Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
32106881 Rheumatoid artrhitis treatment in Brazil: data from a large real-life multicenter study. 2020 Feb 27 BACKGROUND: Last decades witnessed great technological advances in rheumatoid arthritis (RA) management, but their implementation in clinical practice might prove difficult. Despite the efficacy demonstrated in controlled trials this information needs to be confirmed by real life data. This study assessed real-life treatment among RA patients. METHODS: REAL study included Brazilian RA patients from eleven centers. Interview and medical records were performed. Continuous variables were compared using Student's t or Mann-Whitney and categorical variables were assessed with chi-square or Fisher's exact tests. RESULTS: 1115 patients were included, women 89.5%. Median age 56.6 years, disease duration 152.5 months; 78.7% were rheumatoid fator positive; 55.2% had erosive disease; DAS28 (disease activity index-28 joints) = 3.5, HAQ (health assessment questionnaire) =0.875. The median duration of symptoms until the start of first DMARD was 12 months. A total of 529 (47.2%) patients used corticosteroids; 1022 (90.8%) were on conventional synthetic (cs) DMARDs and 406 (36.1%) on biological (b) DMARDs. Methotrexate (MTX) was the most frequent csDMARD: 748 (66.5%) patients, followed by leflunomide (LFN), used by 381 (33.9%) of patients. MTX was associated to LFN in 142 (12.6%) patients. Only five (0.4%) patients used triple therapy (MTX + hydroxychloroquine + sulfasalazine) or sulfasalazine in monotherapy. CONCLUSIONS: Despite advances in therapeutic resources, roughly half RA patients failed achieve T2T goals and 55.2% developed erosive disease. The frequent use of corticosteroids and delay in initiating DMARDs were demonstrated. Issues concerning timely access to medical care are crucial for effective management.
32929336 Near-infrared fluorescence imaging-guided focused ultrasound-mediated therapy against Rheu 2020 Rheumatoid arthritis (RA), a common inflammatory disorder of the joints characterized by synovitis and pannus formation, often results in irreversible joint erosion and disability. Methotrexate (MTX) is the first-line drug against RA, but the therapeutic effects are sub-optimal due to its poor retention at the target sites and systemic side effects. Multifunctional nanoparticles are highly promising agents for minimally invasive, traceable and effective targeted therapy. Methods: This study developed iRGD peptide-functionalized echogenic liposomes (iELPs) which encapsulates MTX and indocyanine green (ICG) fluorescent probe through the thin film-hydration method. Results: The resulting iELPs showed high affinity for endothelial cells overexpressing αvβ3 integrin, favorable acoustic response and fluorescence tracking properties. Also, near-infrared (NIR) fluorescence imaging of iELPs and ultrasound-triggered drug release of MTX were proved in a mouse RA model, greatly improving the therapeutic efficacy and reducing MTX side effects. Histological assessment of the articular tissues further revealed significantly lower inflammatory cell infiltration and angiogenesis in the iELPs-treated and sonicated mice. Conclusion: Our study provides a promising nanoplatform for integrating ultrasound-controlled drug release and NIR fluorescence imaging for RA treatment.
33318522 Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in r 2020 Dec 14 This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan-Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.
33602481 A pragmatic non-invasive assessment of liver fibrosis in patients with psoriasis, rheumato 2020 Jan BACKGROUND AND AIMS: The reported hepatotoxicity of methotrexate underlines the need for a repeated non-invasive and reliable evaluation of liver fibrosis. We estimated, using a non-invasive strategy, the prevalence of significant liver fibrosis in patients treated by methotrexate and the predictors of significant fibrosis (fibrosis≥F2). METHODS: Fibrosis was prospectively evaluated using 9 non-invasive tests in consecutive patients with psoriasis, rheumatoid arthritis, or Crohn's disease. Significant fibrosis was assessed without liver biopsy by defining a "specific method" (result given by the majority of the tests) and a "sensitive method" (at least one test indicating a stage≥F2). RESULTS: One hundred and thirty-one patients (66 Psoriasis, 40 rheumatoid arthritis, and 25 Crohn's disease) were enrolled, including 83 receiving methotrexate. Seven tests were performed on average per patient, with a complete concordance in 75% of cases. Fibroscan® was interpretable in only 61% of patients. The best performances (AUROC>0.9) for predicting significant fibrosis were obtained by tests dedicated to steatohepatitis (FibroMeter NAFLD, NFS and FPI). The prevalence of fibrosis≥F2 according to the "specific" or the "sensitive" assessment of fibrosis was 10% and 28%, respectively. Methotrexate exposure did not influence the fibrosis stage. Factors independently associated with significant fibrosis according our "sensitive method" were age, male gender, and metabolic syndrome. CONCLUSION: We provided a non-invasive approach for identifying liver fibrosis≥F2 by using 8 biochemical tests and Fibroscan®. In this population, the risk of significant fibrosis was related to age, male gender, and presence of metabolic syndrome, but was not influenced by methotrexate.
