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ID PMID Title PublicationDate abstract
31639706 Transition of Methotrexate Polyglutamate Drug Monitoring Assay from Venipuncture to Capill 2019 Jul OBJECTIVE: Methotrexate (MTX) polyglutamate (MTXPG(3)) levels from isolated red blood cells (RBCs) collected by venipuncture have clinical utility in guiding MTX dosing for patients with rheumatoid arthritis (RA). Our objective was to transition this RBC-based therapeutic drug monitoring (TDM) assay to dried capillary blood collected by fingerstick. METHODS: Patients with RA treated with MTX were enrolled. Specimens were collected by fingerstick (volumetric absorptive microsampler) and venipuncture to measure MTXPG(3) from dried capillary blood, total venous blood, and isolated RBCs. MTXPG(3) levels from dried capillary blood were measured using LC-MS/MS, converted to RBC equivalent (nmol/L), and compared with those from isolated RBCs (reference method). Following transition to fingerstick collection, comparability in the distributions of dried capillary and venipuncture-based RBC MTXPG(3) levels was assessed using the Kolmogorov-Smirnov (K-S) test. RESULTS: Intraday and interday precision ranged from 2.0% to 10.9% and 3.1% to 10.8%, respectively, at MTXPG(3) concentrations ranging from 5 to 100 nmol/L. In 106 participants treated with MTX, MTXPG(3) levels from total venous and dried capillary blood were comparable [slope = 0.97 (95% CI, 0.92-1.03); R (2) = 0.92]. Dried capillary blood MTXPG(3) converted to RBC equivalent was similar to levels from isolated RBCs (30 ± 18 nmol/L vs 33 ± 19 nmol/L; n = 106). After implementation in the clinical laboratory, RBC equivalents MTXPG(3) from the fingerstick method were similar to levels from venipuncture [39 ± 22 nmol/L (n = 825) vs 39 ± 24 nmol/L (n = 47935)] (K-S test P = 0.09). Underexposure to MTX (MTXPG(3) ≤5 nmol/L RBCs) was detected in 7.0% and 8.5% patient specimens collected using the fingerstick and venipuncture methods, respectively. CONCLUSION: Capillary blood MTXPG(3) levels can be used to guide MTX dosing in TDM practice.
31281705 Mixed Cryoglobulinemia in a Patient with Juvenile Idiopathic Arthritis. 2019 Cryoglobulinemia is a rare illness of cryoglobulin accumulation in the blood which can typically present with arthralgia, purpura, skin ulcers, glomerulonephritis, and peripheral neuropathy. It is classified as mixed cryoglobulinemia when cryoglobulins contain more than one immune component such as IgM rheumatoid factor and polyclonal IgG. Typically, it presents in the setting of clonal hematologic disease, viral infection, or certain connective tissue diseases. Herein, we report the case of a 24-year-old man diagnosed and treated as mixed cryoglobulinemia in the setting of juvenile idiopathic arthritis (JIA). Investigations for viral etiologies, including HBV, HCV, and HIV, and all serologic tests were negative. Additionally serum protein and urine protein electrophoresis did not reveal monoclonal gammopathy; however, testing for plasma cryoglobulins was positive, and qualitative analysis revealed a faint polyclonal pattern. Thus, he was diagnosed with cryoglobulinemia in the setting of JIA, which has not been reported in the literature before. He dramatically improved upon initiation of rituximab and methotrexate.
31154343 Methotrexate-induced iatrogenic immunodeficiency-associated lymphoproliferative disorder c 2019 May 31 Hypercalcaemia is a rare but potentially life-threatening consequence of malignancies. Solid cancers, such as lymphomas, increase serum calcium primarily through parathyroid hormone-related protein or ectopic production of 1alpha-hydroxylase. We present a case of 56-year-old woman with Sjogren's syndrome and psoriasis in the setting of chronic methotrexate (MTX) use who developed worsening hypercalcaemia and symptoms suggestive of lymphoma. Pathology results diagnosed her with MTX-induced iatrogenic immunodeficiency-associated lymphoproliferative disorder (LPD). This case reminds clinicians that chronic MTX use is associated with LPDs and can ultimately lead to hypercalcaemia. The patient's MTX and other immunosuppressive medications were stopped, and her calcium corrected with fluids and calcitonin. At her 8-month follow-up postdischarge, the patient was asymptomatic with normal laboratory results and in partial clinical remission.
