Receiving Tumor Necrosis Factor Inhibitors Research Articles

The rs11568820 Variant in the Promoter Region of Vitamin D Receptor Gene Is Associated with Clinical Remission in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors.

The vitamin D receptor (VDR), binding to the active form of the vitamin, promotes the transcription of numerous genes involved in the proliferation of immune cells, cytokine production and lymphocyte activation. It is known that vitamin D deficiency can influence the risk of developing rheumatoid arthritis (RA) or modulate its disease activity. The aim of this study was to investigate a possible association between the rs11568820 (C > T) polymorphism in the promoter region of VDR gene and the response to therapy with anti-TNF drugs in patients with RA. A total of 178 consecutive Italian patients with RA treated with anti-TNF, naïve for biological therapy, were recruited. Disease activity data were evaluated using specific indices such as DAS28, CDAI and SDAI, measured at the start of therapy and subsequently at 22, 52, 104 and 240 weeks. A statistically significant association emerged between the rs11568820 variant allele of VDR gene and failure to remission assessed by CDAI and SDAI at 52 weeks, and by DAS28, CDAI and SDAI at 104 weeks of follow-up. Furthermore, the variant allele of this polymorphism was observed more frequently in patients who did not undergo sustained remission calculated by CDAI and SDAI. The variant T allele of rs11568820 in VDR gene is associated with a reduced remission rate with anti-TNFα drugs. These data suggest the role of VDR genetic variability in the response to therapy and in the achievement of remission.

Neoehrlichia mikurensis is uncommon in rheumatological patients receiving tumour necrosis factor inhibitors and in blood donors: a retrospective cohort study

IntroductionNeoehrlichia mikurensis is a tick-borne bacterium that primarily causes disease in immunocompromised patients. The bacterium has been detected in ticks throughout Europe, with a 0%–25% prevalence. N. mikurensis infection presents...

Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.

To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.

Hematologic Malignancy Risk in Inflammatory Arthritis Patients Treated with TNF Inhibitors: The Real-Life Data from the HUR-BIO Registry.

This study aimed to assess the incidence of hematologic malignancy (HM) among inflammatory arthritis (IA) patients receiving tumor necrosis factor inhibitors (TNFi) compared with the general Turkish population. HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center biological disease-modifying anti-rheumatic drug(bDMARD) registry since 2005. Patients with IA, including rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis who had at least one visit after the TNFi were screened from 2005 to November 2021. Standardized incidence rates (SIR) were calculated after adjustment for age and gender and compared with the 2017 Turkish National Cancer Registry (TNCR). Of the 6139 patients registered in the HUR-BIO, 5355 used any TNFi at least once. The median follow-up duration was 2.6years for patients receiving TNFi. Thirteen patients developed a HM on follow-up. In these patients, the median age at the IA onset was 38 (range, 26-67), and the median age at the HM diagnosis was 55.5 (range, 38-76). Patients using TNFi had an increased HM incidence (SIR 4.23, 95% confidence interval (CI) 2.35-7.05). Ten patients with HM were under 65years of age. In this group, there was a higher incidence of HM in both men (SIR 5.15, 95% CI 1.88-11.43) and women (SIR 4.76, 95% CI 1.74-10.55). The risk of HMs in inflammatory arthritis patients receiving TNFi was four times higher than in the general Turkish population.

Immunosuppressive therapy and humoral response to third mRNA COVID-19 vaccination with a six-month interval in rheumatic disease patients.

To evaluate the long-term impact of immunosuppressive therapeutic agents on antibody response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with autoimmune rheumatic diseases (AIRD) in order to propose a strategy for annual vaccination. This prospective multicentre cohort study evaluated the humoral response to second and third BNT162b2 and/or mRNA-1273 vaccines in 382 Japanese AIRD patients classified into 12 different medication groups and in 326 healthy controls (HCs). The third vaccination was administered six months after the second vaccination. Antibody titres were measured using the Elecsys Anti-SARS-CoV-2 S assay. The seroconversion rate and antibody titres were lower in AIRD patients than in HCs 3-6 weeks after the second vaccination and 3-6 weeks after the third vaccination. Seroconversion rates were <90% after the third vaccination in patients receiving mycophenolate mofetil and rituximab. Antibody levels after the third vaccination were significantly lower in the groups prescribed TNF inhibitor with or without methotrexate, abatacept and rituximab or cyclophosphamide than those of HCs in a multivariate analysis adjusting for age, sex, and glucocorticoid dosage.The third vaccination induced an adequate humoral response in patients treated with sulfasalazine, bucillamine, methotrexate monotherapy, iguratimod, interleukin-6 inhibitors or calcineurin inhibitors including tacrolimus. Repeated vaccinations in many immunosuppressed patients produced antibody responses similar to those observed in HCs. In contrast, annual vaccination in patients receiving TNF inhibitors, abatacept, mycophenolate mofetil and rituximab may require caution.

