Modifying Anti-rheumatic Drugs Research Articles

Difficult-to-treat psoriatic arthritis. Data from the All-Russian registry of patients with psoriatic arthritis

Objective: to characterize patients with difficult-to-treat (D2T) psoriatic arthritis (PsA) and to assess risk factors for its development.Material and methods. The study included 263 PsA patients treated with biologic disease- modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) and followed up for ≥2 years in the All-Russian Registry of PsA Patients. All patients underwent a standard clinical and laboratory examination, and concomitant diseases were recorded. PsA activity was assessed using DAPSA index and minimal disease activity criteria.Results and discussion. 152 (57.8%) patients who received 1 bDMARD/tsDMARD for 2 years achieved remission/low disease activity (LDA) according to DAPSA and were categorized as having non-D2T PsA. Other 111 (42.2%) patients switched ≥2 bDMARDs/tsDMARDs within 2 years, 71 (27%) of them achieved remission/LDS, and 40 (15.2%) patients who continued to have high or moderate PsA activity met the D2T criteria. A comparative analysis of 40 patients (20 men and 20 women) with D2T PsA and 152 patients (78 men and 74 women) with PsA who did not fulfil the D2T criteria was performed. It was found that patients with D2T PsA had a significantly longer duration of PsA (p=0.017), more frequent polyarthritis (p=0.014), dactylitis (p=0.004), enthesitis (p=0.001), BSA >10% (p=0.008), onycholysis (p=0.001), HAQ >0.5 (p=0.039), depression (p=0.007) and elevated blood uric acid levels (p=0.023).Conclusion. In real-life clinical practice, the D2T variant of PsA is reported in 15% of cases. Treatment-resistant PsA patients are characterized by a longer duration of PsA, more widespread severe psoriasis with onycholysis and are more likely to have polyarthritis, dactylitis, enthesitis and functional disorders at the time of bDMARD prescription, as well as concomitant diseases, especially depression and hyperuricaemia.

Effect of Probiotic Supplementation on Disease Activity in Rheumatoid Arthritis Patients

Abstract Background Rheumatoid arthritis (RA), a prevalent inflammatory arthritis with a global incidence of 0.5–1%, is characterized by autoimmune-driven articular pain, cartilage degradation, bone destruction, and functional disability. Emerging evidence suggests a potential link between alterations in gastrointestinal microflora and the development of autoimmune diseases, including RA. Probiotic bacteria have gained attention as a potential adjunctive therapy due to their immunomodulatory properties, offering promise for improving clinical and metabolic outcomes in RA patients. Aim of the Work To study the effects of probiotic supplementation on clinical status of patients with RA. Patients and Methods Sixty Egyptian RA patients aged 18-60 years, diagnosed and screened in the Rheumatology department at Ain Shams University Hospital, were enrolled in this study. The patients were divided into two groups: group A received daily probiotic supplementation for 8 weeks, while group B served as the control. Detailed clinical assessments and laboratory investigations were conducted. Results There were no significant differences in age, sex distribution, disease duration, or disease- modifying antirheumatic drugs (DMARDs) usage between the two groups, consistent with previous research. The probiotic regimen included Lactobacillus acidophilus and Bifidobacterium animalis. Conclusion Probiotic supplementation in RA patients yielded mixed results in this study, with improvements in TJC and ESR but no significant changes in SJC, CRP, or disease activity scores. Further research is needed to elucidate the complex relationship between gut microbiota and RA pathogenesis and to determine the optimal probiotic regimen for improving clinical outcomes in RA patients.

Prevention of Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Persistent Low-grade In-flammation May be an Impediment Needing Attention

Objective: To determine the status of ‘residual inflammatory risk’ (RIR) and ‘residual cholesterol risk’ (RCR) in patients with Rheumatoid Arthritis (RA) in remission with the aim of estimating their atheroscle-rotic cardiovascular disease (ASCVD) risk. Methods: The study included patients with RA in remission during their last two clinic visits on treatment with disease- mod-ifying anti-rheumatic drugs (DMARDs). Using the QRISK-3 calculator, participants were stratified into four risk categories for ASCVD: ‘Very high’, ‘High’, ‘Moderate’, and ‘Low’. Patients were prescribed lipid-lowering drugs targeting low-density lipoprotein cholesterol (LDL-C) levels to <50 mg/dl, <70 mg/dl, <100 mg/dl or <130 mg/dl, respectively. Those with a history of ASCVD before or during the follow-up period was excluded from the study. Multimorbidity were also recorded in all the patients. Results: The study included 130 patients with RA in remission. The results showed that despite being in remission and taking treatment for lipid control, 81 (62%) and 91 (70%) patients still had ‘RIR’ and ‘RCR’, respectively. Hypertension, hypothyroidism, type-2 diabetes mellitus and obesity were the common multimorbidity. Conclusions: Persistent RIR in 62% of patients despite being in remission, could possibly be due to the current ‘liberal’ definition of RA permitting hs-CRP level up to <10 mg/l, which is five-fold higher than the recommended <2 mg/l for ASCVD prevention. Hence it may be necessary to revise the definition of ‘remission’ in RA factoring in the suggested lower level of hs-CRP. Additionally, rheumatologists might need to be more vigilant in lipid management with appropriate patient education regarding RCR.

Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Trends and frontiers of research on pharmacoeconomics from 2012-2021: a scientometric analysis.

BackgroundResearch on pharmacoeconomics (PE) promotes the rational allocation of medical resources, which has received attention in the last decade. We conducted a scientometric analysis of PE to determine the current status and frontiers, and promote cooperation and development.MethodsThe Web of Science Core Collection-Science Citation Index Expanded was adopted to retrieve publications associated with PE from 2012–2021. After screening publications, CiteSpace 3.8.R3 was used to conduct a scientometric analysis. We analyzed terms, including publications and citations, countries/regions, institutions, journals, authors, keywords, and references.ResultsIn total, 4,715 documents published from 2012–2021 were included in this study, of which 3,829 were articles and 886 were reviews. The documents were cited 54,596 times, at an average of 11.58 times per document. 121 countries/regions and 410 institutions were involved. The top 3 countries/regions by the number of publications were the United States of America (n=1,790), England (n=601), and China (n=403), while the institution with the most publications was Pfizer. Pharmacoeconomics was the main journal of PE, with 310 publications in all, and the top 3 cited journals were New England Journal of Medicine (citation times =1,620), Value in Health (citation times =1,306), and Lancet (citation times =1,255). Bin Wu was the most productive author (n=16), while World Health Organization was the most influential author (citation times =387). 524 keywords altogether were found, and the top 3 keywords by frequency were therapy (frequency =318), impact (frequency =305), and cost-effectiveness (frequency =296). The keyword “modifying antirheumatic drug” associated with rheumatoid arthritis (RA) has continued bursting from 2016–2021. Guide to the methods of technology appraisal 2013 by the National Institute for Health and Care Excellence, was the most frequently cited publication on PE (citation times =65). Cluster 0 labeled as “cost-effectiveness analysis” (CEA) was the largest and latest cluster, and its citing articles focused on the CEA of first-line treatment for non-small cell lung cancer (NSCLC).ConclusionsThe economic analysis of disease-modifying antirheumatic drugs related to RA was a popular topic in the last 6 years, and CEA of NSCLC first-line treatment was at the frontier of PE.

POS1184 AUTOIMMUNE SYSTEMIC DISEASES AND COVID-19 INFECTION

Background:Covid-19 infection poses a serious challenge for immune-compromised patients. This is likely due to a combination of immune dysfunction, immunosuppressive therapy and excess co-morbidities. Little is known about the impact of Coronavirus disease 2019 (COVID-19) in patients with inflammatory autoimmune systemic diseases.Objectives:The aim of this study is to describe clinical characteristics of patients with autoimmune systemic diseases and COVID-19, and to identify baseline variables associated with a severe infection requiring hospitalization.Methods:A telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis), idiopathic inflammatory myopathies (IIM), ANCA-associated vasculitis (AAV) was administered. Data extraction included diagnosis, disease activity status, demographics, disease duration, occupational exposure, adherence to social distancing advise, therapy, comorbidities, and laboratory tests. Covid-19 was classified as definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by a nasopharyngeal SARS-CoV-2 polymerase chain reaction test. Comparisons between patients with or without hospitalization were performed.Results:512 patients (median age 53,4 ± 14,3 years) with autoimmune systemic diseases (234 IA, 182 SLE, 42 SSc, 31 IIM, 23 AAV) were included in the study. 89 patients (58 woman, 31 men) developed at least one symptom (fever, asthenia, chills, cough, sore throat, dyspnea, chest pain, headaches, arthralgias, myalgias, odynophagia, diarrhea, conjunctivitis, hypo-, ageusia, hypo-, anosmia) of COVID-19 and were PCR test positive. Of patients with COVID – 19 infection 54 patients were treated with methylprednisolone, 36 – with methotrexate, 34 – with hydroxychloroquine, 26- with biologics, 10 - with azathioprine, 6 - with cyclophosphamide prior to their COVID-19 illness.Conclusion:Covid-19 is more frequent in the subgroup of patients without therapy with modifying anti-rheumatic drugs, which might play some protective role against the most harmful manifestations of Covid-19. 21 patients required hospitalization - these were more frequently men, older and with comorbidities (cardio-respiratory illness, renal diseases, diabetes mellitus). Male sex, previous coronary and lung disease, serum creatinine level, proteinuria, glucocorticoids use > 5 mg/day, were associated to hospitalization. Patients with inflammatory arthritis do not seen to be at higher risk for infection or a severe course of COVID-19.

