Use Of Leflunomide Research Articles

Prevalence and Risk Factors of Cardiovascular Disease in Rheumatoid Arthritis Patients: A Comparative Analysis of Real-World Data.

Rheumatoid arthritis (RA) is linked to cardiovascular disease (CVD), due to chronic inflammation and traditional CVD risk factors. This study evaluates CVD and related risk factors in RA patients compared to age and gender-matched controls without inflammatory diseases, and differences within RA patients with and without CVD. This retrospective case-control study reviewed medical records of 405 RA patients (cases) and 950 control patients who attended rheumatology clinics in two branches of a private hospital between January 2021 and January 2024 to assess cardiovascular disease prevalence and associated risk factors. RA patients, with a mean age of 59 (± 23) years, disease duration of 89.5 months, and a female-to-male ratio of 4:1, exhibited a higher prevalence of CVD compared to controls (p = 0.01), despite similar classical risk factors. Logistic regression identified RA as an independent risk factor for CVD (p = 0.02, odds ratio = 1.9). RA patients with CVD were typically older males (p < 0.001), presenting with higher rates of hypertension (p < 0.001), hyperlipidemia (p < 0.001), diabetes (p = 0.002), and chronic kidney disease (p < 0.001). Arrhythmias (p < 0.001) and heart failure (p < 0.001) were prevalent among this subgroup, along with elevated creatinine levels and reduced glomerular filtration rates (p < 0.001 each). Treatment patterns indicated lower use of methotrexate (p = 0.003) and higher use of leflunomide (p = 0.02) among RA patients with CVD. CVD in RA patients is multifactorial, involving both chronic systemic inflammation and classical CVD risk factors. Further research is necessary to advance our understanding of CVD in RA patients and to optimize treatment strategies for improved outcomes.

Treatment with Leflunomide in Conjunction with Glucocorticoids for Dogs with Immune-Mediated Polyarthritis Is Not Associated with Improved Outcomes: A Retrospective Cohort Study of 93 Dogs from Australia (2017-2024).

Immune-mediated polyarthritis (IMPA) has a relatively high relapse rate compared to other immune-mediated diseases. Leflunomide is frequently used to treat dogs with IMPA in conjunction with prednisolone. This retrospective cohort study aimed to evaluate the therapeutic efficacy of leflunomide as an adjunctive therapy to prednisolone in reducing relapse and mortality rates in dogs diagnosed with IMPA in Australia. The medical records of client-owned dogs diagnosed with IMPA at a specialist referral hospital in Southeast Queensland from 2017 to 2024 were reviewed. A total of 93 dogs were included in this study, divided into two groups based on the treatment received: Group PRED, consisting of 53 dogs treated with prednisolone as the sole immunosuppressive agent, and Group L+PRED, consisting of 40 dogs that received leflunomide as adjunctive therapy alongside prednisolone. Data collected included breed, age, weight, sex, serum C-reactive protein concentration, results of synovial fluid analysis and microbial culture, treatment protocol, relapse rates and time to relapse, and mortality rates. There was no difference in relapse or mortality rates, time to relapse, nor time to discontinue prednisolone between the PRED and L+PRED groups. The L+PRED group had higher body weights and lower prednisolone dose rate at discharge compared to those in the PRED group. This study demonstrated that the use of leflunomide as an adjunctive therapy to prednisolone for the treatment of dogs with IMPA had no improved outcomes, reduced relapse rates, or shortening in the duration of prednisolone therapy when compared to dogs receiving prednisolone monotherapy.

Gastrointestinal symptoms in patients using methotrexate: A cross-sectional study in a sample with rheumatoid arthritis

BackgroundGastrointestinal intolerance is common in rheumatoid arthritis (RA) patients using methotrexate and may lead to treatment discontinuation. AimTo study the prevalence of gastrointestinal symptoms in a sample of RA methotrexate users as well as its possible association with clinical and epidemiological variables. MethodsCross-sectional study of 192 patients with gastrointestinal symptoms using the MISS (methotrexate intolerance severity score). Clinical and epidemiological variables were collected through chart review and direct questioning. Patients’ adherence to methotrexate was evaluated through Moriski–Green–Levin questionnaire. ResultsThe prevalence of gastrointestinal complaints was high with 55.7% of the sample classified as intolerant. Nausea and pain after drug ingestion were the most common reported complaints. This intolerance was associated with afro-descendant background (p=0.02); presence of associated fibromyalgia (p=0.04), concomitant use of glucocorticoids (p=0.03) and Jak inhibitors (0.03). A tendency towards association with leflunomide use was observed (p=0.06). Logistic regression was used to test drug associations with methotrexate intolerance, and showed that glucocorticoid use was independently associated with methotrexate intolerance OR=1.85; 95% CI=1.01–3.44; p=0.04. Route of administration, presence of previous gastric complaints, age and methotrexate dose did not interfere with MISS. MISS results were associated with moderate adherence to the drug. ConclusionsThere is a high rate of methotrexate intolerance that is more common in afro-descendants, those with associated fibromyalgia, glucocorticoid and Jak inhibitors users.