31699619 [Methotrexate in juvenile idiopathic arthritis. Adverse effects and associated factors]. 2020 Mar INTRODUCTION: Methotrexate (MTX) is the drug of choice for juvenile idiopathic arthritis. Its clinical efficacy is limited due to the development of adverse effects (AEs). PATIENTS AND METHODS: A retrospective observational study was conducted on the AEs associated with MTX therapy in children diagnosed with juvenile idiopathic arthritis followed-up in a tertiary hospital between 2008 and 2016. RESULTS: The study included a total of 107 patients, of whom 71 (66.3%) were girls (66.3%). The median age at diagnosis was 6.4 years (IQR 3.1-12.4), with a median follow-up of 45.7 months (IQR 28.8-92.4). There were 48 patients (44.9%) with oligoarthritis, and 26 children (24.3%) with rheumatoid-factor negative polyarthritis. Of these, 52/107 (48.6%) developed AEs, with the most frequent being gastrointestinal symptoms (35.6%) and behavioural problems (35.6%). An age older than 6 years at the beginning of therapy increased the risk of developing AEs, both in the univariate (OR=3.5; 95% CI: 1.5-7.3) and multivariate (12% increase per year) analyses. The doses used, administration route, or International League of Associations for Rheumatology (ILAR) classification, were not associated with the development of AEs. Twenty children required a dosage or route of administration modification, which resolved the AE in 11 (55%) cases. MTX was interrupted due to the development of AEs in 37/107 patients (34.6%), mainly due to increased plasma transaminases (n=14, 37.8%), gastrointestinal symptoms (n=9, 24.3%) and behavioural problems (n=6, 16.3%). CONCLUSIONS: MTX is the therapy of choice for patients with juvenile idiopathic arthritis, but 50% of the children develop some form of AE. Although the AEs are not severe, they lead to interruption of therapy in 35% of the children.
31890337 Analytical methodologies for determination of methotrexate and its metabolites in pharmace 2019 Dec Methotrexate (MTX) is a folate antagonist drug used for several diseases, such as cancers, various malignancies, rheumatoid arthritis (RA) and inflammatory bowel disease. Due to its structural features, including the presence of two carboxylic acid groups and its low native fluorescence, there are some challenges to develop analytical methods for its determination. MTX is metabolized to 7-hydroxymethotrexate (7-OH-MTX), 2,4-diamino-N10-methylpteroic acid (DAMPA), and the active MTX polyglutamates (MTXPGs) in the liver, intestine, and red blood cells (RBCs), respectively. Additionally, the drug has a narrow therapeutic range; hence, its therapeutic drug monitoring (TDM) is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity. Due to environmental toxicity of MTX; its sensitive, fast and low cost determination in workplace environments is of great interest. A large number of methodologies including high performance liquid chromatography equipped with UV-visible, fluorescence, or electrochemical detection, liquid chromatography-mass spectroscopy, capillary electrophoresis, UV-visible spectrophotometry, and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical, biological, and environmental samples. This paper will attempt to review several published methodologies and the instrumental conditions, which have been applied to measure MTX and its metabolites within the last decade.
30945961 The contradictory inefficacy of methotrexate in hidradenitis suppurativa: a need to revise 2020 Jun The pathogenesis of hidradenitis suppurativa (HS) centers around Th17/Treg dysfunction illustrated by lesional elevation of IL-17A, IL-6, and other inflammatory mediators resulting in a chronic feed-forward inflammatory cascade. Similar inflammatory mechanisms have been identified in psoriasis and rheumatoid arthritis (RA) in which traditional immunosuppressants (including methotrexate) are routinely used with reasonable levels of disease control. Methotrexate's mechanism of action in these instances includes downregulation of the Th17 axis via alterations in dendritic cell and T-cell activity and maturation. Published data suggest methotrexate in an ineffective therapy in HS, which does not pair with our current understanding of the mechanisms of disease. The reasons behind this, including are discussed. Some HS patients may benefit from drugs such as methotrexate, and acknowledgment of the potential of disease heterogeneity will allow exploration of which factors may enable identification of such individuals.
