[Efficacy and safety of levilimab in the treatment of patients with rheumatoid arthritis].

AIM: Evaluation in real clinical practice of the effectiveness and safety of levilimab therapy in patients with highly and moderately active rheumatoid arthritis (RA). MATERIALS AND METHODS: A prospective observational study (6 months) involving 35 patients with RA (29 women and 6 men, mean age 53.17±13.2 years) who were treated at the Ochapovsky Regional Clinic Hospital of Krasnodar Region. All patients included in the study were prescribed the drug levilimab (Ilsira). RESULTS: After 1 month of observation, there was a decrease in the clinical and laboratory activity of the process in the form of a decrease in the number of painful joints - 17.0 (14.0; 20.0) vs 8.0 (6.0; 10.0); p=0.000001, number of swollen joints - 3.0 (2.0; 4.0) vs 0.0 (0.0; 0.0); p=0.000002, reduction in pain intensity according to visual analog scale - 60.0 (60.0; 70.0) mm vs 30.0 (20.0; 40.0) mm (p=0.000001). Also, by the end of the first month of therapy, there was a decrease in clinical activity indices DAS28-ESR by 43%, SDAI by 60%, CDAI by 55%. Positive dynamics of laboratory parameters were noted - a decrease in erythrocyte sedimentation rate by 76%, a decrease in C-reactive protein level by 98%. By the 6th month of therapy, a decrease in RF by 36% and ACCP by 11% was recorded, but the dynamics of these indicators did not reach statistical significance. By the end of 4 weeks of treatment, 24 (68.6%) patients showed an increase in the level of total blood cholesterol - 5.1 (3.91; 6.0) mmol/L vs 6.1 (4.99; 7.07) mmol/L (p=0.000006), while 11 (45.8%) patients from this group had initially elevated cholesterol levels (6.4±0.6 mmol/L). In 5 (14.3%) patients, an increase in alanine aminotransferase (ALT) was recorded in the 4th week - 17.0 (11.0; 25.0) U/L vs 32.0 (22.0; 43.0) U/L (p=0.000062) and aspartate aminotransferase (AST) - 19.0 (14.0; 24.0) U/L vs 25.0 (18.0; 36.0) U/L (p=0.000171), in 1 (2.85%) of the patient, an increase in ALT and AST above normal was noted (ALT 144 U/L, AST 52 U/L), which required discontinuation of levilimab. In 2 (5.7%) patients, by the end of the 4th week a decrease in the absolute number of neutrophils was registered - 3.2 (2.6; 4.0)×10E9/L vs 2.3 (2.0; 2.5)×10E9/L (p=0.002), which did not require discontinuation of treatment, since the number of cells remained more than 1×10E9/L. During treatment with levilimab 162 mg subcutaneously once a week, the proportion of patients taking prednisolone decreased from 46% at the start of therapy to 11% at the end of 6 months of therapy. CONCLUSION: Levilimab is a highly effective drug for the treatment of patients with highly and moderately active RA and has a favorable tolerability and safety profile.

Effectiveness of methotrexate and bridging glucocorticoids with or without early introduction of a 6-month course of etanercept in early RA: results of the 2-year, pragmatic, randomised CareRA2020 trial.

OBJECTIVES: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt. METHODS: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups. RESULTS: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%). CONCLUSION: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104. TRIAL REGISTRATION NUMBER: NCT03649061. CTR PILOT APPROVAL BELGIUM: S59474, EudraCT number: 2017-004054-41.

Advances in Systemic Lupus Erythematosus Treatment With Monoclonal Antibodies: A Mini-Review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs and systems. It is characterized by the production of abnormal antibodies that attack healthy cells and tissues. The disease presents a wide range of symptoms and severity, from mild to severe. Diagnosis can be complex, but the classification criteria of the American College of Rheumatology (ACR) help to facilitate it. Incidence and prevalence vary considerably worldwide, mainly affecting adult women between the third and fourth decades of life, although it can also occur in childhood. The prognosis of SLE has improved over time, but there is still a risk of irreversible organ damage. Treatment is individualized for each patient and is based on immunosuppression and the use of corticosteroids. Biological therapies, such as monoclonal antibodies, have emerged as a more specific alternative. Methotrexate, antimalarials, glucocorticoids, immunosuppressants, and monoclonal antibodies are some of the medications used to treat SLE. New therapeutic strategies are currently being developed, such as targeted therapies, immunomodulators, and biological agents. Treatment adherence, monitoring, and regular follow-up are important aspects of SLE management. This article aims to describe the characteristics of the new monoclonal antibody therapies that exist for the management of SLE.

Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study.

OBJECTIVES: Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX). METHODS: In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks (BEL/ST; reference arm) was included. PRIMARY ENDPOINT: proportion of patients achieving disease control (SLE Disease Activity Index-2000 (SLEDAI-2K) ≤2; without immunosuppressants; prednisone equivalent ≤5 mg/day) at week 52 with BEL/RTX versus BEL/PBO. Major (alpha-controlled) secondary endpoints: proportion of patients with clinical remission (week 64; clinical SLEDAI-2K=0, without immunosuppressants/corticosteroids); proportion of patients with disease control (week 104). Other assessments: disease control duration, anti-dsDNA antibody, C3/C4 and B cells/B-cell subsets. RESULTS: The modified intention-to-treat population included 263 patients. Overall, 16.7% (12/72) of BEL/PBO and 19.4% (28/144) of BEL/RTX patients achieved disease control (OR (95% CI) 1.27 (0.60 to 2.71); p=0.5342) at week 52. For major secondary endpoints, differences between BEL/RTX and BEL/PBO were not statistically significant. Anti-dsDNA antibodies and most assessed B cells/B-cell subsets were lower with BEL/RTX versus BEL/PBO. Mean disease control duration through 52 weeks was significantly greater with BEL/RTX versus BEL/PBO. CONCLUSIONS: BEL/RTX showed no superiority over BEL/PBO for most endpoints analysed; however, it led to significant improvements in disease activity markers compared with BEL/PBO. Further investigation of combination treatment is warranted. TRIAL REGISTRATION NUMBER: NCT03312907.

Axial Disease in Psoriatic Arthritis: A Challenging Domain in Clinical Practice.

Psoriatic arthritis (PsA) is a chronic inflammatory condition affecting about one-third of individuals with psoriasis. Defining axial involvement in PsA (axPsA) remains debated. While rheumatologists guide clinical practice, consensus on axPsA is still lacking. This paper explores historical and upcoming definitions from the Axial Involvement in Psoriatic Arthritis (AXIS) study, which aims to establish a validated axPsA definition. Epidemiological data reveal diverse axPsA prevalence rates, emphasizing its complex relationship with peripheral arthritis and enthesitis. Unique genetic, clinical, and radiological features differentiate axPsA from ankylosing spondylitis (AS), necessitating refined classification criteria. The recommendations from the Assessment of Spondylarthritis international Society (ASAS) provide valuable guidance due to the limited direct evidence. Emerging therapies, including interleukin-23 (IL-23) inhibitors or Janus kinase (JAK) inhibitors, are under investigation for axPsA. Currently, secukinumab, an interleukin-17 (IL-17) inhibitor, is an evidence-based option for axPsA management. However, given the variability in individual patient responses and disease manifestations, personalized, evidence-based treatment approaches remain essential for optimizing patient outcomes. In the final section, two real-life cases illustrate the challenges in managing axPsA, emphasizing the importance of tailored therapies. Achieving precision in defining axPsA remains a formidable task, making detailed criteria essential for effective strategies and improving patient outcomes.

Real-World Adherence and Drug Survival of Biologics among Patients with Ankylosing Spondylitis.

