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ID PMID Title PublicationDate abstract
33179261 Risk of haematological events and preventive effect of folic acid in methotrexate users wi 2021 May Although methotrexate (MTX) for rheumatoid arthritis (RA) sometimes causes severe haematological toxicities in users with chronic kidney disease (CKD), data are limited regarding the risk of these events and the preventive effect of folic acid. This study evaluated the risk of haematological toxicities and the efficacy of folic acid in MTX users with CKD using the Japanese Adverse Drug Event Report. In total, 5,648 oral MTX users with RA were identified, including 630 with haematological toxicities. MTX users with CKD had significantly increased risk of haematological toxicities compared with those without CKD when folic acid was not used (OR 3.72; 95% CI 2.87-4.81; P < 0.01). Multivariate logistic analysis showed that the risk of haematological toxicities was significantly decreased by only folic acid (OR 0.16; 95% CI 0.04-0.62; P < 0.01). This result provides useful information for preventing severe haematological toxicities in MTX users with CKD and RA.
32885317 Cumulative incidence of femoral localized periosteal thickening (beaking) preceding atypic 2021 Feb The incidence of localized periosteal thickening (LPT, also termed beaking) of the lateral cortex that often precedes an atypical femoral fracture (AFF) was not high in patients with rheumatoid arthritis (RA) but incomplete AFFs developed in two patients. Higher-dose prednisolone was a significant risk factor for LPT in patients with RA. INTRODUCTION: Atypical femoral fractures (AFFs) are stress fractures; bisphosphonate (BP) use is a major risk factor for the development of such fractures. Localized periosteal thickening (LPT, also termed beaking) of the lateral cortex often precedes a complete or incomplete AFF. We evaluated the incidence of latent LPT in patients with rheumatoid arthritis (RA), to evaluate LPT progression, and to define LPT risk factors. METHODS: A total of 254 patients with RA were included; all underwent annual X-ray evaluation, dual-energy X-ray absorptiometry, and analyses of serum and bone metabolic markers for 2-3 years. LPT of the lateral cortex was sought in femoral X-rays. RESULTS: The incidence of LPT was 2.4% (6/254). Among patients on both BP and prednisolone (PSL) at enrollment, the incidence was 2.3% (3/131). Two femurs of two patients with LPT developed incomplete AFFs; LPT was extensive and associated with endosteal thickening. One patient had been on BP and PSL and microscopic polyangiitis was comorbidity. The other was on a selective estrogen receptor modulator and PSL. A daily PSL dose >5 mg (OR 11.4; 95%CI 2.15-60.2; p = 0.004) and higher-dose methotrexate (OR 1.22; 95%CI 1.01-1.49; p = 0.043) were significant risk factors for LPT. CONCLUSIONS: The incidence of latent LPT was not high (2.4%) but incomplete AFFs developed in two RA patients. Higher-dose PSL because of a comorbid disease requiring glucocorticoid treatment other than RA or refractory RA were risk factors for LPT; X-ray screening for latent LPT would usefully prevent complete AFFs.
32216091 Most Appropriate Conventional Disease-Modifying Antirheumatic Drug to Combine With Differe 2021 Jun OBJECTIVE: In rheumatoid arthritis, the association between advanced therapies (including biologic disease-modifying antirheumatic drugs [DMARDs] and targeted synthetic DMARDs) and methotrexate (MTX) is recommended by international societies. When MTX cannot be used, other conventional synthetic DMARDs (csDMARDs) may be proposed. We aimed to compare the safety and efficacy of MTX and non-MTX csDMARDs in combination with advanced therapies. METHODS: We systematically searched the literature for studies comparing the effectiveness, retention rate, and safety of MTX versus non-MTX csDMARDs (leflunomide or others) in combination with tumor necrosis factor inhibitors (TNFi), abatacept, rituximab, tocilizumab, and JAK inhibitors. Meta-analysis was performed with RevMan, using an inverse variance approach with fixed or random-effects models. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated. RESULTS: The literature search revealed 3,842 articles; 41 studies were included for the systematic literature review and 21 for the meta-analysis: 13 with TNFi, 3 with abatacept, and 5 with rituximab. For TNFi, the European Alliance of Associations for Rheumatology (EULAR) response at 6 months was lower for patients receiving non-MTX csDMARDs than for those using MTX (RR 0.93 [95% CI 0.87, 1.0], P = 0.04; n = 3,843; I(2) = 28%), with a lower retention rate at 12 months. For abatacept, effectiveness and safety were similar between the 2 groups. For rituximab, a good EULAR response was higher with leflunomide than MTX (RR 1.38 [95% CI 1.13, 1.68], P = 0.001; n = 2,078; I(2) = 0%), with similar adverse event rates. Meta-analysis for tocilizumab or JAK inhibitors could not be performed. CONCLUSION: The different csDMARDs seem safe and efficient to combine with advanced therapies in RA patients. Although MTX seems slightly superior to other csDMARDs in combination with TNFi, leflunomide might be superior to MTX in combination with rituximab.
