Use Of bDMARDs Research Articles

Clinical characteristics of flares in patients with rheumatoid arthritis after total hip and total knee arthroplasty.

Clinical characteristics of flares in patients with rheumatoid arthritis after total hip and total knee arthroplasty.

Knowledge mapping of biological disease-modifying anti-rheumatic drugs for axial spondyloarthritis: a bibliometric study.

Various biological disease-modifying anti-rheumatic drugs (bDMARDs) have been applied for treating axial spondyloarthritis (axSpA). However, there is a glaring absence of a bibliometric analysis on bDMARDs against axSpA. Articles related to use of bDMARDs in treating axSpA published from 2004 to 2022 were searched from the Web of Science Core Collection. VOS viewer 1.6.18 and CiteSpace 6.1.R2 were used to analyze and visualize the quantity and citations of publications, as well as to identify "research hotspots" and trends in this field. BibExcel version 1.0.0 and gCLUTO version 1.0 were used to build matrices for bi-clustering analysis. A total of 2546 articles referring to bDMARDs for treatment of axSpA were included in this bibliometric analysis. Overall, the number of publications has been increasing steadily annually. The USA (23.21%, 591 publications) ranked first with the largest output of papers, followed by Germany, and the Netherlands. Rheumazentrum Ruhrgebiet ranked first as the most frequent publisher (119 articles). Annals of the Rheumatic Diseases published the most documents (6.76%, 172 publications) in this field. The predominant hotspots have been "tuberculosis," "IL-17," and "quality of life" in the field until 2020. Since 2015, "biosimilar pharmaceuticals" has retained the popularity. Current research hotspots are "spinal radiographic progression," Janus kinase (JAK) inhibitors, and adverse events (AEs). Machine learning has become popular gradually. Globally, there has been a steady increase in the number of studies on bDMARDs use against axSpA. JAK inhibitors, spinal radiographic progression, biosimilar pharmaceuticals, and AEs are current research hotspots. Machine learning is emerging research hotspots and trends in this field.

Risk of infection from glucocorticoid and methotrexate interaction in patients with rheumatoid arthritis using biologics: A retrospective cohort study.

This retrospective cohort study aimed to evaluate the effect of the interaction between methotrexate and glucocorticoids on the risk of developing bacterial infections in patients with rheumatoid arthritis (RA) using biological disease-modifying antirheumatic drugs (bDMARDs). We used the 2005-2018 JMDC claims database, a nationwide claims database in Japan. From the database of 7 175 048 patients, study patients were obtained by applying the following exclusion criteria: no use of bDMARDs; without information on the date of prescription; without RA as a disease; other than the new users of bDMARDs; and age <18 years. The exposures were glucocorticoids and methotrexate, and the outcome was bacterial infection. The interaction effects were examined using multivariate Cox regression analysis. Bacterial infections were identified according to antibiotic prescription and International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. A total of 2837 RA patients were identified, with a median age of 50 years. The incidence of infection was 16.8% (95% confidence interval: 15.5-18.3). The interaction term for the doses of glucocorticoids and methotrexate was significant. Additionally, a higher dose of glucocorticoid was a significant risk factor for developing bacterial infections on the side of high doses of methotrexate. The incidence of bacterial infections tended to increase significantly with increasing methotrexate doses coprescribed with glucocorticoids ≥5 mg or glucocorticoid doses coprescribed with methotrexate ≥8 mg. Our results indicate a potential association between methotrexate dose and bacterial infections during bDMARDs administration with glucocorticoids in patients with RA.

Vaccinology in pediatric rheumatology: Past, present and future.