Incidence of severe infection in patients with rheumatoid arthritis taking biologic agents: a systematic review.

The objective of this review was to estimate the population-based incidence and determine the types of severe infection and deaths experienced by patients with rheumatoid arthritis taking biologic agents. Since the late 1990s, various biologic and synthetic drugs have been developed to treat rheumatoid arthritis. In recent years, the incidence of severe infection in patients with rheumatoid arthritis in Western nations has been determined by observational studies; however, no systematic review has been conducted on this topic. The following inclusion criteria were considered: i) observational studies on patients with rheumatoid arthritis treated with biologic agents; ii) studies reporting the number of severe infections requiring hospitalization for treatment; iii) studies reporting person-years of observation data; and iv) studies based on rheumatoid arthritis registries, medical records from rheumatology centers, or insurance claim databases. PubMed, CINAHL, Embase, and Web of Science were searched to identify published studies. The reference lists of all studies selected for critical appraisal were screened for additional studies. Unpublished studies were searched on MedNar and OpenGrey databases. All the searches were updated on December 6, 2021. After removing the duplicates, 2 independent reviewers screened titles and abstracts against the inclusion criteria and then assessed full texts against the criteria. Two reviewers independently appraised the study and outcome levels for methodological quality using the critical appraisal instrument for cohort studies from JBI. Two reviewers extracted the relevant information related to severe infection and drugs. Fifty-two studies from 21 countries reported severe infection rates associated with using 8 biologic agents, plus nonbiologic disease-modifying antirheumatic drugs. In total, 18,428 infections with 395,065 person-years of biologic drug exposure were included in the analysis. Thirty-five studies included infections in outpatients receiving intravenous antibiotic therapy. Fifteen studies reported the first episode of infection, and the remaining studies did not specify either the first or all of the episodes of infection. Inclusion of viral infection and/or opportunistic infection varied among studies. Fifteen studies reported the site of infection; respiratory, skin/soft tissue, urinary tract, and sepsis/bacteremia were commonly reported. Ten studies reported the case fatality rates, ranging from 2.5% to 22.2%. Meta-analysis was conducted for 8 biologic agents and conventional disease-modifying antirheumatic drugs. The infection rate varied from 0.9 to 18.1/100 person-years. The meta-analysis revealed an infection rate of 5.0/100 person-years (95% CI 3.8-6.7) among patients receiving tumor necrosis factor inhibitors (heterogeneity 98.2%). The meta-analysis for the other 3 biologic agents revealed a point estimate of 5.5 to 8.7/100 person-years with high heterogeneity. Sensitivity analysis indicated that registry-based studies were less likely to have very low or very high infection rates compared with other data sources. The definition of infection, the patient composition of the cohorts, and the type of databases appeared to be the primary sources of clinical and methodological heterogeneity. Due to high statistical heterogeneity, the meta-analysis was not suited to estimating a summary measure of the infection rate. Developing standardized data collection is necessary to compare infection rates across studies. PROSPERO CRD42020175137.

Depression, anxiety and adjustment disorder among patients with psoriasis receiving systemic agents: A retrospective cohort study in Quebec, Canada