Objectives: The objective of this study was to evaluate the real-world drug survival, adherence, and discontinuation risk of biologics disease-modifying anti-rheumatic drugs (bDMARDs) among patients with ankylosing spondylitis (AS). Methods: This was a retrospective study using a computerized database. Biologic-naïve and biologic-experienced AS patients who initiated treatment with bDMARDs (tumor necrosis factor alpha inhibitors {TNF-αis} or interleukin-17 inhibitor {IL-17i}) during 2015-2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Drug survival was analyzed using Kaplan-Meier estimates. Risk of discontinuation was estimated by the Cox proportional hazard model. Results: We identified 343 eligible patients utilizing 481 lines of therapy. The mean age was 44.6 years (SD ± 13.4), 57.7% were males, and 69.7% were biologic-naïve at baseline. The proportion of highly adherent patients (PDC ≥ 0.8) in the biologic-naïve group was 63.5% for golimumab, 69.2% for etanercept, and 71.6% for adalimumab (p > 0.9). Among the biologic-experienced group, secukinumab had the highest proportion of adherent patients (75.7%) and etanercept the lowest (50.0%) reaching statistical difference (p < 0.001). The Kaplan-Meier analysis did not show a significant difference in drug survival in either the biologic-naïve or the biologic-experienced groups (p = 0.85). Multivariable analysis demonstrated a similar risk for discontinuation for etanercept, golimumab, and secukinumab compared with adalimumab, regardless of biologic-experience status. Conclusions: Adherence, drug survival, and risk for discontinuation were similar for all TNF-αis and the IL-17i SEC, regardless of biologic-experience status. As drug survival is an indirect measure of drug efficacy, n, in real-world settings, we believe caregivers can integrate these results into treatment considerations.

Does Body Mass Index Impact the Clinical Response to Dupilumab Therapy in Atopic Dermatitis? A Monocentric Study of 170 Patients.

Background: Dupilumab is a monoclonal antibody used for the treatment of moderate/severe atopic dermatitis (AD). In recent years, several studies have confirmed the positive association between AD and overweight/obesity, and a report demonstrated the effect of weight reduction on the improvement of AD symptoms. Methods: The weight of 170 patients under treatment with dupilumab was recorded at baseline and after 48 weeks (T48). Clinical monitoring was mainly conducted using the Eczema Area and Severity Index (EASI). The study aimed to assess a possible correlation between the clinical outcome of dupilumab therapy and BMI. Results: Although not statistically significant, patients with a BMI < 25 have a higher EASI percentage improvement than patients with a BMI ≥ 25 at any time point, and the percentage of overweight and obese patients that does not reach EASI-75 at T48 is higher compared to normal-weight patients (13.5% vs. 5.9%). Despite this, in the multivariate regression analysis, no baseline characteristic, including BMI, appears to increase the risk of not reaching EASI-75. In addition, the results show no differences in BMI between baseline and T48 in any age/sex group. Conclusions: The results suggest that overweight and obese patients have a lower response to dupilumab when considering the EASI score, but this difference does not appear to be clinically significant. Furthermore, dupilumab treatment does not seem to impact weight.

Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis.

OBJECTIVES: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA. METHODS: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease. RESULTS: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk. CONCLUSIONS: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.

Education level and biologic therapy are the related factors of mucosal healing in Patients with Crohn's disease.

BACKGROUND AND STUDY AIMS: Mucosal healing (MH) is a crucial indicator of therapeutic effectiveness and prognosis in Crohn's disease (CD). Rapid achievement and long-term maintenance of MH can alleviate the financial and psychological burden on patients. This study aimed to investigate the factors associated with MH in CD patients and enhance clinicians' understanding. PATIENTS AND METHODS: Patients diagnosed with CD between January 2010 and December 2019 at our hospital were included and divided into two groups based on the attainment of MH during the follow-up period. Demographic data, symptoms, disease classification, laboratory examination results, and treatments were collected and compared between the two groups. Factors with a P-value <0.2 were subjected to multivariate logistic regression analysis to identify the related factors of MH. RESULTS: Multivariate logistic regression analysis of CD patients revealed that educational level [odds ratio (OR) = 8.167, 95 % confidence interval (CI) 1.440-46.303, P = 0.018] and biological therapy (OR = 15.291, 95 % CI 1.404-166.543, P = 0.025) were associated with MH. CONCLUSION: Educational level and biological therapy are factors related to MH in CD patients. These findings suggest that the use of biological therapy and patients' better understanding of the disease contribute to achieving MH.

No difference in clinical parameters and drug retention in PsA patients receiving b/tsDMARD monotherapy versus combination with methotrexate: data from the RABBIT-SpA registry.