32654596 Contributing factors of clinical outcomes at 1 year post-diagnosis in early rheumatoid art 2021 Mar OBJECTIVES: To determine whether specific parameters contribute to clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis (RA) patients under the 'treat-to-target' strategy in clinical practice. METHODS: We retrospectively analyzed 125 RA patients selected according to the following criteria; the patients' symptom duration was ≤6 months, and none had experience with DMARDs. We evaluated the patients' clinical disease activity at baseline and 1 year of treatment and the musculoskeletal ultrasound (MSUS)-detected synovitis activity at baseline. We performed an analysis to identify parameters that contribute to SDAI remission and the use of biologic/targeted synthetic (b/ts) DMARDs at 1 year post-diagnosis. RESULTS: Forty-seven patients received b/tsDMARDs therapy, and 58 patients achieved SDAI remission at 1 year post-diagnosis. Rheumatoid factor positivity, low patient's/evaluator's global assessment at baseline, and methotrexate use at 1 year post-diagnosis were associated with SDAI remission. The baseline clinical disease activity and MSUS scores were not associated with SDAI remission. Anti-cyclic citrullinated peptide antibody positivity/high titer and high swollen joint counts or the presence of severe synovial hypertrophy at baseline were associated with the use of b/tsDMARDs therapy. CONCLUSION: The value of the expected poor-prognosis factors may be diminished by intensive therapy within the 'windows of opportunity'.
34569001 Development of PBPK model for intra-articular injection in human: methotrexate solution an 2021 Dec A physiologically based model describing the dissolution, diffusion, and transfer of drug from the intra-articular (IA) space to the plasma, was developed for GastroPlus® v9.8. The model is subdivided into compartments representing the synovial fluid, synovium, and cartilage. The synovium is broken up into two sublayers. The intimal layer acts as a diffusion barrier between the synovial fluid and the subintimal layer. The subintimal layer of the synovium has fenestrated capillaries that allow the free drug to be transported into systemic circulation. The articular cartilage is broken up into 10 diffusion sublayers as it is much thicker than the synovium. The cartilage acts as a depot tissue for the drug to diffuse into from synovial fluid. At later times, the drug will diffuse from the cartilage back into synovial fluid once a portion of the dose enters systemic circulation. In this study, a listing of all relevant details and equations for the model is presented. Methotrexate was chosen as a case study to show the application and utility of the model, based on the availability of intravenous (IV), oral (PO) and IA administration data in patients presenting rheumatoid arthritis (RA) symptoms. Systemic disposition of methotrexate in RA patients was described by compartmental pharmacokinetic (PK) model with PK parameters extracted using the PKPlus™ module in GastroPlus®. The systemic PK parameters were validated by simulating PO administration of methotrexate before being used for simulation of IA administration. For methotrexate, the concentrations of drug in the synovial fluid and plasma were well described after adjustments of physiological parameters to account for RA disease state, and with certain assumptions about binding and diffusion. The results indicate that the model can correctly describe PK profiles resulting from administration in the IA space, however, additional cases studies will be required to evaluate ability of the model to scale between species and/or doses.