Gastroduodenal effects of leflunomide under experimental adjuvant-induced rheumatoid arthritis and comorbid arterial hypertension

Use of leflunomide (LEF), a synthetic immunosuppressor, for the treatment of rheumatoid arthritis (RA), has become an innovation in the management of the disease. Despite the widely and successfully use of the LEF for RA treatment, its pharmacological properties and side effects are not well understood. The aim of the study was to examine the gastroduodenal effects of prolonged enteral use of the LEF in adjuvant-induced RA and comorbid arterial hypertension (AH). The experiments were carried out on male and female mature nonlinear rats, which were divided into five groups. The animals of control group (n = 10) were treated with starch suspension, the animals of the second group (n = 15) were injected with complete Freund’s adjuvant – adjuvant-induced arthritis (AA), the third group (n = 15) AA and comorbid AH (salt-loading model), the fourth group (n = 15) consisted of animals with AA treated with LEF, the fifth group (n = 15) – animals with comorbid condition (AA + AH), which were treated by LEF. Administering of starch-LEF suspension into the stomach was carried out through a special metal probe to rats with adjuvant-induced arthritis and comorbid pathology once daily for the first 3 days at a dose of 15 mg/kg (shock dose) and then at a dose of 1.5 mg/kg (therapeutic dose) for the next 53 days. After finishing the experiments, gastroduodenal toxic effects of the drug were determined according to the frequency of rats with pathological lesions (hyperemia, petechiae, edema, ulcers) and intensity of the damages using a point scale. It has been established that prolonged use of the LEF leads to high levels of gastroduodenal toxicity in rats with adjuvant-induced arthritis and combined pathological condition: an increase in the frequency of rats with gastroduodenal mucosal pathology and intensity of various types of damages (petechiae, edema, ulcers). LEF induced higher prevalence of duodenal than gastric toxicity in rats with both adjuvant-induced arthritis and arterial hypertension comorbidity. Thus, gastroduodenal mucosa pathology after prolonged use of LEF in adjuvant-induced arthritis and comorbid state increases a need for adjuvant therapy to prevent such adverse effects. Moreover, further pharmacological research in order to introduce appropriate drugs is recommended. Furthermore, conducting preclinical and clinical studies to understand the pharmacokinetics, mechanisms of action, and interaction of LEF, in particular, with antihypertensive and gastroprotective agents seem necessary. Implementation of the results of the study in healthcare practice will help to optimize the treatment regimen for rheumatoid arthritis and comorbidities.

Leflunomide-Associated Wound Complication After Cochlear Implantation: A Case Report.

Cochlear implantation has become an increasingly common strategy for aural rehabilitation in patients with severe to profound hearing loss who no longer benefit from conventional amplification. In conjunction, immunosuppressive therapies (e.g. disease-modifying anti rheumatic drugs (DMARDs) have become the keystone of management in numerous autoimmune conditions. Given the increasing prevalence of both, a greater proportion of patients will undergo cochlear implantation while on immune-modulating medications. While these medications are usually well tolerated, immunosuppression may put patients a higher risk for device infections. At present, this is not extensively studied within the cochlear implant literature. We conducted a retrospective chart review and review of the literature.Results:We present the case of an 81-year-old male who experienced wound dehiscence and infection secondary to leflunomide use for treatment of rheumatoid arthritis. Resolution of these issues was noted with a therapeutic drug holiday, and the patient has subsequently undergone re-implantation without issue.Conclusions:The case highlights a potential CI-associated wound complication in the setting of DMARD therapy. Given the increasing prevalence of both CIs and immunosuppressive therapy, future study on the potential for interaction is warranted to identify the best management strategy in the perioperative setting.