AbstractIntroductionPatients with psoriasis are at risk of depression, anxiety and adjustment disorder (DAAD). Randomized control trials reported improvement in depression and anxiety symptoms among patients with psoriasis receiving tumour necrosis factor inhibitors and ustekinumab (TNFi/UST) versus placebo and conventional systemic agents (CSA). The risk of DAAD among TNFi/UST versus CSA users was not assessed in real‐world settings.ObjectiveTo compare DAAD incidence among patients with psoriasis using CSA and subsequently received (vs. not) TNFi/UST.MethodsWe conducted a retrospective cohort study using the province of Quebec health administrative databases (1997–2015). Among adult patients with a diagnosis of psoriasis and initiating a CSA, we included those who later initiated a TNFi/UST, as a switch or add‐on, at the date of their first prescription fill (index‐date). We also included TNFi/UST nonusers at a date chosen to match the time between the first CSA and the index date of a random TNFi/UST user. TNFi/UST nonusers were classified into current or previous CSA users according to their last CSA received in the 90 days before or after their index date. Marginal structural Cox regression models weighted by the inverse probability of exposure compared the risk of DAAD between TNFi/UST, current and previous CSA users. Additional analyses were conducted by age group and sex.ResultsOur cohort included 1333 patients with psoriasis: 183 TNFi/UST users, 625 current CSA users and 525 previous CSA users. TNFi/UST users were at a lower risk of DAAD versus previous CSA users (hazard ratio 0.48, 95% confidence intervals: 0.28–0.94). The reduction in risk among TNFi/UST users was not statistically significant versus current CSA users. Similar results were observed across different age groups and sex.ConclusionAmong patients with psoriasis receiving CSA, those who were subsequently dispensed TNFi/UST were at a lower risk of DAAD compared to those who did not receive these agents.

Infection risk in psoriatic patients receiving tumour necrosis factor inhibitors: a 20-year systematic review and meta-analysis of randomized controlled trials.

Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ClinicalTrials.gov databases from inception to December 31, 2021. We included double-blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel-Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I-squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta-analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02-1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61-1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94-1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00-1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03-1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02-1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis.

Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy.

ObjectiveImmunogenicity and safety following receipt of the standard SARS–CoV‐2 vaccination regimen in patients with immune‐mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2‐dose regimen and a third dose of SARS–CoV‐2 vaccine in IMID patients receiving immunosuppressive therapy.MethodsAdult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2‐dose SARS–CoV‐2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor‐binding domain (RBD) of the SARS–CoV‐2 spike protein were performed prior to and 2–4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor‐binding domain of the full‐length SARS–Cov‐2 spike protein, were allotted a third vaccine dose.ResultsA total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti‐RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192–4,191) than in controls (median 3,355 AU/ml [IQR 896–7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA–1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable.ConclusionIMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

Clinical Features and Drug Retention of TNF Inhibitors in Older Patients with Ankylosing Spondylitis: Results from the KOBIO Registry.

This study aimed to analyse the clinical features and outcomes of and reasons for discontinuing tumour necrosis factor (TNF) inhibitor therapy in older patients with ankylosing spondylitis (AS). Data were extracted from the nationwide Korean College of Rheumatology Biologics registry. Clinical variables and outcomes were compared, and drug retention rate was evaluated. Among 1524 patients with AS treated with TNF inhibitors, 306 were aged ≥ 50 years ('older patients'). Fewer patients were male, the incidence of hypertension and diabetes was higher (all p < 0.001), and the proportion of peripheral arthritis (35.6 vs. 27.1%), Ankylosing Spondylitis Disease Activity Score‒erythrocyte sedimentation rate (4.0 ± 1.1 vs. 3.6 ± 1.0), and Bath Ankylosing Spondylitis Functional Index (4.2 ± 2.6 vs. 3.3 ± 2.5) were all higher in older patients. Although the drug retention rate was lower (log-rank p = 0.018) and lack of efficacy and adverse events were more frequent in older patients (both p < 0.001), drug retention rates were not different after propensity score matching (log-rank p = 0.23). Improvements in disease activity and manifestations were comparable between groups, except for the incidence of peripheral arthritis, which decreased significantly less in older patients over 3 and 5 years. Improvements in disease-related clinical factors and drug retention rates were not different between older and younger patients with AS receiving TNF inhibitors. However, the incidence of adverse events was higher in older patients.

Treatment Patterns Among Patients with Rheumatoid Arthritis in Puerto Rico.