32711117 Risk factors associated with initiation of a biologic disease modifying anti-rheumatic dru 2021 Jan OBJECTIVE: To identify risk factors of biological disease-modifying anti-rheumatic drugs (bDMARDs) initiation in patients with rheumatoid arthritis (RA). METHODS: Using the 2002-2016 Korea National Health Insurance database, we conducted a nested case-control study on seropositive RA patients. Cases (bDMARD users) and controls (users of conventional synthetic DMARDs only) were 1:4 matched on the calendar year/month of RA diagnosis and index dates (bDMARD initiation dates). Potential risk factors from two time periods, 1-year post-RA-diagnosis and 1-year pre-index, were separately assessed on the association with bDMARD initiation by conditional logistic regression analyses. RESULTS: The study included 6985 cases and 27,940 controls. Older age, female gender, use of methotrexate (MTX), leflunomide, or tacrolimus as a first csDMARD, higher initial MTX dose, and initial csDMARD combination during 1-year post-diagnosis were negatively associated with later bDMARD initiation, while use of sulfasalazine as a first csDMARD, corticosteroid therapy, and higher maximal MTX dose were positively associated. Among covariates from 1-year period before bDMARD initiation, use of leflunomide, sulfasalazine, or tacrolimus, parenteral MTX, higher maximal MTX dose, corticosteroid, and csDMARD combination were positively associated with subsequent bDMARD initiation. Effects of comorbidities on bDMARD initiation were heterogenous across involved systems. CONCLUSION: In this population-based nationwide study, we identified period-specific risk factors of bDMARD initiation among RA patients in Korea. Overall, initial aggressive RA treatment after diagnosis was associated with less use of later bDMARD, while highly intensive therapy observed just before bDMARD initiation rather reflects refractory nature of RA during this period, and did not prevent bDMARD use.
33783311 Acute hepatitis E in an immunocompromised patient with seropositive rheumatoid arthritis o 2021 Jul We report the case of a 61-year old female with a 20-year history of seropositive rheumatoid arthritis (RA) who developed acute hepatitis. Her arthritis had been treated with methotrexate (MTX) since 2003 and, following an increase in disease activity, Rituximab (RTX) was commenced in January 2017. In May 2020, routine blood tests showed a new elevation in her liver profile, although synthetic function was preserved. A standard liver screen found no cause for her acutely abnormal lab values. Upon additional serological testing, the patient was confirmed to have acute hepatitis E virus (HEV). Her primary complaint at the time was fatigue. Within a month, her liver blood tests spontaneously improved and her symptoms resolved with conservative management.
34586516 Factors associated with frailty in Japanese patients with rheumatoid arthritis: results fr 2022 Feb This study aimed to evaluate the prevalence of, and the factors associated with, frailty in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires, which included the 5-item frailty screening index. Patients were classified as frail, prefrail, or robust based on the 5 components of the frailty screening index. Logistic regression analyses were used to evaluate associations between clinical variables and frailty. Among 3,290 Japanese patients with RA (86.7% female, mean age 62.4 years) who participated this frailty study, 549 (16.7%) patients were categorized as frailty, 2,063 (62.7%) as prefrailty, and 678 (20.6%) as robust. In multivariable models, body mass index (BMI) ≥ 25 kg/m(2) (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.41 to 2.47), BMI < 18.5 kg/m(2) (OR 1.31, 95% CI 1.00 to 1.71), disease activity scores in 28 joints (DAS28) (OR 1.32, 95% CI 1.18 to 1.47), Japanese version of Health Assessment Questionnaire disability index (J-HAQ) (OR 1.26, 95% CI 1.04 to 1.52), the European Quality of Life-5 Dimensions (EQ-5D) (OR 0.80, 95% CI 0.74 to 0.85), non-steroidal anti-inflammatory drug (NSAID) use (OR 1.59, 95% CI 1.23 to 1.98), and methotrexate (MTX) use (OR 0.75, 95% CI 0.60 to 0.94) were significantly (P < 0.05) associated with frailty. BMI (both overweight and underweight), DAS28, J-HAQ, EQ-5D, NSAID use, and MTX nonuse appear to be associated with frailty in Japanese patients with RA. Key Points • This is the largest study showing the prevalence and the associated factors of frailty in patients with RA. • Maintaining normal BMI appears to be important for preventing frailty in patients with RA. • We confirmed the significant associations of frailty with high disease activity, high degree of disability, and poor health related QOL in Japanese patients with RA. • NSAID use and MTX nonuse were associated with the frailty in Japanese patients with RA, which could be explained by patients' background.