Management and Successful Desensitization in a Patient with Abatacept-Induced Anaphylaxis

ABSTRACT Abatacept is a fusion protein that blocks T cell activation. It is used in a variety of conditions including organ transplantation, immune deficiency, and autoimmune diseases. Even though abatacept-induced adverse events are observed, hypersensitivity reactions are rare. Desensitization protocols that can be implemented in the case of hypersensitivity reactions are present in the literature for many biological agents. However, a desensitization protocol for abatacept has not yet been established. Our patient, who was started on one of the biological agents, abatacept, for rheumatoid arthritis due to insufficient response to disease- modifying antirheumatic drugs, developed immediate hypersensitivity reaction with the first dose. Since it was planned to continue the treatment, abatacept desensitization was performed. The rapid desensitization protocol performed with prior premedication was successful and the patient was able to receive subsequent doses of abatacept using the same protocol. Keywords: Abatacept, anaphylaxis, desensitization

Predictors of joint damage in patients with rheumatoid arthritis: focus on short- and long-term effects of intra-articular glucocorticoid injections.

Background/AimsTo investigate the short- and long-term efficacy of intra-articular glucocorticoid injections (IAGI) in patients with rheumatoid arthritis (RA).MethodsThis was a retrospective study of RA patients who had active arthritis in the hand or wrist joints and who received IAGI (or not) as an adjunct to disease-modifying antirheumatic drugs (DMARDs). Short-term efficacy was assessed based on changes in the disease activity score in 28 joints (DAS28) after 3 months and long-term efficacy was assessed based on changes in the van der Heijde Sharp score (HSS) of hand radiographs over 2 years. Radiographic progression was defined as ΔHSS/year ≥ 2. Logistic regression analysis identified predictors of early achievement of low disease activity (LDA) and radiographic progression.ResultsOverall, 126 RA patients received IAGI into the hand or wrist joints and 107 were IAGI-naive. After 3 months, 67% of IAGI-treated patients and 48% of IAGI-naive patients achieved LDA (p = 0.002). Over the next 2 years, 35% of patients treated with IAGI showed radiographic progression compared with 27% of IAGI-naive patients (p = 0.2). IAGI plus biologic DMARDs was associated with achievement of LDA in 3 months. Achieving LDA in 3 months (odds ratio [OR], 0.403; 95% confidence interval [CI], 0.192 to 0.847), wrist arthritis (OR, 2.408; 95% CI, 1.184 to 4.897), and baseline HSS (OR, 1.021; 95% CI, 1.003 to 1.039) were associated with radiographic progression.ConclusionsIAGI was associated with early achievement of LDA. LDA was associated with slower radiographic progression. The wrist is more vulnerable to joint damage and requires more aggressive treatment.

Фармакоэкономические аспекты терапии ингибиторами янус-киназ пациентов с ревматоидным артритом, не ответивших на стандартные базисные противовоспалительные препараты

Фармакоэкономические аспекты терапии ингибиторами янус-киназ пациентов с ревматоидным артритом, не ответивших на стандартные базисные противовоспалительные препараты

Artritis reumatoidea asociada a colangitis biliar primaria bajo tratamiento con medicamentos biológicos

The therapeutic approach of patients with two or more autoimmune diseases is quite a challenge, especially when the treatment of one of them, can precipitate the progression of the other. Even though the association of rheumatoid arthritis (RA) and primary biliary cholangitis (PBC) is rare; when both coexist, the use of methotrexate and other hepatotoxic drugs should be used with caution. With a most widespread indication of biologic disease- modifying antirheumatic drugs (bDMARDs) some reports of patients with RA and PBC treated with etanercept, infliximab, rituximab, tocilizumab and abatacept have been published. We report a case series that includes 4 patients with RA and PBC treated with bDMARDs. This is the first report to describe two cases in which golimumab was used to control RA and the second to report patients who received adalimumab and abatacept. Three cases of patients treated with rituximab have been published to date. None of the patients of our report suffered a progression of their PBC; matter in fact, two of them showed an improvement in their biochemical parameters. PBC symptoms did not get worse in any of the patients. On the contrary, laboratory parameters improved in two of the four patients.