32700608 Patient-ready syringes containing 25 mg/mL methotrexate can be kept at temperature rangi 2022 Mar BACKGROUND: Methotrexate (MTX) is a mainstay drug in the treatment of psoriatic and rheumatologic conditions. Subcutaneous MTX has become a feasible treatment alternative with the development of prefilled syringes or autoinjectors containing MTX solution that can be self-administered by the patient at home. However, MTX prefilled auto-injector pens are still not available in some countries. OBJECTIVE: This study aimed to investigate the stability and sterility of 25 mg/mL MTX solution in a disposable plastic syringe over a 12-week period under light protection at temperatures of 4 °C, 25 °C, and 37 °C. METHODS: This study was conducted during November 2019 to February 2020 at the Faculty of Medicine Siriraj Hospital, Mahidol University. Stability was evaluated using ultra-high-performance liquid chromatography technique, and sterility was assessed by cultures for bacterial and fungal contamination. RESULTS: Our results revealed that patient-ready syringes containing 25 mg/mL MTX solution can be prepared in advance and kept for up to 12 weeks under light protection, and they can be kept at temperatures ranging from 4 to 37 °C. CONCLUSION: This system for delivering MTX to patients that are refractory to or intolerant of oral MTX via a self-administered pre-filled syringe is both efficient and easy to implement in care settings where commercially alternatives are not yet available.
32482645 Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results 2020 Sep OBJECTIVES: To evaluate the 2-year clinical effectiveness of two gradual tapering strategies. The first strategy consisted of tapering the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) first (i.e., methotrexate in ~90%), followed by the tumour necrosis factor inhibitor (TNF-inhibitor), the second strategy consisted of tapering the TNF-inhibitor first, followed by the csDMARD. METHODS: This multicentre single-blinded randomised controlled trial included patients with rheumatoid arthritis (RA) with well-controlled disease for ≥3 consecutive months, defined as a Disease Activity Score (DAS) measured in 44 joints ≤2.4 and a swollen joint count ≤1, which was achieved with a csDMARD and a TNF-inhibitor. Eligible patients were randomised into gradual tapering the csDMARD followed by the TNF-inhibitor, or vice versa. The primary outcome was the number of disease flares. Secondary outcomes were DMARD-free remission (DFR), DAS, functional ability (Health Assessment Questionnaire Disability Index (HAQ-DI)) and radiographic progression. RESULTS: 189 patients were randomly assigned to tapering their csDMARD (n=94) or TNF-inhibitor (n=95) first. The cumulative flare rate after 24 months was, respectively, 61% (95% CI 50% to 71%) and 62% (95% CI 52% to 72%). The patients who tapered their csDMARD first were more often able to go through the entire tapering protocol and reached DFR more often than the group that tapered the TNF-inhibitor first (32% vs 20% (p=0.12) and 21% vs 10% (p=0.07), respectively). Mean DAS and HAQ-DI over time, and radiographic progression did not differ between groups (p=0.45, p=0.17, p=0.8, respectively). CONCLUSION: The order of tapering did not affect flare rates, DAS or HAQ-DI. DFR was achievable in 15% of patients with established RA, slightly more frequent in patients that first tapered csDMARDs. Because of similar effects from a clinical viewpoint, financial arguments may influence the decision to taper TNF-inhibitors first.
