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RMD Open May 2024To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs.
OBJECTIVE
To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting.
METHODS
Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression.
RESULTS
A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients.
CONCLUSION
Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.
Topics: Humans; Purines; Sulfonamides; Arthritis, Rheumatoid; Pyrazoles; Azetidines; Male; Female; Middle Aged; Antirheumatic Agents; Aged; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Treatment Failure; Adult; Patient Reported Outcome Measures; Severity of Illness Index
PubMed: 38816210
DOI: 10.1136/rmdopen-2024-004291 -
Respiratory Research May 2024To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome...
OBJECTIVE
To investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome (ASS).
METHODS
This study included 115 anti-Jo-1-positive patients with ASS who were admitted to China-Japan Friendship Hospital between 2009 and 2019. Anti-Jo-1 antibody serum levels at initial admission and follow-up were determined by enzyme-linked immunosorbent assay (ELISA). Global and organ disease activity was assessed at baseline and follow-up according to the International Myositis Assessment and Clinical Studies guidelines.
RESULTS
Among enrolled patients, 70 (60.9%) patients initially presented with interstitial lung disease (ILD), and 46 (40%) patients presented with with muscle weakness at initial admission. At baseline, patients with ILD had lower levels of anti-Jo-1 antibodies than those without ILD (p = 0.012). Baseline anti-Jo-1 antibody levels were higher in patients with muscle weakness, skin involvement, and arthritis (all p < 0.05) compared to those without these manifestations. Baseline anti-Jo-1 antibody levels were positively correlated with skin visual analogue scale (VAS) scores (r = 0.25, p = 0.006), but not with disease activity in other organs. However, changes in anti-Jo-1 antibody levels were significantly positively correlated with the changes in PGA (β = 0.002, p = 0.001), muscle (β = 0.003, p < 0.0001), and pulmonary (β = 0.002, p = 0.013) VAS scores, but not with skin and joint VAS scores. Older age of onset (hazard ratio [HR] 1.069, 95% confidence interval [CI]:1.010-1.133, p = 0.022) and higher C-reactive protein (CRP) levels (HR 1.333, 95% CI: 1.035-1.717, p = 0.026) were risk factors for death.
CONCLUSION
Anti-Jo-1 titers appear to correlate more with disease activity changes over time rather than with organ involvement at baseline, which provides better clinical guidance for assessing the disease course using anti-Jo-1 levels.
Topics: Humans; Myositis; Male; Female; Middle Aged; Prognosis; Adult; Antibodies, Antinuclear; Follow-Up Studies; Aged; Retrospective Studies; Biomarkers; Lung Diseases, Interstitial
PubMed: 38811943
DOI: 10.1186/s12931-024-02851-w -
Dermatology Practical & Conceptual Apr 2024Psoriasis is a systemic disease of the skin and nails associated with a wide range of comorbidities such as depression, psoriatic arthritis and metabolic syndrome.
INTRODUCTION
Psoriasis is a systemic disease of the skin and nails associated with a wide range of comorbidities such as depression, psoriatic arthritis and metabolic syndrome.
OBJECTIVES
The study aimed to examine a potential association between inflammatory markers (C- reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and depression in patients with psoriasis.
METHODS
A total of 80 individuals were enrolled in the study. Case participants included 28 patients diagnosed with Psoriasis (Beck Depression Inventory-II: :0-13) and 24 patients diagnosed with Psoriasis and Depression (Beck Depression Inventory-II:14-63). Twenty-eight (28) healthy participants comprised the control group.Psoriasis severity was evaluated by using Psoriasis Area and Severity Index, Physician Global Assessment, Body Surface Area and Dermatology Life Quality Index. Written approval was obtained for its use in this study: Cardiff University (09/2015). Other factors considered in the study were obesity using the Body Mass Index, the levels of stress using the Beck Anxiety Inventory, and the presence of insomnia using the Athens Insomnia Scale. Blood draws and inflammatory markers measurements were performed for all participants.
RESULTS
Both CRP and ESR levels were higher in the case group (ie Psoriasis and Depression and Psoriasis) compared to healthy controls. Furthermore, psoriatic patients with depression showed increased CRP and ESR levels compared to those of psoriatic patients without depression.
CONCLUSIONS
The evaluation of both CRP and ESR and their use to detect the presence of depression in patients with psoriasis can be an important tool for their holistic treatment of theirs.
