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Objective: This study aims to evaluate the active and chronic lesions in sacroiliac joints and lumbar spine over a decade of TNFi therapy in patients with AS. Methods: The study enrolled patients with AS under treatment with a TNFi for over a decade. The patients underwent a new MRI scan of their lumbar spine and sacroiliac joint (SIJ). Two readers evaluated all images. Inflammation of SIJ (SIS), SIJ structural damage (SSS) including Fat Metaplasia, Erosions, Backfill and Ankylosis, and Spondyloarthritis Research Consortium of Canada Bone marrow edema (SPARCC) spine score were recorded. Results: In the study, 15 patients were included, with 80% being male. The mean age during their first MRI was 38.1 (± 11.9) years old, and the majority (86.7%) tested positive for HLA-B27. While TNFi improved both BASDAI and BASFI scores, there was a noticeable increase in MRI acute lesions in the SIJ over time, where the median score increased from 0 (0–4) to 3 (0–10) after ten years (p = 0.028). After a decade of treatment, the median SPARCC spine score also increased from 0 (0–9) to 5 (0–16), p = 0.093. Finally, it was observed that there was a significant positive correlation between ESR and SIS erosions in cases of chronic lesions (r = 0.819, p < 0.001). Conclusions: While TNFi have significantly improved the treatment of AS, this study shows that acute lesions can still develop despite treatment. A personalized approach that adapts MRI assessment to each patient's specific requirements may help detect changes early and enable doctors to intervene promptly to prevent further damage. [ABSTRACT FROM AUTHOR]

Objectives: To update an evidence base informing the 2024 Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA) in older adults. Methods: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs, CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results: Observational studies confirmed a pivotal role of methotrexate in the treatment of older RA patients. The meta-analysis showed that tumour necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that biological disease-modifying antirheumatic drugs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs. Conclusions: This systematic review provides the necessary evidence for developing 2024 Japan College of Rheumatology clinical practice guidelines for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired. [ABSTRACT FROM AUTHOR]

Background: Switching between therapies is a recommended strategy for psoriatic arthritis (PsA) patients who experience treatment failure; however, studies including real-life data are scarce. Objectives: To assess the incidence rate (IR) of switching between biologics and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) due to inefficacy in PsA, and to compare the risk of switching due to inefficacy across different b/tsDMARDs groups. Design: A longitudinal retrospective study, spanning from 2007 to 2022, was conducted on patients with PsA treated with b/tsDMARDs at an outpatient rheumatology clinic. Methods: The primary outcome was switching between b/tsDMARDs due to inefficacy. The independent variable was the exposure to b/tsDMARDs during follow-up. As covariates, clinical, treatment-related, and sociodemographic variables were considered. Survival techniques were run to estimate the IR of switching due to inefficacy per 100 patients*year and confidence interval at 95% (95% CI). Cox multivariate regression analyses were run to assess the risk of b/tsDMARDs switching due to inefficacy, expressed as hazard ratio (HR) and 95% CI. Results: In all, 141 patients were included, with 893.09 patients*year follow-ups. 52.48% of them were females in their fifties. In total, 262 courses of treatment were recorded. During the study period, 56 patients presented 121 switches and 103 related to inefficacy (IR: 11.53 (9.51–13.98)). Tumor necrosis factor-alpha inhibitors (TNFi) showed the lowest IR. In the bivariate analysis, all b/tsDMARDs had more risk of switching compared to TNFi (HR: anti-lL-17 vs TNFi: 2.26 (1.17–4.36); others vs TNFi: 3.21 (1.59–6.45)); however, this statistical significance was no longer present in the multivariate analysis once adjustments were made for the covariates. Still, the final model achieved statistical significance in the following variables: gender, clinical symptoms, prescription year, therapy courses, glucocorticoids, and sulfasalazine. Conclusion: In this study, we did not find differences in the rate of switching due to inefficacy among different groups of b/tsDMARDs. Other concomitant treatments, sociodemographic, and clinical variables were identified as risk factors for switching due to inefficacy. Plain language summary: Changes due to drug failure between biologic therapies: a real-life study in psoriatic arthritis patients Introduction: We wanted to evaluate how often patients with psoriatic arthritis change between different drugs because the drugs weren't working well enough. Additionally, we evaluated which factors could influence the change due to drug failure. The studied drugs are biological therapies that are arthritis-modifying drugs designed early in the last decade to prevent or reduce inflammation caused by the disease. Methods: We included patients from 2007 to 2022 in which their consultant rheumatologist had decided to commence them on biologic therapy. We studied the changes due to drug failure, we also included sociodemographic, clinical and treatments information. Results: The study comprised 141 patients. 52% were women in their fifties. We found that 56 patients change drugs 121 times, with 103 of those changes due to failure drug. This means about 11 out of every 100 patients change their biologic therapy each year. There was no difference in the risk of change between the different studied biologic therapies. Women, those with inflammatory back pain, and those who had tried many different drugs were more likely to change due to drug failure. Using additional therapies like glucocorticoids and sulfasalazine also increased the probability of biologic therapy change. Conclusion: Our work did not find differences in the risk of change due to drug failure among different biologic therapies. [ABSTRACT FROM AUTHOR]

Objective To investigate whether biological DMARDs affect the risk of aseptic loosening after total hip/knee arthroplasty (THA/TKA) in patients with RA. Methods We retrospectively identified all patients suffering from RA who underwent THA/TKA at our academic centre between 2002 and 2015 and linked them with an existing prospective observational RA database at our institution. The risk of aseptic loosening was estimated using radiological signs of component loosening (RCL). A time-dependent Cox regression analysis was used to compare the risk of implant loosening between patients treated with traditional DMARDS and biological DMARDs, or alternately both over time. Results A total of 155 consecutive total joint arthroplasties (TJAs) (103 TKA vs 52 THA) was retrospectively included in the study. Mean age at implantation was 59 ± 13 years. Mean follow-up time was 69 ± 43 months. Overall, 48 (31%) TJAs showed signs of RCL, with 28 (27.2%) RCLs occurring after TKA compared with 20 after THA (38.5%). A significant difference regarding the incidence of RCL between the traditional DMARDs group (39 cases of RCL, 35%) and the biological DMARDs group (nine cases of RCL, 21%) (P  = 0.026) was observed using the log-rank test. This was also true when using a time-dependent Cox regression with therapy as well as arthroplasty location (hip vs knee) as variables (P  = 0.0447). Conclusion Biological DMARDs may reduce the incidence of aseptic loosening after TJA in patients with RA compared with traditional DMARDs. This effect seems to be more pronounced after TKA than THA. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate factors associated with impaired physical function [defined as Health Assessment Questionnaire Disability Index (HAQ-DI) >0.5] of old-old (aged 75–84 years) patients with rheumatoid arthritis. Methods: Data from 15,185 rheumatoid arthritis patients in the National Database of Rheumatic Disease in Japan were extracted from 2017 to 2018. We enrolled 3708 patients aged 55–84 years in Simplified Disease Activity Index (SDAI) ≤11 and Steinbrocker Stage I/II. Factors associated with HAQ-DI >0.5 were analysed by multivariable logistic regression. Results: About half of the old-old patients received methotrexate, which was lower than middle-aged (55–64 years) and young-old patients (65–74 years). The proportion of glucocorticoids in the old-old patients was highest among the three groups, and biological disease-modifying antirheumatic drugs were similarly used. The prevalence of HAQ-DI >0.5 was significantly higher in old-old patients with low disease activity than in those with remission. The same was true in the middle-aged and young-old patients. Multivariable analysis showed age, higher SDAI, glucocorticoid use, and methotrexate nonuse were significantly associated with HAQ-DI >0.5 in the old-old patients. Conclusions: Achieving SDAI remission was an ideal goal for old-old patients in terms of physical function. Glucocorticoids and a low proportion of methotrexate use may influence the physical function of old-old patients. [ABSTRACT FROM AUTHOR]

