Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics.
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SUBMITTER: Cantini F
PROVIDER: S-EPMC5474286 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:OBJECTIVES:This study aimed to assess the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) treated with any of the commercially available tumour necrosis factor inhibitors (TNFis) in Slovenia. DESIGN:This is a cohort, registry (biorx.si) cross-linked with the Slovenian National TB Registry. SETTING:National, involving all Slovenian rheumatology centres (six secondary and two secondary/tertiary). PARTICIPANTS:2429 patients with RA, AS or PsA exposed to at least one TNFi participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES:The primary outcome measures were age-adjusted and sex-adjusted TB incidence rates (IRs) and the standardised incidence ratios (SIRs) compared with the general population exploring different TNFi exposure windows. The secondary outcome measures were a detailed characterisation of the national latent tuberculosis infection (LTBI) screening and TB chemoprophylaxis protocol implementation. RESULTS:Among the 2429 patients exposed to at least one TNFi for a total of 10?445 (49% RA, 33% AS and 18% PsA) person-years (PY), 99% completed LTBI screening and 6% required TB chemoprophylaxis. Six RA (three adalimumab, three certolizumab), two PsA (two golimumab) and zero AS patients developed TB. Five out of eight had miliary TB, three out of eight had pulmonary TB and two patients died. The age-standardised and sex-standardised TB IR (95% CI) per 100?000 PYs/SIRs (95% CI) compared with the general Slovenian population for the current TNFi exposure were 52 (0 to 110)/6.7 (0.6 to 80), 47 (0 to 110)/6.1 (0.3 to 105), 45 (0 to 109)/5.8 (0.3 to 112) overall, in RA and PsA, respectively. CONCLUSIONS:The TB IR in the Slovenian patients with RA, AS and PsA treated with TNFi was comparable with TB IRs in TB non-endemic countries with less than a tenth of the patients requiring TB chemoprophylaxis.
| S-EPMC7045120 | biostudies-literature
Project description:ImportanceApproximately one-quarter of the global population have latent tuberculosis infection (LTBI), and tuberculosis (TB) is accountable for more than 1.5 million deaths annually. Methotrexate, cyclosporine, and tumor necrosis factor inhibitors may be associated with increased risk of TB and LTBI reactivation, although data are limited on the risks of TB with use of newer biologics.ObjectiveTo assess the association of secukinumab with reporting of active TB development, TB reactivation, and LTBI activation as an adverse event (AE) in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis.Design, setting, and participantsThis pooled cohort study pooled data from 28 clinical trials of secukinumab used in psoriasis (17 phase 3 or 3b and 2 phase 4 trials), psoriatic arthritis (5 phase 3 trials), and ankylosing spondylitis (4 phase 3 trials). A search of the Novartis Secukinumab Compound Pool Database was conducted for the 28 trials. All trial participants who had received at least 1 approved subcutaneous dose of secukinumab (150 mg or 300 mg) were included. Before randomization in these trials, patients underwent screening for TB. Patients with active TB were excluded, and patients with LTBI were treated according to local guidelines. Data were analyzed from the start of treatment in the individual studies through December 25, 2018.Main outcomes and measuresReporting of active TB or LTBI as an AE over a 5-year period using exposure-adjusted incidence rates (EAIR; incidence rates per 100 patient-years).ResultsA total of 12 319 patients were included, of whom 8819 patients had psoriasis (71.6%; 5930 men [67.2%]; mean [SD] age, of 44.9 [13.5] years), 2523 had psoriatic arthritis (20.5%; 1323 women [52.4%]; mean [SD] age, 48.8 [12.1] years), and 977 had ankylosing spondylitis (7.3%; 658 men [67.3%]; mean [SD] age, 42.3 [11.9] years). In the total population, 684 patients (5.6%) had tested positive for LTBI at screening. Over 5 years, LTBI as an AE during secukinumab treatment was reported in 13 patients (0.1% of 12 319). Of these 13 patients, 6 had a prior positive LTBI test result, and 7 were newly diagnosed as having LTBI. Four of the 7 patients had psoriasis (EAIR, 0.03; 95% CI, 0.01-0.07), 1 had psoriatic arthritis (EAIR, 0.02; 95% CI, 0.00-0.11), and 2 had ankylosing spondylitis (EAIR, 0.08; 95% CI, 0.01-0.28). No cases of active TB were reported.Conclusions and relevanceThis study found that LTBI reported as an AE after secukinumab treatment was uncommon and appeared to support the use of secukinumab in chronic systemic inflammatory conditions.