30906560 A rare case of lymphadenitis and pulmonary disease caused by Mycobacterium paraffinicum. 2019 May With over 150 species, non-tuberculous mycobacteria are increasingly recognized to be important human pathogens that pose diagnostic and management challenges. We report a rare case of cervical lymphadenitis and pulmonary disease caused by Mycobacterium paraffinicum in a 64-year-old man who presented with three-month history of increasing right-sided painless neck lump. His medical history included rheumatoid arthritis, which was managed with leflunomide and methotrexate. Computed tomography scans of his neck and thorax revealed a right lower neck and supraclavicular fossa cystic mass with peripheral enhancement and bilateral multiple small pulmonary nodules. M. paraffinicum was cultured from a fine-needle aspiration of the mass. Two out of three sputa were acid-fast bacilli smear positive but cultures did not yield any viable organism. He developed spontaneous discharge of purulent material via a sinus, which drained over two months and recovered with a completely healed sinus without any further treatment.
31448336 Poor communication by health care professionals may lead to life-threatening complications 2019 We report two cases which highlight the fact how poor communication leads to dangerously poor health outcome. We present the case of a 50-year-old woman recently diagnosed with rheumatoid arthritis from Southern Nepal presented to Patan hospital with multiple episodes of vomiting and oral ulcers following the intake of methotrexate every day for 11 days, who was managed in the intensive care unit. Similarly, we present a 40-year-old man with ileo-caecal tuberculosis who was prescribed with anti-tubercular therapy (ATT) and prednisolone, who failed to take ATT due to poor communication and presented to Patan Hospital with features of disseminated tuberculosis following intake of 2 weeks of prednisolone alone. These were events that could have been easily prevented with proper communication skills. Improvement of communication between doctors and patients is paramount so that life-threatening events like these could be avoided.
31217209 Eosinophilic granulomatosis with polyangiitis in a Nigerian woman. 2019 Jun 18 Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss Syndrome, is a systemic autoimmune disease that is usually associated with asthma and eosinophilia. It is a rare condition associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of a 52-year-old Nigerian woman who presented with bilateral leg swelling with multiple ulcers, background history of allergic rhinitis and chronic sinusitis since adolescence. There were also associated symptoms of peripheral neuropathy, weight loss, peripheral blood eosinophilia and positive perinuclear ANCA and she was previously managed for rheumatoid arthritis and asthma. She fulfilled the American College of Rheumatology criteria for EGPA and was treated with glucocorticoids and methotrexate which led to significant improvement of her symptoms.
30813268 Chronic Hepatitis E in Rheumatology and Internal Medicine Patients: A Retrospective Multic 2019 Feb 22 Objectives: Hepatitis E virus (HEV) infection is a pandemic with regional outbreaks, including in industrialized countries. HEV infection is usually self-limiting but can progress to chronic hepatitis E in transplant recipients and HIV-infected patients. Whether other immunocompromised hosts, including rheumatology and internal medicine patients, are at risk of developing chronic HEV infection is unclear. Methods: We conducted a retrospective European multicenter cohort study involving 21 rheumatology and internal medicine patients with HEV infection between April 2014 and April 2016. The underlying diseases included rheumatoid arthritis (n = 5), psoriatic arthritis (n = 4), other variants of chronic arthritis (n = 4), primary immunodeficiency (n = 3), systemic granulomatosis (n = 2), lupus erythematosus (n = 1), Erdheim⁻Chester disease (n = 1), and retroperitoneal fibrosis (n = 1). Results: HEV infection lasting longer than 3 months was observed in seven (33%) patients, including two (40%) patients with rheumatoid arthritis, three (100%) patients with primary immunodeficiency, one (100%) patient with retroperitoneal fibrosis and one (100%) patient with systemic granulomatosis. Patients with HEV infection lasting longer than 3 months were treated with methotrexate without corticosteroids (n = 2), mycophenolate mofetil/prednisone (n = 1), and sirolimus/prednisone (n = 1). Overall, 8/21 (38%) and 11/21 (52%) patients cleared HEV with and without ribavirin treatment, respectively. One patient experienced an HEV relapse after initially successful ribavirin therapy. One patient (5%) was lost to follow-up, and no patients died from hepatic complications. Conclusion: Rheumatology and internal medicine patients, including patients treated with methotrexate without corticosteroids, are at risk of developing chronic HEV infection. Rheumatology and internal medicine patients with abnormal liver tests should be screened for HEV infection.