Objectives: We evaluate the socioeconomic impact of treatment with biological and targeted synthetic disease–modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis. Methods: We analysed data retrospectively from the prospective observational CorEvitas RA Japan Registry (March 2016–February 2020). Patients were categorised into paid workers (PWs) and home workers (HWs) and further based on drug classes. We assessed medication persistence, treatment outcomes, health care resource utilisation, and socioeconomic impact over 12 months, including direct (drugs and health care resource utilisation) and indirect (loss of productivity) costs. Results: Overall, 187 PWs and 114 HWs were identified. Over 12 months, medication persistence was high, treatment outcomes improved, and outpatient visits reduced in both groups. Following treatment initiation, direct costs increased, whereas indirect (loss of productivity) costs decreased in both groups. The unadjusted socioeconomic impact [Japanese yen (JPY)] increased across all drug classes in PWs (range: 29,700–151,700) and HWs (range: −28,700 to 83,000). Adjusted change in monthly socioeconomic impact was JPY 29,700–138,900 for PWs and JPY −28,000 to 92,800 for HWs. Conclusions: In this study of Japanese patients with rheumatoid arthritis, the socioeconomic burden increased across patient groups and drug classes. The decrease in indirect (loss of productivity) costs partially offset the increase in direct costs. [ABSTRACT FROM AUTHOR]

Introduction: Immune-mediated skin lesions (IMSL) can be very disabling leading to treatment discontinuation. Although these lesions have rarely been previously described, the true incidence is unknown. Objective: To explore the cumulative incidence, management and outcomes of IMSL related to bDMARD in a large cohort of patients with chronic inflammatory rheumatic diseases. To explore possible associations and risk factors for IMSL development. Methods: A retrospective single-center study of patients with rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA) that had been treated with at least one bDMARD for at least 6 months was conducted. IMSL related to bDMARD characteristics and outcomes were collected. Results: A total of 989 patients with RA, SpA and PsA were included. Twenty-seven patients (2.7%) presented IMSL potentially related to bDMARD, being psoriasis the most common IMSL (n=12, 44.4%), followed by drug-induced lupus erythematosus (n=6), alopecia areata (n=3) and leukocytoclastic vasculitis (n=2). IMSL led to withdrawal of bDMARD in 18 of the 27 patients (66.7%). Patients with IMSL had younger age at diagnosis (p=0.038), longer disease duration (p=0.018), longer duration of bDMARD treatment (p=0.008), and higher number of previous bDMARDs (p<0.001) than patients without IMSL. In the group of patients with IMSL there was a significantly higher percentage of patients treated with adalimumab (p<0.001). In multivariable regression model, the number of previous bDMARDs (OR 2.13, 95%CI 1.47-3.10, p<0.001) and treatment with adalimumab (OR 4.60, 95%CI 1.96-10.80, p<0.001) were statistically significant predictive factors for IMSL development. Conclusion: In our study, IMSL related to bDMARDs had an estimated cumulative incidence of 2.7%. Younger age at diagnosis, longer disease duration, longer duration of bDMARD treatment, higher number of previous bDMARDs and treatment with adalimumab were independently associated with an increased risk of IMSL development. [ABSTRACT FROM AUTHOR]

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) is a term to describe a group of chronic inflammatory rheumatic diseases, which have common pathophysiological, genetic, and clinical features. Under the umbrella term SpA, two main groups are subsumed: axial SpA (radiographic axSpA and non-radiographic axSpA) and peripheral SpA (with the leading representative being psoriatic arthritis (PsA) but also arthritis associated with inflammatory bowel disease (IBD), reactive arthritis, and undifferentiated pSpA). The key clinical symptom in axSpA is chronic back pain, typically with inflammatory characteristics, which starts in early adulthood, while the leading clinical manifestations of peripheral SpA (pSpA) are arthritis, enthesitis, and/or dactylitis. Furthermore, extra-musculoskeletal manifestations (EMMs) (acute anterior uveitis, psoriasis, and IBD) can accompany axial or peripheral symptoms. All these factors need to be taken into account when making treatment decisions in SpA patients. Despite the major advances in the treatment landscape over the past two decades with the introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) and most recently targeted synthetic DMARDs (tsDMARDs), a relevant proportion of patients still does not achieve the desired state of remission (=absence of disease activity). With this implementation of new treatment modalities, clinicians now have more choices to make in the treatment algorithms. However, despite generalized treatment recommendations, all factors need to be carefully considered when deciding on the optimal treatment strategy for an individual patient in clinical practice, aiming at an important first step towards personalized treatment strategies in SpA. In this narrative review, we focus on the efficacy of approved and emerging treatment options in axSpA and PsA as the main representative of pSpA and discuss their selective effect on the different manifestations associated with SpA to provide guidance on drivers of treatment decisions in specific situations. • SpA presents diverse phenotypes, crucial for guiding treatment decisions. • Despite significant treatment innovations, many patients still fail to reach clinical remission. • Recent ASAS/EULAR and GRAPPA updates impact treatment strategies for axSpA and PsA. • This review explores how treatment choices address specific SpA manifestations, aiming toward precision medicine. [ABSTRACT FROM AUTHOR]

Biological disease-modifying anti-rheumatic drugs (bDMARDs) are widely used for the management of rheumatoid arthritis, although their benefits are counterweight by an increased risk of infections. In the present study, we used administrative data to compare the risk of severe infections among different classes of bDMARDs. A retrospective cohort study was conducted using Administrative Health Databases of the Piedmont Region, Italy. Relevant data were obtained from: (1) the inhabitants registry, (2) hospital discharge records, and (3) the co-payment exemption registry and (4) drug claims registry. Fine and Gray competing risk models were fitted to evaluate the association between the use of different types of bDMARDs and occurrence of severe infection accounting for treatment interruption as competing risk. A total of 1780 new users of bDMARDs were identified. Among them, 50 hospitalizations for infection occurred during the study period. The use of Tocilizumab was associated with an increased risk of infection, compared to tumor necrosis factor (TNF) inhibitor drugs (sub-distribution hazard ratios-sHR: 2.510; 95% CI: 1.279–4.926), whereas no difference in the risk of severe infection was found for abatacept (sHR: 0.584; 95% CI: 0.234–1.457). bDMARDs treatment is generally safe in clinical practice with slight but important differences among classes. The increased risk of infection associated with tocilizumab use should be taken into account when balancing the risk and benefits of starting a treatment with this drug. [ABSTRACT FROM AUTHOR]

PurposeWe validated the one-year effectiveness of strategic treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs) based on peripheral T-lymphocytic phenotyping and explored the impact of treatment on T helper lymphocytic phenotypes.MethodsNinety-seven patients were registered in this study. One-year treatment response was compared between the two groups: the strategic bDMARDs treatment group (n = 41), in which bDMARDs were selected based on peripheral blood lymphocyte analysis, and the standard bDMARDs treatment group (n = 56), in which the patients underwent no strategic selection of bDMARDs and phenotyping. Changes in helper T lymphocytic phenotypes were evaluated after 1-year post-treatment.ResultsIn the standard bDMARDs treatment group, 23 patients (42.6%) achieved disease activity in psoriatic arthritis (DAPSA)-remission (REM), and 23 of 46 (50.0%) achieved PASI 90. In the strategic bDMARDs treatment group, 22 (53.7%) achieved DAPSA-REM, and 26 of 35 (74.2%) achieved PASI90. The rate of achieving minimal disease activity (MDA) and DAPSA-REM at month 6, DAPSA-low disease activity (LDA) at months 6 and 12, and PASI 90 at month 12 were significantly higher in the strategic bDMARDs treatment group. After treatment with ustekinumab, the proportion of aTh1/CD4 (%) significantly decreased. The percent reduction in activated Th17 cells was significantly higher in IL-17-i cells than in UST/TNF-i cells.ConclusionsThe results of this study demonstrate the 1-year effectiveness of precision medicine based on peripheral T-lymphocytic phenotyping in terms of DAPSA and MDA. Analysis of data from real-world clinical practice showed that the impact on the immune system varied among bDMARDs. However, because psoriatic arthritis has very high heterogeneity, it may be necessary to conduct studies with a larger sample size, perhaps drawing samples from multiple institutions.

