Improvement In Rheumatoid Arthritis Disease Activity Research Articles

Erosion regression in patients with rheumatoid arthritis after upadacitinib-a pilot study using high resolution peripheral quantitative computed tomography.

To evaluate whether inhibition of Janus kinases (JAK) 1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active rheumatoid arthritis (RA). This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15 mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23 ± 3.26mm3 vs control group: 1.32 ± 6.05mm3, p= 0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p= 0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p= 0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Despite a similar improvement in RA disease activity after upadacitinib compared with csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof-of-concept, open, prospective, clinical study

BackgroundA consistent connection has been increasingly reported between rheumatoid arthritis (RA), insulin resistance (IR), and type 2 diabetes (T2D). The β-cell apoptosis induced by pro-inflammatory cytokines, which could be exaggerated in the context of RA, is associated with increased expression pro-apoptotic proteins, which is dependent on JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) activation. On these bases, we aimed to evaluate if the administration of tofacitinib, a potent and selective JAK inhibitor, could simultaneously improve glycaemic parameters and inflammatory markers in patients with RA and comorbid T2D.MethodsThe primary endpoint was the change in the 1998-updated homeostatic model assessment of IR (HOMA2-IR) after 6 months of treatment with tofacitinib in RA patients with T2D. Consecutive RA patients with T2D diagnosis were included in this proof-of-concept, open, prospective, clinical study, which was planned before the recent emergence of safety signals about tofacitinib. Additional endpoints were also assessed regarding RA disease activity and metabolic parameters.ResultsForty consecutive RA patients with T2D were included (female sex 68.9%, mean age of 63.4 ± 9.9 years). During 6-month follow-up, a progressive reduction of HOMA2-IR was observed in RA patients with T2D treated with tofacitinib. Specifically, a significant effect of tofacitinib was shown on the overall reduction of HOMA2-IR (β = − 1.1, p = 0.019, 95%CI − 1.5 to − 0.76). Also, HOMA2-β enhanced in these patients highlighting an improvement of insulin sensitivity. Furthermore, although a longer follow-up is required, a trend in glycated haemoglobin reduction was also recorded. The administration of tofacitinib induced an improvement in RA disease activity, and a significant reduction of DAS28-CRP and SDAI was observed; 76.8% of patients achieved a good clinical response. In this study, no major adverse events (AEs) were retrieved without the identification of new safety signals. Specifically, no life-threatening AEs and cardiovascular and/or thromboembolic events were recorded.ConclusionsThe administration of tofacitinib in RA with T2D led to a simultaneous improvement of IR and inflammatory disease activity, inducing a “bidirectional” benefit in these patients. However, further specific designed and powered studies are warranted to entirely evaluate the metabolic effects of tofacitinib in RA patients with T2D.

Erosion Regression in Patients with RA After Upadacitinib-A Pilot Study Using High Resolution Peripheral Quantitative Computed Tomography

Background: Janus kinases inhibitor (JAKi) is a potent drug in treating patients with rheumatoid arthritis (RA). However, the effect of JAKi on finite structural changes remained uncertain. This study aims to investigate the effect of JAKi on erosion repair evaluated by high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active RA. Methods: This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with [Formula: see text]1 bone erosion on HR-pQCT. They were given upadacitinib 15mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Results: Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23± 3.26mm3vs control group: 1.32± 6.05mm3, p=0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p=0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p=0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Conclusion: Despite a similar improvement in RA disease activity after upadacitinib compared to csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

Clinical observations of osteoporosis in Japanese patients with rheumatoid arthritis.

Osteoporosis is one of the major adverse outcomes in patients with rheumatoid arthritis (RA). Recently, we and others have been reported many clinical observations related to osteoporosis in Japanese RA patients. In this article, I reviewed these findings. Japanese patients with RA have a 2-fold risk of fractures compared with those without RA. Among the fractures in Japanese RA patients, three-quarters of the fractures were non-vertebral fractures. The incidence of non-vertebral fractures did not change, despite an improvement in RA disease activity. Older age, female gender, history of fractures, history of total knee replacements, disease activity scores in 28 joints (DAS28), health assessment questionnaire disability index (HAQ-DI), low bone mineral density, glucocorticoid dose, and vitamin D deficiency were significantly associated with fractures. Older age, high body mass index (BMI), HAQ-DI, and polypharmacy were significantly associated with falls. BMI (both overweight and underweight), DAS28, and HAQ-DI were significantly associated with frailty. Half and three-quarters of Japanese men and women with RA had vitamin D deficiency, respectively. The incidence of osteonecrosis of the jaw may be higher in Japanese RA patients than in those without RA. Undertreatment of osteoporosis appears to exist in Japanese patients with RA.