33541985 First use of tofacitinib to treat an immune checkpoint inhibitor-induced arthritis. 2021 Feb 4 Immune checkpoint inhibitors have revolutionised cancer treatment; however, immune-related adverse events do occur, with up to 7% developing inflammatory arthritis. Common rheumatoid arthritis therapies such as methotrexate, prednisolone and biologics have been used to treat this arthritis in small, uncontrolled case series with varying success. In this case of personalised medicine, we report the first use of tofacitinib, a small molecular inhibitor of the Janus kinase-signal transducer and activator of transcription pathway, to treat checkpoint inhibitor-related inflammatory arthritis. This resulted in a rapid clinical response and complete, sustained remission of the arthritis with associated marked reduction in synovial molecular and cellular immune response.
34369364 Prognostic signature of interferon-γ and interleurkin-17A in early rheumatoid arthritis. 2022 May OBJECTIVES: CD4+ T cells are crucial for the pathogenesis of rheumatoid arthritis (RA). Here, we evaluated gene expression in CD4+ T cells in early RA, and main purpose of present study was to seek the changes in CD4+ T-cell-related cytokines according to RA progression. METHODS: Early RA was defined as methotrexate (MTX)-naïve patients. Established RA was defined as patients with more than 6 months of DMARDs. Patients with osteoarthritis were evaluated as controls. Microarray analysis was used to identify overexpressed genes in CD4+ T cells, and RT-qPCR was used to validate. Plasma cytokine were measured in patients with early and established RA, and correlations with disease activity were assessed in patients with early RA, whereas clinical prognosis was assessed in established patients with RA. RESULTS: Thirty-four genes showed overexpression in CD4+ T cells from patients with early RA compared with OA controls. Nineteen were related to interferon (IFN)-γ, and eight were related to interleukin (IL)-17A. Plasma levels of IL-17A, IL-6, IL-12, and TNF-α correlated with IFN-γ, and correlation coefficient was highest between DAS28-ESR and plasma IFN-γ levels in patients with early RA (Rho=0.553, p=0.0025). In established RA with low disease activity, drug reduction group showed lower plasma IFN-γ and IL-17A than drug maintenance/relapse group (13.61±5.75 vs. 29.89±18.72, p<0.001; and 10.91±3.92 vs. 21.04±12.81 pg/mL, p<0.001, respectively). CONCLUSIONS: The IFN-γ and IL-17 gene signature in CD4+ T cells was significantly increased in early RA. Patients with established RA with low levels of IFN-γ and IL-17A could be eligible for dose reduction.