31693324 2019 Apr 17 INFLAMMATORY BOWEL DISEASE: Inflammatory bowel disease (IBD) is a disease involving inflammation conditions located in colon and small intestines. Ulcerative colitis (UC) and Crohn’s disease (CD) are two primary types of IBD with different characteristics. UC is a mucosal disease that often affects the rectum and all or part of the colon. Sometimes it is difficult to distinguish UC and CD clinically. The symptoms commonly seen in the patients with UC include diarrhea, rectal bleeding, tenesmus, passage of mucus, and crampy abdominal pain. The inflammation may cause major consequences, particularly a fibrostenotic obstructing pattern or a penetrating fistulous pattern. Depending on disease severity, the options of conventional treatment for IBD include 5-aminosalicylic acid agents, glucocorticoids, antibiotics, and immunomodulators. Immunomodulators include azathioprine, 6-mercaptopurine, methotrexate, and cyclosporine, and modify the activities of the immune system. The use of immunomodulators are associated with minor or severe adverse events, such as headache, infection, and certain cancers. Due to such risks, the use of immunomodulators needs to be closely monitored. Conventionally, a “step-up” treatment strategy usually include a sequential use of aminosalicylates, steroids, immunomodulators, and finally biologics. Medications such as 5-aminosalicylic acids or prednisolone are tried first. Biologics or pharmacological immunomodulators are particularly useful when patients are not responsive to steroids for induction or relapse prevention. BIOLOGICS: Recent advances in IBD treatment include biologics (also called biologic agents or biologic therapies), particularly for patients unresponsive to conventional therapy. Biologics are protein-based molecules that can block inflammation in several immune-related diseases.(,) The first biologic approved for IBD is infliximab, a chimeric immunoglobulin (IgG)1 antibody against tumor necrosis factor (TNF)-α. The usual dose of infliximab is to repeat infusion 5mg/kg every eight weeks. Infliximab was approved by Health Canada to treat rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, CD, fistulizing Crohn disease (FCD), and UC. Currently, three types of biologics are approved for the treatment of one or both primary types of IBD: anti-TNF agents (infliximab, adalimumab, and golimumab), anti-integrin agents (vedolizumab) and anti-interleukin (IL) 12/23 IgG1 kappa agents (ustekinumab).(,) PLACE IN THERAPY: Health Canada has approved several biologics or biosimilars for the treatment of ulcerative colitis in patients without adequate response to conventional therapy, including infliximab and vedolizumab. Although, infliximab and other biologics are often reserved for patients unresponsive to conventional therapy,(,) some practitioners argue that early adoption of biologics or immunomodulators may be beneficial to patients with IBD. The benefits of early adoption may include avoiding toxic effects of immunomodulators and fewer adverse effects related to conventional therapy. It is uncertain whether early adoption of biologics or immunomodulators may be beneficial to patients with UC. This study aims to review the literature and understand the effectiveness and cost-effectiveness of biologics and immunomodulators among UC patients naïve to both types of drugs.