E034 Drug-induced accelerated nodulosis in a patient with rheumatoid arthritis

Abstract Background/Aims Drug-induced accelerated nodulosis (DIAN) is characterized by the occurrence or progression of multiple subcutaneous nodules in a patient treated for rheumatoid arthritis (RA). It was first and most commonly reported with methotrexate in RA patients. Methods A 37-year-old normotensive, non-diabetic, seropositive rheumatoid arthritis female presented with complaints of nodules over the bilateral hands and feet from the last three months. The treatment history included methotrexate therapy (10 mg/week) for one year. Methotrexate-induced rheumatoid accelerated nodulosis (MIAN) was suspected. Methotrexate was stopped and hydroxychloroquine was added considering the low disease activity. The nodules decreased in number as well as size. On follow-up, she presented with increased multiple joint pain and swelling with ESR 60 mm/hour, CRP 13.6 mg/L, and leflunomide was added. After six months of leflunomide use, she again developed multiple bilateral nodules on the extensor and palmar surface of fingers and feet, ranging from 0.5 to 1 cm. The CRP was 9.2 mg/L, ESR 80 mm/hour, complete blood count showed mild anaemia with normal renal and liver function tests. The nodule biopsy showed palisading granuloma consisting of lymphocytes and histiocytes in mid and deep reticular dermis with large foci of fibrin deposition and collagen degeneration s/o rheumatoid nodule. Leflunomide was stopped. Results The leflunomide was switched to sulfasalazine along with colchicine, and hydroxychloroquine was continued. The patient is doing well on follow-up in terms of disease activity and nodule size. Palmeiro. A.G., et al. 2022 reviewed 39 studies from 1st Jan 1988 to 1st Jan 2022 and found 109 cases of accelerated nodulosis. 99 patients had RA, methotrexate was the culprit drug in 89, followed by etanercept in 7 and leflunomide was in just 3 patients. Although there are no exact treatment guidelines, tumour necrosis factor inhibitors were avoided due to increased nodulosis risk. Recently, Valor-Méndez. L., et al 2020 reported improved nodulosis with Janus Kinase inhibitors like baricitinib, which seems to be a future option. Histologically, rheumatoid nodules and accelerated nodulosis are indistinguishable. The exact pathogenesis is unknown but, polymorphic variants of methionine synthase reductase or haplotype HLA-DRB1*0401, and adenosine A1 receptor promotion in multinucleated giant cells are associated. Conclusion Drug-induced accelerated nodulosis (DIAN) and MIAN are not that rare but diagnosis is challenging. It causes significant morbidity and affects the quality of life because of the predominant involvement of hands and feet. It should be suspected especially when disease activity is low or rapidly progressive nodules with a change in immunotherapy. Partial to total improvement can be achieved by identifying and stopping the culprit drug. We need specific guidelines, more treatment options, and a specific national registry to report such adverse effects with biologics and non-biologic disease-modifying antirheumatic drugs. Disclosure H. Singh: None. R. Kaur: None. G. Mohan: None.

Use of leflunomide among girls and women of childbearing age and occurrence of leflunomide-exposed pregnancies in Germany

Leflunomide is contraindicated during pregnancy and treatment cessation is recommended two years before pregnancy. We aimed to describe leflunomide use in women of childbearing age in Germany, the occurrence of pregnancies in women using leflunomide and malformations among children possibly exposed in utero. Using the GePaRD database (claims data, ∼20% of the German population), we determined annual age-standardized prevalences of leflunomide use between 2004 and 2019 among females aged 13–49 years. Further, we estimated the number of exposed pregnancies by assessing whether the exposure window assigned to the last dispensation before pregnancy (days covered by the dispensation plus two years) overlapped the onset of pregnancy or whether there was a dispensation in the first eight weeks of pregnancy. For exposed live births, a mother-baby linkage was performed and the presence of congenital malformation was assessed. The age-standardized prevalence of leflunomide use ranged between 0.34 and 0.46 per 1000 females during the study period. About one third of the users were ≤40 years. We identified 205 leflunomide-exposed pregnancies ending during the study period. 71% of these pregnancies ended in a live birth (26% preterm) and 10% in an induced abortion. In 86% of the live births (n=125) the mother-baby linkage was successful. Among these 125 children, 13 children (10%) had congenital malformations. In conclusion, we observed a considerable number of pregnancies in women using leflunomide in the two years before or during early pregnancy. This highlights the importance of monitoring the implementation of existing risk minimization measures for leflunomide in Germany.

Leflunomide as adjunct therapy for BK viremia management in pediatric kidney transplant recipients.