IntroductionRacial and ethnic disparities in rheumatoid arthritis (RA) have been identified in the United States, with higher levels of disease activity and worse functional status reported in Hispanic patients compared with their white counterparts. Although RA is one of the most prevalent health conditions in Puerto Rico, few studies have previously examined the characteristics or treatment patterns of patients receiving biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in this population.MethodsThis was a retrospective cohort study using data extracted from the Advanced Business Management Organization database, which represents around 70% of pharmacy claims in Puerto Rico. Patients with RA were included if they had ≥ 1 prescription for any approved b/tsDMARD during the index period (January 2016 to July 2018), and ≥ 2 years of follow-up. The objective was to describe and compare the demographic and clinical characteristics of patients with RA being treated with b/tsDMARD therapy in Puerto Rico, and to evaluate the treatment patterns among these patients.ResultsMost patients (74%) received tumor necrosis factor inhibitors (TNFis) as index therapy, followed by abatacept (17%), Janus kinase inhibitors (JAKis; 5%), and other non-TNFis (4%). Similar trends were observed in subsequent lines of therapy, although abatacept was more frequently used in these later lines versus index therapy. At 2 years, 62% of patients had discontinued their index therapy and 17% had switched to an alternative b/tsDMARD; only 21% persisted with index therapy. The percentage of patients who were persistent with their index therapy at the end of year 2 was 28% for JAKis, 36% for abatacept, 41% for TNFis, and 45% for other non-TNFis.ConclusionsThese findings demonstrate that despite the availability of several b/tsDMARDs, patients with RA in Puerto Rico still experience substantial treatment disruption, with almost two-thirds of patients discontinuing their index therapy within 2 years.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00408-7.

Characteristics, Comorbidities, and Outcomes of SARS-CoV-2 Infection in Patients With Autoimmune Conditions Treated With Systemic Therapies: A Population-based Study.

To describe characteristics and coronavirus disease 2019 (COVID-19) clinical outcomes of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ulcerative colitis (UC) receiving systemic therapies vs the general population. This descriptive retrospective cohort study used data from the United States Optum deidentified COVID-19 electronic health record dataset (2007-2020). Adults with COVID-19 were stratified into 3 disease cohorts (patients with RA, PsA, or UC who had received systemic therapy) and a comparator cohort not meeting these criteria. Incidence proportions of hospitalization and clinical manifestations of interest were calculated. Using logistic regression analyses, risk of endpoints was estimated, adjusting for demographics and demographics plus comorbidities. This analysis (February 1 to December 9, 2020) included 315,101 patients with COVID-19. Adjusting for demographics, COVID-19 patients with RA (n = 2306) had an increased risk of hospitalization (OR 1.54, 95% CI 1.39-1.70) and in-hospital death (OR 1.61, 95% CI 1.30-2.00) compared with the comparator cohort (n = 311,563). The increased risk was also observed when adjusted for demographics plus comorbidities (hospitalization OR 1.25, 95% CI 1.13-1.39 and in-hospital death OR 1.35, 95% CI 1.09-1.68]). The risk of hospitalization was lower in COVID-19 patients with RA receiving tumor necrosis factor inhibitors (TNFi) vs non-TNFi biologics (OR 0.32, 95% CI 0.20-0.53) and the comparator cohort (OR 0.77, 95% CI 0.51-1.17). The risk of hospitalization due to COVID-19 was similar between patients receiving tofacitinib and the comparator cohort. Compared with the comparator cohort, patients with RA were at a higher risk of more severe or critical COVID-19 and, except for non-TNFi biologics, systemic therapies did not further increase the risk. (ENCePP; registration no. EU PAS 35384).

The risk factors and incidence of major infectious diseases in patients with ankylosing spondylitis receiving tumor necrosis factor inhibitors

Objectives This study aimed to evaluate the risk factor and incidence of infections in patients receiving tumor necrosis factor inhibitor (TNFi) therapy for ankylosing spondylitis using data from the national health insurance service. Methods This was a retrospective cohort study. Data regarding patients with ankylosing spondylitis prescribed TNFis were obtained from an insurance claims database of the Health Insurance Review & Assessment Service in Korea. Outcomes used were incidence rates of serious infection, pneumonia, tuberculosis, and herpes zoster during the follow-up period as well as the relationship between each TNFi and sex, hazard ratio (HR) of infection-related risk factors, and incidence of infections. Results A total of 2515 patients were included. There were no significant differences among the hazard ratios of TNFis for serious infection, pneumonia, and herpes zoster. However, the hazard ratio of tuberculosis was significantly higher for infliximab than for etanercept (adjusted HR 8.40 [95% confidence interval: 1.06–66.91]). In the subgroup analysis by sex, women treated with golimumab had a significantly higher hazard of herpes zoster than those treated with etanercept (adjusted HR 12.40 [95% confidence interval: 1.40–109.58]). Conclusion We recommend that risk factors for these infectious diseases be identified prior to prescribing TNFis in these patients.