33119861 Switching to Biosimilar SDZ-ADL in Patients with Moderate-to-Severe Active Rheumatoid Arth 2020 Dec BACKGROUND: Sandoz adalimumab SDZ-ADL (GP-2017) is an approved adalimumab biosimilar with similar efficacy and comparable safety and immunogenicity to reference adalimumab (ref-ADL) as confirmed by analytical, pharmacokinetic and confirmatory studies. ADMYRA, a phase III double-blind study, was conducted with an aim to generate efficacy, safety and immunogenicity comparability data in patients with moderate-to-severe rheumatoid arthritis (RA) having inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). The study also evaluated an aspect of 'switching' reference product to the biosimilar in terms of efficacy, safety and immunogenicity up to Week 48. METHODS: Eligible patients (N = 353) were randomized 1:1 to receive subcutaneous (sc) SDZ-ADL 40 mg (n = 177) or ref-ADL (n = 176) every other week from Week 0 to Week 24. At Week 24, all patients with at least a moderate response by Disease Activity Score-28 including high-sensitivity C-reactive protein (DAS28-CRP) in the SDZ-ADL group continued SDZ-ADL (n = 159), and in the ref-ADL group were switched to SDZ-ADL (n = 166), treated for up to 46 weeks. The primary endpoint was change in DAS28-CRP from baseline at Week 12. Other efficacy endpoints included proportion of patients with European League Against Rheumatism (EULAR) response, EULAR remission, Boolean remission, safety and immunogenicity. RESULTS: The DAS28-CRP score changes from baseline at Week 12 were similar between SDZ-ADL (- 2.16) and ref-ADL (- 2.18) with a mean difference (95% CI) of 0.02 (- 0.24 to 0.27), which was within the pre-specified equivalence margin of ± 0.6. After switching treatment from ref-ADL to SDZ-ADL, the mean DAS28-CRP change was similar between the SDZ-ADL and 'ref-ADL/switched SDZ-ADL' group (- 3.09 vs - 3.05). The proportion of patients with good/moderate EULAR response was 69.2%/29.0% in the SDZ-ADL group and 68.0%/29.6% in the 'ref-ADL/switched SDZ-ADL' group. The proportion of patients in EULAR remission was 51.4% and 54.4% and in Boolean remission was 16.8% and 21.6% for SDZ-ADL and 'ref-ADL/switched SDZ-ADL' groups, respectively. The secondary endpoints were similar across the treatment groups. The incidence of adverse events (AEs) and injection-site reactions were low and similar between SDZ-ADL and 'ref-ADL/switched SDZ-ADL' groups (AEs 70.6% vs 68.8%, injection-site reactions 4.0% vs 6.3%), and most of these patients experienced AEs of mild or moderate severity. Antidrug antibodies were detected in 24.2% and 25.6% of patients treated with SDZ-ADL and 'ref-ADL/switched SDZ-ADL', respectively, from baseline to Week 48, of which 72.5% in SDZ-ADL and 79.1% in 'ref-ADL/switched SDZ-ADL' groups were neutralizing. CONCLUSIONS: In patients with moderate-to-severe RA who had an inadequate response to DMARDs, SDZ-ADL demonstrated a similar efficacy and a comparable safety and immunogenicity profile to ref-ADL. Efficacy was sustained after switching from ref-ADL to SDZ-ADL with no impact on safety (NCT02744755).
32736973 Lower Extremity Non-Blanchable Purpura Secondary to Methotrexate Toxicity: A Case Report. 2020 Nov Methotrexate is an antimetabolite drug that works as a folic acid analogue to inhibit DNA synthesis. This drug is commonly used for treating conditions such as psoriasis, rheumatoid arthritis, atopic dermatitis, and collagen disease. Although methotrexate may have common adverse effects such as bone marrow suppression and liver abnormalities, less commonly encountered side effects include lower extremity cutaneous blistering and skin necrosis. To our knowledge, there have been no case reports that have described methotrexate toxicity to the foot and ankle. This case report highlights a case of a 61-year-old patient who initially presented to our hospital with a 2-day history of worsening pain, swelling, and blistering of his feet. The patient's initial diagnosis was secondary to burns; however, with thorough investigation, imaging, and a punch biopsy, the final diagnosis was secondary to methotrexate toxicity. This case emphasizes the importance of a thorough history and physical examination for proper diagnosis and treatment of the adverse effect of methotrexate toxicity.