With the introduction of biological disease-modifying antirheumatic drugs (bDMARDs), the treatment of pediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) has advanced from the "Stone Age" to modern times, resulting in much better clinical outcomes. However, everything comes with a price, and use of new bDMARDs has resulted in an increased risk of infections. Therefore, preventing infections in pedAIIRD patients is one of the top priorities. The most effective preventive measure against infection is vaccination. The first study on humoral immunity after vaccination in pediatric rheumatology was published in 1974 and on safety in 1993. For many years, data about safety and immunogenicity in pedAIIRD patients were available only for non-live vaccines and the first studies on live-attenuated vaccines in pedAIIRD patients treated with immunosuppressive therapy were available only after 2007. Even today the data are limited, especially for children treated with bDMARDs. Vaccinations with non-live vaccines are nowadays recommended, although their long-term immunogenicity and efficacy in pedAIIRD patients are still under investigation. Vaccinations with live-attenuated vaccines are not universally recommended in immunosuppressed patients. However, measles-mumps-rubella booster and varicella zoster virus vaccination can be considered under specific conditions. Additional research is needed to provide more evidence on safety and immunogenicity, especially regarding live-attenuated vaccines in immunosuppressed patients with pedAIIRD. Due to the limited number of these patients, well-designed, prospective, international studies are needed. Further challenges were presented by the COVID-19 pandemic. This mini review article reviews past and present data and discusses the future of vaccinology in pediatric rheumatology.

Patterns and factors associated with pneumococcal vaccination in a prospective cohort of 1,697 patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort. Multi-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later. One thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58-59.85), history of cancer (OR = 2.35, 95% CI: 1.09-5.06), bDMARD use (OR = 1.85, 95% CI: 1.29-2.65), seropositivity (OR = 1.47, 95% CI: 1.05-2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17-1.51). Male sex (OR = 0.65, 95% CI: 0.43-0.99) was a negative predictor for pneumococcal vaccination during follow-up. Despite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a "vaccination culture" in RA patients.

Tuberculosis in patients using biological disease-modifying antirheumatic drugs

Aim: In rheumatic diseases, the possibility of developing tuberculosis (TB) increases due to both the disease itself and the biological disease-modifying antirheumatic drugs (bDMARDs) used for treatment. In our study, we aimed to investigate the causes and risk factors of TB infection in patients using bDMARDs for rheumatological diseases.Methods: Demographic, radiological, laboratory data, tuberculin skin test (TST) results, duration of disease, and medications used in TB patients were recorded in 531 patients who were using bDMARD with the diagnosis of rheumatologic disease.Results: TB developed in 5 (0.9%) of 531 patients. TB was detected in 10% of the anakinra users, 2.4% of the infliximab users, 1.4% of the certolizumab users, 1.2% of the etanercept users, and 0.9% of the adalimumab users. The mean duration of bDMARD use until TB development was 28 months. All the cases were female, and the mean age was 53.8 years.Conclusion: Our study highlights the importance of routine chest X-ray, cervical-supraclavicular lymphadenopathy (LAP) examination, annual TST follow-up, and symptom questioning in TST-negative or anergic patients using bDMARDs.

Antirheumatic treatment, disease activity and risk of Staphylococcus aureus bacteraemia in rheumatoid arthritis: a nationwide nested case–control study

ObjectivesTo assess how biological disease-modifying antirheumatic drugs (bDMARDs), glucocorticoids and disease activity affect risk of Staphylococcus aureus bacteraemia (SAB) in patients with rheumatoid arthritis (RA).MethodsIn a nationwide cohort of patients...

Real-world comparative effectiveness of bDMARDs and JAK inhibitors in elderly patients with rheumatoid arthritis.

In this retrospective cohort study, we compared the retention rates and effectiveness of biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (targeted disease modifying antirheumatic drug [tsDMARDs]: Janus kinase inhibitors [JAKi]) in elderly patients with RA. One hundred thirty-four elderly RA patients (≥65 years) who were initiated with bDMARDs (n = 80) or JAKi (n = 54) between 2016 and 2020 in our institute were enrolled in this analysis. Follow-up was conducted at 4-week intervals from the start of bDMARDs or JAKi. We compared the drug retention and clinical response at 24 week between elderly RA patients treated with bDMARDs and JAKi. In the demographic data, more disease duration, the proportion of previous bDMARDs use and less the proportion of glucocorticoid use in JAKi group was significantly observed compared to the bDMARDs group. Otherwise, there was no significant difference in the other variables between the bDMARDs and JAKi groups. In the JAKi group, drug retention rate was not significantly different compared to the bDMARDs group (HR: 0.723, 95% CI: 0.406–1.289, P = .266). Also, there was no significant difference in the proportion of patients achieving good or moderate European alliance of associations for rheumatology (EULAR) response at 24 week between these two groups (bDMARDs; 88.6% vs JAKi; 91.8%, P = .158). In elderly RA patients initiated with bDMARDs or JAKi, drug retention rates of these targeted therapies did not differ significantly between these two groups. These findings suggest that elderly RA patients can achieve similar clinical improvement after initiating bDMARDs or JAKi.