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

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. 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. 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. 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. 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. 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. 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.

S855 Characteristics, Comorbidities, and Outcomes of SARS-CoV-2 Infection in Patients With Conditions Treated With Systemic Immunosuppressive Therapies: A Population-Based Study

Introduction: We describe the characteristics and COVID-19 clinical outcomes in this pt population, compared with the general population. Methods: This descriptive retrospective cohort study used data from the US Optum® deidentified COVID-19 electronic health record dataset (2007–2020). Adults with COVID-19 were stratified into 3 disease cohorts (pts with rheumatoid arthritis [RA], psoriatic arthritis [PsA], or UC who had received systemic immunosuppressive therapy) and a comparator cohort that did not meet these criteria. Incidence proportions of hospitalization, intensive care unit admission, in-hospital death, all-cause mortality, and clinical manifestations of interest were calculated. Logistic regression was used in exploratory analyses to estimate the risk of endpoints, adjusting for demographics (age, sex, race, region), and demographics plus comorbidities. Results: This analysis (Feb 01–Dec 09, 2020) included 315,101 COVID-19 pts. The incidence of hospitalization due to COVID-19 was greatest in the RA cohort compared with the PsA, UC, and comparator cohorts (Table). Adjusting for demographics, and demographics plus comorbidities, COVID-19 pts with RA had an increased risk of hospitalization and in-hospital death, compared with the comparator cohort (Figure). Adjusting for demographics, pts with UC had an increased risk of hospitalization; after adjustment for demographics plus comorbidities, the risk was no longer statistically significant (Figure). There was no statistically significant increased risk of hospitalization among pts with PsA (Figure). The risk of hospitalization was lower in COVID-19 pts with RA receiving tumor necrosis factor inhibitors (TNFi) vs non-TNFi biologics (0.32 [0.20, 0.53]) and vs the comparator cohort (0.77 [0.51, 1.17]). Compared with the comparator cohort, the risk of hospitalization due to COVID-19 was similar between pts with RA receiving tofacitinib (1.06 [0.55, 2.05]), JAK inhibitors (1.26 [0.74, 2.16]) or csDMARDs (1.21 [1.02, 1.44]). The risk of hospitalization due to COVID-19 was greater in pts with RA receiving non-TNFi biologics vs the comparator cohort (2.33 [1.79, 3.04]). A similar analysis was not performed for the UC and PsA cohorts due to small sample sizes. Conclusion: Compared with the comparator cohort, pts with RA were at a higher risk of more severe COVID-19, and except for non-TNFi biologics, immunosuppressive therapies in general did not further increase the risk. COVID-19 outcomes in pts with UC were generally similar to the comparator cohort.Figure 1.: Adjusted odds ratios of each endpoint in the (A) RA cohort, (B) UC cohort, and (C) PsA cohort vs the comparator cohort. a.Covariates included in logistic regression models were age, sex, race, and region; b.Covariates included in logistic regression models were age, sex, race, region, lung disease (interstitial lung disease, asthma, and chronic obstructive pulmonary disease), VTE, hypertension, coronary artery disease, serious infections (hospitalized), cancer, diabetes, CKD or dialysis, and liver disease, except for UC, which did not include serious infections (hospitalized). Odds ratios using this model are only displayed for endpoints for which there were ≥ 30 events; c.Serious infections (hospitalized) was not included as a covariate; d.CKD/dialysis was not included as a covariate; e. VTE was not included as a covariate. ARDS, acute respiratory distress syndrome; CI, confidence interval; CKD, chronic kidney disease; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; PsA, psoriatic arthritis; RA, rheumatoid arthritis; UC, ulcerative colitis.Table 1.: Baseline Characteristics and IPs of Clinical Manifestations/Outcomes in the RA, PsA, UC, and Comparator Cohorts. a.At least 1 diagnosis of RA, PsA, or UC, and treatment with IM therapy (JAK inhibitor, TNFi, non-TNFi biologic, or csDMARD) within 2 yrs prior to SARS-CoV-2 diagnosis date; b.Absence of a diagnosis of RA, PsA, or UC, and no treatment with IM therapy within 2 yrs prior to SARS-CoV-2 diagnosis date; c.Baseline was defined as within 6 months prior to SARS-CoV-2 diagnosis date; d.csDMARDs included auranofin, aurothioglucose, azathioprine, chloroquine hydrochloride, chloroquine phosphate, cyclophosphamide, cyclosporine, gold sodium thiomalate, hydroxychloroquine sulfate, leflunomide, mercaptopurine, mesalamine, methotrexate, minocycline hydrochloride, n-acetylpenicillamine, penicillamine, primaquine, sulfasalazine, tacrolimus, and thalidomide; e.Within 90 days prior to SARS-CoV-2 diagnosis date; f.Denominator is the number of pts hospitalized within 30 days of SARS-CoV-2 diagnosis; defined as death during hospitalization; g.Within 90 days of SARS-CoV-2 diagnosis date; h.Within 30 days of SARS-CoV-2 diagnosis date. ARDS, acute respiratory distress syndrome; CI, confidence interval; csDMARD, conventional synthetic disease-modifying antirheumatic drug; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; IM, immunomodulatory; IP, incidence proportion; IV, intravenous; JAK, Janus kinase; N, number of pts in the cohort; n, number of pts in the specified category; PsA, psoriatic arthritis; pts, patients; RA, rheumatoid arthritis; TNFi, tumor necrosis factor inhibitor; UC, ulcerative colitis.