BK viremia after kidney transplantation (KT) poses significant risk for BK virus-associated nephropathy and impacts graft survival. Conventional treatment involves reduction of immunosuppression, which in turn may increase risk for rejection. To address this dilemma, use of anti-viral therapy with immunosuppressive properties such as leflunomide is an attractive option. We performed a multi-center, retrospective chart review to report tolerability and effectiveness of leflunomide use for the eradication of BK viremia and prevention of BK virus-associated nephropathy in pediatric KT recipients. Seventy patients prescribed leflunomide were included and were followed up from initiation until 1 year following leflunomide completion. BK viremia was eradicated in 64 (91.4%) patients including 8 of 11 with nephropathy (BKVN) on initial biopsy. Reduced anti-proliferative medication (AP) dosing was not associated with increase in biopsy proven rejection (BPAR). However, complete discontinuation of AP during leflunomide therapy was associated with increase in BPAR in uni- and multivariate logistic regression, as was targeted reduction in calcineurin inhibitor (CNI) trough goals. One graft was lost to BKVN. There was no significant association found between time to BK eradication and leflunomide trough concentration, mycophenolate dose reduction, or steroid use (univariate logistic regression). Few leflunomide adverse drug reactions (ADR) were reported (most commonly: gastrointestinal, hematologic). Leflunomide is a promising adjunctive treatment to immunosuppression reduction for BK virus eradication with minimal ADR. AP reduction, not discontinuation, and judicious reduction in CNI trough goals with close monitoring, is a promising strategy for treatment of BK viremia with concomitant use of leflunomide therapy.

Prevalence and Risk Factors of COVID-19 Reinfection in Patients with Rheumatoid Arthritis: A Retrospective Observational Study.

To identify the prevalence and risk factors of coronavirus disease 2019 (COVID-19) reinfection in patients with rheumatoid arthritis (RA). This study retrospectively analyzed patients with RA with a documented COVID-19 infection between January 2021 and December 2022 at a tertiary hospital in Seoul, South Korea. Reinfection was defined as a subsequent positive test result for severe acute respiratory syndrome coronavirus 2 at least 3 months after the initial infection. Cox proportional hazards models with backward elimination were employed to assess the association between potential risk factors and risk of reinfection. Of 351 included patients with RA {female, 81.5%; median age, 58.0 years [interquartile range (IQR), 48.0-66.0]}, 252 (71.8%) were treated with methotrexate and 12 (3.4%) received leflunomide during the initial infection. Over a median follow-up of 1.5 (IQR, 1.1-1.6) years, 43 (12.3%) patients experienced reinfection, equating to an incidence rate of 8.97 per 100 patient-years. The median time interval between infections was 0.8 (IQR, 0.6-1.2) years. Among the risk factors, leflunomide use showed a significant association with reinfection (hazard ratio, 2.968; 95% confidence interval, 1.057-8.335; p=0.039). However, no significant changes occurred in disease activity following reinfection [disease activity score using 28 joints: baseline median, 2.3 (IQR, 1.9-2.8); post-reinfection median, 2.3 (IQR, 1.8-2.6), p for change=0.895]. In this retrospective cohort study of patients with RA with COVID-19 infection, approximately 12% of patients experienced reinfection without significant change in disease activity. Leflunomide use was associated with a higher risk of reinfection.

Systematic review of phenotypes and genotypes of patients with gastrointestinal defects and immunodeficiency syndrome-1 (GIDID1) (related to TTC7A).

The objective was to conduct a comprehensive review of the morbidity and mortality observed in published patients with gastrointestinal defects and immunodeficiency syndrome-1 (GIDID1) related to TTC7A abnormalities. This included phenotypic, genotypic, and therapeutic aspects. Twenty-seven articles were included, which represented a total of 83 patients. Mortality was of 65.8% of the cases with a mean death at 11.8 months. The mortality rate was 197.1 per 1,000 patients-years, which is significantly higher than other enteropathy types caused by defects in epithelial trafficking and polarity (such as MOY5B, STX3, EPCAM, SPINT2, TTC37 and SKIV2L). Prematurity was also significant, with an average gestational age of 34.8 weeks. Antenatal signs were observed in 30 patients, including 14 cases of hydramnios. Three distinct phenotypic associations were identified: immune deficiency and multiple intestinal atresia without enteropathy (ID/MI), immune deficiency and enteropathy without atresia (ID/E), and immune deficiency with multiple intestinal atresia and enteropathy (ID/ MIA/E). The mortality rates for these groups were 91.6%, 47.3% and 55.5%, respectively (p = 0.03), at earlier age of mortality for the ID/MIA phenotype and a later one for the ID/E phenotype. ELA syndrome (Enteropathy, Lymphopenia and Alopecia) was only observed in the ID/E group. Among the three genotypes (double variant Nonsense NS/NS, variant Missense/Nonsense MS/NS, double variant Missense MS/MS), NS/NS was significantly associated with the ID/MIA phenotype (77.8%), while MS/MS was associated with the ID/E phenotype (73.7%). Few therapies have been shown to be effective in treating enteropathy, particularly immunosuppressive therapies and hematopoietic stem cell transplants. The use of Leflunomide in one patient did not yield successful treatment outcomes. In conclusion, we confirm association between mortality and phenotype, which is itself linked to genotype.

Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway.

The probability of cardiovascular events has been reported lower in rheumatoid arthritis (RA) patients treated with leflunomide. However, the anti-atherosclerotic and cardiovascular protective effects and metabolism of leflunomide are not explored. In this study, we assessed the potential benefits of leflunomide on atherosclerosis and revealed the underlying mechanism. ApoE-/- mice were fed a western diet (WD) alone or supplemented with leflunomide (20 mg/kg, oral gavage, once per day) for 12 weeks. Samples of the aorta, heart, liver, serum, and macrophages were collected. We found that leflunomide significantly reduced lesion size in both en-face aortas and aortic root in WD-fed ApoE-/- mice. Leflunomide also obviously improved dyslipidemia, reduced hepatic lipid content, and improved disorders of glucose and lipid metabolism in vivo. RNA-Seq results showed that leflunomide effectively regulated the genes' expression involved in the lipid metabolism pathway. Importantly, leflunomide significantly increased the phosphorylation levels of AMPKα and acetyl-CoA carboxylase (ACC) in vivo. Furthermore, leflunomide and its active metabolite teriflunomide suppressed lipid accumulation in free fatty acid (FFA)-induced AML12 cells and improved endothelial dysfunction in palmitic acid (PA)-induced HUVECs through activating AMPK signaling and inhibiting dihydroorotate dehydrogenase (DHODH) signaling pathway. We present evidence that leflunomide and teriflunomide ameliorate atherosclerosis by regulating lipid metabolism and endothelial dysfunction. Our findings suggest a promising use of antirheumatic small-molecule drugs leflunomide and teriflunomide for the treatment of atherosclerosis and related cardiovascular diseases (CVDs).

Initial Rheumatoid Arthritis Treatment: Does Female Age Matter?

Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting females. In RA, the treat to target strategy necessitates an early and intensive approach to achieve disease control. (1, 2) However, the therapeutic options can adversely affect reproductive health and pregnancy. Hence, the age of female patients at presentation might be a factor in decision making; although, there is a scarcity of evidence to support this hypothesis. We analyzed prescribing trends in Kuwait to examine the effect of female age on initial treatment decision. Methods Retrospective analysis of patients enrolled in the Kuwait RA Registry from 2012 to 2024. Baseline characteristics and medication prescribed at the initial visit were analyzed based on age group. Results 1101 female patients were included and stratified into two age groups [Formula: see text]49 years and &gt;49 years. 30.8% were [Formula: see text]49 years and had a higher proportion of rheumatoid factor (RF) n Anti-CCP positivity (82.4% vs 75.5%, p=0.087). There was no significant difference in the mean DAS-28 at baseline (3.2 vs 3.1, p=0.32). A numerically higher proportion of patients started methotrexate (MTX) in the &gt;49 years group (59.4% vs 54%, p=0.090). No statistically significant difference was found between the groups in sulfasalazine (SSZ), hydroxychloroquine (HCQ), or leflunomide (Lef) use. Rituximab was the most prescribed biologic with no statistical difference between the groups in prescription rate (p=0.822); TNF inhibitors (TNFi) were prescribed more often in the &gt;49 years group (16.5% vs 11%, p=0.022); adalimumab, highest TNFi, prescription was not statistically different between the groups; Etanercept was prescribed more often the &gt;49 years group (7.7% vs 4.7% and 5% vs 1.2%) respectively. There was no statistical difference between the groups in monotherapy vs. combination therapy treatment strategy. Discussion &amp; Conclusion This study showed that age at presentation does not significantly influence the initial choice of Disease-Modifying Anti-Rheumatic Drugs in female RA patients in Kuwait. Other factors, such as completion of family and patient preferences, likely play a more critical role in treatment decisions. Further research is needed to explore these influences and optimize management strategies for RA in women, particularly concerning reproductive health.