Dynamics of patient reported outcomes during the use various biological disease-modifying antirheumatic drugs for rheumatoid arthritis

One of the main tasks of modern complex therapy of rheumatoid arthritis (RA) is to improve the quality of life of patients. To do this, it is necessary not only to achieve remission or low activity, but also to successfully control the main, most painful, manifestations of the disease. Therefore, when evaluating the results of RA treatment, the dynamics of not only standard indices (DAS28 (Disease Activity Score 28), CDAI (Clinical Disease Activity Index), SDAI (Simplified Disease Activity Index)), but also the so-called “patient reported outcomes” (PRO) – a patient’s global assessment of disease activity (PGA), pain, functional disorders and fatigue.This review examines the effect of one of the main classes of anti–rheumatic drugs - biological disease-modifying antirheumatic drugs (bDMARDs) on the PROs. The results of a series of randomized controlled trials are presented, in which changes in PROs were studied using various tumor necrosis factor α (TNF-α) inhibitors, abatacept T-lymphocyte co-stimulation inhibitor, rituximab CD20 inhibitor and interleukin (IL) 6 inhibitors.The use of bDMARDs in combination with methotrexate (MTX) provides a reduction in PGA and pain by 50-60%, functional disorders according to HAQ (Health Assessment Questionnaire) and fatigue according to FACIT-F (Functional Assessment of Chronic Illness Therapy – Fatigue) – by 15-30%. B DMARDs monotherapy (with the exception of the effect of tocilizumab on HAQ) does not exceed MTX monotherapy in its effect on PROs. Monotherapy with tocilizumab provides more favorable dynamics of PGA and pain than monotherapy with TNF-α inhibitors. An important advantage of IL-6 inhibitors is the rapid achievement of a clinical effect, which is noted already in the first 2 weeks after the first administration of the drug.

Serum cholesterol loading capacity on macrophages is linked to coronary atherosclerosis and cardiovascular event risk in rheumatoid arthritis

ObjectivesCholesterol loading capacity (CLC) describes the ability of serum to deliver cholesterol to cells. It is linked to foam cell formation, a pivotal step in atherosclerotic plaque development. We evaluate...

PHARAO study: drug treatment of inflammatory rheumatic diseases : Guideline-conform treatment with biologics follows availability of biosimilars

With the introduction of tumor necrosis factor (TNF) alpha inhibitors, the treatment of inflammatory rheumatic diseases (IRD) has undergone afundamental change. Several of the originally high-priced biologics are now accessible as lower cost biosimilars, removing asignificant impediment to prescription. The present study investigated whether the availability of biosimilars is associated with an improvement in the care of IRD. Moreover, the subjective acceptance of biosimilars by physicians and patients was investigated and compared with objectifiable parameters. Pseudonymized claims data of the Bavarian Association of Statutory Health Insurance Physicians from 2014 to 2019 as well as apaper and pencil survey of patients and rheumatologists formed the data basis of the study. During the observation period, the proportion of diagnosed patients receiving drug therapy increased from 38.5% to 43.2%. Also, the care changed in terms of the prescribed agents. Conventional drug therapy declined overall and, in particular, glucocorticoid prescriptions decreased from 39.3% in 2014 to 34.3% in 2019. At the same time, the proportion of targeted treatments increased from 12.3% to 20.4%. The median duration of basic treatment before first-time bDMARD use dropped from 3.15years in 2014 to 2.17years in 2019. Over the observation period, in which three biosimilars entered the market, the care of patients with IRD improved both quantitatively and qualitatively. The market share of biosimilars increased in parallel with this development. With an overall high acceptance of biosimilars, the assessment of the disease course by physicians and patients indicates aslight subjectively perceived advantage of therapy with originals compared to biosimilars, which, however, is not confirmed when standardized scores are applied. Apossible explanation for this might be anocebo effect, which could be minimized by suitable communication strategies.