The Safety and Immunologic Effectiveness of the Live Varicella-Zoster Vaccine in Patients Receiving Tumor Necrosis Factor Inhibitor Therapy : A Randomized Controlled Trial.

The safety and effectiveness of live virus vaccines, such as the varicella-zoster vaccine, are unknown in patients with inflammatory diseases receiving immunomodulatory therapy such as tumor necrosis factor inhibitors (TNFis). To evaluate the safety and immunogenicity of the live attenuated zoster vaccine (ZVL) in patients receiving TNFis. Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02538341). Academic and community-based rheumatology, gastroenterology, and dermatology practices. Adults aged 50 years or older receiving TNFis for any indication. Random assignment to ZVL versus placebo. Glycoprotein enzyme-linked immunosorbent assay (gpELISA) and enzyme-linked immunosorbent spot (ELISpot) from serum and peripheral blood mononuclear cells measured at baseline and 6 weeks after vaccination. Suspected varicella infection or herpes zoster was clinically assessed using digital photographs and polymerase chain reaction on vesicular fluid. Between March 2015 and December 2018, 617 participants were randomly assigned in a 1:1 ratio to receive ZVL (n = 310) or placebo (n = 307) at 33 centers. Mean age was 62.7 years (SD, 7.5); 66.1% of participants were female, 90% were White, 8.2% were Black, and 5.9% were Hispanic. The most common TNFi indications were rheumatoid arthritis (57.6%) and psoriatic arthritis (24.1%); TNFi medications were adalimumab (32.7%), infliximab (31.3%), etanercept (21.2%), golimumab (9.1%), and certolizumab (5.7%). Concomitant therapies included methotrexate (48.0%) and oral glucocorticoids (10.5%). Through week 6, no cases of confirmed varicella infection were found; cumulative incidence of varicella infection or shingles was 0.0% (95% CI, 0.0% to 1.2%). At 6 weeks, compared with baseline, the mean increases in geometric mean fold rise as measured by gpELISA and ELISpot were 1.33 percentage points (CI, 1.17 to 1.51 percentage points) and 1.39 percentage points (CI, 1.07 to 1.82 percentage points), respectively. Potentially limited generalizability to patients receiving other types of immunomodulators. This trial informs safety concerns related to use of live virus vaccines in patients receiving biologics. The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology.

What Is the Risk of Reactivation in Patients with Resolved and Past HBV Infection During Immunosuppressive Therapy If HBV-DNA Negative before Treatment?

Reactivation of Hepatitis B (HBVr) related to immunosuppressive drug therapy (ISDT) in patients with resolved and past infection is a challenging entity. The number of prospective long-term studies is limited. Two groups of patients with resolved and past HBV infection were analyzed prospectively. The patients were further categorized as 266 patients receiving ISDT (group 1) and 246 patients receiving antineoplastic therapy (group 2). We did not detect any cases of HBVr among 108 patients receiving rituximab (71 of which were anti-HBc positive only), 111 patients receiving tumor necrosis factor inhibitors (66 of which were anti-HBc positive only), and 42 patients receiving high-dose glucocorticoids for more than 4 weeks (24 of which were anti-HBc positive only) during a mean follow-up time of more than 24 months. Subgroup analysis of the anti-HBs (+) patients showed that in group A (anti-HBs >1000 mIU/mL) the antibody levels did not change; in group B (anti-HBs between 100 and 1000 mIU/mL) the antibody levels changed non-significantly (P = .25), and in Group C (anti-HBs between 0 and 100 mIU/mL) the antibody levels declined significantly (P = .002). Furthermore, 16 patients in Group C had an anti-HBs loss during follow-up, but no HBVr was detected. The risk of HBVr by immunosuppressive therapy in this group may be lower than that suspected in the literature and anti- HBs levels may not seem to correlate with the risk of reactivation.