34586472 Comparison between leflunomide and sulfasalazine based triple therapy in methotrexate ref 2022 May To compare efficacy and safety of two different combination csDMARD therapy in Methotrexate-failed Rheumatoid arthritis patients. In this 24-week open-label, parallel-group non-inferiority, single-center clinical trial, Methotrexate-failed Rheumatoid arthritis patients with disease duration < 2 years, were randomized to either of the two treatment regimens-Methotrexate + Leflunomide + Hydroxychloroquine or Methotrexate + Sulfasalazine + Hydroxychloroquine. Primary endpoint was proportion of patients achieving EULAR good response at 12 weeks. Non-inferiority of Leflunomide based therapy was confirmed if the upper limit of the 2-sided 95% confidence interval of treatment difference between the 2 groups was lower than the selected non-inferiority margin of (- 20%) in primary endpoint at 12 weeks. Secondary endpoints were improvement in DAS28, functional outcome and adverse events at 24 weeks. 136 eligible patients were randomized to either Leflunomide or Sulfasalazine group (68 in each group).63 and 59 patients in Leflunomide and 66 and 61 patients in Sulfasalazine group completed 12 and 24 weeks of trial, respectively. In Intension-to-treat analysis, EULAR good response was achieved by 58.8% and 54.4% patients (p = 0.7) at the end of 12 weeks, and 61.7% and 64.7% patients (p = 0.8) at the end of 24 weeks-in Leflunomide and Sulfasalazine group respectively. At 12 weeks, the difference in EULAR good response with 2-sided 95% confidence interval between 2 groups was 4.4% (- 12%, 20%) in intention-to-treat and 5.8% (- 11%, 23%) in perprotocol analysis.15 and 21 adverse events were recorded in Leflunomide and Sulfasalazine group respectively. Parenteral Methotrexate was required more in Sulfasalazine group due to gastrointestinal intolerance. Leflunomide based csDMARD therapy is non-inferior to Sulfasalazine based csDMARD therapy in Methotrexate-failed Rheumatoid arthritis patients with comparable safety profile. Trial registered at clinicaltrials.gov (NCT02930343) dated 10.09.2016.
33931278 Long-term outcomes and duration of outdoor ambulation following primary total knee arthrop 2022 Mar BACKGROUND: The medical treatment of rheumatoid arthritis (RA) has made remarkable progress with the introduction of methotrexate and biological agents. However, there have been few reports of long-term results of total knee arthroplasty (TKA) for RA since the introduction of these drugs. Ambulation is an important form of exercise for maintaining health. We investigated the long-term outcomes and the ability to walk outdoors following TKA in patients with RA. METHODS: We retrospectively reviewed 142 patients with RA (201 knees) who had undergone primary TKA. The mean follow-up was 10.6 years. RESULTS: Markers of RA disease activity all improved significantly postoperatively. Mean Japanese Orthopedic Association scores improved from 49.3 points before surgery to 81.8 at follow-up. The mean maximum flexion angle improved from 107.8° to 112.9°. The causes of TKA revision comprised 2 mechanical loosening, 1 late infection, and 1 fracture of the femoral condyle. The survival rate of TKA was 96.6% at 15 years. Fifty-five patients were not able to walk outdoors. The rate of inability to ambulate outdoors was 38.3 per 1000 person-years. The survival rate of ability to ambulate outdoors were 48.8% at 15 years. Preoperative advanced age, low body weight, steroid use and non-use of biologics were identified as risk factors for inability to ambulate outdoors. CONCLUSIONS: Although the cumulative survival rate of TKA implants was as good as 96.6% in 15 years, the cumulative rate of ability to ambulate outdoors was only 48.8%. The reason for the inability to walk outdoors was thought to be mainly due to deterioration of RA, comorbidity or muscular weakness associated with aging, rather than knee dysfunction.
34846624 Use of biologic agents and methotrexate improves renal manifestation and outcome in patien 2022 Apr BACKGROUND AND PURPOSE: We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA). METHODS: We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990-1999 (n = 48); period 2, 2000-2009(n = 57); period 3, 2010-2019 (n = 51). RESULTS: Membranous nephropathy, nephrosclerosis, AA-amyloidosis, and IgA nephropathy were the four major renal manifestations of RA. AA-amyloidosis was diagnosed by kidney biopsy in 21 patients: period 1, 7 patients (15%); period 2, 10 patients (18%); and period 3, 4 patients (8%). The 4 patients in period 3 were in the years 2010-2014, and no new case of AA-amyloidosis was recorded from 2015 to 2019. In all 21 of the patients with AA-amyloidosis, neither a biologic agent nor methotrexate was administered. Fifteen of the 21 patients required dialysis, and 13 died in periods 1-3 because of amyloid-related cardiac dysfunction less than 2 years after the initiation of dialysis. Two of them are doing well using biologic agent despite dialysis. The remaining three patients who received a biologic agent or methotrexate does not progress to end-stage renal failure. In addition, the other renal complications showing progression to dialysis also decreased over time. CONCLUSION: Advances in treatment strategies have improved renal outcome and reduced mortality in patients with RA.