Clinical and economic evaluation of the use of biologic disease-modifying antirheumatic drugs and targeted synthetic antirheumatic drugs for ankylosing spondylitis in context of the Russian healthcare system

Objective: clinical and economic evaluation of the use of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), Janus kinase inhibitors (iJAK), for the treatment of ankylosing spondylitis (AS).Patients and methods. Among comparison technologies for further analysis were included: adalimumab (ADA), golimumab (GLM), ixekizumab (IXE), secukinumab (SEC), tofacitinib (TOFA), certolizumab pegol (CZP), upadacitinib (UPA), etanercept (ETC). The efficacy and safety of the bDMARDs and tsDMARDs included in the study were evaluated based on the results of a systematic search and analysis of data on the comparative clinical efficacy and safety of their use. Any phase III randomized controlled trials of drugs used to treat active AS in adults (age ≥18) were considered as an investigational treatment versus placebo or versus another active drug. Analysis of the economic consequences of the use of bDMARDs and tsDMARDs for AS treatment was carried out only taking into account drug therapy. For the clinical and economic evaluation of the use of bDMARDs and tsDMARDs, the cost minimization indicator was calculated. As a criterion for clinical and economic efficiency and for the analysis of the impact on the budget, the cost per responder (CpR) indicator was estimated, which was calculated based on the cost of treating AS by the time the response was achieved according to the ASAS20/40 criteria and BASDAI50.Results and discussion. The results of the meta-analysis indicated a greater effectiveness of bDMARDs and iJAK compared with placebo in terms of the frequency of achieving ASAS 20/40, BASDAI 50 criteria. From an economic point of view, compared with the reference (minimum) value (ETC biosimilar, Erelzi®), the difference in the treatment cost of 1 patient with AS during the year varied widely (from +4.22 to +40.29%) and depended on the selected therapy option. At the same time, UPA 15 mg was characterized by the lowest cost of a course of treatment in the first year among original drugs. Among the original drugs, the lowest CpR values before reaching the ASAS20 criterion were in ADA (380,986.58 rubles), ETC (426,868.81 rubles), GLM (559,619.28 rubles) and UPA 15 mg (582,003.89 rub.), according to the ASAS40 criterion – for ADA (534,518.49 rubles.), ETC (726,347.45 rubles) and UPA 15 mg (557,753.73 rubles), according to the BASDAI50 criterion – for ADA (488,911.11 rubles), ETC (636,386.99 rubles) and UPA 15 mg (640,204.28 rubles).Conclusion. The study confirmed the clinical and economic feasibility of using various options for treatment of AS in real practice, including bDMARDs and iJAK. At the same time, the use of original drugs is not always associated with significant costs per 1 patient who responded to treatment. The creation of full-fledged patient registries will make it possible to introduce a system for monitoring clinical outcomes depending on the chosen treatment strategy, as well as smooth out the assumptions and limitations that are used in the study of the clinical and economic aspects of medical technologies, which will save resources and increase the availability of drugs for patients with rheumatic diseases.

HLA-Cw6 allele and biologic therapy are protective factors against liver fibrosis in psoriatic arthritis patients.