Abstract Background Prevention of illness due to infection by influenza viruses is important for children with rheumatic diseases. Biological disease modifying antirheumatic drugs have become increasingly important in the treatment of juvenile idiopathic arthritis, and combinations of immunosuppressive drugs are used for the treatment of systemic disorders, which increase the risk of secondary immunodeficiency. Therefore, we investigated whether children with rheumatic disease can mount a protective antibody response after influenza immunization. Methods The prospective multicentre cohort study was conducted in Denmark during the influenza season 2015–2016. Children with rheumatic disease aged six months to 19 years were eligible. Controls were immunologically healthy children. A blood sample was collected before and after vaccination and analysed by haemagglutination inhibition (HI) assay for the 2015–2016 influenza vaccine-strains. In case of flu-like symptoms the child was tested for influenza. For statistical analyses the patients were grouped according to medical treatment or disease. Results A total of 226 patients and 15 controls were enrolled. No differences were found for the increase of antibodies from pre-vaccine to post-vaccine between the groups in our primary analyses: A/Cal H1N1pdm09 (p = 0.28), A/Swi H3N2 (p = 0.15) and B/Phu Yamagata (p = 0.08). Only when combining patients across groups a lower increase in antibodies was found compared to controls. Among all patients the pre-vaccine rates for seroprotection using the HI-titer cut-off ≥ 40 were 93.1–97.0 % for all three strains. For seroprotection using the HI-titer cut-off ≥ 110 the pre-vaccine rates for all patients were 14.9–43.6 % for all three strains and an increase in the proportions of patients being seroprotected after vaccination was found for A/Cal H1N1pdm09 and A/Swi H3N2. None of the children with flu-like symptoms tested positive for the vaccine strains. Conclusions Children with rheumatic diseases increase in antibody titres after influenza immunization, however, it remains uncertain whether a protective level is achieved.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

Elderly-onset rheumatoid arthritis (EORA) is characterized by acute onset and clinical features of high disease activity. Anti-cyclic citrullinated peptide antibody (ACPA) positivity or the presence of bone erosions predicts a radiological joint destruction of EORA, but ACPA-negative EORA with a polymyalgia rheumatica (PMR) phenotype may also present. Biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors were beneficial both in older and in younger patients in terms of risk--benefit balance. Implementation of a treat-to-target strategy could improve EORA outcomes, but older patients have more age-related comorbidities and interstitial lung disease than younger patients. Baseline comorbidities, more frequent methotrexate dose-dependent adverse events, serious infections, cardiovascular disease events, and malignancy all influence the choice of treatment and the treatment goals for older patients. Based on articles reviewed here, it is suggested that current treatment strategies for younger patients are also useful for ACPA- positive EORA and for ACPA-negative EORA with bone erosion. Differential diagnosis of ACPA-negative EORA without erosive arthritis and PMR with peripheral manifestations is challenging, and the treatment strategy of patients presenting with this overlap phenotype remained unclear. An appropriate treatment strategy for all patients with EORA still needs to be developed. [ABSTRACT FROM AUTHOR]

Objectives: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a rare but important comorbidity of rheumatoid arthritis (RA). Our objective was to investigate the association between NTM-PD and RA, especially regarding the immunosuppressive treatment of RA such as biological disease-modifying antirheumatic drugs (bDMARDs). Methods: We conducted a retrospective, single-centre cohort study. All RA patients regularly followed up at our rheumatology division in December 2012 were included in the study, and followed for 5 years. Results: At baseline, 26 of 1639 RA patients had NTM-PD. During the observation period, 14 were newly diagnosed with NTM-PD. For new diagnosis of NTM-PD, bDMARD use at baseline was not a significant risk factor. Among the 40 patients with NTM-PD, 16 were treated with a total of 27 bDMARDs after NTM-PD diagnosis. They did not present with a greater exacerbation of NTM-PD than those not treated with bDMARDs (25 vs. 17%, p=.52). A total of 55 patients died, but nobody died of NTM-PD. NTM-PD was not associated with worse mortality in multivariate analysis (hazard ratio, 2.0; 95% CI, 0.6--6.4; p=.26). Conclusions: Biological DMARD was not associated with worse prognosis of NTM- PD. Careful use of bDMARDs could be tolerated in RA patients with NTM-PD. [ABSTRACT FROM AUTHOR]

Objectives To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound. Methods The randomized, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses. Results Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo [−9 (0.9) vs −6 (0.9), difference (95% CI): −3 (−6, −1); one-sided P= 0.004] at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported. Conclusion This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients. Trial registration ClinicalTrials.gov; NCT02662985. [ABSTRACT FROM AUTHOR]

Objectives: To provide an evidence base for clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA) in older adults. Methods: PubMed, Cochrane library, and Japan Centra Revuo Medicina databases were searched for articles published between 1990 and 2019. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system, with some modifications. Results: Among 702 identified articles, there were 5 post-hoc analyses of randomized controlled trials and 10 observational studies. Meta-analysis of the former yielded a mean difference of the van der Heijde-modified total Sharp score of -2.79 (95% confidence interval [CI] -3.74 to -1.84) for treatment with tumor necrosis factor inhibitors. The risk ratio (RR) for the American College of Rheumatology 50% response rate, and for serious adverse events was 2.83 (95%CI 1.90-4.21) and 1.32 (95%CI 0.53-3.31), respectively, for Janus kinase inhibitors. Meta-analysis of the observational studies yielded an RR for disease activity score-28 remission and serious infections of 0.76 (95%CI 0.64-0.91) and 1.92 (95%CI 1.31-2.81) for older-versus-younger patients receiving biological disease-modifying antirheumatic drugs, respectively. Conclusion: This systematic review provides the necessary evidence for developing CPG for the management of RA in older adults. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis, which can involve multiple systems. Patients with RA may have a variety of comorbidities, including cardiovascular disease (CVD), lung cancer, lymphoma, infection, osteoporosis, fatigue, depression, colon cancer, breast cancer, prostate cancer, and Alzheimer's disease. Among these comorbidities, the incidence of CVD, lung cancer, lymphoma, infection, and osteoporosis is higher. CVD is a serious complication of RA. The risk of CVD and associated mortality rate in patients with RA is high, and the treatment rate is low. In addition to traditional risk factors, such as age, sex, blood pressure, and diabetes, RA is also associated with inflammation. Furthermore, therapeutic drugs for RA, including non-steroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying anti-rheumatic drugs, have beneficial or harmful effects on cardiovascular events in patients with RA. This article discusses the effects of therapeutic drugs for RA on cardiovascular events.