31838637 Safety and efficacy of tocilizumab as monotherapy or in combination with methotrexate in T 2020 May OBJECTIVES: We aimed to assess the safety and efficacy of tocilizumab as monotherapy or in combination with methotrexate in a routine clinical practice setting in Tunisian patients with RA who did not respond to conventional treatment with disease-modifying anti-rheumatic drugs (DMARDs-IR). METHOD: A total of 51 DMARDs-IR adult patients with moderate to severe RA participated in a phase IIIb, open-label clinical trial. Patients received 8 mg/kg of tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 24 weeks. The study was extended to 24 other weeks for those who had at least a moderate response at the end of the initial phase. Safety and efficacy of tocilizumab were analysed. RESULTS: Four patients discontinued treatment prematurely due to an adverse event. The most common AEs were hypercholesterolemia (18 cases), increased triglycerides (17 cases), increased transaminases (15 cases), rash (14 cases), neutropenia (7 cases), digestive disorders (3 cases) and respiratory disorders (3 cases). After 52 weeks, 90.5% of patients responded to treatment. At the end of the study, 61.9% of the patients had a mild RA and almost 50% of patients were in remission. Overall, 29.2, 6.3 and 4.3% of patients achieved ACR20, ACR50 and ACR70 responses, respectively. Additionally, the study showed a significant improvement in all individual parameters of ACR core data. CONCLUSIONS: Treatment with tocilizumab was well tolerated and showed a fast and sustained efficacy in Tunisian patients with moderate to severe active RA who had an inadequate response to DMARDs.Key Points• Up to 40% of RA patients remain inadequate responders to a prior csDMARD or a tumour necrosis factor α inhibitor (TNFi) biological agent. A non-TNF biological agent like tocilizumab with or without methotrexate is recommended in those patients.• In this study, tocilizumab treatment improved the number of responders, the number of patients in remission, and the evolution of disease activity. The meaningful clinical improvement seen denotes a rapid and sustained response to treatment.• Tocilizumab presented a favourable safety profile with few withdrawals due to AEs, consistently with what was observed in other trials.• This study provides new information about the safety and efficacy of tocilizumab in a patient population resembling that expected in clinical practice among the Tunisian population.
32638504 Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-Naive Patients With Modera 2020 Oct OBJECTIVE: The SELECT-EARLY trial was undertaken to study the effect of upadacitinib, an oral, reversible Janus kinase 1-selective inhibitor, as monotherapy in patients with predominantly early rheumatoid arthritis who were naive for or had limited exposure to methotrexate (MTX). METHODS: Patients (n = 947) were randomized 1:1:1 to receive once-daily doses of upadacitinib 15 mg or 30 mg or weekly MTX (7.5-20 mg/week) for 24 weeks. The primary end points were the proportion of patients who met the American College of Rheumatology 50% (ACR50) improvement criteria at week 12, and the proportion in whom a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) of <2.6 was achieved at week 24. Data are presented through week 24. RESULTS: At baseline, the median disease duration was 0.5 years (range 0-44 years). A total of 840 patients (89%) completed 24 weeks of treatment. The study met both primary end points for upadacitinib 15 mg and 30 mg versus MTX (ACR50 was achieved at week 12 in 52% and 56% of patients, respectively, versus 28% [P < 0.001], and DAS28-CRP <2.6 was achieved at week 24 in 48% and 50% of patients, respectively, versus 19% [P < 0.001]). Statistically significant and clinically meaningful improvements in multiple patient-reported outcomes (PROs) were recorded for both upadacitinib doses versus MTX. Overall, 88% of patients receiving upadacitinib 15 mg and 89% of patients receiving 30 mg, respectively, had no radiographic progression (modified total Sharp score ≤0) compared to 78% of those receiving MTX (P < 0.01). Through week 24, the frequency of treatment-emergent adverse events was similar between the MTX arm (65%) and upadacitinib 15 mg arm (64%), but was slightly higher in the upadacitinib 30 mg arm (71%). Six deaths were reported (2 in the upadacitinib 15 mg arm, 3 in the upadacitinib 30 mg arm, and 1 in the MTX arm). CONCLUSION: Our findings indicate that patients receiving either dose of upadacitinib monotherapy experienced significant improvements in clinical, radiographic, and PROs compared to patients receiving MTX.