To evaluate the association between liver fibrosis and the HLACw6 allele in psoriatic arthritis (PsA) patients. A retrospective longitudinal study involving PsA patients with determination of the HLA-Cw6 allele was performed. Liver fibrosis was estimated by using the FIB-4 (fibrosis-4) score. A multivariate logistic model was undertaken to assess the odds ratio (OR), with its 95% confidence interval, of liver fibrosis after adjustment for potential confounding factors. A total of 209 PsA patients were included: 25.3% HLA-Cw6 were positive, 59.8% were receiving biological disease-modifying anti-rheumatic drugs (bDMARDs), 29.6% had arterial hypertension (AHT), 24% dyslipidaemia, and 4.2% acute myocardial infarction (AMI). The HLA-Cw6 allele was more frequent in PsA patients with normal FIB-4 values (p=0.024), as opposed to AHT (p=0.002), AMI (p=0.023) and dyslipidaemia (p=0.030), which were found more frequently in subjects with altered FIB-4 values. The presence HLA-Cw6 and the use of bDMARDs were confirmed as protective factors against liver fibrosis (OR 0.210, 0.062-0.707, p=0.012 and OR 0.397, 0.166-0.949, p=0.038, respectively). Conversely, AHT emerged as a risk factor (OR 2.973, 1.125-7.858, p=0.028). In PsA, the HLA-Cw6 allele and bDMARDs behave as protective factors for liver fibrosis, while AHT is an independent risk factor.

Effectiveness and baseline predictive factors for Tofacitinib response in rheumatoid arthritis in a real-world setting: A national multicenter study

Background: Evidence of effectiveness and safety of tofacitinib (TOF) in the real-world setting in Latin America is currently limited and crucial to complement long-term extension data from randomized controlled trials. Methods: Patients initiated on TOF between 2014 and 2020 with RA (ACR/EULAR, 2010 criteria) were analyzed. The primary end point at month 3 was remission measured by DAS28-ESR. Secondary end points included prognostic factors for remission at 3 months and of monotherapy at month 12. Results: Overall, 134 RA patients were analyzed. Remission was achieved in 38.06% at month 3. In univariate analysis, persistent disease activity at 3 months was observed in those patients with longer duration of disease, structural radiological damage, higher baseline DAS28-ESR and greater frequency in previous use of bDMARD. In multivariate analysis, previous use of bDMARD was significantly associated with a decrease in the probability of remission at 3 months. At 12 months, TOF monotherapy group was elderly (p = 0.009) and had a trend for lower frequency of anti-CCP. Treatment persistence was 94.78% at 3 months, 82.84% at 6 months and 66.42% at 12 months. Conclusions: Clinical remission at 3 months was negatively associated with prior bDMARD and poor prognostic factors. TOF monotherapy at 12 months was more common in elderly patients.

Implications of Persistent Pain in Patients With Rheumatoid Arthritis Despite Remission Status: Data From the KOBIO Registry.

This study aimed to assess the prevalence of pain in patients with RA in clinical remission and analyze the demographic and clinical characteristics of those who experienced persistent pain despite remission status. Data from 1,891 patients with RA registered on the Korean College of Rheumatology Biologics and Targeted Therapy registry were obtained. Remission was defined as a Disease Activity Score of 28 joints-erythrocyte sedimentation rate (ESR) <2.6. Pain intensity was classified as severe (pain visual analog scale [VAS] ≥7), moderate (4≤VAS<7), or mild (VAS <4). Our analysis showed that 52.6% of patients complained of severe pain at the start of or during switching biological disease-modifying anti-rheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs). Despite having a 36.0% (n=680) remission rate after the use of bDMARDs or tsDMARDs at their 1-year follow-up, 21.5% (n=146) of these patients had moderate-to-severe pain, higher frequency of foot erosions, and comorbidities, such as mental illness, endocrine, renal, and neurological disorders, than patients with a milder degree of pain. The multivariable regression analysis showed that presence of foot erosions, neurological disorders, and use of corticosteroids were independently associated with moderate-to-severe pain in patients with RA despite being in remission. The level of ESR and use of Janus kinase inhibitors were inversely associated with moderate-to-severe pain. Persistent pain and discomfort continue to be a problem for patients with RA in clinical remission. Continued research on insistent pain in patients with RA is warranted to better alleviate distress and improve the quality of life in patients.