PubMed: 38810053
DOI: 10.5826/dpc.1402a104 -
RMD Open May 2024To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years.
METHODS
Patients with rheumatoid arthritis and inadequate response to methotrexate were randomised to receive upadacitinib 15 mg once daily, placebo or adalimumab 40 mg every other week, all with concomitant methotrexate. By week 26, patients with insufficient response to randomised treatment were rescued; patients remaining on placebo switched to upadacitinib. Patients completing the 48-week double-blind period could enter a long-term extension. Safety and efficacy were assessed through week 264, with radiographic progression analysed through week 192. Safety was assessed by treatment-emergent adverse events (TEAEs). Efficacy was analysed by randomised group (non-responder imputation (NRI)) or treatment sequence (as observed).
RESULTS
Rates of TEAEs were generally similar with upadacitinib versus adalimumab, although numerically higher rates of herpes zoster, lymphopenia, creatine phosphokinase elevation, hepatic disorder and non-melanoma skin cancer were reported with upadacitinib. Numerically greater proportions of patients randomised to upadacitinib versus adalimumab achieved clinical responses (NRI); Clinical Disease Activity Index remission (≤2.8) and Disease Activity Score based on C reactive protein <2.6 were achieved by 24.6% vs 18.7% (nominal p=0.042) and 31.8% vs 23.2% (nominal p=0.006), respectively. Radiographic progression was numerically lower with continuous upadacitinib versus adalimumab at week 192.
CONCLUSION
The safety profile of upadacitinib through 5 years was consistent with the known safety profile of upadacitinib, with no new safety risks. Clinical responses were numerically higher with upadacitinib versus adalimumab at 5 years. Upadacitinib demonstrates a favourable benefit-risk profile for long-term rheumatoid arthritis treatment.
TRIAL REGISTRATION NUMBER
NCT02629159.
Topics: Humans; Arthritis, Rheumatoid; Adalimumab; Heterocyclic Compounds, 3-Ring; Female; Antirheumatic Agents; Male; Middle Aged; Treatment Outcome; Double-Blind Method; Adult; Methotrexate; Aged; Drug Therapy, Combination
PubMed: 38806190
DOI: 10.1136/rmdopen-2023-004007 -
Journal of Inflammation Research 2024Rheumatoid arthritis (RA) is a chronic systemic immune disease characterized by joint synovitis, but there are differences in clinical manifestations and serum test...
BACKGROUND
Rheumatoid arthritis (RA) is a chronic systemic immune disease characterized by joint synovitis, but there are differences in clinical manifestations and serum test results among different patients.
METHODS
This is a bioinformatics study. We first obtained the gene expression profile of RA and normal synovium from the database, and screened the differentially expressed immune related genes for enrichment analysis. Subsequently, we classified RA into three subtypes by unsupervised clustering of serum gene expression profiles based on immune enrichment scores. Then, the enrichment and clinical characteristics of different subtypes were analyzed. Finally, according to the infiltration of different subtypes of immune cells, diagnostic markers were screened and verified by qRT-PCR.
RESULTS
C1 subtype is related to the increase of neutrophils, C-reactive protein and erythrocyte sedimentation rate, and joint pain is more significant in patients. C2 subtype is related to the expression of CD8+T cells and Tregs, and patients have mild joint pain symptoms. The RF value of C3 subtype is higher, and the expression of various immune cells is increased. CD4 T cells, NK cells activated, macrophages M1 and neutrophils are immune cells significantly infiltrated in synovium and serum of RA patients. IFNGR1, TRAC, IFITM1 can be used as diagnostic markers of different subtypes.
CONCLUSION
In this study, RA patients were divided into different immune molecular subtypes based on gene expression profile, and immune diagnostic markers were screened, which provided a new idea for the diagnosis and treatment of RA.
PubMed: 38800595
DOI: 10.2147/JIR.S395566 -
Reumatologia 2024This study aimed to investigate the effect of vitamin D supplementation therapy on disease activity and fatigue in rheumatoid arthritis (RA) patients.
INTRODUCTION
This study aimed to investigate the effect of vitamin D supplementation therapy on disease activity and fatigue in rheumatoid arthritis (RA) patients.
MATERIAL AND METHODS
A prospective randomized clinical trial was conducted at rheumatology clinics in Tripoli Central Hospital, Libya. The eligible patients received disease-modifying antirheumatic drugs (DMARDs) and were divided into two groups: group A received 50,000 IU of vitamin D once a week; while group B received conventional DMARDs without vitamin D supplementation. The groups were monitored for 12 weeks.