Introduction: Disease-modifying anti-rheumatic drugs (DMARDs) have improved the outcomes of patients with rheumatoid arthritis (RA). DMARDs are classified into three categories: conventional synthetic DMARDs, biological DMARDs (including biosimilars), and targeted synthetic DMARDs. DMARDs, by way of their effect on the immune system, are associated with increased risk of adverse events, including infections, malignancies, cardiovascular disease, gastrointestinal perforations, and other less common events., Areas Covered: In this narrative literature review performed with searches of the PubMed database from 1 January 2010 through 1 January 2023, we compare the risk of safety events between DMARDs using data from both randomized clinical trials and observational studies., Expert Opinion: DMARD use in RA is associated with higher rates of serious infections, tuberculosis reactivation, opportunistic infections, and possibly malignancies. Specific biologic DMARDs and higher doses are associated with elevated risks of various adverse events (gastrointestinal perforations, thromboembolism, serious infection). Shared decision-making is paramount when choosing a treatment regimen for patients based on their own comorbidities. JAKi are the newest class of medications used for RA with robust safety data provided in clinical trials. However, more real-world evidence and phase-IV pharmacovigilance data are needed to better understand comparative safety profile of DMARDs in RA.

Background: The aim of this study is to assess treatment patterns and pharmaco-utilization in patients with psoriatic arthritis (PsA) in Italy. Methods: A retrospective analysis using administrative databases of six Local Health Units was performed. All adult patients with PsA diagnosis and ≥1 prescription for biologic/targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) from January 2010 to March 2017 were included. The date of first b/tsDMARD prescription was defined index-date. Follow-up lasted 1-year post index-date. Patients without b/tsDMARDs prescription pre index-date were defined bionaïve. Results: Of the 1,056 patients included, 33% received adalimumab, 30% etanercept, 10% golimumab, 9% secukinumab, 7% infliximab, 6% ustekinumab, 4% certolizumab, and 1% apremilast. During follow-up, persistence with b/tsDMARDs was observed in 79.8% of patients, 10.8% switched therapies, dose change occurred in 15.8% of patients, 47.4% received an add-on. Among bionaïve patients (n = 591), 67.0% were persistent with b/tsDMARDs, 10.1% switched therapy, 14.5% required a dose change and 45.8% an add-on. Discontinuation was observed in 10.6% of total PsA population and in 24.8% of bionaïve patients. Conclusion: This analysis provided insights on drug utilization patterns for PsA in an Italian real-world setting. Our results show that treatment regimen changes occur in a high proportion of PsA patients. [ABSTRACT FROM AUTHOR]

Keywords: Psoriatic arthritis; personalize medicine; precision medicine; immunophenotype; biological DMARDs EN Psoriatic arthritis personalize medicine precision medicine immunophenotype biological DMARDs 799 802 4 09/13/21 20210801 NES 210801 1. This, combined with complex statistical analyses, is a potential step in the right direction to help re-define the PsA treatment algorithm and therefore optimize patients' treatment without delay. Group for research and assessment of psoriasis and psoriatic arthritis 2015 treatment recommendations for psoriatic arthritis. Nonetheless, this proof-of-concept study exemplifies a promising approach and exciting potential for personalizing PsA therapy, especially in the context the expanding treatment choices. [Extracted from the article]

Abstract Introduction This open-label study evaluated the immunogenicity, safety, and efficacy of sarilumab monotherapy in patients with active, moderate-to-severe rheumatoid arthritis (RA) and inadequate response or intolerance to prior conventional synthetic disease-modifying antirheumatic drugs. Methods Adults with RA (n = 132) were randomized to receive subcutaneous sarilumab (150 [n = 65] or 200 mg [n = 67]) every 2 weeks (q2w) for 24 weeks. Endpoints included incidence of antidrug antibodies (ADAs) at week 24, safety, and efficacy. Results Persistent ADAs occurred in eight patients (12.3%) receiving sarilumab 150 mg q2w, seven of whom (10.8%) had neutralizing antibodies (NAbs), and in four patients (6.1%) receiving sarilumab 200 mg q2w, two of whom (3.0%) had NAbs; all exhibited low antibody titers. Infections and neutropenia were the most common adverse events (AEs). There were three serious AEs, no reports of anaphylaxis, and few hypersensitivity reactions (e.g., rash) with no notable differences in hypersensitivity reactions in ADA-positive patients relative to ADA-negative patients. Changes in absolute neutrophil count, alanine aminotransferase level, and platelet count were consistent with interleukin-6 signaling blockade and in agreement with previous observations. At week 24, overall American College of Rheumatology 20%/50%/70% improvement criteria responses were 73.8%/53.8%/29.2%, respectively, with sarilumab 150 mg q2w and 71.6%/50.7%/29.9% with sarilumab 200 mg q2w. No patients with an ADA-positive response showed loss of efficacy. Conclusions ADA titers were low and persistent ADAs and NAbs occurred relatively infrequently in both sarilumab dose groups. ADA did not meaningfully impact the safety or efficacy of either dose of sarilumab over 24 weeks. Trial Registration ClinicalTrials.gov, identifier NCT02121210. Funding Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Plain Language Summary Plain language summary available for this article.

Aim: To compare the levels of serum calprotectin (sCal) in patients with juvenile idiopathic arthritis (JIA) depending on the type of therapy to assess the disease activity comprehensively for further treatment correction. Material and methods: We determined the sCal levels in 74 JIA patients who had normal C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels. High-sensitivity C-reactive protein was evaluated in 16 patients. All children were divided into 2 groups depending on the type of therapy. Group I consisted of 33 children on methotrexate (MTX) therapy, 11 of which were in the state of clinical pharmacologic remission. Group II included 41 children treated with biological Disease-Modifying Antirheumatic Drugs (bDMARDs), 14 of which achieved the state of clinical pharmacologic remission. A results analysis was carried out according to the Mann-Whitney U test. A Spearman rank correlation was performed to define the type of correlation between the indicators. Results: sCal level was 5.5 times higher in patients with JIA (3,300 μg/L), compared with healthy children (600 μg/L) (p = 0.015). The highest sCal level observed was among the patients in Group I, who received MTX exclusively both in the active phase of the disease (U = 71.5, p = 0.000006) and in the state of clinical pharmacologic remission (U = 11, p = 0.00034). There was a moderate positive correlation of sCal level and disease activity indices, such as the 27-joint Juvenile Arthritis Disease Activity Score (JADAS27) (Spearman’s rho = 0.58, p = 0.0001) and high-sensitivity CRP (Spearman’s rho = 0.56, p = 0.024). Conclusions: sCal levels should be used to monitor the subclinical inflammatory activity in patients with JIA. The use of bDMARDs in JIA treatment is effective.

Background: Prevention of illness due to infection by influenza viruses is important for children with rheumatic diseases. Biological disease modifying antirheumatic drugs have become increasingly important in the treatment of juvenile idiopathic arthritis, and combinations of immunosuppressive drugs are used for the treatment of systemic disorders, which increase the risk of secondary immunodeficiency. Therefore, we investigated whether children with rheumatic disease can mount a protective antibody response after influenza immunization. Methods: The prospective multicentre cohort study was conducted in Denmark during the influenza season 2015–2016. Children with rheumatic disease aged six months to 19 years were eligible. Controls were immunologically healthy children. A blood sample was collected before and after vaccination and analysed by haemagglutination inhibition (HI) assay for the 2015–2016 influenza vaccine-strains. In case of flu-like symptoms the child was tested for influenza. For statistical analyses the patients were grouped according to medical treatment or disease. Results: A total of 226 patients and 15 controls were enrolled. No differences were found for the increase of antibodies from pre-vaccine to post-vaccine between the groups in our primary analyses: A/Cal H1N1pdm09 (p = 0.28), A/Swi H3N2 (p = 0.15) and B/Phu Yamagata (p = 0.08). Only when combining patients across groups a lower increase in antibodies was found compared to controls. Among all patients the pre-vaccine rates for seroprotection using the HI-titer cut-off ≥ 40 were 93.1–97.0 % for all three strains. For seroprotection using the HI-titer cut-off ≥ 110 the pre-vaccine rates for all patients were 14.9–43.6 % for all three strains and an increase in the proportions of patients being seroprotected after vaccination was found for A/Cal H1N1pdm09 and A/Swi H3N2. None of the children with flu-like symptoms tested positive for the vaccine strains. Conclusions: Children with rheumatic diseases increase in antibody titres after influenza immunization, however, it remains uncertain whether a protective level is achieved. [ABSTRACT FROM AUTHOR]