Tuberculosis despite latent infection screening and treatment in patients receiving TNF inhibitor therapy

Although latent tuberculosis infection (LTBI) treatment is given before anti-tumor necrosis factor (TNF) treatment, tuberculosis (TB) still develops in these patients and the risk factors are not well known. Besides, there is little data on the safety of isoniazid (INH) treatment in this group of patients. This study aimed to determine the risk factors for the development of tuberculosis and the safety of LTBI in such patients. All patients (n=665) given anti-TNF in a single center were included in this study. Complete data were obtained from the records of 389 patients. Seven patients (1.1%) were diagnosed with TB. There was no significant difference in age, gender, smoking rate, comorbidities, leukocyte counts, hemoglobin, creatinine, AST, ALT, protein levels, and tuberculin reaction between patients with and without TB. Of 389 patients, 289 (76%) had received INH prophylaxis, including 43 tuberculin-negative patients. Thirty patients had anti-TNF use prior to INH prophylaxis. None of these patients had TB in the follow-up period. Seven patients who developed TB had completed LTBI treatment, including one patient who was tuberculin-negative. The time from the completion of INH treatment to the diagnosis of TB was 6-61 months. None had any history of contact with TB during this period. INH treatment was associated with hepatotoxicity in 49 patients (17%); all resolved without any need to stop INH. Patients on anti-TNF treatment had a high rate of TB despite INH prophylaxis, but no risk factor for TB development was identified. Mild hepatotoxicity frequently developed during LTBI treatment. Key Points • Tuberculosis still develops in patients treated with tumor necrosis factor (TNF)-inhibitors despite prior screening and treatment for latent tuberculosis infection (LTBI). • In this cohort, all patients in whom tuberculosis developed had been treated for LTBI and all but one were initially tuberculin-positive. No risk factors have been identified. • The current policy of treating tuberculin-positive patients with a 9-month INH regimen does not seem to be fully effective in preventing tuberculosis.

Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.

Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity. Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment. Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study-Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.

Overall survival in patients with rheumatoid arthritis and solid malignancies receiving biologic disease-modifying antirheumatic therapy.

The effects of biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and cancer are largely unknown. We examined overall survival (OS) in patients with RA and solid malignancies receiving bDMARDs. We performed a retrospective cohort study of patients with RA and solid malignancies seen at MD Anderson Cancer Center between 2002 and 2014. Cox proportional hazard regression models, stratified by tumor type and stage, were fit evaluating use of bDMARDs as a time fixed and time varying covariate. We identified 431 RA patients with solid malignancies: 111 (26%) received bDMARDs after their cancer diagnosis. Median OS from cancer diagnosis was 16.1years. Of the patients receiving bDMARDs, most had localized disease, and only 14 (13%) had advanced cancer. In the stratified Cox models no statistically significant differences were observed between patients who received tumor necrosis factor inhibitors (TNFi) or patients who received nonTNFi, compared with those who did not receive bDMARDs (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.31, 1.44; HR, 1.10; 95% CI, 0.26, 4.60 respectively). In breast cancer patients, those receiving TNFi or nonTNFi had a numerically higher but statistically nonsignificant HR compared with those who did not receive bDMARD: HR, 1.40 (95% CI, 0.42, 4.73), and HR, 1.37 (95% CI, 0.22, 8.42) respectively. No significant differences in OS were observed between patients who received bDMARDs and those who did not. Additional data is needed to evaluate other cancer outcomes such as recurrence and progression, and patients with advanced cancer. Key Points •We found no statistically significant differences in OS between patients with RA and concomitant solid malignancies who received bDMARDs and those who did not. •Most patients who received bDMARDs had been diagnosed with early stage cancer •As few patients with advanced cancer received bDMARDs safety for this group cannot be established •No significant differences were observed between TNFi and nonTNFi, but the sample size was small.