RESULTS
The study included 68 RA patients, with the majority being female (75%). There were no significant differences in parameters such as age, sex, duration of illness, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), calcium, and vitamin D levels, as well as DAS28 (Disease Activity Score with 28-joint count) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) levels between these two groups at baseline. After 12 weeks, group A showed a significant improvement in mean vitamin D levels and FACIT-F scores compared to group B. The increase in vitamin D levels in group A (24.21 ±4.81 nmol/l) was higher than that in group B (5.76 ±3.36 nmol/l). Furthermore, the FACIT-F score in group A was in the normal range (mean: 39.36 ±6.15), whereas group B still exhibited "abnormal" FACIT-F < 27.75 ±4.41. Correlation analysis indicated a positive correlation between FACIT-F and vitamin D levels, suggesting that higher vitamin D levels were associated with improved fatigue. Additionally, a weak inverse correlation was observed between DAS28 and vitamin D levels though the difference was not statistically significant ( > 0.05). Finally, the correlation between DAS28 and FACIT-F was positive ( = 0.557, = 0.000).
CONCLUSIONS
The results of the recent study indicated that vitamin D (50,000 IU of cholecalciferol) supplementation had a positive impact in RA patients compared to conventional DMARDs drugs, as was clear from the significant FACIT-F.
PubMed: 38799782
DOI: 10.5114/reum/187391 -
International Journal of Molecular... May 2024The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are...
Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies.
The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are associated with autoimmunity. Peptidylarginine deiminase (PAD) enzymes can citrullinate self-proteins related to rheumatoid arthritis (RA) that induce the production of anti-citrullinated protein antibodies (ACPAs) and lead to inflammation and joint damage. The present investigation was carried out to demonstrate the expression of homologs of PADs or arginine deiminases (ADs) and citrullinated proteins in members of the human microbiota. To achieve the objective, we used 17 microbial strains and specific polyclonal antibodies (pAbs) of the synthetic peptide derived from residues 100-200 of human PAD2 (anti-PAD2 pAb), and the recombinant fragment of amino acids 326 and 611 of human PAD4 (anti-PAD4 pAb), a human anti-citrulline pAb, and affinity ACPAs of an RA patient. Western blot (WB), enzyme-linked immunosorbent assay (ELISA), elution, and a test with Griess reagent were used. This is a cross-sectional case-control study on patients diagnosed with RA and control subjects. Inferential statistics were applied using the non-parametric Kruskal-Wallis test and Mann-Whitney U test generated in the SPSS program. Some members of phyla Firmicutes and Proteobacteria harbor homologs of PADs/ADs and citrullinated antigens that are reactive to the ACPAs of RA patients. Microbial citrullinome and homolog enzymes of PADs/ADs are extensive in the human microbiome and are involved in the production of ACPAs. Our findings suggest a molecular link between microorganisms of a dysbiotic microbiota and RA pathogenesis.
Topics: Humans; Citrullination; Anti-Citrullinated Protein Antibodies; Protein-Arginine Deiminases; Arthritis, Rheumatoid; Microbiota; Protein-Arginine Deiminase Type 2; Protein-Arginine Deiminase Type 4; Female; Citrulline; Case-Control Studies; Male; Cross-Sectional Studies; Adult; Middle Aged; Hydrolases
PubMed: 38791230
DOI: 10.3390/ijms25105192 -
Biomedicines Apr 2024Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical...
Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide antibodies (ACPAs), specified as cyclic citrullinated peptide 2 (CCP2), were included. Their exhaled NO levels were measured, and the alveolar concentration, the airway compartment diffusing capacity and the airway wall concentration of NO were estimated using the Högman-Meriläinen algorithm. The disease activity was measured using the Disease Activity Score for 28 joints. Serum samples were analysed for anti-CCP2, rheumatoid factor, free secretory component, secretory component containing ACPAs, antibodies against (Rgp) and total levels of IgA, IgA1 and IgA2. Significant negative correlations were found between the airway wall concentration of NO and the number of swollen joints (Rho -0.48, = 0.004), between the airway wall concentration of NO and IgA rheumatoid factor (Rho -0.41, = 0.017), between the alveolar concentration and free secretory component (Rho -0.35, = 0.023) and between the alveolar concentration and C-reactive protein (Rho -0.36, = 0.016), but none were found for anti-CCP2, IgM rheumatoid factor or the anti-Rgp levels. In conclusion, altered NO levels, particularly its production in the airway walls, may have a role in the pathogenesis of ACPA-positive RA.