32203525 Tumor Necrosis Factor (TNF) blocking agents are associated with lower risk for Alzheimer's 2020 This large, retrospective case-control study of electronic health records from 56 million unique adult patients examined whether or not treatment with a Tumor Necrosis Factor (TNF) blocking agent is associated with lower risk for Alzheimer's disease (AD) in patients with rheumatoid arthritis (RA), psoriasis, and other inflammatory diseases which are mediated in part by TNF and for which a TNF blocker is an approved treatment. The analysis compared the diagnosis of AD as an outcome measure in patients receiving at least one prescription for a TNF blocking agent (etanercept, adalimumab, and infliximab) or for methotrexate. Adjusted odds ratios (AORs) were estimated using the Cochran-Mantel-Haenszel (CMH) method and presented with 95% confidence intervals (CIs) and p-values. RA was associated with a higher risk for AD (Adjusted Odds Ratio (AOR) = 2.06, 95% Confidence Interval: (2.02-2.10), P-value <0.0001) as did psoriasis (AOR = 1.37 (1.31-1.42), P <0.0001), ankylosing spondylitis (AOR = 1.57 (1.39-1.77), P <0.0001), inflammatory bowel disease (AOR = 2.46 (2.33-2.59), P < 0.0001), ulcerative colitis (AOR = 1.82 (1.74-1.91), P <0.0001), and Crohn's disease (AOR = 2.33 (2.22-2.43), P <0.0001). The risk for AD in patients with RA was lower among patients treated with etanercept (AOR = 0.34 (0.25-0.47), P <0.0001), adalimumab (AOR = 0.28 (0.19-0.39), P < 0.0001), or infliximab (AOR = 0.52 (0.39-0.69), P <0.0001). Methotrexate was also associated with a lower risk for AD (AOR = 0.64 (0.61-0.68), P <0.0001), while lower risk was found in patients with a prescription history for both a TNF blocker and methotrexate. Etanercept and adalimumab also were associated with lower risk for AD in patients with psoriasis: AOR = 0.47 (0.30-0.73 and 0.41 (0.20-0.76), respectively. There was no effect of gender or race, while younger patients showed greater benefit from a TNF blocker than did older patients. This study identifies a subset of patients in whom systemic inflammation contributes to risk for AD through a pathological mechanism involving TNF and who therefore may benefit from treatment with a TNF blocking agent.
31619597 Pulmonary Intravascular Large B-cell Lymphoma in a Patient Administered Methotrexate for R 2020 Feb 1 A 70-year-old woman with rheumatoid arthritis undergoing methotrexate (MTX) treatment presented with dyspnea and a subfever. Computed tomography (CT) revealed a diffuse minimal ground-glass appearance in both lungs and splenomegaly. The gallium scintigram showed a diffuse, mild uptake in both lungs and the spleen. The lung biopsy specimen revealed the presence of CD20-positive atypical lymphocytes in the small pulmonary vessels. The patient was diagnosed with pulmonary intravascular diffuse large B-cell lymphoma (IVLBCL) and exhibited spontaneous regression after MTX was discontinued. This report describes a rare case of MTX-associated lymphoproliferative disorder expressing pulmonary IVLBCL.