34553318 Prescribing Trends of Biologic Disease-Modifying Anti-rheumatic Drugs Using a Claims Datab 2021 Nov BACKGROUND AND OBJECTIVE: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are used either when conventional synthetic DMARDs are ineffective or when disease activity is high and with poor prognostic factors, based on various clinical guidelines. The purpose of this study was to investigate the prescribing trends of bDMARDs for patients with rheumatoid arthritis in Japan, and to clarify whether the pharmacological therapy of bDMARDs is administered based on guidelines. METHODS: We conducted a descriptive epidemiological study from 2012 to 2018 using the JMDC Claims Database, a nationwide claims database, and described the annual changes based on the number of patients prescribed bDMARDs. Anti-rheumatic drugs were identified based on the Anatomical Therapeutic Chemical codes, including methotrexate, glucocorticoids, non-steroidal anti-inflammatory drugs and bDMARDs. RESULTS: From the database including 6,862,244 people, the data of 6407 patients with rheumatoid arthritis were extracted. The present study demonstrated that the proportion of patients prescribed bDMARDs was 1.0 per 1000 people, with those aged ≥ 65 years being the most common age group. The proportion of patients with rheumatoid arthritis who were prescribed bDMARDs increased significantly over time (p < 0.0001). Additionally, the concomitant proportions of methotrexate (p < 0.0001), non-steroidal anti-inflammatory drugs (p < 0.0001) and glucocorticoids (p = 0.0001) prescribed with bDMARDs decreased significantly over time. CONCLUSIONS: The increase in bDMARD monotherapy may be attributed to the new bDMARDs that have been launched sequentially; furthermore, physicians have come to recognise monotherapy as the mainstay of treatment. Future studies must accumulate evidence on the long-term efficacy and safety of bDMARDs.
34236743 Patient's experiences of the barriers and facilitators to Methotrexate. 2022 Mar OBJECTIVE: To investigate the barriers and facilitators of adherence to methotrexate (MTX) in people with rheumatic diseases and to explore the experience of shared decision-making. METHODS: A qualitative study was carried out. People diagnosed with inflammatory arthritides or systemic autoimmune diseases and who were treated with MTX were invited to participate in focus groups. The discourse was coded and synthesised with a content analysis approach. RESULTS: The groups included 12 representative patients (rheumatoid arthritis, spondylarthritis, and systemic lupus erythematosus, taking either oral or subcutaneous MTX). Four main themes were identified: (1) drug-related aspects (package insert, adverse events, administration, and difficulties with treatment); (2) patient-physician relationship; (3) social environment (lack of visibility of rheumatic diseases and the support of patient associations); and (4) medication and medical care practicalities (information, reliable sources, and expanding knowledge in other health areas). CONCLUSIONS: Aspects identified might help improve adherence, including quality information, especially on adverse events, the role of the setting, and shared decision-making.
31789997 Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score in Brazi 2021 Sep 1 INTRODUCTION: The Methotrexate Intolerance Severity Score (MISS) questionnaire is used to identify intolerance to methotrexate (MTX), but it is not available in the Brazilian Portuguese language. OBJECTIVE: The aim of this study was to adapt and validate the MISS in Brazilian Portuguese. METHODS: The Brazilian Portuguese version of the MISS was developed following the Guidelines for the Process of Cross-cultural Adaptation of Self-report Measures. The new version was tested in 120 patients with rheumatoid arthritis. For the reliability assessment, the Cronbach α coefficient was used. The receiver operating characteristic curve was constructed with the objective of finding the best cutoff point for MTX intolerance and weighing the sensitivity and specificity. The concordance among the results was analyzed using the κ coefficient and factorial analysis with varimax rotation. RESULTS: This methodological study developed and applied a culturally acceptable Brazilian Portuguese version of the MISS. The MISS questionnaire presented internal consistency classified as "very good" because Cronbach α is equal to 0.83 (95% confidence interval, 0.79-0.87). The suitability of the data for factorial analysis was demonstrated using the Kaiser-Meyer-Olkin sample adequacy test (KMO = 0.723) and Bartlett sphericity test (χ2 = 499.98, p < 0.001). It was observed that a factorial analysis with 3 factors is preferred; the receiver operating characteristic curve of the MISS score was considered the cutoff point at 6 points (sensitivity 100% and specificity 89.4%). CONCLUSIONS: The Brazilian Portuguese version of the MISS is valid and reliable for the detection of MTX intolerance in clinical practice.