Purpose: We explored changes in health services utilization associated with the Biosimilars Initiative introduced in British Columbia on May 27, 2019. To maintain drug coverage, the policy requires users of originator infliximab or etanercept to transition to biosimilar versions. We present a three‐month interim analysis of this initiative. Methods: We conducted a rapid monitoring analysis to evaluate changes in health services utilization three months after the policy was introduced compared with a three‐year period before the policy's introduction. Using the administrative claims data of the British Columbia Ministry of Health, we assembled three historical cohorts and one policy cohort of users of each originator drug (8 cohorts in total). Cumulative incidences of medication refills, switching, and visits to physicians were the outcome measures used to compare policy and historical cohorts. Likelihood ratios were used to quantify statistical differences between each policy cohort and its respective historical controls. Likelihood ratios above 7.1 were considered statistically significant. Results: The four infliximab cohorts included 436 patients on average, mean age 56 to 59, 53% to 55% females. The four etanercept cohorts included 1826 patients on average, mean age 57 to 58, 60% to 63% females. Three months after the policy's introduction, 21% of patients treated in the policy cohorts transitioned to the biosimilar versions. Health services utilization in the policy cohorts were consistent with the historical cohorts. Conclusions: An increase in visits to physicians was expected but not detected in the first three months of the Biosimilars Initiative. The impacts of the policy will continue to be monitored. [ABSTRACT FROM AUTHOR]

Purpose To describe a rapid monitoring plan to assess the impacts of a shift in drug coverage for biosimilar drugs in British Columbia following the introduction of a new policy on 27 May 2019. The Biosimilars Initiative requires users of originator infliximab or etanercept to switch to biosimilar versions of those drugs to maintain coverage. We propose a signal‐detection method to provide near‐real‐time information to policymakers on the impacts of the policy change. Methods: The exposure will be the Biosimilars Initiative, a policy affecting patients using originator infliximab (Remicade) and etanercept (Enbrel) for approved rheumatologic or dermatologic indications. Two policy cohorts and six historical control cohorts of patients using originator infliximab or etanercept will be assembled using linked and de‐identified data from the British Columbia Ministry of Health. Patients will be identified during the 6‐month period before the policy anniversary. Outcomes will include medication refills and switching, hospital admissions, emergency department visits, and physician visits. Summary outcome measures, such as cumulative incidence or average quantity as applicable, will be examined daily and reported monthly for 1 year. Outcomes in the policy cohorts will be compared with historical controls using likelihood ratios. Results: The results of this rapid monitoring plan will be based on analyses involving approximately 9000 patients: four infliximab cohorts of approximately 430 patients and four etanercept cohorts of approximately 1800 patients. Conclusions: Rapid monitoring results will inform ongoing policy decisions related to the Biosimilars Initiative, in terms of impacts on both patient health and health services utilization. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of rheumatic diseases has been greatly advanced by the introduction of biological molecular-targeted therapies. However, owing to their high heterogeneity at the molecular and clinical levels, treatment of rheumatic diseases can often be challenging. Hence, it especially important to select the most optimal targeted therapy for individual patients. There are ten biologics available for the treatment of psoriatic arthritis; however, how each of these can be used most effectively is unclear. Areas covered: We conducted a narrative review to elucidate whether stratifying psoriatic arthritis patients to select specific molecular-targeted therapies would improve treatment outcomes. We explored the potential of precision medicine in which patients with psoriatic arthritis are stratified by lymphocyte flow cytometry to select specific targeted therapies. Expert opinion: There is insufficient evidence to allow meta-analysis to stratify psoriatic arthritis patients to select specific molecular-targeted therapies. However, selecting specific biologics according to different immunophenotypes of peripheral blood lymphocytes in psoriatic arthritis was shown to produce high therapeutic responses; in other words, the potential of precision medicine was suggested. Such an approach can be applied to other diseases with various clinical features, including spondyloarthritis and systemic lupus erythematous. [ABSTRACT FROM AUTHOR]

Objectives: We evaluate the socioeconomic impact of treatment with biological and targeted synthetic disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis., Methods: We analysed data retrospectively from the prospective observational CorEvitas RA Japan Registry (March 2016-February 2020). Patients were categorised into paid workers (PWs) and home workers (HWs) and further based on drug classes. We assessed medication persistence, treatment outcomes, health care resource utilisation, and socioeconomic impact over 12 months, including direct (drugs and health care resource utilisation) and indirect (loss of productivity) costs., Results: Overall, 187 PWs and 114 HWs were identified. Over 12 months, medication persistence was high, treatment outcomes improved, and outpatient visits reduced in both groups. Following treatment initiation, direct costs increased, whereas indirect (loss of productivity) costs decreased in both groups. The unadjusted socioeconomic impact [Japanese yen (JPY)] increased across all drug classes in PWs (range: 29,700-151,700) and HWs (range: -28,700 to 83,000). Adjusted change in monthly socioeconomic impact was JPY 29,700-138,900 for PWs and JPY -28,000 to 92,800 for HWs., Conclusions: In this study of Japanese patients with rheumatoid arthritis, the socioeconomic burden increased across patient groups and drug classes. The decrease in indirect (loss of productivity) costs partially offset the increase in direct costs., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objectives: We aimed to investigate factors associated with impaired physical function [defined as Health Assessment Questionnaire Disability Index (HAQ-DI) >0.5] of old-old (aged 75-84 years) patients with rheumatoid arthritis., Methods: Data from 15,185 rheumatoid arthritis patients in the National Database of Rheumatic Disease in Japan were extracted from 2017 to 2018. We enrolled 3708 patients aged 55-84 years in Simplified Disease Activity Index (SDAI) ≤11 and Steinbrocker Stage I/II. Factors associated with HAQ-DI >0.5 were analysed by multivariable logistic regression., Results: About half of the old-old patients received methotrexate, which was lower than middle-aged (55-64 years) and young-old patients (65-74 years). The proportion of glucocorticoids in the old-old patients was highest among the three groups, and biological disease-modifying antirheumatic drugs were similarly used. The prevalence of HAQ-DI >0.5 was significantly higher in old-old patients with low disease activity than in those with remission. The same was true in the middle-aged and young-old patients. Multivariable analysis showed age, higher SDAI, glucocorticoid use, and methotrexate nonuse were significantly associated with HAQ-DI >0.5 in the old-old patients., Conclusions: Achieving SDAI remission was an ideal goal for old-old patients in terms of physical function. Glucocorticoids and a low proportion of methotrexate use may influence the physical function of old-old patients., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objective: To study the clinical effectiveness and long-term retention rate of abatacept (ABA) in elderly rheumatoid arthritis (RA) patients in daily clinical practice. Methods: A retrospective cohort study was performed using data from a multicenter registry. Our study population comprised 500 consecutive RA patients treated with ABA. We compared clinical effectiveness and ABA retention rates between the Young (≤62 years), Middle (62 to 72 years), and Elderly (≥72 years) groups. We also performed separate examinations to identify predictive factors for ABA discontinuation in those with versus those without concomitant methotrexate (MTX) treatment. Results: Mean age was 52.7 years in the Young group, 67.7 years in the Middle group, and 78.1 years in the Elderly group. No significant group-dependent differences were found in mean DAS28 score, categorical distribution of DAS28, and EULAR response rate across the 52 weeks. The ABA retention rates at three years as determined by the Kaplan-Meier method were similar in all three groups. Patient age was not a significant predictor of ABA discontinuation due to adverse events in patients with concomitant MTX; however, it was found to be a significant predictor for those who did not use MTX (Cox hazard model). Conclusion: ABA would be a reasonable treatment option for elderly RA patients from the viewpoints of both clinical effectiveness and long-term retention. However, physicians should watch carefully for any serious adverse reactions in elderly RA patients with intolerance to MTX. [ABSTRACT FROM AUTHOR]

