUP] 54 [/SUP], Rebecca Grainger[SUP] 55 [/SUP], Jonathan S Hausmann[SUP] 56 57 [/SUP], Jean W Liew[SUP] 58 [/SUP], Emily Sirotich[SUP] 59 60 [/SUP], Paul Sufka[SUP] 61 [/SUP], Philip C Robinson[SUP] 62 63 [/SUP], Pedro M Machado[SUP] 64 65 66 [/SUP], Christopher E M Griffiths[SUP] 8 9 [/SUP], Jonathan N Barker[SUP] 67 [/SUP], Catherine H Smith[SUP] 4 5 [/SUP], Jinoos Yazdany[SUP] 2 [/SUP], Michael D Kappelman[SUP] 3 [/SUP], Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Allianc; Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection (PsoProtect); the Secure Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD); and the COVID-19 Global Rheumatology Alliance (GRA)
Collaborators, Affiliations
- PMID: 34661663
- DOI: 10.1001/jamanetworkopen.2021.29639
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.