34633502 [Visceral leishmaniasis mimicking Felty's syndrome in rheumatoid arthritis treated with me 2022 Apr Visceral leishmaniasis (VL) is a chronic parasitic disease caused by pathogens of the genus Leishmania, which can mimic numerous diseases. The leading symptoms of VL (splenomegaly, pancytopenia, fever) can be misinterpreted, especially if autoantibodies are detected, and lead to the misdiagnosis of an underlying rheumatic disease (e.g. systemic lupus erythematosus, Felty's syndrome). Proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) play an important role in infection control. In this context, there are increasing reports of VL as an opportunistic infection during treatment with anti-TNF‑α agents. A case of VL mimicking Felty's syndrome in a patient with rheumatoid arthritis treated with methotrexate and etanercept is presented.
34461001 Methotrexate Hepatotoxicity Monitoring Guidelines in Psoriasis and Rheumatoid Arthritis: I 2021 Aug Methotrexate therapy has evolved over the years to become a fundamental component in the management of rheumatoid arthritis and psoriasis. Liver toxicity remains an ever-present concern when prescribing methotrexate. As such, methotrexate liver toxicity monitoring guidelines have been developed independently by rheumatologists and dermatologists. The main differentiating factor between the dermatology and rheumatology guidelines is risk stratification. Dermatology guidelines are largely based off of the presence or absence of hepatoxicity risk factors (alcohol usage, obesity, type II diabetes, among other) while the rheumatology guidelines do not emphasize this distinction. Thus, the aim of this review is to identify why these screening guidelines differences exist and discuss if the differences in stratification and screening are valid. We will also briefly examine alternatives to the current gold standard hepatoxicity screening test: the liver biopsy.
34470830 Lymphoma complicating rheumatoid arthritis: results from a French case-control study. 2021 Sep OBJECTIVES: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. METHODS: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. RESULTS: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. CONCLUSION: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.
31789996 Contraceptive Use in Women of Childbearing Ability With Rheumatoid Arthritis. 2021 Apr 1 BACKGROUND/OBJECTIVE: Rheumatoid arthritis (RA) is a complex disease that may require treatment with one or several disease-modifying antirheumatic drugs (DMARDs). Many DMARDs have potential teratogenic effects or are newer agents with limited safety data in pregnancy. This study evaluated 20 common RA medications and the rate of contraceptive prescribing and counseling patterns in women with RA of childbearing ability. METHODS: This was an observational study of women with RA and childbearing ability aged 18 to 44 years who were seen at an academic rheumatology clinic from April 1, 2014, to March 31, 2016. Descriptive statistics and univariate logistic regression were used for analysis. RESULTS: One hundred fifty women were included in the analysis. The majority of patients were taking methotrexate (55.3%), followed by chronic prednisone (31.3%) and hydroxychloroquine (28.7%). A documented method of contraception was noted in 64/150 (42.7%). For women on contraception, most used combined oral contraceptives (31/64, 48.4%) or levonorgestrel intrauterine device (10/64, 15.6%). Of the 86 patients not on contraception, 19 (22.1%) received counseling regarding a pregnancy plan. CONCLUSIONS: Most women with RA of childbearing age and ability were not using contraception. Among these patients, only a minority prescribed DMARD therapy had documented pregnancy or contraceptive counseling. Women with RA who were prescribed with a DMARD should discuss the use of effective contraception with their provider if sexually active and not desiring pregnancy or wanting to avoid potential teratogenic effects. Potential strategies are discussed to improve healthcare delivery to this population in hopes of avoiding unintended pregnancy and potential teratogenic effects of RA medications.