Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Factors Associated With Maintenance of Remission Following Change From Combination Therapy to Monotherapy in Patients With Rheumatoid Arthritis

Objective Some patients with rheumatoid arthritis (RA) who persist in remission may decide to stop their therapy. We evaluated baseline characteristics associated with remaining in remission or low disease activity (LDA) following medication withdrawal. Methods The Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis (SEAM-RA) was a phase III, multicenter, randomized withdrawal, double-blind, controlled study in patients with RA on methotrexate (MTX) + etanercept (ETN). If remission (Simplified Disease Activity Index [SDAI] ≤ 3.3) was sustained through a 24-week run-in period, patients then entered a 48-week double-blind period and were randomized 2:2:1 to receive MTX monotherapy, ETN monotherapy, or continue combination therapy. Multivariate logistic regression analysis was performed to identify baseline factors associated with remission or LDA at the end of both periods. Results Of 371 patients enrolled, 253 entered the double-blind period. After adjusting for other factors, covariates associated with achieving SDAI remission at the end of the run-in period included younger age, longer duration of MTX treatment, and less severe clinical disease variables. Covariates associated with maintaining remission/LDA at the end of the 48-week double-blind period included lower patient global assessment of disease activity (PtGA), lower C-reactive protein, rheumatoid factor (RF) negativity, longer RA duration in the MTX arm, shorter duration of ETN treatment, and lower magnesium. Conclusion These findings indicate patients with overall lower disease activity are more likely to remain in SDAI remission/LDA after switching from combination therapy to monotherapy. RF-negative status and lower PtGA scores were strongly associated with increased likelihood of remaining in remission/LDA with MTX or ETN monotherapy. (SEAM-RA; ClinicalTrials.gov: NCT02373813

Tocilizumab Patterns of Use, Effectiveness, and Safety in Patients with Rheumatoid Arthritis : Final Results from a Set of Multi-National Non-Interventional Studies

INTRODUCTION: The objective of this study was to observe the patterns of usage, efficacy, and safety of tocilizumab (TCZ) in clinical practice in patients with rheumatoid arthritis. METHODS: Data on the real-world usage, efficacy, and safety of TCZ were collected from patients during routine follow-up visits conducted over a 6-month period. Patients were grouped by previous exposure to biologic therapies (biologic exposed vs. biologic naive). RESULTS: Of 1912 patients enrolled from 16 countries, 639 (33.4%) received TCZ monotherapy and 1273 (66.6%) received TCZ combination therapy. At baseline, 1073 patients (56.1%) were biologic naive and 839 (43.9%) were biologic exposed. At 6 months, 1504 patients (78.7%) continued to receive TCZ treatment, with no descriptive differences in retention rates between biologic-exposed and biologic-naive patients and between patients receiving TCZ monotherapy or combination therapy. Dose and use of methotrexate and prednisone were reduced at 6 months. Efficacy at 6 months, including patient-reported outcomes, was demonstrated in both biologic-naive and biologic-exposed groups. Adverse events (AEs) occurred in 817 patients [42.7%; incidence rate: 179 events per 100 patient-years (PY)], and serious AEs (SAEs) occurred in 118 patients (6.2%; 17 events per 100 PY), with comparable rates of AEs and SAEs between subgroups. CONCLUSION: In routine clinical practice, TCZ discontinuation rates were low and unaffected by prior use of biologics. Effectiveness was similar between groups, and no new safety signals were identified

Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (similar to 10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile

Intracapsular pressure and interleukin-1β cytokine in hips with acetabular dysplasia

Background and purpose Several studies have demonstrated an increased intracapsular pressure in several hip disorders such as septic arthritis, synovitis, and trauma. We therefore measured the intracapsular pressure in different positions in early dysplasic hips and its relation to the concentration of interleukin-1β (IL-1β), the volume of joint fluid, and the clinical and radiographic findings before a periacetabular osteotomy

Safety and effectiveness of switching from infliximab to etanercept in patients with rheumatoid arthritis: results from a large Japanese postmarketing surveillance study