A RETROSPECTIVE ANALYSIS OF GLUCORTICOSTEROIDS UTILIZATIONAMONG PATIENTS WITHRHEUMATOID ARTHRITIS

Background:Glucocorticoid therapy is used widely in patients with rheumatoid arthritis(RA). Recently, treatment guidelines recommendglucorticosteroids (GCs) use in low dose and for a short time in RA. However, for many patients, it is still difficult to withdraw GCs once initiated. Objectives: to analyzeGCs utilization in RA patients and to evaluate the effects of increasing cumulativedoses on theprevalence of potential GCs related adverse events. Methods:we enrolled patients with RA. Corticoid exposure was defined: duration (short ≤6 months and long &gt;6months), average daily dose (low ≤ 2.5mg, medium 2.5mg &lt; ≤ 7.5mg and high &gt; 7.5mg). Effect of increasing cumulative GCs doses on adverse events development were analyzed usingchi-square test or Fischers exact test. Regression models were used to identify the factors favoring GCs discontinuation. Results:a total of 168 RA were included (84 patients usedbDMARDs). The median of cumulative GCs dose was 14400mg. the majority of GCs users were prescribed high doseof GCs (54.3%) for a long duration (98.7%). Skin events (71.5%) were the majorside effects. Higher cumulative GCs doses compared with lower doses had increased incidence of diabetes, cardiovascular and ophthalmologic events (p=0.04, p=0.001, p=0.02 respectively).The prevalence of RA patients having withdrawnGCs was 38.7%. It was negatively associated in multivariable regression with RA duration (OR:0.8, IC95%:0.6-0.9). Surprisingly, there was no association in logistic regression with bDMARD use. Conclusions:GCs were used with high dose and for a long duration for the majority of our RA patients.

Pharmacoeconomic rationale for switching patients with rheumatic diseases from original biologic disease-modifying antirheumatic drugs to biosimilars in context of the Russian healthcare system

Objective: to analyze the pharmacoeconomic efficiency of biosimilars in context of national healthcare system.Material and methods. Based on the developed interactive pharmacoeconomic model, we made an analysis of the impact on the budget of treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), patients with psoriatic arthritis (PsA) were analyzed separately, within the framework of the study a cost-effectiveness analysis of bDMARD and tsDMARD therapy was performed to determine the preferred alternative in RA.Results and discussion. The performed pharmacoeconomic analysis confirmed the research hypothesis on the economic feasibility of transferring patients with rheumatic diseases (RA, PsA and SpA) receiving original bDMARDs to biosimilars in the context of Russian healthcare system. According to the cost analysis, biosimilars, except for infliximab, are characterized by comparatively less cost of a treatment course than the original drugs. The results of the budget impact analysis and cost analysis prove the economic feasibility of switching patients from original bDMARDs to biosimilars. At the same time, the parameters of the current and planned distributions entered in the calculations of the analysis of the impact on the budget, indicate the need of the professional community and patients for a wider use of innovative original bDMARDs that are under patent protection. At the same time, in the context of budgetary constraints, switching to biosimilars remains perhaps the only available strategy for increasing the coverage of patients with innovative drugs. It has been established that the etanercept biosimilar (ETC) Erelzy® has the lowest cost-effectiveness value. At the same time, ETC is characterized by the highest clinical efficiency, which makes it possible to determine the specified ETC biosimilar as strictly preferable from the point of view of the cost-effectiveness analysis.Conclusion. It can be assumed that in the absence of medical contraindications, switching of RA patients to ETC from other bDMARDs will be accompanied by better control of the disease, and the presence of biosimilars of ETCs, including the drug Erelzi®, which are among bDMARDs with the lowest cost of treatment course, will save funds, that can be rerouted to extend the coverage of patients with bDMARDs or increase the proportion of innovative bDMARDs.