Gut microbial determinants of clinically important improvement in patients with rheumatoid arthritis

BackgroundRapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between the gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity.MethodsWe conducted a retrospective, observational cohort study on patients diagnosed with RA between 1988 and 2014. Whole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points approximately 6–12 months apart. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups: MCII+ (who achieved MCII; n = 12) and MCII− (who did not achieve MCII; n = 20). Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up.ResultsWe found age to be the largest determinant of the overall compositional variance in the gut microbiome (R2 = 7.7%, P = 0.001, PERMANOVA). Interestingly, the next factor identified to explain the most variance in the gut microbiome was MCII status (R2 = 3.8%, P = 0.005). Additionally, by looking at patients’ baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Eubacterium sp. 3_1_31. Notably, patients who achieved clinical improvement had higher alpha-diversity in their gut microbiomes at both baseline and follow-up visits. Functional profiling identified fifteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine, L-methionine, and tetrahydrofolate, to be differentially abundant between the MCII patient groups. Moreover, MCII+ and MCII− groups showed significantly different fold-changes (from baseline to follow-up) in eight microbial taxa and in seven biochemical pathways. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patients will achieve MCII (balanced accuracy = 90.0%, leave-one-out cross-validation), demonstrating potential clinical utility of gut microbiome profiles.ConclusionsOur findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, modifying the gut microbiome to enhance clinical outcome may hold promise as a future treatment for RA.

Biosimilars in Saudi Arabia: a single-centre, open-label case series examining infliximab switching

Background: A biosimilar version of infliximab ( CT-P13) was recently approved for use in Saudi Arabia. Clinical data support its use in the treatment of rheumatic disease, however, there is a lack of local data regarding the efficacy and tolerability of CT-P13 among patients with rheumatological disorders in Saudi Arabia. Objectives: To investigate the feasibility, tolerability and immunogenicity of switching from originator infliximab to biosimilar infliximab, CT-P13, in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and Behçet’s disease (BD). Methodology: The study included patients who were being treated with originator infliximab in the Department of Rheumatology in Khamis Mushayt General Hospital, Saudi Arabia, and were required to switch to biosimilar infliximab (CT-P13) between January 2018 and June 2019. Patient follow-up was carried out every three months for one year. The disease activity score 28 (DAS28) was used to assess RA severity. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was used to measure disease activity in patients with AS, while BD disease activity was based on clinical assessment. Results: In total, 13 patients (six with RA, five with AS and two with BD) were switched to biosimilar infliximab. The majority (n = 11/13) remained on biosimilar infliximab throughout the follow-up period with no reported major adverse events. Overall, there was a significant improvement in RA disease activity following biosimilar treatment, with the mean DAS28 decreasing from 3.61±1.24 before biosimilar therapy to 2.63±1.54 one year after switching. Conclusion: In patients with AS, BD, or RA who switched from originator infliximab to the biosimilar, CT-P13, we did not observe any significant differences in tolerability or efficacy between biosimilar and originator. Furthermore, disease activity significantly declined in RA patients following biosimilar treatment

Effect of periodontal therapy on disease activity in patients of rheumatoid arthritis with chronic periodontitis

BackgroundEvidence have been proposed a positive association between severity of Periodontitis and Rheumatoid arthritis (RA) activity, individuals with advanced RA are more likely to develop periodontal problems compared to their non-RA counterparts, and vice versa. Studies have been suggested that RA manifest as a result of an inflammatory imbalance and autoimmunity. In this perspective, treatment modalities that lead to inhibition of proinflammatory mediators, may prove beneficial for reducing the severity of RA. This study examined the effects of non surgical periodontal therapy (NSPT) on disease activity of RA. MethodsDiagnosed patients of active rheumatoid arthritis with chronic periodontitis were recruited in this study and divided in to treatment and controls groups, both groups were similar in all demographics assessed. Treatment group (n = 20) and controls group (n = 20) underwent assessment for periodontal clinical parameters (plaque index, gingival index, probing pocket depth, clinical attachment level), Rheumatologic clinical (simplified disease activity index) and biochemical parameters(C-reactive protein, Rheumatoid factor, Anti-cyclic citrullinated protein) at baseline and 8 weeks. Serum levels of biochemical parameters were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe statistically significant (p < 0.001) reduction observed in mean values of PI, GI, PPD, CAL, SDAI in treatment group at 8weeks after NSPT as compare to control group. However serum level of ACCPA, CRP and RF did not show statistically significant (p > 0.05) changes from baseline to reassessment (8 weeks) in both groups. ConclusionsThe improvement in RA disease activity may occurs after non surgical periodontal therapy.