31389299 Probing the structural interactions between methotrexate and dexamethasone with muscle cys 2020 Jul Drug protein interactions have gained considerable attention over the past many years. In the current communication the association of muscle cystatin (MC) with anti-rheumatic drugs methotrexate and dexamethasone was studied by thiol proteinase inhibitor assay, ultra violet (UV) absorption, fluorescence spectroscopy, and fluorescence transform infra-red spectroscopy (FTIR). A static pattern of quenching was noticed between muscle cystatin and methotrexate (MTX). Binding constant (K(a)) of methotrexate to muscle cystatin was found to be 1 × 10(-7) M(-1) and the stoichiometry of binding was calculated to be one. Fluorescence measurement of the emission quenching reveals that the quenching process of cystatin by dexamethasone (DXN) was also static. The stoichiometry of binding and binding constant was also obtained. Additional evidence regarding MTX-MC and DXN-MC was obtained from UV spectroscopy and FTIR spectroscopic results. Such spectroscopic studies would help in modelling new candidate drugs for rheumatoid arthritis based on their cystatin binding profile.Communicated by Ramaswamy H. Sarma.
31993584 LC-MS metabolomics comparisons of cancer cell and macrophage responses to methotrexate and 2019 Dec Methotrexate (MTX) is a folate analogue antimetabolite widely used for the treatment of rheumatoid arthritis and cancer. A number of studies have shown that MTX delivered via nanoparticle carriers is more potent against cancer cells than free MTX, a phenomenon attributed to higher cellular uptake of the particles compared to the saturable folate receptor pathway. In this study, a cell-based global metabolic profiling approach was applied to study the effects of MTX in both free drug form and when encapsulated in -poly(lactide-co-glycolide) (PLGA) nanoparticles on a cancer cell line, A549, and also on human-like THP-1 macrophages. The results showed that MTX loaded nanoparticles had less impact on the macrophages than free MTX, and the effects on macrophages were limited to changes in nucleotide metabolism and suppression of the tricarboxylic acid cycle, whereas free MTX also led to a drop in glycolytic activity and impairment in redox homeostasis. In contrast, MTX loaded nanoparticles showed a greater impact on A549 cells than the free drug, which was in accord with studies in other cell lines in prior literature with MTX-carrier nanoparticles.
31493201 Pathogenesis, Diagnosis and Management of Polymyalgia Rheumatica. 2019 Nov Polymyalgia rheumatica is an inflammatory rheumatic disease of the elderly characterised by pain and stiffness in the neck and pelvic girdle, and is the second most common inflammatory rheumatic condition in this age group, after rheumatoid arthritis. Polymyalgia rheumatica can occur independently or in association with giant cell arteritis, which is the most common form of primary vasculitis. The diagnosis of polymyalgia rheumatica is usually based on clinical presentation and increase of inflammatory markers. There are no pathognomonic findings that can confirm the diagnosis. However, different imaging techniques, especially ultrasonography, can assist in the identification of polymyalgia rheumatica. Glucocorticoids are the cornerstone of the treatment of polymyalgia rheumatica, but they might be associated with different adverse events. A subgroup of patients presents with a refractory disease course and, in these cases, adding methotrexate as a steroid-sparing agent could be useful. In this review, we summarise the latest findings regarding the pathogenesis, diagnosis and management of polymyalgia rheumatica and try to highlight the possible pitfalls, especially in elderly patients.