Rheumatoid arthritis patients initiating rituximab with low number of previous bDMARDs failures may effectively reduce rituximab dose and experience fewer serious adverse events than patients on full dose: a 5-year cohort study

BackgroundRituximab is used for the treatment of active rheumatoid arthritis. In the present study, we examined the long-term flare risk and safety of reduced doses of rituximab.Patients-methodsThis was a prospective, observational, single-center study of patients starting rituximab on standard dose (SD). Patients were switched to low dose (LD) (1 g every 6 months), based on the treating rheumatologist’s decision after having achieved sustained clinical responses, while the rest of the patients continued on standard dose (SD). During a 60-month period, we assessed (Kaplan–Meier survival analysis) the relapse rate (increase ≥ 1.2 in DAS28-ESR for ≥ 6 months) and discontinuations due to treatment failure in the low dose group, and we compared the incidence of serious adverse events (SAEs) between LD and SD groups.ResultsOut of 361 patients [females 83.4%, mean age 61.9 (10.6) years, seropositive 50.3%, median total comorbidities count 4], 81 patients (22.4%) entered LD in a median time of 24 months (95% CI 18–30 months). Seropositivity (OR 1.823), more than 2 previous bDMARDs failures (OR 0.428), and DAS28 < 4.88 at 6 months (OR 2.329) predicted the odds of entering LD (p < 0.05 for all). During 60 months of follow-up, only 7.5% of patients on LD relapsed. Patients on LD had significantly less SAEs and all-cause hospitalizations as compared to the SD group (p < 0.05 for all). Linear regression analysis showed that previous hospitalization while on bDMARDs (p < 0.0001), use of prednisolone > 5 mg/day while on rituximab (p < 0.0001), and a history of ≥ 2 previous csDMARDs (p = 0.041) predicted the risk of SAEs.ConclusionIn a cohort of patients with established RA and significant comorbidities who taper rituximab after substantial initial disease activity improvement, a low rate of relapses and lower risk of SAEs compared to SD were recorded. Seropositivity, a lower number of previous bDMARDs use, and lower DAS28 at 6 months predicted the probability of entering the LD regimen.

Association between biologic therapy and fracture incidence in patients with selected rheumatic and autoimmune diseases: A systematic review and meta-analysis of randomized controlled trials

ObjectivesTo investigate the effect of biologic therapy on risk of fracture in selected rheumatic and autoimmune diseases. MethodsThe PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to June 4, 2021. Randomized clinical trials (RCTs) comparing biological disease-modifying antirheumatic drugs (bDMARDs) with non-bDMARDs or placebo in patients with five selected rheumatic and autoimmune diseases were included. Meta-analyses were conducted to calculate the odds ratio (OR) with 95 % confidence intervals (CIs) for major osteoporotic fracture, hip fracture, osteoporotic non-vertebral fracture, and total fracture. ResultsA total of 100 RCTs involving 51,413 participants fulfilled the inclusion criteria. In patients with psoriasis (Ps), and psoriatic arthritis (PsA), compared with placebo or non-bDMARDs therapy, the risk of major osteoporotic fracture (OR, 0.34 [95 %Cl, 0.15–0.76], p = 0.009), hip fracture (OR, 0.22 [95 %Cl, 0.05–0.89], p = 0.03), and osteoporotic non-vertebral fracture (OR, 0.26 [95 %Cl, 0.10–0.62], p = 0.003) were significantly decreased with the use of bDMARDs. In patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), systemic lupus erythematosus (SLE), and inflammatory bowel diseases (IBD), the risk of fracture were not changed with biologic treatment. ConclusionsThe existing evidence from RCTs indicated the use of bDMARDs was associated with a low risk of major osteoporotic fracture, hip fracture, and osteoporotic non-vertebral fracture in patients with Ps and PsA. There are still urgent needs for studies regarding the actions of biologic therapies on the risk of bone fractures in systemic inflammatory diseases.