32852623 COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients se 2020 Nov INTRODUCTION: Covid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic. METHOD: This observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1) definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2) highly suspected Covid-19 disease: presence of highly suggestive symptoms, in absence of a swab test. RESULTS: A significantly higher prevalence of patients with definite diagnosis of Covid-19 disease, or with highly suspected Covid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to "Italian general population" (p = .030, p = .001, p = .000, respectively); and for definite + highly suspected diagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population). Moreover, significantly higher prevalence of definite + highly suspected diagnosis of Covid-19 disease was found either in patients with various "connective tissue diseases" compared to "inflammatory arthritis group" (p < .000), or in patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs treatments (p = .011). CONCLUSIONS: The finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases. Key Points • Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients' increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement. • The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing. • Patients with "connective tissue diseases" show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to "inflammatory arthritis group". • Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.
30576759 TNF-α inhibitor-induced psoriasis: A decade of experience at the Cleveland Clinic. 2020 Dec BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitor (TNFI)-induced psoriasis remains poorly understood despite having been described 15 years ago. As TNFIs often provide life-changing patient benefits, understanding effective treatments for TNFI-induced psoriasis is important. OBJECTIVE: We characterized a cohort of patients with TNFI-induced psoriasis whose psoriasis was specifically diagnosed and managed or comanaged by dermatologists at a single tertiary care institution over a 10-year period. METHODS: Retrospective review of patients in whom TNFI-induced psoriasis was diagnosed between 2003 and 2013. RESULTS: A total of 102 patients with TNFI-induced psoriasis were identified. The mean age of onset was 40 years, and there was a female predominance (73.5%). Crohn's disease (in 48% of cases) and rheumatoid arthritis (in 24.5% of cases) were the most common primary conditions. Infliximab (in 52% of cases) was the most common inciting agent. The most common TNFI-induced psoriasis subtypes were plaque-type psoriasis (49.5%), scalp psoriasis (47.5%), and palmoplantar pustulosis (41%). Topical medications alone improved or resolved TNFI-induced psoriasis in 63.5% of patients, and cyclosporine and methotrexate (>10 mg weekly) were often effective if topicals failed. Discontinuation of the inciting TNFI with or without other interventions improved or resolved TNFI-induced psoriasis in 67% of refractory cases, whereas switching TNFIs resulted in persistence or recurrence in 64%. LIMITATIONS: Retrospective nature of the study and the fact that some patients may have developed typical psoriasis unresponsive to TNFIs. CONCLUSION: Our study cohort represents the largest single-institution cohort of patients with TNFI-induced psoriasis diagnosed and managed or comanaged by dermatologists to date. On the basis of our findings, we propose a treatment algorithm for TNFI-induced psoriasis.
31897527 Acute Effects of Glucocorticoid Treatment, TNFα or IL-6R Blockade on Bone Turnover Marker 2020 Apr Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 play a fundamental role in bone loss in rheumatoid arthritis (RA), partly due to the inhibition of the Wnt canonical pathway. The aim of our study was to investigate the short-term effects of three different treatments on Wnt inhibitors (Dkk-1 and sclerostin) and on bone turnover markers (BTMs): N-propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (β-CTX-I). We performed a retrospective analysis of prospectively collected data. We enrolled women affected by early RA (< 12 months) with active disease (DAS28 ≥ 2.6) despite a 6-month treatment with methotrexate (10-15 mg/week), who then started certolizumab pegol, tocilizumab, or methyl-prednisolone (8 mg/daily). Patients were divided into three groups according to the treatment. Blood samples were collected at baseline, week 1, and week 4. We selected 14 patients treated with certolizumab pegol, 14 patients with tocilizumab, and 20 patients with methyl-prednisolone. No difference between any of the tested parameters was found at baseline. β-CTX-I, Dkk-1, and sclerostin decreased after 1 week of treatment with certolizumab pegol (- 27% ± 21.5, - 50% ± 13.2, and - 30% ± 30.4, respectively, p < 0.05). Methyl-prednisolone induced similar changes, albeit less marked, on β-CTX-I and Wnt inhibitors, with a decrease in PINP (- 16.1% ± 16.5, p < 0.05). Tocilizumab did not significantly affect BTMs or Wnt inhibitors. No significant changes were found for PTH and 25OHD. In the first four weeks of treatment, TNFα inhibition showed strong effects on BTMs and Wnt inhibitors, differently from IL-6 blockade. Glucocorticoids induced similar changes; nonetheless, they showed undesired effects on bone formation.