BACKGROUND: The potential benefit of methotrexate (MTX) in combination with biologic (b) and targeted synthetic (ts) disease modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA) is still a matter of debate. OBJECTIVES: To compare clinical and patient reported characteristics as well as drug retention rates in PsA patients receiving b/tsDMARD monotherapy or in combination with MTX. METHODS: RABBIT-SpA is a prospective longitudinal cohort study including axSpA and PsA patients. In this analysis, PsA patients were stratified into two groups: starting b/tsDMARD as monotherapy or in combination with MTX. Treatment retention was compared by drug survival analysis. RESULTS: 69% of the patients (n=900) started b/tsDMARD as monotherapy while 31% were treated in combination with MTX (n=405). At baseline, clinical domains like skin, nail and joint affection, dactylitis, enthesitis and axial involvement were similar between the groups. Only the patients' satisfaction concerning tolerability of the previous treatment was significantly better in the combination group at treatment start. Drug retention rates did not differ between the groups (p=0.4). At 6/12 months, 66%/48% of patients in monotherapy and 67%/48% in the combination group were still on their original treatment. CONCLUSIONS: We did not identify any clinical parameters with notable influence on the choice of b/tsDMARD mono or MTX-combination therapy in PsA. Drug retention rates are similar between mono and combination therapy. It seems that the decision to continue MTX at initiation of b/tsDMARDs is mostly based on the subjective tolerability of MTX treatment.

Survey of Potential Drug Interactions, Use of Non-Medical Health Products, and Immunization Status among Patients Receiving Targeted Therapies.

In recent years, several changes have occurred in the management of chronic immunological conditions with the emerging use of targeted therapies. This two-phase cross-sectional study was conducted through structured in-person interviews in 2018-2019 and 2022. Additional data sources included ambulatory medical records and the itemized reimbursement reporting interface of the National Health Insurance Fund. Drug interactions were analyzed using the UpToDate Lexicomp, Medscape drug interaction checker, and Drugs.com databases. The chi-square test was used, and odds ratios (ORs) were calculated. In total, 185 patients participated. In 53% of patients (n = 53), a serious drug-drug interaction (DDI) was identified (mean number: 1.07 ± 1.43, 0-7), whereas this value was 38% (n = 38) for potential drug-supplement interactions (mean number: 0.58 ± 0.85, 0-3) and 47% (n = 47) for potential targeted drug interactions (0.72 ± 0.97, 0-5) in 2018. In 2022, 78% of patients (n = 66) were identified as having a serious DDI (mean number: 2.27 ± 2.69, 0-19), 66% (n = 56) had a potential drug-supplement interaction (mean number: 2.33 ± 2.69, 0-13), and 79% (n = 67) had a potential targeted drug interactions (1.35 ± 1.04, 0-5). Older age (>60 years; OR: 2.062), female sex (OR: 3.387), and polypharmacy (OR: 5.276) were identified as the main risk factors. Screening methods and drug interaction databases do not keep pace with the emergence of new therapeutics.

Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.

OBJECTIVES: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT). METHODS: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking. RESULTS: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks. CONCLUSIONS: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice. TRIAL REGISTRATION NUMBER: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

Inflammatory Cytokines and Clinical Outcome Following Biological Therapy in Adult Bio-Naïve Psoriasis Patients.

Inflammatory cytokines may hold the key to the clinical evolution of psoriasis. The aims of this study are to find a correlation between levels of inflammatory cytokines such as TNF-α, IL-23, IL-17A, and IL-17F and disease duration and severity scores in psoriasis; to test if the decrease in any of the aforementioned cytokines is correlated with an amelioration in disease severity scores; and to analyze if any of the four biologic agents used are linked with a greater decrease in overall cytokine levels. We enrolled 23 adult patients under treatment with ixekizumab, secukinumab, guselkumab, or adalimumab and measured psoriasis disease severity scores PASI (Psoriasis Area Severity Index) and DLQI (Dermatology Life Quality Index), as well as the levels of the aforementioned cytokines at the start of therapy and after 3 months of continuous treatment. Inclusion criteria were the presence of psoriasis, age above 18 years and the need to initiate biological therapy (lack of response to standard treatment). Biological therapies resulted in an amelioration of PASI and DLQI scores, as well as levels of TNF-α, IL-23 and IL-17F. Disease duration and PASI and DLQI scores did not correlate with cytokine levels except DLQI and IL-23 score, in a paradoxically inversely proportional manner. IL-23, in particular, could be a useful biomarker for checking treatment response in psoriasis.

Effect of biologic agents and inflammation on lipid levels and cardiovascular risk in rheumatoid arthritis patients.