Antirheumatic drugs and the risk of nonalcoholic fatty liver disease in patients with rheumatoid arthritis: A nationwide, population-based cohort study.

To assess the association between antirheumatic drugs and of the risk of nonalcoholic fatty liver disease (NAFLD) in a nationwide rheumatoid arthritis (RA) cohort. Using claim data from the 2000-2020 National Health Insurance Research Database, we identified 21 457 incident patients with RA from 2002 to 2020 without prior liver diseases. A time-varying multivariable Cox regression model was applied to estimate for the association of NAFLD with the use of antirheumatic drugs after adjusting potential confounders, show as adjusted hazard ratios (aHRs) with 95% confidence interval (CIs). Subgroup analyses were conducted based on age-, sex-, and obesity-related comorbidities. Multivariable time-dependent Cox regression analyses showed that defined daily dose (DDD) of NSAID (aHR, 1.03; 95% CI: 1.02-1.05) and prednisolone equivalent dose >5 mg/day (aHR, 2.39; 95% CI: 1.85-3.09) were risk factors of NAFLD in patients with RA, while prednisolone equivalent dose ≤5 mg/day (aHR of 0.53; 95% CI: 0.40-0.71) and HCQ use (aHR of 0.75; 95% CI: 0.60-0.93) were associated with a decreased risk of NAFLD. In addition, a history of hospitalizations, number of outpatient visits, age, male, and leflunomide use were associated with the development of NAFLD in some subgroups. This study reveals that NSAID use and prednisolone equivalent dose >5 mg/day were associated with an increased risk of NAFLD in patients with RA, while the use of HCQ and prednisolone equivalent dose ≤5 mg/day decreased the risk of NAFLD.

Unveiling difficult-to-treat rheumatoid arthritis: long-term impact of biologic or targeted synthetic DMARDs from the KOBIO registry

BackgroundWhile the availability of biological or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) has improved outcomes for rheumatoid arthritis (RA) patients, there remains a subset of individuals who fail to achieve low disease activity or remission despite multiple cycles of b/tsDMARDs. This state is referred to as 'difficult-to-treat (D2T)' RA.MethodsData from the Korean College of Rheumatology Biologics registry were utilized to analyze patients with RA who were treated with b/tsDMARDs.ResultsAmong 2,321 RA patients with RA treated with b/tsDMARDs, 271 (11.7%) were diagnosed with D2T RA. Lower age (OR = 0.98, p < 0.001), longer disease duration (OR = 1.06, p < 0.001), lower patient global assessment (OR = 0.89, p = 0.045), higher SDAI (OR = 1.06, p = 0.014) and RAPID3 (OR = 1.06, p = 0.002), lower RF positivity (OR = 0.65, p = 0.04), and lower prior use of methotrexate (OR = 0.44, p = 0.008), sulfasalazine (OR = 0.59, p = 0.003), and leflunomide (OR = 0.67, p = 0.013) were associated with D2T RA. The drug survival rate of b/tsDMARDs did not differ between patients with D2T RA and non-D2T RA (p = 0.35). However, the drug survival of individual b/tsDMARD differed between patients with D2T RA and non-D2T RA after eight years. Patients with D2T RA withdrew from b/tsDMARDs due to inefficacy more frequently than those without D2T RA (p < 0.001).ConclusionsD2T RA patients experienced higher disease activity despite maintaining b/tsDMARD therapy. Withdrawal rates due to inefficacy were higher in D2T RA. Effective therapeutic strategies are needed to improve disease control and treatment outcomes in this unique patient population.

New-onset atrial fibrillation in seropositive rheumatoid arthritis: association with disease-modifying anti-rheumatic drugs treatment.