31268376 Sarilumab monotherapy or in combination with non-methotrexate disease-modifying antirheuma 2020 Mar Objectives: To determine long-term safety and efficacy of sarilumab as monotherapy or with non-methotrexate (MTX) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in Japanese patients with active rheumatoid arthritis (RA).Methods: In this double-blind, randomized study (NCT02373202), patients received subcutaneous sarilumab 150 mg q2w (S150) or 200 mg q2w (S200) as monotherapy or with non-MTX csDMARDs for 52 weeks. The primary endpoint was safety.Results: Sixty-one patients received monotherapy (S150, n = 30; S200, n = 31) and 30 received combination therapy (S150 + csDMARDs, n = 15; S200 + csDMARDs, n = 15). Rates of treatment-emergent adverse events (TEAEs) were 83.3%/90.3%/93.3%/86.7% for S150/S200/S150 + csDMARDs/S200 + csDMARDs, respectively. Nasopharyngitis and neutropenia were the most frequently reported TEAEs. One serious infection was reported in each monotherapy group and in the S200 + csDMARDs group. There were no cases of grade 4 neutropenia; no patients with grade 3 neutropenia experienced associated serious infection. Improvements in ACR20/50/70 response rates were generally similar between the two monotherapy groups and between the two combination groups; improvements in physical function (Health Assessment Questionnaire-Disability Index, HAQ-DI) and DAS28-CRP were observed at weeks 24 and 52 (all groups).Conclusion: The safety profile of sarilumab was consistent with known class effects of interleukin-6 signaling blockade therapeutics. Sarilumab as mono- or combination therapy improved clinical signs/symptoms and physical function in Japanese RA patients.
32687015 Rapidly progressive glomerulonephritis after introduction of certolizumab pegol: a case re 2021 Jan Tumour necrosis factor (TNF) inhibitors are used against a variety of connective tissue diseases, including rheumatoid arthritis. Contrarily, although rare, TNF inhibitors are known to induce autoimmune diseases, such as systemic lupus erythematosus and psoriasis as a paradoxical reaction. We experienced a case of rapidly progressive glomerulonephritis after introduction of certolizumab pegol. The patient was a 30-year-old woman who was previously diagnosed with rheumatoid arthritis in X-8. She received treatment with methotrexate (8 mg/week) and infliximab (3 mg/kg/8 weeks), following which she showed low disease activity and remission. In September X-1, methotrexate and infliximab were discontinued and certolizumab pegol was introduced because she desired to bear children. In March X, the patient experienced renal dysfunction, and urinary protein analysis revealed positivity for myeloperoxidase anti-neutrophil cytoplasmic autoantibody. Renal biopsy showed crescentic glomerulonephritis, and the patient was diagnosed with rapidly progressive glomerulonephritis due to TNF inhibitor-induced microscopic polyangiitis. As she desired to bear children, rituximab was introduced in addition to corticosteroids, which led to remission of the symptoms. TNF inhibitors should be discontinued in patients who develop rapidly progressive glomerulonephritis, and these patients should be treated with immunosuppressive drugs, such as massive corticosteroids and cyclophosphamide. In the present case, rituximab was useful for not only the treatment, but also for the preservation of fertility.
32961930 Methrotexate Treatment Inmunomodulates Abnormal Cytokine Expression by T CD4 Lymphocytes P 2020 Sep 18 CD4(+)T-lymphocytes are relevant in the pathogenesis of rheumatoid arthritis (RA), however, their potential involvement in early RA remains elusive. Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug (DMARD), but its mechanism has not been fully established. In 47 new-onset DMARD-naïve RA patients, we investigated the pattern of IFNγ, IL-4 and IL-17A expression by naïve (T(N)), central (T(CM)), effector memory (T(EM)) and effector (T(E)) CD4(+) subsets; their STAT-1, STAT-6 and STAT-3 transcription factors phosphorylation, and the circulating levels of IFNγ, IL-4 and IL-17. We also studied the RA patients after 3 and 6 months of MTX treatment and according their clinical response. CD4(+)T-lymphocyte subsets and cytokine expression were measured using flow cytometry. New-onset DMARD-naïve RA patients showed a significant expansion of IL-17A(+), IFNγ(+) and IL-17A(+)IFNγ(+) CD4(+)T-lymphocyte subsets and increased intracellular STAT-1 and STAT-3 phosphorylation. Under basal conditions, nonresponder patients showed increased numbers of circulating IL-17A producing T(N) and T(MC) CD4(+)T-lymphocytes and IFNγ producing T(N), T(CM), T(EM) CD4(+)T-lymphocytes with respect to responders. After 6 months, the numbers of CD4(+)IL-17A(+)T(N) remained significantly increased in nonresponders. In conclusion, CD4(+)T-lymphocytes in new-onset DMARD-naïve RA patients show IL-17A and IFNγ abnormalities in T(N), indicating their relevant role in early disease pathogenesis. Different patterns of CD4(+) modulation are identified in MTX responders and nonresponders.