BACKGROUND: Cardiovascular disease (CVD) is the main cause of mortality in Rheumatoid Arthritis (RA). OBJECTIVE: To investigate the effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) on lipids and CVD risk and evaluate associations with changes in systemic inflammation. METHODS: Patients with RA initiating a bDMARD were evaluated at baseline, 3 and 6 months later. Longitudinal mixed effects models examined the association of individual biologics with changes in lipid levelsm Reynolds Risk Score (RRS) and Framingham risk score. Mediation by CRP, clinical disease activity index (CDAI) or swollen joint count on lipid changes were modeled using structural equation models. The correlation between CRP changes and LDL changes was estimated. Changes of LDL-C at 6 months among patients with low baseline LDL-C (<90 mg/dl) vs higher baseline LDL-C(90-130, and >130 mg/dl) were compared. The association between LDL-C changes across baseline LDL-C groups and disease activity improvement was evaluated. RESULTS: 1698 bDMARD initiations were analyzed. Patients initiating tocilizumab had a significant increase in lipid levels but RRS at 3 and 6 months was similar across all biologics. Framingham risk score increased for patients treated with tocilizumab. Mediator analyses were statistically significant for the effects of CRP on lipid levels. Increases in LDL-C from baseline were independent of clinical response. An association of changes from baseline CRP and LDL-C were observed across all of the bDMARDs studied. CONCLUSION: Moderate increases in lipid levels on bDMARD treatment were not associated with an increased CVD risk by RRS regardless of the bDMARD initiated. Changes in CRP were significantly associated with changes in lipids in a mediator analysis.

Efficacy and safety of first-line biological DMARDs in rheumatoid arthritis patients with chronic kidney disease.

OBJECTIVE: To evaluate the efficacy and safety of first-line biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with chronic kidney disease (CKD), including those undergoing haemodialysis (HD). METHODS: This retrospective cohort study included 425 patients with RA prescribed their first bDMARDs at two hospitals from 2004 to 2021. Patients were categorised by kidney function and bDMARD modality (TNFα inhibitors (TNFαis), interleukin-6 inhibitors (IL-6is), cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4-Ig)). The primary outcome was the 36-month drug retention rate, with secondary outcomes including changes in Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate (ESR), prednisolone dosage and reasons for discontinuation. RESULTS: The 36-month drug retention rates by estimated glomerular filtration rate (eGFR) (≥60, 30-60, <30 mL/min/1.73 m2) were as follows: all bDMARDs (45.2%, 32.0%, 41.4%), TNFαis (45.3%, 28.2%, 34.0%), IL-6is (47.4%, 66.7%, 71.4%) and CTLA-4Ig (50.0%, 31.3%, 33.3%). Even in groups with lower kidney function, the drug retention rate of bDMARDs was generally maintained. However, the retention rate of TNFαis was significantly lower in patients with eGFR <30 mL/min/1.73 m2. IL-6is showed the highest retention rate and the lowest discontinuation rate due to ineffectiveness in this group (HR 0.11, 95% CI 0.02 to 0.85, p=0.03). All bDMARDs improved DAS28-CRP/ESR and reduced prednisolone dosage across all groups. CONCLUSION: bDMARDs demonstrated effective and safe profiles in patients with RA with CKD, even among patients on HD. In particular, IL-6is had a significantly higher drug retention rate in patients with an eGFR of <30 mL/min/1.73 m2 and fewer discontinuations due to ineffectiveness. IL-6is were more efficacious as monotherapy compared with the other bDMARDs.

Early identification of rheumatoid arthritis: does it induce treatment-related cost savings?