30907188 Treat to target approach for asthma. 2020 Jun Recognition that about half of asthma deaths might be preventable if recommended guidelines are followed suggests that better implementation of established management strategies is needed. However, to achieve a further substantive reduction in asthma mortality, novel strategies will also be required. It is well established that asthma is a disease of chronic inflammation, with episodes of worsening inflammation associated with increased symptoms and/or exacerbations; however, current guidelines paradoxically recommend that initial treatment is only symptomatic, rather than directed at the underlying inflammatory mechanism. The "Treat to target" (TTT) approach has become a popular concept in the medical management of several common chronic conditions, including rheumatoid arthritis (RA), diabetes, hypertension and hyperlipidemia. For example, as part of a TTT approach, rheumatologists recommend methotrexate for RA with onset within 6 months. Applying the TTT approach to asthma, the primary target could be clinical remission and the primary goals as follows: eliminate symptoms and exacerbation risk; prevent airway remodeling; and normalize lung function. To construct a TTT algorithm for chronic asthma, the proposal is to eradicate short-acting β2-agonists (SABA) at all asthma severity levels and replace SABA with "Anti-Inflammatory Reliever Therapy" (AIR), using inhaled corticosteroids (ICS)/SABA or ICS/formoterol. For individuals with equal to or less than 12 months' history of symptoms, fewer than two symptoms per month, no exacerbations in the last 12 months and normal lung function, the recommendation is early initiation of ICS/SABA or ICS/formoterol as AIR.
31186658 Alpha7 nAChR Expression Is Correlated with Arthritis Development and Inhibited by Sinomeni 2019 Sinomenine (SIN) is the active ingredient of the Chinese herb Sinomenium acutum that has been used to treat rheumatoid arthritis (RA) for about 30 years in China. Marked expression of the alpha7 nicotinic acetylcholine receptor (α7nAChR) in the joint synovium of RA patients suggested a relationship between α7nAChR and RA. This study investigated the relationship between α7nAChR and RA development and the effects of SIN on α7nAChR expression in vivo and in vitro. Sprague-Dawley rats were injected with complete Freund's adjuvant to induce arthritis and then treated with SIN or methotrexate (MTX) from day 0 to day 30. Four clinical parameters-paw volume, arthritic index (AI), serum TNF-α concentration, and erythrocyte sedimentation rate (ESR)-were measured. Splenic lymphocytes were isolated for Bacille Calmette Guerin (BCG) stimulation. α7nAChR expression in tissues and cells was examined by RT-PCR, western blot, immunofluorescence, flow cytometry, and immunohistochemistry. Cell proliferation was evaluated by the CCK-8 assay. The relationship between α7nAChR expression and the four clinical parameters was analyzed by single-factor correlation analysis. Our results showed that the paw volume, AI, TNF-α concentration, and ESR in adjuvant-induced arthritic (AIA) rats were reduced by SIN or MTX treatment. SIN decreased α7nAChR expression in tissues and cells compared to the model group, while MTX had no significant effect on α7nAChR expression. Moreover, there was a positive relationship between α7nAChR expression and paw swelling, AI, and TNF-α concentration. Splenic lymphocyte activation was accompanied by increased α7nAChR expression, while SIN treatment inhibited cell activation and downregulated α7nAChR expression. α7nAChR expression showed a positive correlation with the progression of RA in AIA rats that may involve lymphocyte activation. Different from MTX, the inhibition of SIN on α7nAChR expression might contribute to its antiarthritic effect, suggesting that SIN could be an important supplement to the treatment strategy for RA.
30959363 Successful manual reduction for ureterosciatic hernia: A case report. 2019 INTRODUCTION: Sciatic hernias are the least common type of pelvic floor hernias. The purpose of this study was to present a novel technique for manual reduction and to conduct a systematic review of previous reports of sciatic hernias to characterize them and review the outcomes. PRESENTATION OF CASE: An 86-year-old female presented with left-sided lumbar pain. She had a past medical history of rheumatoid arthritis and was treated with prednisolone and methotrexate. Her left abdomen and left lumbar area were tender. An unenhanced abdominal computed tomography scan revealed invagination of the left ureter into the left sciatic foramen and a dilated left proximal ureter and renal pelvis. Ultrasonography showed an invaginated left ureter viewing from the left buttock. She was diagnosed with a sciatic hernia. Ultrasound-guided manual transvaginal reduction was performed. Post-procedure unenhanced abdominal computed tomography scan confirmed reduction of the ureter. After 10-months of follow-up, there is no evidence of recurrence. DISCUSSION: Previous reports of patients with sciatic hernia were identified. Clinical data associated with the hernia, reduction technique and clinical outcomes were collected for 72 patients. Open reduction was performed in 24 patients. A ureteral stent was placed in eight patients when the hernia contained the ureter. Four postoperative complications including one death were reported in adults. There were no reports of closed manual reduction. CONCLUSION: A sciatic hernia in women may be manually reduced without surgery. Further reviews of this rare entity are needed to determine the best management strategy.