32080104 A systematic review and meta-analysis of rituximab combined with methotrexate versus metho 2020 Feb BACKGROUND: This meta-analysis aimed to explore the efficacy and safety of rituximab combined with methotrexate (MTX) versus MTX alone in the treatment of rheumatoid arthritis (RA). METHODS: We performed an electronic search of PubMed (1950-January 2018), EMBASE (1974-January 2018), the Cochrane Library (January 2018 Issue 3), the Google database (1950-January 2018), and the Chinese Wanfang database (1950-January 2018). Only randomized controlled trials (RCTs) were included. The American College of Rheumatology 20% improvement criteria (ACR20), ACR50, ACR70, total complication rate, and infection rate were the outcomes. A fixed/random effects model was used according to the heterogeneity assessed by the I statistic. Data analysis was performed using Stata 12.0 software. RESULTS: A total of five RCTs with 3299 patients (rituximab combined with MTX group = 1787, MTX only group = 1512) were included in the meta-analysis. The pooled risk ratio showed that the administration of rituximab combined with MTX was associated with more ACR20, ACR50, and ACR70 than the administration of MTX only (P < .05). There were no significant differences between the two groups in terms of the total complication rate and the infection rate (P > .05). CONCLUSION: The administration of rituximab combined with MTX was effective and safe for RA patients. Additional high-quality RCTs with long-term follow-ups should be conducted in the future to identify the potential complications in the long term.
31233281 Efficacy and Safety of Long-Term Baricitinib With and Without Methotrexate for the Treatme 2020 Aug OBJECTIVE: To evaluate the long-term efficacy and safety of maintaining baricitinib monotherapy in patients with active rheumatoid arthritis (RA) originally treated with baricitinib monotherapy or switched from methotrexate (MTX) or the combination of baricitinib plus MTX to baricitinib monotherapy. METHODS: This is a post hoc analysis of patients from the RA-BEGIN study who entered a long-term extension, RA-BEYOND, and were assessed for up to 24 weeks. In RA-BEGIN, MTX-naive patients with early active RA were randomized to MTX monotherapy, baricitinib 4 mg monotherapy, or baricitinib 4 mg plus MTX. At week 52, all patients entering RA-BEYOND received baricitinib 4 mg monotherapy. MTX could be prescribed during RA-BEYOND at the investigator's discretion. RESULTS: Patients in RA-BEYOND who were not rescued in RA-BEGIN (n = 423) were evaluated. Of these, 47% continued baricitinib monotherapy and 53% added MTX, with similar proportions from the 3 original arms. Patients with lower disease activity at the RA-BEYOND baseline generally continued to do well with baricitinib monotherapy as assessed by the Simplified Disease Activity Index, the Clinical Disease Activity Index, and the Health Assessment Questionnaire disability index scores. Patients prescribed MTX had higher disease activity at the RA-BEYOND baseline and had improved disease activity after the addition of MTX. Safety outcomes were similar across treatment groups. CONCLUSION: Many patients responded well to continued baricitinib monotherapy or to switching to baricitinib monotherapy from MTX monotherapy or baricitinib plus MTX, showing sustained or improved disease control. The groups of patients who had less disease control on their original therapies showed sustained or improved disease control with the addition of MTX to baricitinib.