OBJECTIVE: Early diagnosis and treatment-start is key for rheumatoid arthritis (RA), but the economic effect of an early versus a later diagnosis has never been investigated. We aimed to investigate whether early diagnosis of RA is associated with lower treatment-related costs compared with later diagnosis. METHODS: Patients with RA consecutively included in the Leiden Early Arthritis Clinic between 2011 and 2017 were studied (n=431). Symptom duration was defined as the time between symptom onset and first presentation at the outpatient clinic; early treatment start was defined as symptom duration <12 weeks. Information on disease-modifying anti-rheumatic drug use per patient over 5 years was obtained from prescription data from patient records. Prices were used from 2022 and 2012 (proxy of time of prescription) to study the impact of changes in drug costs. Autoantibody-positive and autoantibody-negative RA were studied separately because differences in disease severity may influence costs. RESULTS: Within autoantibody-negative RA, costs were 316% higher in the late compared with the early group (ß=4.16 (95% CI 1.57 to 11.1); €4856 vs €1159). When using 2012 prices, results were similar. For autoantibody-positive RA, costs were 19% higher in the late group (€9418 vs €7934, ß=1.19, 0.57 to 2.47). This effect was present but smaller when using 2012 prices. Within patients with autoantibody-positive RA using biologicals, late treatment start was associated with 46% higher costs (ß=1.46 (0.91 to 2.33)); higher costs were also seen when using 2012 prices. CONCLUSION: When RA is detected within 12 weeks after symptom onset, treatment-related costs were lower in both autoantibody-negative and autoantibody-positive RA. This study is the first to report how early diagnosis and treatment start impact treatment-related costs.

Clinical and structural damage outcomes in axial spondyloarthritis patients receiving NSAIDs or advanced therapies: a description of a real-life cohort.

Introduction: This study aims to describe the clinical characteristics, disease activity, and structural damage in patients with axial spondyloarthritis (axSpA) who receive chronic treatment with nonsteroideal anti-inflammatory drugs (NSAIDs) or advanced therapies in a clinical setting. Methods: Cross-sectional study on axSpA patients consecutively recruited from the outpatient clinic of a tertiary hospital. We collected data on clinical and demographic characteristics, as well as treatment patterns involving NSAIDs and advanced therapies. Structural damage was assessed using mSASSS. Results: Overall, data from 193 axSpA patients (83% ankylosing spondylitis) were gathered, with a mean disease duration of 21.4 years. Of these, 85 patients (44%) were exclusively taking NSAIDs, while 108 (56%) were receiving advanced therapies, with TNF inhibitors being the predominant choice (93 out of 108, 86.1%). Among patients using NSAIDs, 64.7% followed an on-demand dosing regimen, while only 17.6% used full doses. Disease activity was low, with a mean BASDAI of 3.1 and a mean ASDAS-CRP of 1.8. In comparison to patients under chronic NSAID treatment, those taking advanced therapies were primarily male (69.4% versus 51.8%, p = 0.025) and significantly younger (mean age of 49 versus 53.9 years, p = 0.033). Additionally, patients on advanced therapies exhibited lower ASDAS-CRP (p = 0.046), although CRP serum levels and BASDAI scores did not differ between the two groups. In the multivariable analysis, therapy (NSAID versus biological treatment) was not independently associated with ASDAS-CRP, BASDAI or mSASSS. Conclusion: This cross-sectional analysis of a real-world cohort of axSpA patients shows positive clinical and radiological outcomes for both NSAIDs and advanced therapies.

Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis.

OBJECTIVE: To evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity. PATIENTS AND METHODS: We performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score<26. Additional assessments included various cognitive tests (STROOP, forward and backward digit spans), anxiety and depression scales (Hospital Anxiety and Depression Scale), quality of life measures (Quality of Life-Rheumatoid Arthritis) and average inflammatory activity according to the 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) into high activity (DAS28≥3.2) and low activity (DAS28<3.2) groups, also CRP levels and interleukin 6 (IL-6) levels were measured using an ELISA. RESULTS: The study population comprised 140 participants, 70 patients with RA and 70 controls. Patients more frequently experienced cognitive impairment than controls (60% vs 40%; p=0.019) and had lower mean (SD) values in the MoCA (23.6 (3.9) vs 25.1 (3.4); p=0.019. As for subtests of the MoCA, involvement was more marked in patients than in controls for the visuospatial-executive (p=0.030), memory (p=0.026) and abstraction (p=0.039) domains. Additionally, patients scored lower on executive function, as assessed by the backward digit span test (4.0 (1.7) vs 4.7 (1.9); p=0.039). Cognitive impairment is associated with age and a lower educational level in the general population, and among patients with RA with educational level, obesity and average inflammatory activity (DAS28, CRP, and IL-6). CONCLUSIONS: Patients with RA with high inflammatory activity are more susceptible to cognitive impairment, which specifically affects the domains of visuospatial, memory, abstraction and executive function.