Tumor necrosis factor inhibitors and methotrexate are associated with decreased COVID-19-related hospitalization: Follow up of "Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors and methotrexate".
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SUBMITTER: Cahn RT
PROVIDER: S-EPMC9912810 | biostudies-literature | 2023 Jun
REPOSITORIES: biostudies-literature
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Tumor necrosis factor inhibitors and methotrexate are associated with decreased COVID-19-related hospitalization: Follow up of "Clinical outcomes of COVID-19 in patients taking tumor necrosis factor inhibitors and methotrexate".
Cahn Rachel Tallman RT Zinn Zachary Z Kolodney Michael S MS
Journal of the American Academy of Dermatology 20230210 6
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Project description:The risk of coronavirus disease 2019 (COVID-19) and its complications among patients with psoriasis treated by tumor necrosis factor inhibitors (TNFis) remains to be decisively delineated. We aimed to assess the risk of COVID-19 infection, COVID-19-associated hospitalization, and mortality among Israeli patients with psoriasis treated by TNFi relative to other systemic agents. A population-based cohort study was conducted to compare psoriasis patients treated by TNFi (n = 1943), with those treated by methotrexate (n = 1929), ustekinumab (n = 348), and acitretin (n = 1892) regarding COVID-19 outcomes. Risk of investigated outcomes was assessed using uni- and multi-variate Cox regression analyses. The incidence rate of COVID-19, COVID-19-associated hospitalization, and mortality in the TNFi group was 35.8 (95% CI, 26.1-47.9), 0.8 (95% CI, 0.0-4.2), and 0.0 per 1000 person-years, respectively. Exposure to TNFi was associated with a comparable risk of COVID-19 infection [adjusted hazard ration (HR) for TNFi vs methotrexate: 1.07 (95% CI, 0.67-1.71); TNFi vs ustekinumab: 1.07 (95% CI, 0.48-2.40); TNFi vs acitretin: 0.98 (95% CI, 0.61-1.57)]. TNFi was associated with a decreased risk of COVID-19-associated hospitalization relative to methotrexate (adjusted HR, 0.10; 95% CI, 0.01-0.82) and ustekinumab (adjusted HR, 0.04; 95% CI, 0.00-0.64), but not to acitretin (adjusted HR, 1.00; 95% CI, 0.16-6.16). No significant difference in COVID-19-associated mortality was found between the four different groups. TNFi was associated with a decreased risk of admissions due to COVID-19. Our findings substantiate the continuation of TNFi treatment during the pandemic. TNFi may be positively considered in patients with moderate-to-severe psoriasis warranting systemic treatment during the pandemic.
| S-EPMC8209905 | biostudies-literature
Project description:ImportanceAlthough 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.ObjectiveTo 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 participantsThis 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.ExposuresTreatment 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 measuresThe 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.ResultsA 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 relevanceIn 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.
| S-EPMC8524310 | biostudies-literature
Project description:BackgroundPersistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections.MethodsA systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality.ResultsTwelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments. In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies.ConclusionFor persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown.
| S-EPMC8444402 | biostudies-literature
Project description:BackgroundTo determine whether initiation of a tumor necrosis factor inhibitor (TNFi) or methotrexate improves hemoglobin A1c in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) who also have diabetes mellitus (DM).MethodsA retrospective cohort study was conducted in Optum's de-identified Clinformatics® Data Mart Database, an administrative claims database, using data from 2000 to 2014. Patients with PsA, RA, or AS, with DM (defined by ICD-9-CM codes) and/or HbA1c ≥7%, who newly initiated either a TNFi, MTX, or metformin (positive control) were identified. The change in HbA1c after drug initiation was calculated. Statistical differences in the change in HbA1c between drugs were assessed using the Wilcoxon rank sum test and linear regression models adjusting for potential confounders.ResultsAmong 10,389 drug initiations in 9541 patients with PsA, RA, or AS, and available HbA1c values, HbA1c was ≥7 at baseline in 254 (35%) TNFi initiations, 361(37%) MTX initiations, and 2144 (50%) metformin initiations. Median HbA1c change was - 0.35 (IQR -1.10, 0.30) after TNFi initiation, - 0.40 (IQR -1.20, 0.30) after MTX initiation, and - 0.80 (IQR -1.60, - 0.10) after metformin initiation. In adjusted analyses, TNFi initiators had less of a decrease in HbA1c compared to MTX initiators (β 0.22, 95% CI: 0.004, 0.43), p = 0.046. Metformin initiators had a significantly greater decrease in HbA1c than MTX, β - 0.38 (95% CI: - 0.52, - 0.23), p < 0.001. Glucocorticoid use was not accounted for in the models.ConclusionHbA1c decreased with TNFi initiation or MTX initiation. Reductions in HbA1c after initiation of a TNFi or MTX are about half (~ 0.4 units) the decrease observed after initiation of metformin.
| S-EPMC7466800 | biostudies-literature
Project description:To identify predictors of the receipt of medical care, including the receipt of pre-drug screening, for diagnostically targeted fungal or mycobacterial infections among patients prescribed a tumor necrosis factor inhibitor (TNFi).We conducted a case-control study using deidentified patient health claims information from a data set representing a commercially insured US population of 15 million patients annually from January 1, 2007 to December 31, 2009. Descriptive statistics as well as a 2-sample t-test, chi-square test of association, Fisher's exact test, and multivariate logistic regression were used for data analysis.A total of 30,772 patients received a TNFi during the study period. Of these, 158 patients (0.51%) developed targeted fungal and/or mycobacterial infections (cases). The median number of infections per case was 1.0 (interquartile range 1.0-2.0). Tuberculosis was diagnosed in 61% of cases, followed by histoplasmosis in 60%, nontuberculous mycobacterial infections in 11%, coccidioidomycosis in 10%, unspecified fungal infection in 8%, blastomycosis in 4%, cryptococcal infection in 3%, and pneumocystosis in 2%. Compared to controls (n = 474), a higher proportion of cases were prescribed prednisone (55% versus 37%; P < 0.001). Patients who were prescribed prednisone during the study period were twice as likely as those not taking prednisone to seek medical care attributable to a targeted fungal or mycobacterial infection (odds ratio 2.03; P < 0.001).Development of a targeted fungal or mycobacterial infection among patients taking a TNFi is rare. Concomitant use of prednisone predicted development of such infections.
