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Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands.

ABSTRACT: We aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0-7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3-2.2) and 0.8 years (95% CI, 0.5-1.0) (p = 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), remission (16%), pregnancy (30%), or patient preference (10%). Multivariable Cox regression analyses for discontinuation due to inefficacy or adverse events showed that concomitant use of csDMARDs (HR = 1.32, p < 0.001) positively while RF positivity negatively (HR = 0.82, p = 0.03) influenced biological survival. ACPA positivity was associated with the inability to discontinue biologicals after achieving remission (HR = 1.43, p = 0.023). Second-line TNF inhibitor survival was similar between patients with a primary and secondary non-response on the first-line TNF inhibitor (HR = 1.28, p = 0.34). Biological survival diminishes with the number of biologicals used. Biological survival is prolonged if patients use csDMARDs. RF was negatively associated with biological survival. ACPA was negatively associated with the inability to discontinue biologicals after achieving remission. Therefore, tailoring treatment based upon autoantibody status might be the first step towards personalized medicine in RA. Key Points • Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored. • We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached. • The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.

SUBMITTER: van Mulligen E

PROVIDER: S-EPMC8121743 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient's response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX). Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81-0.95; p < 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79-0.94; p < 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05-1.36; p < 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68-1.00; p < 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding. Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.

Project description:IntroductionThis study was conducted to observe patterns of use of the interleukin-6 receptor-alpha inhibitor tocilizumab in routine clinical practice in patients with rheumatoid arthritis (RA).MethodsThis was a 12-month noninterventional, observational study in adult patients with RA who initiated tocilizumab in routine practice in Canada according to the local product monograph. The primary end point was the proportion of patients receiving tocilizumab at 6 months. Secondary end points were treatment patterns, effectiveness, and safety of tocilizumab over 12 months.ResultsOf 200 patients who initiated tocilizumab (91.0% at 8 mg/kg), 67 (33.5%) received tocilizumab monotherapy and 133 (66.5%) received tocilizumab combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Kaplan-Meier analysis estimated that 85% (95% CI 74-92%) of monotherapy and 89% (95% CI 82-93%) of combination therapy patients continued to receive tocilizumab at 6 months (log-rank p = 0.0888). During the observation period, 12 (17.9%) monotherapy and 27 (20.3%) combination therapy patients withdrew from the study. At month 12, 58.5% in the monotherapy group and 59.3% in the combination therapy group achieved Disease Activity Score at 28 joints remission (≤ 2.6), 25.6% and 24.7% achieved Simplified Disease Activity Index remission (≤ 3.3), and 18.2% and 22.3% achieved Clinical Disease Activity Index remission (≤ 2.8), respectively. Rates of serious adverse events and serious infections were found in 29.6/100 patient-years (PY) and 3.1/100 PY, respectively, for monotherapy and 19.2/100 PY and 4.8/100 PY, respectively, for combination therapy.ConclusionsPatients initiating tocilizumab in routine practice had comparable effectiveness and safety outcomes regardless of whether they received tocilizumab as monotherapy or as combination therapy with csDMARDs.Trial registrationClinicalTrials.gov identifier, NCT01613378 FUNDING: F. Hoffmann-La Roche (Roche) Canada.

Project description:BackgroundThe treatment of rheumatoid arthritis is based on the use of disease-modifying antirheumatic drugs (DMARDs). Tocilizumab can be used as monotherapy or in combination with conventional synthetic DMARDs for the treatment of moderate-to-severe active rheumatoid arthritis. Subcutaneous (SC) and intravenous forms of the drug are available, but the SC form is more widely used.ObjectiveTo understand the real-world dose modification patterns of SC tocilizumab in the treatment of patients with rheumatoid arthritis in the United States.MethodsData were obtained from the Truven (now IBM) MarketScan and Optum Clinformatics databases. Patients were included if they had ≥1 pharmacy claims for SC tocilizumab and met other inclusion criteria. The mean, standard deviation, and median values were reported for the continuous variables, and frequency was reported for the categorical variables. Kaplan-Meier analysis was used to analyze the time to first dose modification. Logistic regression modeling was used to identify predictors of the likelihood of dose modification.ResultsThe study included 1266 patients in the Truven database and 512 patients in the Optum database who had commercial or Medicare Advantage or supplemental insurance. Of the patients who started treatment with biweekly SC tocilizumab (48% each in the Truven and Optum databases), 37% in Truven and 40% in Optum had dose escalation to a weekly dose. Of those who started weekly SC tocilizumab (43% in the Truven and 49% in the Optum databases), 3% (Truven) and 4% (Optum) had dose reduction. The remaining patients started alternative SC tocilizumab doses. Overall, 60% and 68% of patients in the Truven and Optum cohorts, respectively, initiated or escalated to the higher weekly dose of tocilizumab; the mean time to dose escalation was 126 days and 112 days, respectively. In the Truven cohort, corticosteroid use, age, and anemia were the main predictors for dose escalation. In the Optum cohort, female patients had increased odds of dose escalation compared with male patients.ConclusionThe dosing trends observed in this study show that physicians have taken advantage of the option to increase SC tocilizumab dosing, but only a few providers chose to reduce the dose. This trend in dose modification may increase the costs related to SC tocilizumab therapy.