| S-EPMC7527940 | biostudies-literature
Project description:ObjectiveThe aim of this study was to establish guidelines for the optimization of biologic therapies for health professionals involved in the management of patients with RA, AS and PsA.MethodsRecommendations were established via consensus by a panel of experts in rheumatology and hospital pharmacy, based on analysis of available scientific evidence obtained from four systematic reviews and on the clinical experience of panellists. The Delphi method was used to evaluate these recommendations, both between panellists and among a wider group of rheumatologists.ResultsPrevious concepts concerning better management of RA, AS and PsA were reviewed and, more specifically, guidelines for the optimization of biologic therapies used to treat these diseases were formulated. Recommendations were made with the aim of establishing a plan for when and how to taper biologic treatment in patients with these diseases.ConclusionThe recommendations established herein aim not only to provide advice on how to improve the risk:benefit ratio and efficiency of such treatments, but also to reduce variability in daily clinical practice in the use of biologic therapies for rheumatic diseases.
| S-EPMC4473767 | biostudies-literature
Project description:The treatment of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) positively changed since the introduction of anti-TNF? drugs. These treatments were shown to reduce the symptoms and signs of the diseases and improve the quality of life. However, a variable percentage of patients do not respond to anti-TNF? or can exhibit a loss of response and, furthermore, despite anti-TNF? drugs' proven efficacy in reducing peripheral radiographic progression in PsA, the impact in reducing radiographic damage in AS is still debated. Recently, the discovery of new pathogenic mechanisms paved the way to the development of new drugs that target other pro-inflammatory cytokines. In particular, the inhibition of interleukin (IL)-17, which is the principal cytokine produced by Th17 lymphocytes, a pro-inflammatory subset involved in both inflammation and new bone formation in AS and PsA, demonstrated promising results. The new molecule secukinumab, an IL-17A inhibitor, showed its efficacy and safety in phase III randomized clinical trials in AS and PsA and is the first non-anti-TNF? biologic approved for the treatment of AS, providing a useful alternative treatment strategy in both diseases. The aim of this article was to review the pathophysiological basis, the efficacy and the safety of secukinumab treatment in AS and PsA patients.
| S-EPMC5085310 | biostudies-literature
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:ObjectiveFrailty is associated with disability and mortality independent of age. Although studies have evaluated frailty in rheumatoid arthritis (RA), information on the prevalence of frailty in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) is limited. We aimed to determine the prevalence of frailty in AS and PsA and to evaluate whether characteristics known to be associated with frailty, including anxiety, differ among these three types of inflammatory arthritis.MethodsWe performed a cross sectional study of Centers for Medicare & Medicaid Services (CMS) beneficiaries aged 65 years or older with AS, PsA, or RA enrolled in 2014. We operationalized frailty using a validated claims-based frailty index. We also explored the prevalence of frailty among CMS beneficiaries younger than age 65 years with work disability, a younger population that also may be at risk of frailty.ResultsThe prevalence of frailty in beneficiaries aged 65 years or older with AS and PsA was 45.2% and 46.7%, respectively, significantly lower than in RA (65.9%, P < 0.05). The prevalence of frailty in beneficiaries less than 65 years old was much lower overall, though still highest in RA; 11.7%, 4.4%, and 7.0% in RA, AS, and PsA, respectively (P < 0.05). Anxiety was significantly associated with frailty in subjects of all ages, particularly among those less than 65 years old (P < 0.05).ConclusionAlmost half of beneficiaries with AS or PsA aged 65 years old or older were frail, higher than in younger disabled beneficiaries. Further studies are needed to understand the risks of developing frailty in these diseases. Frailty was associated with anxiety, particularly in the younger age groups.
| S-EPMC8992466 | biostudies-literature
Project description:IntroductionThis article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators.MethodsThis integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years).ResultsMedian treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan-Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs.ConclusionRates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA.Trial registrationClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373.