Introduction: This open-label study evaluated the immunogenicity, safety, and efficacy of sarilumab monotherapy in patients with active, moderate-to-severe rheumatoid arthritis (RA) and inadequate response or intolerance to prior conventional synthetic disease-modifying antirheumatic drugs. Methods: Adults with RA (n = 132) were randomized to receive subcutaneous sarilumab (150 [n = 65] or 200 mg [n = 67]) every 2 weeks (q2w) for 24 weeks. Endpoints included incidence of antidrug antibodies (ADAs) at week 24, safety, and efficacy. Results: Persistent ADAs occurred in eight patients (12.3%) receiving sarilumab 150 mg q2w, seven of whom (10.8%) had neutralizing antibodies (NAbs), and in four patients (6.1%) receiving sarilumab 200 mg q2w, two of whom (3.0%) had NAbs; all exhibited low antibody titers. Infections and neutropenia were the most common adverse events (AEs). There were three serious AEs, no reports of anaphylaxis, and few hypersensitivity reactions (e.g., rash) with no notable differences in hypersensitivity reactions in ADA-positive patients relative to ADA-negative patients. Changes in absolute neutrophil count, alanine aminotransferase level, and platelet count were consistent with interleukin-6 signaling blockade and in agreement with previous observations. At week 24, overall American College of Rheumatology 20%/50%/70% improvement criteria responses were 73.8%/53.8%/29.2%, respectively, with sarilumab 150 mg q2w and 71.6%/50.7%/29.9% with sarilumab 200 mg q2w. No patients with an ADA-positive response showed loss of efficacy. Conclusions: ADA titers were low and persistent ADAs and NAbs occurred relatively infrequently in both sarilumab dose groups. ADA did not meaningfully impact the safety or efficacy of either dose of sarilumab over 24 weeks. Trial Registration: ClinicalTrials.gov, identifier NCT02121210. Funding: Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Plain Language Summary: Plain language summary available for this article. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. Methods: A retrospective cohort study was performed using data from a multicentre registry. A total of 176 consecutive rheumatoid arthritis patients treated with abatacept were included. The propensity score based on multiple baseline characteristic variables was calculated, and 41 of 86 patients treated without MTX (MTX(−)) and 41 of 90 patients treated with concomitant MTX (MTX(+)) were statistically extracted and analysed. Clinical outcomes were evaluated and compared between the two groups over a 52-week period. Results: Baseline characteristics were statistically comparable. No significant differences were observed in the following clinical outcomes from baseline throughout the 52-week period: drug retention rate (MTX(−)/MTX(+) 79.1%/80.5%), mean change in disease activity score based on 28 joints (DAS28-CRP) from baseline (− 1.35/− 1.54), low disease activity rate (48.8%/43.9%), clinical remission rate (31.7%/36.6%), moderate European League Against Rheumatism (EULAR) response rate (68.3%/68.3%), and good EULAR response rate (36.6%/41.1%) at 52 weeks. Conclusion: In rheumatoid arthritis patients with similar background characteristics undergoing abatacept treatment, concomitant MTX does not seem to affect clinical outcomes. Abatacept would be a suitable treatment option in daily clinical practice in patients with contraindications to MTX. Key Points: • This is the first study to directly compare the clinical efficacy and safety of abatacept between patients with and without concomitant methotrexate (MTX) treatment in 'real-world' settings using the propensity score matching method. • There were no significant differences in clinical outcomes of abatacept between patients with and without concomitant MTX treatment. • We used data from a large Japanese multicentre registry for biologics in rheumatoid arthritis, thereby decreasing selection bias based on the personal preferences of physicians. [ABSTRACT FROM AUTHOR]

Objectives We sought to investigate the selection of specific biological DMARDs (bDMARDs) based on characteristic lymphocyte phenotypes for treating PsA. Methods Of 64 patients with PsA resistant to MTX, 26 underwent bDMARDs therapy selected according to phenotypic differences in peripheral helper T cells on 8-colour flow cytometry. The efficacies of this strategic treatment and the standard treatment administered to the other 38 patients were evaluated at 6 months. Results The 26 patients with PsA in the strategic treatment group were classified into the following four types based on peripheral blood analysis: (i) CXCR3+CCR6−CD38+HLA-DR+ activated Th1 cell–predominant type, (ii) CXCR3−CCR6+ CD38+HLA-DR+ activated Th17 cell–predominant type, (iii) Th1/Th17-high type and (iv) Th1/Th17-low type. Accordingly, ustekinumab was administered to the activated Th1 cell–predominant patients, secukinumab to the activated Th17 cell–predominant patients, secukinumab or TNF inhibitor to the Th1/Th17-high patients, and TNF inhibitor to the Th1/Th17-low patients. After 6 months of strategic treatment, there was a significant decrease in simplified disease activity index (SDAI) (from 16.2 to 3.52), DAS28 (ESR) (from 4.13 to 2.27) and psoriasis area and severity index (from 8.36 to 2.40). Low disease activity by SDAI was achieved in 24 (92.3%) of the 26 patients. The rate of low disease activity achievement according to SDAI at 6 months was significantly higher in the strategic bDMARDs treatment group compared with that of the standard bDMARDs treatment group. Conclusion Strategic treatment in which different bDMARDs were selected according to phenotypic differences in helper T cells showed significantly higher efficacy than standard bDMARD therapy, indicating the value of precision medicine. [ABSTRACT FROM AUTHOR]

Abstract Objective To assess trends in the length and readability of informed consent forms (ICFs) for industry-sponsored multinational clinical trials (RCTs) in rheumatology over a 17-year period. Additionally, to assess the health literacy (HL) and perceptions of ICFs among participants of current RCTs. Methods The readability of ICFs conducted at an outpatient rheumatology clinic between 1999 and 2016 were assessed using the INFLESZ scale. Patients' HL was assessed using SALHSA-50 and STOFHLA. Patient opinions were assessed using a self-reported, in-office questionnaire with an independent patient sample who had signed an ICF in the past 6 months. Results Thirty-nine ICFs about 22 drugs from 13 pharmaceutical companies were analyzed. The global mean readability was 57 ± 3 (95% CI: 56–58), and all ICFs were categorized as either "somewhat difficult to read" or "average." Readability remained at these levels without significant changes from 1999 to 2016. The mean length of the ICFs written between 1999 and 2005 was 13 ± 5 pages, with a significant increase thereafter (mean 22 ± 8 pages, p = 0.004). Depending on the instrument, of 95 patients participating in the HL assessment, between 18% and 44% had limited HL. Of 90 patients participating in the perceptions questionnaire, 84% reported understanding the ICF well. However, 2–57% misunderstood basic concepts, including the study drug name and placebo. Conclusions The disparity between the readability of ICFs with patients' HL and their comprehension of ICFs continues, even after decades of attempts of regulatory agencies and numerous published suggestions. [ABSTRACT FROM AUTHOR]