Project description:Objective:To assess methotrexate (MTX) adherence using the Medication Event Monitoring System (MEMS) and characterize associations with adherence in patients with rheumatoid arthritis (RA). Methods:Eligible patients participated in Forward, the National Databank for Rheumatic Diseases, and recently (12 months or sooner) initiated oral MTX. MEMS was used to compile MTX weekly dosing over 24 weeks. The Beliefs about Medicines Questionnaire (BMQ) was completed, and baseline demographics and disease characteristics obtained. MTX adherence (percentage of weeks dose taken correctly), implementation (percentage of weeks dose taken correctly from initiation until last dose), and persistence (duration from initiation to last dose) were calculated. Analyses measured associations between patient characteristics and adherence, modeled using logistic generalized estimating equations and censored Poisson regression, and persistence modeled using Cox regression. Results:Overall, 60 of 119 eligible patients were included in the analysis. MTX adherence, implementation, and persistence were 75%, 80%, and 83%, respectively, at 24 weeks. Demographics and disease characteristics were generally similar between patients with 1 week or less and 2 weeks or more of missed MTX. Unemployment, less disability, higher Patient Global scores, and no prior disease-modifying antirheumatic drug (DMARD) use were associated with correct dosing. No significant differences in adherence were observed between patients receiving concomitant MTX versus MTX monotherapy, and biologic DMARD-experienced versus biologic DMARD-naïve patients. Higher scores in BMQ Specific Necessity (indicating a greater belief in the necessity of the medication) was associated with a decreased likelihood of dosing at an interval shorter than prescribed (odds ratio 0.89). Conclusion:Even in a participatory group over a short period, MTX adherence was suboptimal and associated with certain demographics, medication experience, and beliefs about medicines. This suggests a need for screening and alternative treatment opportunities in nonadherent MTX patients with RA.

Project description:PurposeRheumatoid arthritis (RA) is an often debilitating autoinflammatory disease. Patients with rheumatoid arthritis are often troubled by co-occurring depression or other psychological manifestations. RA patients have a variety of treatment options available, including biologicals that inhibit cytokines or immune cells. If these cytokines influence the psychological symptoms, then the use of cytokine inhibitors should modulate these symptoms.MethodsA cohort of 209 individuals was recruited. This group included 82 RA patients, 22 healthy subjects, 32 depressed control subjects, and 73 subjects with systemic lupus erythematosus. Of the RA patients, 51% were on a biological therapeutic. ELISA was used to measure cytokine levels. A variety of psychological assessments were used to evaluate depression, anxiety, sleep, fatigue, and relationship status. Clinical values were obtained from medical records.ResultsIL-10 concentration was associated with depressive symptoms in the RA patients, healthy controls, and the lupus patients. In the patients with primary depression, depressive symptoms were associated with IL-6 and TNF-alpha. In RA patients, Tocilizumab use was associated with decreased depressive symptoms. 14 RA patients who were not using biologicals began using them by a one-month follow-up. In these patients, there was no significant change to any value except for fatigue.ConclusionsA variety of both biological and social factors influences depressive symptoms in RA. IL-10 and IL-6 are likely to be involved, since IL-10 concentration was associated with depression and Tocilizumab decreased depressive symptoms in the RA patients. The roles of these cytokines are different in RA and lupus, as high IL-10 in RA is associated with increased depressive symptoms, but high IL-10 in the lupus patients is associated with decreased depression. IL-6 was also associated with depressive symptoms in the patients with primary depression. These results strongly indicate that disease activity, including cytokine levels, has a strong impact on depressive symptoms.

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Factors that influence biological survival in rheumatoid arthritis: results of a real-world academic cohort from the Netherlands.

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