Finding an effective treatment strategy for rheumatoid arthritis (RA) patients who have not benefited from previous tumor necrosis factor–α antagonist treatment is important for minimizing RA disease activity and improving patient outcomes. The aim of this study was to compare the safety and effectiveness of etanercept in patients with and without infliximab (IFX) treatment experience. Patients (n = 7,099) from a large postmarketing observational study of etanercept use in Japan were divided into 2 cohorts based on previous IFX use (pre-IFX and non-IFX). Baseline characteristics were assessed in each cohort. Adverse events (AEs) and European League Against Rheumatism (EULAR) responses were monitored every 4 weeks for 24 weeks. At baseline, pre-IFX patients were younger and had fewer comorbidities and a shorter RA duration than non-IFX patients. During the study, pre-IFX patients received concomitant methotrexate more often than non-IFX patients. The incidence of AEs and serious AEs were significantly lower in pre-IFX patients, as was the percentage of patients who discontinued treatment. Both cohorts had significant improvement (P < 0.001) in EULAR responses at the end of the treatment period. This study demonstrated that etanercept was effective and well tolerated in active RA patients with and without prior IFX treatment

Distinct gut microbiota signatures are associated with severity of metabolic dysfunction-associated steatotic liver disease in people with HIV

The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to severe forms, including metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis, involves metabolic dysfunction, genetics, and gut dysbiosis. People with HIV (PWH) represent a high-risk group for MASLD, but the role of gut microbiota alterations in disease severity within this population remains poorly understood. We prospectively recruited PWH with MASLD, defined as the controlled attenuation parameter (CAP) ≥ 238 dB/m, and excluded those with viral hepatitis coinfection or alcohol abuse. Severe MASLD was defined as the presence of MASH (cytokeratin-18 ≥ 130.5 U/L) and/or significant liver fibrosis (liver stiffness ≥ 7.1 kPa). Stool samples were collected for 16S rRNA gene sequencing to characterize gut microbiota composition. Functional predictions were generated using PICRUSt. The differential abundance of bacterial taxa and predicted functions were analyzed using a generalized linear model with a negative binomial distribution. Among 34 PWH with MASLD, 18 (53%) met the criteria for severe MASLD. Microbiota profiling revealed significant differences in bacterial genera between the PWH with and without severe MASLD. Enrichment was observed in the Ruminococcus gnavus group, Negativibacillus, Holdemanella, Subdoligranulum, the Eubacterium hallii group, and Butyricicoccus, while depletion was seen in Prevotella, Alloprevotella, Dialister, Catenibacterium, the Christensenellaceae R 7 group, Clostridium sensu stricto, Olsenella, Oscillospiraceae UCG-005, Libanicoccus, and the Eubacterium siraeum group. Predicted functional pathways related to fatty acid degradation, folate biosynthesis, and amino acids metabolism did not differ between groups. MASLD severity in PWH is associated with a distinct gut microbiota signature, though not with functional pathway alterations. Microbial profiling may complement existing non-invasive biomarkers for risk stratification in this high-risk population

An open-label pilot study of the effectiveness of adalimumab in patients with rheumatoid arthritis and previous infliximab treatment: relationship to reasons for failure and anti-infliximab antibody status

This prospective open-label pilot study evaluated the effectiveness and safety of adalimumab and the relationship to antibodies against infliximab (IFX) in adult patients with active rheumatoid arthritis (RA) who had been treated previously with IFX and experienced treatment failure owing to lack or loss of response or intolerance. Patients self-administered adalimumab 40 mg subcutaneously every other week for 16 weeks, followed by maintenance therapy for up to Week 56. Measures of effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, 28-joint Disease Activity Score, and the Health Assessment Questionnaire Disability Index. Serum IFX concentrations, human antichimeric antibody against IFX (HACA), adalimumab serum concentrations, antiadalimumab antibody, and safety also were assessed. Of the 41 enrolled patients, 37 completed 16 weeks and 30 completed 56 weeks of treatment. Patients experienced clinically meaningful improvements in all measures of RA activity, with greater response rates observed for patients who had experienced loss of initial response to or intolerance of IFX. At Week 16, 46% of patients achieved an ACR20 and 28% achieved an ACR50; 61% achieved an at least moderate and 17% achieved a good EULAR response. Clinical benefit was maintained through Week 56 in all effectiveness parameters. Baseline HACA status did not significantly impact effectiveness. No new safety signals were observed; neither former IFX intolerance status nor baseline HACA status had a clinically relevant impact on adverse event frequency or severity. Adalimumab was effective and well-tolerated in patients with RA who previously failed IFX therapy, irrespective of reason for discontinuation and of HACA status