• Minimal disease activity (MDA) is an attainable target in real-life psoriatic arthritis (PsA) patients. • Axial involvement in PsA (axPsA) is negatively and independently associated with MDA. • MDA depends on disease features (axPsA) and patients' characteristics (e.g. age, therapy duration, comorbidities-osteoarthritis and fibromyalgia). (1) to describe the frequency of minimal disease activity (MDA) in a real-life psoriatic arthritis (PsA) cohort, (2) to longitudinally explore predictors of MDA; (3) to examine frequency and predictors of low disease activity (LDA) in patients with axial involvement (axPsA). consecutive PsA patients in stable biological/targeted-synthetic Disease-Modifying Anti-Rheumatic Drugs (bDMARDs/tDMARDs) who attended our center were enrolled. Disease activity indices, including MDA and ankylosing spondylitis disease activity score-LDA (ASDAS-LDA) for axPsA, were evaluated at baseline and every 6 months, up to 36 months or bDMARDs/tsDMARDs discontinuation. Patients' history, BMI, comorbidities — including osteoarthritis (OA) and fibromyalgia — were collected. Variables were compared between patients who achieved sustained MDA and those who did not. Multivariable generalized estimating equation (GEE) models were built to identify predictors of MDA and ASDAS-LDA over time. Data were expressed as beta coefficient (95%CI). 104 patients were enrolled, 54% males, mean age 55.7 years; 52% had axPsA. Across all evaluations, 52–61% reached MDA, and 17–24% achieved ASDAS-LDA. AxPsA, fibromyalgia, OA and BMI≥35 were less frequently observed in patients with sustained MDA. The GEE model confirmed the following factors were significantly and independently associated with MDA: age (Beta=–0.05), bDMARDs/tsDMARDs duration (Beta=+0.31), axPsA (Beta=–1.07), fibromyalgia (Beta=–3.35), OA (Beta=–1.87), BMI≥35 (Beta=–2.53). Age (Beta=–0.01), fibromyalgia (Beta=–2.03) and OA (Beta=–1.30) were also independently associated with ASDAS-LDA. MDA is an attainable target in real-life. AxPsA represents a difficult-to-treat subset. Sustained MDA depends on disease features (axPsA) as well as patients' characteristics (e.g. age, bDMARDs/tDMARDs duration, comorbidities). [ABSTRACT FROM AUTHOR]

Objective We examined the treatment patterns among adults with rheumatoid arthritis (RA) and identified factors influencing access to traditional and biological disease modifying antirheumatic drugs (DMARDs). Methods We analyzed visits recorded in the National Ambulatory Medical Care Survey from 2005 to 2014 with a RA diagnosis. The primary outcome was DMARD use (traditional and/or biological). We included prescriptions of all RA-related treatments such as traditional and biological DMARDs, glucocorticoids, gold preparations, immunosuppressants, and non-steroidal anti-inflammatory drugs. Covariates in the logistic regression models included age, gender, race/ethnicity, type of health care coverage, provider type, geographic region, and number of comorbidities. Results Among 1405 visits with a RA diagnosis, 60.4% ( n = 807) were prescribed DMARDs and 23.8% ( n = 334) biological DMARDs. In fully adjusted models, females have 1.57 times higher odds of any DMARD use (95% confidence interval (CI): 1.02–2.46). Also, Medicare beneficiaries as compared to privately insured have 2.31 times higher odds of receiving any DMARDs (95% CI: 1.40–3.82), while visits with specialist vs. general physician are 2.38 times more associated with any DMARD use (95% CI: 1.37–4.14). For biological DMARDs, Medicare beneficiaries were at 2.58 times higher odds (95% CI: 1.42–4.70) than privately insured, while visits with specialist are at 3.37 times higher odds than general physician (95% CI: 1.40–8.23). Conclusion Visits with a specialist and Medicare beneficiaries were significantly associated with any DMARD or biological DMARD use. Additionally, contrary to prior evidence, race/ethnicity was not associated with any DMARD or biological DMARD use, which may indicate reduction in disparity of treatment access. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory joint disease. On a national level in Austria, there are currently no data available on how often and which biological disease modifying antirheumatic drugs (bDMARDs) are prescribed in patients with RA. The aim of the present study was to explore prescription patterns of bDMARDs in RA in Austria with a focus on drug survival.Methods: A retrospective data analysis of bDMARD courses of individual patients with RA that were extracted from the databases of nine Austrian health insurance funds covering 6.1 million (72%) insured people in a 4-year observation period from January 2008 to December 2011. Only patients with first prescriptions of bDMARDs were included. All patients with diagnoses other than RA were excluded.Results: A total of 2906 first prescriptions of bDMARDs were included in the present analysis and 19.35% of RA patients were on bDMARDs in Austria taking into account a prevalence of RA of 0.5%. Tocilizumab showed the longest drug survival after 1 year (73.2%), followed by abatacept which had the longest drug survival after 2 (68.2%) and 3 years (65.2%). The most frequent second bDMARDs switched to were adalimumab (n = 109, 26%), tocilizumab (n = 83, 20%) and etanercept (n = 82, 20%) and 37% of biological DMARDs were prescribed as monotherapy (ranging from 33% with infliximab to 46% with tocilizumab).Conclusions: Our analysis is based on the largest health care database available in Austria. Tocilizumab and abatacept showed the longest drug survival. Adalimumab, tocilizumab and etanercept were the most frequent DMARDs switched to. Of interest was the high number of bDMARD monotherapies. [ABSTRACT FROM AUTHOR]

Objectives: Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). Methods: Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. Results: Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. Conclusions: TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a realworld clinical setting. [ABSTRACT FROM AUTHOR]

Objective. The aim was to evaluate the incidence of serious infusion-related reactions (SIRRs) in RA treated by non-TNF-targeted biologics. Methods. We analysed data from three independent prospective registers, namely autoimmunity and rituximab, Orencia (abatacept) and RA (ORA) and Registry RoAcTEmra (tocilizumab), promoted by the French Society of Rheumatology and including patients with RA. SIRRs were defined by an occurrence during or within 24 h of an infusion and requiring discontinuation of treatment. Characteristics of patients with SIRRs were extracted from the electronic database. Results. Among the 4145 patients, SIRRs occurred in 100 patients: 56 patients with the rituximab cohort (2.8% or 0.7/100 patient-years), 15 with the abatacept cohort (1.5% or 0.6/100 patient-years) and 29 with tocilizumab (1.9% or 1/100 patient-years). No fatal SIRR occurred. A previous mild infusion reaction to non-TNF-targeted biologics was observed in a quarter of patients with SIRRs. After pooled multivariate analysis, positive anti-CCP was associated with a higher risk of SIRR (odds ratio = 2.5; 95% CI: 1.01, 6.17). Absence of concomitant treatment with a synthetic DMARD tended to be associated with a higher (risk of SIRR (odds ratio = 1.67; 95% CI: 1.00, 2.86). Conclusion. In daily practice, SIRRs are slightly more frequent than in clinical trials and rarely life threatening. In common practice, serological status (anti-CCP positivity) and absence of concomitant treatment with a synthetic DMARD increase the risk of SIRR. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To evaluate and compare the retention rate of biological disease‐modifying antirheumatic drugs (bDMARDs) in real‐life practice and identify risk factors related to remission and drug discontinuation in patients with rheumatoid arthritis (RA). Method: A total of 256 patients fulfilling criteria for RA and starting bDMARD between December 2009 and October 2014 were selected from the Rheumatic Disease Prior Authorization registry. Baseline demographic and clinical data were recorded. The cumulative probability of bDMARD discontinuation over 5 years of follow‐up and factors associated with RA remission and bDMARD withdrawal were analyzed. Results: Almost half (46%) of patients were initially treated with rituximab (RTX), with 33% treated with etanercept (ETN) and 21% with infliximab (IFX). Fewer than 10% were subsequently switched to a second bDMARD. The 1‐ and 5‐year remission rates in patients continuing their first bDMARD were 7.2% and 21.5%, respectively. At 5 years, the drug survival rates for RTX, ETN and IFX were 50%, 25% and 22%, respectively. Multivariate analysis showed that RTX was significantly associated with highest drug survival. Relative to RTX, the hazard ratios for discontinuation of IFX and ETN were 2.60 (95% confidence interval [CI] 1.53–4.42) and 2.15 (95% CI 1.36–3.42), respectively. Thirty‐nine percent of patients stopped treatments, due to inadequate response (42%), serious adverse events (22%), nonadherence (14%) or remission/low disease activity (13%). Conclusion: Over 5 years, only one‐third of patients continued using their first bDMARD. The leading cause of drug discontinuation was inadequate response. [ABSTRACT FROM AUTHOR]