31259826 Methotrexate Polyglutamate Values in Children and Adolescents With Acute Lymphoblastic Leu 2019 Aug Inadequate adherence to maintenance therapy is a major cause of relapse in patients with acute lymphoblastic leukemia (ALL). Therapeutic monitoring of mercaptopurine (thiopurine) red cell metabolites to assess adherence has been available for many years. Recently a clinical laboratory improvement amendments of 1988-approved test for methotrexate with three polyglutamate residues (MTXPG3) measured in peripheral blood red cells was approved. MTXPG3 is the primary intracellular metabolite of methotrexate, and like thiopurine metabolites, is retained for the life of the red cell giving an estimate of drug exposure over time. Normative values for MTXPG3 are available for adults and children with rheumatoid arthritis on methotrexate monotherapy, which are not applicable for patients with ALL on maintenance. Older literature on the MTXPG3 fraction in children with ALL is limited. We examined the MTXPG3 levels from 123 samples in 76 patients with ALL on maintenance oral methotrexate and mercaptopurine that were collected for clinical care. Male individuals had significantly higher MTXPG3 levels than female individuals which was unrelated to absolute neutrophil count, age, serum creatinine, and average doses of methotrexate or mercaptopurine. The MTXPG3 5th, 10th, 90th, and 95th percentile values are 0, 8.4, 53, and 64, respectively with a median of 24.7 nmol/L. The low 5th percentile MTXPG3 reflects 6 samples from 3 patients, age 16 to 21 years that were considered poorly adherent before collecting the specimen. As with red cell thiopurine (mercaptopurine) metabolites, MTXPG3 normative values may provide useful information to monitor for poor patient adherence or methotrexate toxicity during maintenance chemotherapy in ALL.
30682899 Hypertrophic cervical spine pachymeningitis due to sarcoidosis: a case report. 2019 Apr Hypertrophic pachymeningitis (HP) is a chronic, progressive diffuse inflammatory condition that leads to thickening of the dura mater and can be idiopathic or associated with sarcoidosis among other disorders. In this case report, we present a rare case of cervical spine HP in a 29-year-old woman in the post-partum period, who had a history of pituitary adenoma and juvenile rheumatoid arthritis. Magnetic resonance imaging (MRI) of the spine revealed a soft tissue mass and moderate cord compression. The patient underwent C3-C7 laminectomy. Pathological analysis of the cervical epidural mass demonstrated a reactive inflammatory cell process. Recurrence of symptoms and worsening of pachymeningitis on imaging studies warranted further work-up which revealed mediastinal/hilar lymphadenopathy. Transbronchial biopsy revealed non-caseating granulomatous disease consistent with sarcoidosis. The patient was started on oral steroids and eventually methotrexate with significant clinical and radiographic improvement. Follow-up imaging studies showed minimal dural thickening in the thoracic spine and eventually complete resolution. HP should be considered in a patient with spinal cord compression, myelopathy, and radicular pain of unclear etiology, and sarcoidosis should be considered in idiopathic cases.