PubMed: 38790926
DOI: 10.3390/biomedicines12050964 -
Arthritis Research & Therapy May 2024Previously, fragments from Sirtuin 1 (SIRT1) were identified in preclinical and clinical samples to display an increase in serum levels for N-terminal (NT) SIRT1 vs....
BACKGROUND
Previously, fragments from Sirtuin 1 (SIRT1) were identified in preclinical and clinical samples to display an increase in serum levels for N-terminal (NT) SIRT1 vs. C-terminal (CT) SIRT1, indicative of early signs of OA. Here we tested NT/CT SIRT1 levels as well as a novel formulated sandwich assay to simultaneously detect both domains of SIRT1 in a manner that may inform us about the levels of full-length SIRT1 in the circulation (flSIRT1) of clinical cohorts undergoing knee joint distraction (KJD).
METHODS
We employed an indirect ELISA assay to test NT- and CT-SIRT1 levels and calculated their ratio. Further, to test flSIRT1 we utilized novel antibodies (Ab), which were validated for site specificity and used in a sandwich ELISA method, wherein the CT-reactive served as capture Ab, and its NT-reactive served as primary detection Ab. This method was employed in human serum samples derived from a two-year longitudinal study of KJD patients. Two-year clinical and structural outcomes were correlated with serum levels of flSIRT1 compared to baseline.
RESULTS
Assessing the cohort, exhibited a significant increase of NT/CT SIRT1 serum levels with increased osteophytes and PIIANP/CTX-II at baseline, while a contradictory increase in NT/CT SIRT1 was associated with less denuded bone, post-KJD. On the other hand, flSIRT1 exhibited an upward trend in serum level, accompanied by reduced denuded bone for 2-year adjusted values. Moreover, 2 year-adjusted flSIRT1 levels displayed a steeper linear regression for cartilage and bone-related structural improvement than those observed for NT/CT SIRT1.
CONCLUSIONS
Our data support that increased flSIRT1 serum levels are a potential molecular endotype for cartilage-related structural improvement post-KJD, while NT/CT SIRT1 appears to correlate with osteophyte and PIIANP/CTX-II reduction at baseline, to potentially indicate baseline OA severity.
Topics: Humans; Sirtuin 1; Female; Male; Middle Aged; Enzyme-Linked Immunosorbent Assay; Osteoarthritis, Knee; Adult; Cartilage, Articular; Longitudinal Studies; Knee Joint; Biomarkers; Aged
PubMed: 38790038
DOI: 10.1186/s13075-024-03342-5 -
Diagnostics (Basel, Switzerland) May 2024Psoriatic disease (PsD) affects multiple clinical domains and causes a significant inflammatory burden in patients, requiring comprehensive evaluation and treatment. In...
Psoriatic disease (PsD) affects multiple clinical domains and causes a significant inflammatory burden in patients, requiring comprehensive evaluation and treatment. In recent years, new molecules such as JAK inhibitors (JAKinhibs) have been developed. These have very clear advantages: they act quickly, have a beneficial effect on pain, are well tolerated and the administration route is oral. Despite all this, there is still little scientific evidence in daily clinical practice. This observational, retrospective, single-center study was carried out in patients diagnosed with PsA in the last two years, who started treatment with Tofacitinib or Upadacitinib due to failure of a DMARD. The data of 32 patients were analyzed, and the majority of them (75%) started treatment with Tofacitinib. Most had moderate arthritis activity and mild psoriasis involvement according to activity indices. Both Tofacitinib and Upadacitinib demonstrated significant efficacy, with rapid and statistically significant improvement in joint and skin activity indices, C-reactive protein reduction, and objective measures of disease activity such as the number of painful and inflamed joints. Although there was some difference in the baseline characteristics of the cohort, treatment responses were comparable or even superior to those in the pivotal clinical trials. In addition, there was a low frequency of mild adverse events leading to treatment discontinuation and no serious adverse events. These findings emphasize the strong efficacy and tolerability of JAKinhibs in daily clinical practice, supporting their role as effective therapeutic options for patients with PsD.
PubMed: 38786286
DOI: 10.3390/diagnostics14100988