Chronic pain and depression in patients with rheumatoid arthritis: results of five - year follow - up

128 patients with reliable diagnosis of RA [111 (86.7%) women and 17 (13.3%) men] were examined. The mean age of patients was 47.4±11.3 years, the median duration of the disease was 96 [48; 228] months. When included in the study in most patients, the activity of RA in DAS28 was moderate (n=56; 43.7%) or high (n=48; 37.5%). BPI (Brief Pain Inventory) scale was used to determine the severity of pain and its impact on various aspects of life. The anxiety - depressive spectrum disorders (ADDs) were diagnosed by psychiatrist during a semistructured interview according to ICD-10 criteria in 123 (96.1%) patients. The severity of depression was determined by the Montgomery-Asberg depression rating scale, anxiety - by Hamilton anxiety scale. For the diagnosis of cognitive impairment used clinical and psychological techniques. Psychopharmacotherapy (PPhT) by antidepressants or anxiolytics is offered to all patients with ADDs, 52 of them agreed to treatment, 71 patients refused. The next groups selected depending on the therapy: 1st - with conventional disease - modifying antirheumatic drugs (cDMARDs; n=39), 2nd - with cDMARDs+PPhT (n=43), 3d - with cDMARDs + biologic (b) DMARDs (n=32), 4th - with cDMARD+bDMARDs+PPhT (n=9). The dynamics of ADDs and outcomes of RA in 5 years were evaluated in 83 (67.5%) patients. When included in the study, 94 (75.2%) patients with RA had moderate and severe pain. According to the regression analysis, the maximum intensity pain in BPImax after 5 years of follow - up associated not the only factors connected with RA - high DAS28, the serum level of C-reactive protein, the degree of radiological stage and functional insufficiency, duration of RA and a lesser duration of glucocorticoids intake, but also with continuing depressive episodes in the framework of recurrent depression and the initial presence of cognitive impairment. The severity of pain after 5 years of follow - up was higher in RA patients receiving only сDMARDs, without the use of bDMARDs and in the absence of PPhT associated with ADDs. Depressive episode within recurrent major depression is a significant factor in the chronicity of pain in patients with RA. Timely effective PPhT of depression, selected taking into account depression structure and personal characteristics of the patient, leads to a steady decrease in the severity of pain in patients with RA.

Economic Benefit of Sponsored Controlled Clinical Trials: The Avoidable Cost in Drugs for the Treatment of Rheumatoid Arthritis

ObjectivesTo estimate the following: (1) the avoidable cost of biologic (bDMARDs) and conventional synthetic Rheumatoid Arthritis (RA) modifying antirheumatic drugs (csDMARDs) during controlled clinical trials (CCTs), their extension period, and for bDMARDs in post study drug programs; and (2) to evaluate the impact on health insurances. MethodsWe analyzed 13 CCTs (233 patients) that evaluated bDMARDs. Avoidable cost was what the health insurance should have paid if the patient had not received the medication from the CCT sponsor and was estimated with a micro-costing approach (bottom-up method). Results were expressed as mean ± standard deviation (SD) or percentages. Approved by the Ethics Committee. ResultsMean age was 50.62 SD 11.8 years, 84% were women, 72% (n = 166) had health insurance. The mean annual cost of bDMARDs was US$ 30 567.40 while the cost for csDMARDs was US$ 104.90 during the CCTs. The mean annual cost in extension periods and post study drug programs for bDMARDs was US$ 36 016.20 and for csDMARs during the extension period was US$ 81.70. The avoidable cost for public health insurances exceeded one million dollars per year. ConclusionThis work describes for the first time in Argentina the significant economic benefit that may represent for RA patients' health insurances the participation in CCTs with bDMARDs. It shows that during the execution of the CCT, its extension periods, or post study access programs, while medication provision is guaranteed, the economic burden imposed by the treatment of the RA is relieved.