Management and therapy of rheumatoid arthritis (RA) has been revolutionized by the development and approval of the first biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumor necrosis factor (TNF) α at the end of the last century. Today, numerous efficacious agents with different modes of action are available and achievement of clinical remission or, at least, low disease activity is the target of therapy. Early therapeutic interventions aiming at a defined goal of therapy (treat to target) are supposed to halt inflammation, improving symptoms and signs, and preserving structural integrity of the joints in RA. Up to now, bDMARDs approved for therapy in RA include agents with five different modes of action: TNF inhibition, T cell co-stimulation blockade, IL-6 receptor inhibition, B cell depletion, and interleukin 1 inhibition. Furthermore, targeted synthetic DMARDs (tsDMARDs) inhibiting Janus kinase (JAK) and biosimilars also are approved for RA. The present review focuses on bDMARDs and tsDMARDS regarding similarities and possible drug-specific advantages in the treatment of RA. Furthermore, compounds not yet approved in RA and biosimilars are discussed. Following the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) recommendations, specific treatment of the disease will be discussed with respect to safety and efficacy. In particular, we discuss the question of favoring specific bDMARDs or tsDMARDs in the two settings of insufficient response to methotrexate and to the first bDMARD, respectively. [ABSTRACT FROM AUTHOR]

Aim To evaluate the correlation between circulating cell-free DNA (ccfDNA) in plasma and clinical disease activities in patients with rheumatoid arthritis (RA). Method The study group included 30 patients with RA who started biological disease-modifying anti-rheumatic drugs (DMARDs) therapy. The concentration of ccfDNA in plasma was measured by quantitative real-time polymerase chain reaction at baseline to 24 weeks in every 4-week period from 30 patients and 21 healthy individuals. We also evaluated the correlation between ccfDNA and the clinical activity or the therapeutic response for biological DMARDs, using the simplified disease activity index (SDAI), Disease Activity Score of 28 joints (erythrocyte sedimentation rate) and the European League Against Rheumatism (EULAR) response criteria. Synovial fluid samples of knee joints were collected from 13 patients with RA and 12 with osteoarthritis (OA) to measure ccfDNA. Result The concentration of ccfDNA in RA patients at baseline was higher than healthy controls ( P = 0.016). After introducing biological DMARDs, ccfDNA was increased until 8 weeks from the baseline, and decreased after 12 weeks. The average of SDAI was improved in all patients enrolled. At 12 weeks after treatment, 15 patients were good responders to the EULAR response criteria, nine showed moderate response and six showed no response. ccfDNA in good responders was increased until 8 weeks, while those of moderate or no response were not ( P = 0.042). In joint fluid of RA patients, ccfDNA was remarkably increased as compared to those from OA ( P = 0.00011). Conclusion After introducing biological DMARDs, increase of ccfDNA at 8 weeks was associated with improvement of disease activities. Compared with biomarkers reported, ccfDNA is able to predict the early therapeutic effects of biological DMARDs in RA patients. [ABSTRACT FROM AUTHOR]

Introduction:Treatment with biological DMARDs (bDMARDs) has meant that remission or low disease activity (LDA) is now a realistic goal for patients with rheumatoid arthritis (RA). However, as in the case of all long-term therapies, potential side-effects give rise to concern. The main reasons for withdrawing or tapering bDMARDs are safety and the sustainability of national healthcare systems. Given these data our review has been focused on important question: whether conventional, including steroids, or bDMARDs can be reduced or even stopped in patients with stable established RA or early RA. Areas covered:The studies included in the evaluation had to be RCTs, observational studies, systematic reviews evaluating the withdrawing or tapering bDMARDs in RA patients who have been on long-term treatment and have achieved remission or LDA. A search was made in the MEDLINE and EMBASE databases from 1980 to May 2016. Expert commentary:There is curently no standardised way of identifying the patients for whom reducing bDMARD therapy is appropriate. Clinical experience and data from de-escalation studies suggest that patients with RA in sustained remission are the best target population for studying drug-tapering regimens, and that LDA should not be considered an adequate indication for bDMARD de-escalation because it could hide a persistent amount of inflammation. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to explore the cost-effectiveness of biological DMARDs (bDMARDs) compared with conventional synthetic DMARDs (csDMARDs) for RA using real-world data from Finnish registers. Methods. RA patients starting their first bDMARD and comparator patients using csDMARDs during 2007-11 were obtained from the National register of biologic treatments in Finland and the Jyväskylä Central Hospital patient records. Propensity score matching was applied to adjust for differences between bDMARD and csDMARD users. Effectiveness was measured in quality-adjusted life years (QALY) and based on the register of biologic treatments in Finland and Jyväskylä Central Hospital patient records, whereas the direct costs were obtained from relevant Finnish national registers. Patients were followed up for 2 years, and both costs and effectiveness for the second year were discounted at 3%. The incremental cost-effectiveness ratio (ICER) with 95% CI was calculated based on bootstrapped mean costs and effectiveness. Results. Of 1581 RA patients meeting study inclusion criteria, 552 bDMARD and 220 csDMARD users were included in analyses after matching. Mean costs for bDMARDs and csDMARDs were €55371 and €24 879, while mean effectiveness was 1.23 and 1.20 QALYs, respectively. Consequent ICER was €902 210/QALY. Results were confirmed in sensitivity analyses. Conclusion. The high incremental cost and the small, non-significant difference in effectiveness resulted in high ICER, suggesting that bDMARDs are not cost-effective. Regardless of matching, latent confounders may introduce bias to the results. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence and the risk factors of surgical-site infection (SSI) and delayed wound healing (DWH) in patients with rheumatoid arthritis (RA) underwent orthopedic surgery. Methods: We reviewed the records of 1036 elective orthopedic procedures undertaken in RA patients. Risk factors for SSI and DWH were assessed by logistic regression analysis using age, body mass index, disease duration, pre-operative laboratory data, surgical procedure, corticosteroid use, co-morbidity, and use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) as variables. Results: SSI and DWH were identified in 19 cases and 15 cases, respectively. One case of SSI and three cases of DWH were recorded among 196 procedures in patients using bDMARDs. Foot and ankle surgery was associated with an increased risk of SSI (odds ratio (OR), 3.167; 95% confidence interval (CI), 1.256-7.986; p=0.015). Total knee arthroplasty (TKA; OR, 4.044; 95% CI, 1.436-11.389; p=0.008) and disease duration (OR, 1.004; 95% CI, 1.000-1.007; p=0.029) were associated with an increased risk of DWH. Conclusions: Our results indicated foot and ankle surgery, and TKA and disease duration as risk factors for SSI and DWH, respectively. bDMARDs was not associated with an increased risk of SSI and DWH. [ABSTRACT FROM AUTHOR]