Atrial fibrillation (AF) is a potentially lethal complication that leads to increased hospitalization, disability and mortality. Furthermore, the risk of cardiovascular disease is increased in RA. We evaluated whether DMARD treatment is associated with incident AF in patients with seropositive RA (SPRA). The South Korean Health Insurance Review and Assessment Service database was used to identify patients newly diagnosed with SPRA between 2010 and 2020. A nested case-control analysis was performed to match AF-affected patients to unaffected controls for age, sex, follow-up duration, and index year of SPRA diagnosis at a 1:4 ratio. Adjusted conditional logistic regression was used to identify the predictive factors for AF. Of the 108 085 patients with SPRA, 2,629 (2.4%) developed new-onset AF, and the proportion of females was ∼67%. In the matched population, pre-existing comorbidities of hypertension, chronic kidney disease, and heart failure were associated with increased risk of AF. Meanwhile, the use of methotrexate (MTX) decreased the risk of incident AF [adjusted odds ratio (aOR), 0.89], whereas the use of leflunomide (LEF) increased AF (aOR, 1.21). In a subgroup of patients aged ≥50 years, LEF and adalimumab increased the occurrence of AF, while MTX decreased AF in males and LEF increased this risk in females. Although the number of subjects developing new-onset AF was small, MTX decreased and LEF increased incident AF in patients with RA. Especially, a distinct pattern of AF risk with DMARDs usage was observed according to age and sex.

Effect of type of disease-modifying antirheumatic drugs on depression and anxiety of patients with rheumatoid arthritis in Saudi Arabia: a cross-sectional study.

Rheumatoid arthritis (RA) can cause depression and anxiety. This study evaluated the factors associated with depression and anxiety in patients with RA and examined the effect of conventional and biologic disease-modifying antirheumatic drugs (DMARDs). This cross-sectional study was conducted in a regional hospital in Riyadh between March and November 2022 and included 213 patients with RA. Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS) and data about patients' DMARDs use was obtained from the hospital's medical records. Based on the HADS scores, 35 (16.4%) and 49 (23%) patients with RA had depression and anxiety, respectively. There was a significant association between the level of depression and anxiety and the use of leflunomide and tocilizumab among patients with RA (p = 0.006 and p = 0.009, respectively). Patients with RA who took leflunomide had significantly higher scores for anxiety (β = 0.158, value of p = 0.037) when compared to patients who did not take leflunomide. Patients with RA who took etanercept showed a significantly lower depression score even after adjusting for confounders, including sociodemographic, clinical, and lifestyle factors (β = -0.189, p = 0.043). The present study highlighted the prevalence of psychiatric disorders among patients with RA and the level of depression and anxiety may differ between patients with RA depending on the type of DMARDs used. We recommend patients with RA be screened regularly for depression and anxiety to avoid further extra-articular systemic complications associated with RA.

A newborn with multiple intestinal atresias found to have variants in tetratricopeptide repeat domain 7A gene

We report a male infant born with multiple intestinal atresias (MIA) prompting early genetic testing. Bi-allelic, compound heterozygous variants in tetratricopeptide repeat domain 7A (TTC7A) gene were identified. TTC7A is involved in transporting phosphatidylinositol 4-kinase IIIα into the plasma membrane (1). Mutations in this gene disrupt intestinal development and polarity, causing intestinal diseases such as atresia, enteropathy, and very early onset inflammatory bowel disease (VEO-IBD), as well as variable degrees of immunodeficiency (1).The identification of variants in TTC7A gene prompted an immune evaluation since as many as 75% of patients with TTC7A mutations reported in the literature have an underlying immunodeficiency (2). Flow cytometry was relatively unremarkable except for a slightly low memory T-cell count and percentage. NK-cell and B-cell numbers and percentages were appropriate for age. His phytohemagglutinin response was relatively low, but still significant, suggesting a possible component of combined immunodeficiency. To further characterize his T-cell function, we assessed his T-cell proliferation response to anti-CD3, which showed moderately decreased response of CD45+ lymphocytes and CD3+ T-cells to soluble anti-CD3 alone. However, co-stimulation with anti-CD3+anti-CD28 and anti-CD3+IL-2 normalized his T-cell proliferative response. Immunoglobulins were all low. Given his subtle T-cell defect and hypogammaglobulinemia, he was classified as having MIA with combined immunodeficiency (MIA-CID) phenotype of TTC7A.Cobalamin was tried in this patient as it has a low side effect profile and showed benefits in gut motility and intestinal tract luminal narrowing in a TTC7A zebrafish model (3). We considered investigational use of leflunomide, which showed the most promising results in the same zebrafish model (3). Bowel and hematopoietic stem-cell transplantation were considered too. Enterectomy was also offered, as this was shown to be effective in a case report of two patients with similar MIA-CID TTC7A phenotype (4). Unfortunately, the patient did not respond to steroids or cobalamin. His clinical condition worsened, and he passed away at four months of age.Mutations in the TTC7A gene result in various gastrointestinal pathologies with varying degrees of immunodeficiency in approximately 75% of patients (2). All patients with MIA or VEO-IBD should have an immune evaluation and genetic testing.