ACPA IgG galactosylation associates with disease activity in pregnant patients with rheumatoid arthritis

ObjectivesPatients with autoantibody-positive rheumatoid arthritis (RA) are less likely to experience pregnancy-induced improvement of RA disease activity (DAS28-C reactive protein (CRP)) compared with patients with autoantibody-negative RA. Anti-citrullinated protein antibodies...

AB0563 Impact of the history and the type of previous biologic treatment on abatacept efficacy in rheumatoid arthritis patients

BackgroundAbatacept (ABT), a selective co-stimulation modulator, is the first in a new class of biologic agents for the treatment of rheumatoid arthritis (RA). Since ABT is often used as second...

OP0024 Safety and efficacy of SBI-087 in subjects with active rheumatoid arthritis in a phase 2 randomized, double-blind, placebo-controlled study

BackgroundSBI-087 is a humanized CD20-directed SMIP™ (mono-specific protein therapeutic) that has been shown to deplete B cells in a dose dependent manner in Phase 1 studies in subjects with stable...

Comparative Effectiveness of Rituximab in Combination with Either Methotrexate or Leflunomide in the Treatment of Rheumatoid Arthritis

To compare the effectiveness and safety of a combination of rituximab (RTX) with either methotrexate (MTX) or leflunomide (LEF) in the treatment of patients with active rheumatoid arthritis (RA) and inadequate response to anti-tumor necrosis factor agents or traditional disease-modifying antirheumatic drugs (DMARD) in a real-world setting. Data from 77 consecutive unselected patients with active RA and treated with at least 1 cycle of RTX (1 g × 2 weeks) plus MTX or LEF were retrospectively collected. A comparative study between the 2 combinations of treatment (RTX+MTX and RTX+LEF) was performed at 6 months of follow-up considering 3 outcomes: the improvement of RA disease activity, the evolution of functional disability, and the tolerability and side effect profile. Of the 77 patients, 45 received RTX+MTX and 32 RTX+LEF. At baseline there were no significant differences between the groups in terms of the main clinical and laboratory data, or in the number of previous DMARD and anti-tumor necrosis factor agents used. At 6 months of follow-up, we did not find significant differences between the 2 combinations in the evolution of RA disease activity (DAS28 response, according to the European League Against Rheumatism (EULAR) improvement criteria) and functional disability progression (health assessment questionnaire) over time. Minor adverse events occurred in 9% of RTX+MTX patients and in 9% of RTX+LEF patients. None of the patients had serious adverse events and none discontinued the treatment during the study period. Our preliminary data support the view that LEF is a useful alternative if MTX is contraindicated, since its effectiveness and safety seem similar.

A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: mechanism, efficacy, and safety

Tripterygium wilfordii Hook F (TwHF) is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). Numerous preclinical studies have demonstrated that the extracts from the root of TwHF inhibit the expression of proinflammatory cytokines, proinflammatory mediators, adhesion molecules, and matrix metalloproteinases by macrophages, lymphocytes, synovial fibroblasts, and chondrocytes. TwHF also induces apoptosis in lymphocytes and synovial fibroblasts and inhibits their proliferation. Except numerous uncontrolled clinical trials, there are some prospective, double-blind, randomized, and placebo/sulfasalazine-controlled trials, also demonstrating greater improvement in RA disease activity by TwHF extract than placebo/sulfasalazine. Radiographic progression in RA may also be retarded by TwHF. Therefore, the immunosuppressive, cartilage protective, and anti-inflammatory effects of TwHF extracts are well demonstrated, and TwHF extract is an alternative disease modifying anti-rheumatic drug (DMARD) for the patients with RA refractory to conventional therapy.

The effectiveness of leflunomide as a co-therapy of tumour necrosis factor inhibitors in rheumatoid arthritis: a population-based study

Background:Randomised trials have demonstrated that the efficacy of anti-tumour necrosis factor (TNF) agents is significantly increased by concomitant methotrexate (MTX) in rheumatoid arthritis (RA). In clinical routine, anti-TNF agents are...

Overcoming drug resistance induced by P-glycoprotein on lymphocytes in patients with refractory rheumatoid arthritis

Objective:P-glycoprotein (P-gp), a member of the ATP-binding cassette transporter family, causes drug resistance by exclusion of intracellular drugs. Here, we elucidate the clinical relevance of P-gp expression on lymphocytes to...