| S-EPMC10796874 | biostudies-literature
Project description:This study aimed to investigate the associations of microRNA (miRs) signatures with cytokines, serum lipids, and disease activity in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA). In total, 65 patients (PsA n = 25, AS n = 25, RA n = 15) and 25 healthy controls (HC) were enrolled into the study. The expression of miR-223-5p, miR-92b-3p, miR-485-3p, miR-10b-5p, let-7d-5p, miR-26a-2-3p, miR-146b-3p, and cytokines levels were measured in sera. DIANA-mirPath analysis was used to predict pathways targeted by the dysregulated miRs. Disease activity scores were calculated. Lipid profile, uric acid, glucose level, and C-reactive protein (CRP) concentrations were determined in the blood. Based on lipid profiles, the PsA group had hypertriglyceridaemia, and RA patients revealed mixed dyslipidaemia, while in AS, no specific changes were found. miR expression analysis revealed upregulation of miR-26a-2-3p and miR-10b-5p in PsA, miR-485-3p in AS, and let-7d-5p in RA. Several correlations between disease activity indexes, metabolites levels, and expression of miRs were observed in PsA, RA, and AS patients. Finally, in ROC analysis, miR-26a-2-3p/miR-485-3p, and let-7d-5p/miR-146b-3p tandems revealed high sensitivity and specificity in distinguishing between PsA, AS, and RA. Our study illustrates the superiority of miR expressions in distinguishing between RA, PsA, and AS. In PsA, a unique regulatory pathway exists through miR-26a-2-3p, miR-223-5p, miR-10b-5p, and miR-92b-3p that converges proatherogenic metabolism and disease activity.
| S-EPMC9024741 | biostudies-literature
Project description:Background Limited information exists comparing the perioperative complications of the different inflammatory arthropathies (IAs) after total hip arthroplasty (THA). Our study was aimed to (1) compare perioperative complications and (2) determine the most common complications between the different IA subtypes compared with patients with primary osteoarthritis (OA) undergoing primary THA and (3) find whether the difference in postoperative complications also exists between different IA after THA. Methods The Nationwide Inpatient Sample (NIS) was used to identify patients with Rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis (AS), and primary OA undergoing unilateral THA between 2005 and 2014. Preoperative diagnosis, comorbidities, and postoperative complications were determined using the International Classification of Disease Clinical Modification version 9 codes. The prevalence of perioperative complications was compared between patients with IA and primary OA and between patients with different IA. Results When compared with patients with primary OA, patients with RA had significantly more postoperative surgical and medical complications. Yet there are just several medical complications differences exist between PA and primary OA or AS and primary OA, including stroke and acute renal failure for psoriatic arthritis and urinary tract infection and pneumonia for AS. What is more, there were also several differences in perioperative medical complications seen in patients with different IA. Conclusion Except for patients with RA, the differences in perioperative complications was small between patients with IA and primary OA and between patients with different types of IA. Supplementary Information The online version contains supplementary material available at 10.1186/s12891-022-05891-9.
| S-EPMC9580196 | biostudies-literature
Project description:ObjectiveRheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) belong to inflammatory rheumatic diseases, the group of conditions of unknown etiology. However, a strong genetic component in their pathogenesis has been well established. A dysregulation of cytokine networks plays an important role in the development of inflammatory arthritis. Interleukin 33 (IL-33) is a recently identified member of the IL-1 family. To date, the significance of IL-33 in inflammatory arthritis has been poorly studied. This research aimed to investigate the potential of IL-33 gene polymorphisms to serve as biomarkers for disease susceptibility and TNF inhibitor response in RA, AS, and PsA patients.Materials and methodsIn total, 735 patients diagnosed with RA, AS, and PsA and 229 healthy individuals were enrolled in the study. Genotyping for three single nucleotide polymorphisms (SNPs) within the IL-33 gene, namely, rs16924159 (A/G), rs10975519 (T/C), and rs7044343 (C/T), was performed using polymerase chain reaction amplification employing LightSNiP assays.ResultsIn the present study, the IL-33 rs10975519 CC genotype was associated with a decreased risk of developing RA in females, while the IL-33 rs16924159 polymorphism was associated with the efficacy of anti-TNF therapy and clinical parameters for RA and AS patients. The IL-33 rs16924159 AA genotype correlated with higher disease activity and worse clinical outcomes in RA patients treated with TNF inhibitors, and AS patients carrying the IL-33 rs16924159 AA genotype had higher disease activity and a worse response to anti-TNF therapy. That indicates a deleterious role of the IL-33 rs16924159 AA genotype in the context of RA, as well as AS.ConclusionsThe obtained results suggest that IL-33 gene polymorphisms might be potential candidate biomarkers of disease susceptibility and anti-TNF treatment response in patients with inflammatory rheumatic diseases.
| S-EPMC8226138 | biostudies-literature