Comics as an educational tool for children with juvenile idiopathic arthritis

BackgroundThis study examined whether the comic book Neta and the Medikidz Explain JIA would improve disease-related knowledge and treatment adherence among patients with juvenile idiopathic arthritis (JIA).MethodsIn this prospective cohort study, JIA patients answered 20 multiple-choice knowledge questions about their disease, before and after reading the comic book. Demographic, clinical, health-related quality of life and adherence data were recorded and correlated to the responses.ResultsWe studied 61 patients with a mean age of 14 ± 3.3 (range 8–18) years, 67% female, 83% Jewish and 17% non-Jewish. Thirty-nine percent had oligoarthritis, 13% systemic, 32% polyarthritis 11% psoriatic and 5% enthesitis-related type JIA. The disease was active in 46%, 40% were treated with biologics/disease modifying anti-rheumatic drugs, and 34% were in remission on medication. Among the 53 patients who completed before and after quizzes, average score increased from 63 to 80% (P < 0.001). Non-Jewish patients initially scored lower than Jewish patients (48%), but their score increased to 79% after reading the comic book. Twenty-seven patients who also completed the quiz 1 year after the first reading retained their knowledge (79%). We did not find a statistically significant correlation between knowledge and age, sex, disease subtype, or Child Health Questionnaire quality of life scores. Adherence to medication use, physical therapy and rheumatology clinic visits were high at baseline; thus, these did not change after reading the comic.ConclusionsThe comic booklet Neta and the Medikidz Explain JIA is a good educational tool for increasing disease-related knowledge in children with JIA.

What Matters to Patients and Physicians When Considering Biologic Therapy for Rheumatoid Arthritis

Objectives: Patients and rheumatologists have a number of options to consider for the treatment of rheumatoid arthritis (RA), including biologic response modifier (BRM) therapy and disease- modifying antirheumatic drugs (DMARDs). The objective of this study was to identify the considerations that are most important to patients and rheumatologists when deciding to initiate BRM therapy for RA. Methods: An online survey was conducted by Harris Interactive® (Rochester, NY) and completed in January 2007. Patients receiving BRMs were asked to rank their considerations in initiating BRM therapy, patients receiving DMARDs were asked to rank their considerations in switching to or initiating BRM therapy, and rheumatologists were asked to rank their considerations in prescribing BRM therapy. Participants arranged the following 9 factors from most to least important: efficacy, safety/side effects, years on market, physician's experience with product, physician's personal preference, method of administration, dosing frequency, cost (out of pocket), and patient support programs. Results: A total of 400 rheumatologists and 729 patients were surveyed (BRMs, n = 504; DMARDs, n = 225). The following factors were ranked consistently high across groups: safety (ranked first, first, and second for BRM patients, DMARD patients, and rheumatologists, respectively), efficacy (second, fourth, and first, respectively), and physician's experience with the drug (third for all 3 groups). Years on market (ranked seventh, sixth, and seventh, respectively) and availability of patient support groups ranked consistently low. Conclusions: When considering BRM therapy for RA, the 3 most important factors for patients and physicians are safety, efficacy, and the physician's experience with the product.

Assessing remission in clinical practice

Remission constitutes the best achievable state in patients with rheumatoid arthritis. We aimed at evaluating sustained remission in a large cohort of patients followed prospectively in clinical practice and to evaluate available instruments to define remission for their stringency in defining this state. We analysed remission and sustained remission in 621 patients who had two consecutive and complete clinical observations; the average period between the two visits was 92 days (median; quartiles: 82; 105). Remission was evaluated according to modified ACR (mACR), 28 Joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) criteria. Sustained remission was defined as remission at both consecutive visits. Patients were treated with traditional disease- modifying antirheumatic drugs, mainly methotrexate, and partly with biological agents (approximately 11%). Remissions at any one of the two visits were seen in 33.5% of patients by SDAI or CDAI, 42.7% by DAS28, and 38.6% by mACR criteria (P < 0.01). Sustained remission was observed in much lower proportions of patients (between 16.7 and 19.6%, dependent on the instrument). Agreement between classifications of remission by kappa-statistics was very good for SDAI vs CDAI, good for DAS28 vs SDAI or CDAI, and only moderate for mACR vs the three other scores. Residual swollen joints were observed in 15% of patients in DAS28 remission (range 1-9), 6% of patients in mACR remission (range 1-8), but only approximately 5% of patients in CDAI or SDAI remission (range 1-2) (P < 0.01). Sustained remission can be observed in 17-20% of patients in clinical practice. CDAI and SDAI remission criteria are more stringent than DAS28 and mACR criteria, since they allow for lesser residual disease activity. Consequently, smaller proportions of patients are classified as in remission by SDAI and CDAI than by DAS28 and mACR criteria. Sustained remission is an achievable goal in clinical practice even with the most stringent of the definitions studied.