30656673 Methotrexate for psoriatic arthritis. 2019 Jan 18 BACKGROUND: Psoriatic arthritis is an inflammatory disease associated with joint damage, impaired function, pain, and reduced quality of life. Methotrexate is a disease-modifying anti-rheumatic drug (DMARD) commonly prescribed to alleviate symptoms, attenuate disease activity, and prevent progression of disease. OBJECTIVES: To assess the benefits and harms of methotrexate for psoriatic arthritis in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the WHO International Clinical Trials Registry Platform, and www.clinicaltrials.gov for relevant records. We searched all databases from inception to 29 January 2018. We handsearched included articles for additional records and contacted study authors for additional unpublished data. We applied no language restrictions. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs that compared methotrexate versus placebo, or versus another DMARD, for adults with psoriatic arthritis. We reported on the following major outcomes: disease response (measured by psoriatic arthritis response criteria (PsARC)), function (measured by the Health Assessment Questionnaire for Rheumatoid Arthritis (HAQ)), health-related quality of life, disease activity (measured by disease activity score (28 joints) with erythrocyte sedimentation rate (DAS28-ESR)), radiographic progression, serious adverse events, and withdrawals due to adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed search results, assessed risk of bias, extracted trial data, and assessed the quality of evidence using the GRADE approach. We undertook meta-analysis only when this was meaningful. MAIN RESULTS: We included in this review eight RCTs conducted in an outpatient setting, in Italy, the United Kingdom, the United States of America, China, Russia, and Bangladesh. Five studies compared methotrexate versus placebo, and four studies compared methotrexate versus other DMARDs. The average age of participants varied across studies (26 to 52 years), as did the average duration of psoriatic arthritis (one to nine years). Doses of methotrexate varied from 7.5 mg to 25 mg orally per week, but most studies administered approximately 15 mg or less orally per week. Risk of bias was generally unclear or high across most domains for all studies. We considered only one study to have low risk of selection and detection bias. The main study informing results of the primary comparison (methotrexate vs placebo up to six months) was at low risk of bias for all domains except attrition bias and reporting bias.We restricted reporting of results to the comparison of methotrexate versus placebo for up to six months. Low-quality evidence (downgraded due to bias and imprecision) from a single study (221 participants; methotrexate dose 15 mg orally or less per week) informed results for disease response, function, and disease activity. Disease response, measured by the proportion who responded to treatment according to PsARC (response indicates improvement), was 41/109 in the methotrexate group and 24/112 in the placebo group (risk ratio (RR) 1.76, 95% confidence interval (CI) 1.14 to 2.70). This equates to an absolute difference of 16% more responders with methotrexate (4% more to 28% more), and a number needed to treat for an additional beneficial outcome (NNTB) of 6 (95% CI 5 to 25). Mean function, measured by the HAQ (scale 0 to 3; 0 meaning no functional impairment; minimum clinically important difference 0.22), was 1.0 points with placebo and 0.3 points better (95% 0.51 better to 0.09 better) with methotrexate; absolute improvement was 10% (3% better to 17% better), and relative improvement 30% (9% better to 51% better). Mean disease activity as measured by the DAS28-ESR (scale of 0 to 10; lower score means lower disease activity; minimum clinically important difference unknown) was 3.8 points in the methotrexate group and 4.06 points in the placebo group; mean difference was -0.26 points (95% CI -0.65 to 0.13); absolute improvement was 3% (7% better to 1% worse), and relative improvement 6% (16% better to 3% worse).Low-quality evidence (downgraded due to risk of bias and imprecision) from three studies (n = 293) informed our results for serious adverse events and withdrawals due to adverse events. Due to low event rates, we are uncertain if methotrexate results show increased risk of serious adverse events or withdrawals due to adverse events compared to placebo. Results show 1/141 serious adverse events in the methotrexate group and 4/152 in the placebo group: RR 0.26 (95% CI 0.03 to 2.26); absolute difference was 2% fewer events with methotrexate (5% fewer to 1% more). In all, 9/141 withdrawals in the methotrexate group were due to adverse events and 7/152 in the placebo group: RR 1.32 (95% CI 0.51 to 3.42); absolute difference was 1% more withdrawals (4% fewer to 6% more).One study measured health-related quality of life but did not report these results. No study measured radiographic progression. AUTHORS' CONCLUSIONS: Low-quality evidence suggests that low-dose (15 mg or less) oral methotrexate might be slightly more effective than placebo when taken for six months; however we are uncertain if it is more harmful. Effects of methotrexate on health-related quality of life, radiographic progression, enthesitis, dactylitis, and fatigue; its benefits beyond six months; and effects of higher-dose methotrexate have not been measured or reported in a randomised placebo-controlled trial.