OP0136 SERUM CHOLESTEROL LOADING CAPACITY ON MACROPHAGES AND INTERACTIONS WITH TREATMENTS ON CORONARY ATHEROSCLEROSIS BURDEN AND EVENT RISK IN RHEUMATOID ARTHRITIS

BackgroundCholesterol loading capacity (CLC) describes the ability of serum to deliver cholesterol to cells. It is linked to foam cell formation, a pivotal step in atherosclerotic plaque development. Rheumatoid arthritis (RA) serum promoted foam cell formation significantly more than control serum. Likewise, RA patients display greater plaque burden and higher-risk features than non-RA controls. bDMARDs and statins lower cardiovascular risk by reducing new coronary plaque formation, promoting regression, altering the composition and stabilizing prevalent atherosclerotic lesions.ObjectivesTo evaluate the associations between CLC, coronary plaque burden and cardiovascular event risk in patients with RA. We further explored the conditioning effects of RA treatments on these relationships.Methods140 patients underwent coronary CT angiography for atherosclerosis evaluation and were prospectively followed for cardiovascular events over 6.0±2.4 years. Coronary artery calcium score (CAC), number of segments with plaque (segment involvement score [SIS]) and plaque composition were assessed. CLC was the macrophage cholesterol content, measured by fluorometric assay, after a 24-hour incubation with whole serum. Robust linear regression examined the effects of CLC and the interaction between CLC and bDMARD use on SIS and CAC. Negative binomial regression evaluated CLC and CLC × bDMARD interaction effects on number of high-risk (low-attenuation) plaques. With data discretized into 1-month intervals, weighted pooled logistic regression models with robust variance estimation evaluated CLC and time-varying bDMARD use as predictors of event risk, and the effect of CLC × time-varying bDMARD use on risk. Stabilized inverse probability of treatment and censoring weights were estimated as a function of ASCVD risk, SIS, RA duration, and baseline and time-varying CRP and statin use.ResultsMean (SD) CLC was 12.67 (2.83) μg/mg protein. In analyses adjusting for ASCVD score, HDL, prednisone and statin use, CLC (per 1-SD unit) was not related to SIS (β -0.05 [95%CI -1.19,0.09]), number of high-risk plaques (rate ratio [RR] 1.20 [95%CI 0.80-1.80]) or ln-transformed CAC (β 0.017 [95%CI -0.133,0.147]). However, in analyses stratified by baseline bDMARD use, CLC (per 1-SD unit) was positively related to number of high-risk plaques (RR 2.14 [95%CI 1.04-4.40]) and ln-transformed CAC (β 0.21 [95%CI 0.01-0.41]) among bDMARD-naïve individuals (Figure 1). In addition, CLC inversely associated with SIS (per SD increment; β -0.16 [95%CI -0.32, -0.01]) only in bDMARD-treated patients. Baseline statin use did not significantly modify the effect of CLC on coronary plaque (not shown). CLC associated with cardiovascular event risk (per SD increment; adjusted odds ratio 2.02 [95%CI 1.27-3.50], p=0.011) covarying for ASCVD score and time-varying bDMARD use. The CLC × time-varying bDMARD use interaction also predicted event risk (p =0.010); current bDMARD use associated with lower event risk at higher (1 SD above the mean) CLC levels (p=0.037) but not average or lower (1 SD below the mean) CLC levels (p=0.064 and 0.756, respectively).ConclusionCLC associated with greater CAC score and high-risk plaque burden in bDMARD-naïve RA patients and lower total plaque burden in bDMARD-treated patients at baseline. CLC also predicted long-term cardiovascular risk and its effect was mitigated by bDMARD use.Disclosure of InterestsGeorge Karpouzas Speakers bureau: Sanofi-Genzyme-Regeneron, Janssen, Bristol-Meyer-Squibb, Consultant of: Sanofi-Genzyme-Regeneron, Janssen, Bristol-Meyer-Squibb, Grant/research support from: Pfizer, Bianca Papotti: None declared, Sarah Ormseth: None declared, Marcella Palumbo: None declared, Elizabeth Hernandez: None declared, Cinzia Marchi: None declared, Francesca Zimetti: None declared, Matthew Budoff Consultant of: Pfizer, Nicoletta Ronda: None declared