| S-EPMC5548176 | biostudies-other
Project description:ObjectiveThe role of methotrexate (MTX) for the treatment of spondyloarthritis (SpA) remains uncertain. Aims were to compare MTX and tumor necrosis factor inhibitor (TNFi) persistence in spondyloarthritis versus rheumatoid arthritis (RA) and to determine whether concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use is associated with improved TNFi persistence in SpA.MethodsThis retrospective cohort study using Optum's deidentified Clinformatics Data Mart Database 2000-2014 identified patients with RA, psoriatic arthritis (PsA), and ankylosing spondylitis (AS) without prior biologic use who were initiating MTX or a TNFi. Cox proportional hazards models compared time to medication discontinuation over the next 2 years between patients with RA, PsA, or AS, adjusting for potential confounders. In similar analyses stratified by disease, Cox models were used to assess whether concomitant use of csDMARD was associated with TNFi persistence.ResultsWe identified 31,527 MTX initiators (26,708 RA, 2939 PsA, 1880 AS) and 34,651 TNFi initiators (24,134 RA, 6705 PsA, 3812 AS). MTX was discontinued sooner in patients with PsA [adjusted HR (aHR) 1.10, 95% CI 1.04-1.16] and AS (aHR 1.23, 1.16-1.31) versus RA, while TNFi were discontinued at similar rates in RA and AS and discontinued later in PsA (aHR 0.93, 0.89-0.97). Concomitant use of MTX (compared to no csDMARD) was associated with lower rates of TNFi discontinuation in RA (aHR 0.85, 0.80-0.89), PsA (aHR 0.81, 0.74-0.89), and AS (aHR 0.79, 0.67-0.93).ConclusionMTX discontinuation occurs sooner in patients with PsA and AS versus RA. Concomitant use of MTX with a TNFi, however, is associated with improved TNFi persistence in all 3 diseases.
| S-EPMC7050382 | biostudies-literature
Project description:IntroductionPsoriatic arthritis (PsA) is a chronic inflammatory disease that can result in significant disability. With the emergence of tumor necrosis factor inhibitors (TNFi), therapeutic outcomes in PsA have improved substantially. The clinical efficacy and the inhibition of radiographic progression demonstrated by TNFi have transformed the management of PsA. However, there is still an unmet need for a subset of patients who do not respond adequately to TNFi. Areas covered: This review provides an overview of the pharmacokinetics of TNFi, the efficacy of TNFi in PsA, and the role of immunogenicity of TNFi in the treatment of PsA. In addition, we address the use of TNFi in the setting of other medications utilized in the treatment of PsA and the potential future role of biosimilars. Expert commentary: Monoclonal antibodies exhibit complex and widely variable pharmacokinetics. The study of factors that can affect the pharmacokinetics, such as immunogenicity, is valuable to further define and understand the use of TNFi in PsA, especially in the subset of patients who do not respond adequately to these agents or lose effectiveness over time.
| S-EPMC6348387 | biostudies-literature
Project description:IntroductionControlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA.MethodsTCZ-naïve patients from the Corrona RA registry with prior exposure to ≥ 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI ≤ 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap).ResultsPatients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups.ConclusionsIn this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity.FundingCorrona, LLC. Plain language summary available for this article.
| S-EPMC6251839 | biostudies-literature
Project description:ObjectiveTo examine the prevalence of side effects with methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA).MethodsThis retrospective analysis, conducted between January 2000 and January 2019, used data from the FORWARD databank. Adult patients enrolled in the registry with self-reported and physician-confirmed diagnosis of PsA or RA were included if they had completed at least one questionnaire before initiating and within 12 months following initiation of MTX or a TNFi. The primary outcome was to examine the prevalence of side effects with MTX and TNFi within the year following treatment initiation. Multivariate logistic regression analysis was performed to examine the association between PsA and RA and the reporting of their side effects.ResultsOverall, 116 patients with PsA and 4247 patients with RA newly initiated MTX, and 124 patients with PsA and 4361 patients with RA newly initiated a TNFi. Patients with PsA were more likely to report MTX-related side effects than those with RA (44.8% vs. 29.4%), whereas similar proportions of patients with PsA and RA reported TNFi-related side effects within the first year (24.2% and 22.8%, respectively). Additionally, patients with PsA initiating MTX were more likely to report nausea, vomiting, abdominal pain, depression, and tinnitus than patients with RA initiating MTX or those with PsA or RA initiating a TNFi.ConclusionPatients with PsA reported more side effects than patients with RA, and this difference was more pronounced in those receiving MTX versus TNFi.
| S-EPMC9661817 | biostudies-literature
Project description:ObjectiveTo describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-α (TNF-α) inhibitors.Patients and methodsThis is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti-TNF-α therapy.ResultsOf 8 patients with vasculitis associated with anti-TNF-α therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients [63%]), with the most common cutaneous lesion being palpable purpura (4 of 5 [80%]). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients [50%]) and kidney (1 patient [13%]). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti-TNF-α therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation.ConclusionCutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed.
| S-EPMC3538488 | biostudies-literature