Effect of Leflunomide Use on 68Ga-DOTATATE Biodistribution in a Case With Neuroendocrine Tumor.

A 58-year-old man who underwent surgery for a well-differentiated neuroendocrine tumor of pancreatic origin was evaluated with 68Ga-DOTATATE PET/CT imaging in the follow-up period. After PET/CT findings consistent with disease remission, the patient was started on leflunomide treatment with the diagnosis of rheumatoid arthritis. The patient received leflunomide for 6 months. Then, 68Ga-DOTATATE PET/CT scan was repeated to evaluate the primary disease outcome. Besides the disease remission, we also observed alterations in DOTATATE uptakes of some tissues and organs. In this case, we present the changes in 68Ga-DOTATATE PET/CT scan findings after leflunomide use.

Better Clinical Results in Rheumatoid Arthritis Patients Treated Under a Multidisciplinary Care Model When Compared with a National Rheumatoid Arthritis Registry.

To describe clinical characteristics and effectiveness of health care in patients with rheumatoid arthritis (RA) as part of a multidisciplinary care model (MCM) in a specialized rheumatology center, compared with the results of a national registry of RA (NARRA) as evidence of real-world management. We conducted a real-world study (July 1, 2018 to June 30, 2019) based on an analysis of electronic health records of a cohort of RA patients managed with the "Treat-to-Target" strategy in a specialized rheumatology center in Colombia with an MCM, compared with the NARRA that includes different models of usual care. We have analyzed 7053 subjects with RA treated at a specialized rheumatology center and 81,492 patients from the NARRA. Cohorts were similar in their baseline characteristics, with women in predominance and diagnosis age close to 50 years. At the time of diagnosis, a higher proportion of clinical diagnostic test use and rheumatology consultation access was observed in the specialized rheumatology center than in the national registry (4-6 per year versus three or less). In addition, higher proportions of patients in remission and low disease activity were reported for the specialized rheumatology center, with a >40% amount of data lost in the national registry. Pharmacological management was similar regarding the analgesic use. In the specialized center, Certolizumab was more frequently used than in the NARRA registry; also, there were significant differences in methotrexate, leflunomide, and sulfasalazine use, being higher in the specialized rheumatology center. The MCM of a specialized center in RA can guarantee comprehensive care, with better access to all the services required to manage the disease. It ensures specialist management and evidence-based care that facilitates the achievement of therapeutic objectives. In addition, better patient records and follow-ups are available to evaluate health outcomes.

Predictors of improvement in disease activity in first hospitalized patients with systemic lupus erythematosus: a multicenter retrospective study of a Chinese cohort

ObjectivesTo analyze the relative factors of improvement in disease activity (IDA) after first hospitalized treatment based on the systemic lupus erythematosus disease activity index (SLEDAI).MethodsA total of 1069 adult systemic lupus erythematosus (SLE) patients who were hospitalized for the first time in 26 hospitals in Jiangsu Province from 1999 to 2009 were retrospectively analyzed. SLEDAI decrease ≥ 4 during hospitalization was identified as IDA. Relative factors of IDA were assessed by univariate and multivariate logistic regression.ResultsA total of 783 (73.2%) adult SLE patients showed IDA after the first hospitalization, while the remaining patients (n = 286) were in the non-IDA group. The IDA group had higher SLEDAI at admission; fewer patients had SLICC/ACR damage index (SDI) ≥ 1, comorbidities at admission, especially Sjögren’s syndrome, abnormal serum creatinine, and glomerular filtration rate. More patients had mucocutaneous and musculoskeletal involvements, leukopenia, increased C-reactive protein, anti-dsDNA antibody positive, and hypocomplementemia at admission and were treated with methotrexate and leflunomide during hospitalization. After multivariate logistic regression analysis, SDI ≥ 1 (P = 0.005) and combined with Sjögren’s syndrome (P < 0.001) at admission had negative association with IDA. Musculoskeletal involvement (P < 0.001), anti-dsDNA antibody positive (P = 0.012), hypocomplementemia (P = 0.001), and use of leflunomide (P = 0.030) were significantly related with IDA.ConclusionOrgan damage or comorbidities at admission were adverse to SLE improvement. Anti-dsDNA antibody positive, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment had positive association with IDA of SLE.Key Points• Organ damage or comorbidities at admission were negatively correlated with SLE improvement.• Anti-dsDNA antibody positivity, hypocomplementemia, musculoskeletal involvements, and leflunomide treatment were positively associated with SLE improvement.