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ID PMID Title PublicationDate abstract
26016638 [Risk of serious infection in patients with rheumatoid arthritis]. 2015 Studies in the pre-biologics era described elevated risk of infection in patients with rheumatoid arthritis (RA). Recently biologics have been popularized and glucocorticoids used still now in RA patients, which can lead to various infections. Incidence rates of infection in RA patients are reported to be higher than that in the general population. Several factors such as higher age, comorbidities including chronic lung disease and diabetes mellitus, and glucocorticoids are known to increase risk of serious infection. Significant correlation between methotrexate and infection is not established. Whether biologics, especially inhibitors of tumor necrosis factor alpha, increase the risk for infection is still controversial even with randomized control studies and the meta-analyses; however, time-dependent decrease of the risk was revealed. Our three-year analysis of RA patients for infections requiring hospitalization included 5441 patient-years (PY) in total and detected an incidence rate of 3.4/100 PY, of which the risk factors were higher age (70 years of age or older), male sex, progressed stage of arthritis, functional disorders, and use of glucocorticoids or biologics. Such risk factors should be kept in mind for therapeutic decisions in individual patients with RA.
26866506 Brief Report: Intensification to Triple Therapy After Treatment With Nonbiologic Disease-M 2016 Jul OBJECTIVE: Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease-modifying antirheumatic drugs (DMARDs) have similar efficacy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate intensification to triple therapy after initial nonbiologic prescription among patients with RA. METHODS: The use of triple therapy among patients with RA in 2009-2014 was evaluated using US insurance claims data. Patients with a health care visit for RA and an initial nonbiologic DMARD prescription were included. Frequencies of intensification to triple therapy or a biologic DMARD and rates of intensification per 6-month time period were calculated. Using Cox regression, we evaluated whether sociodemographic, temporal, geographic, clinical, and health care utilization factors were associated with intensification to triple therapy. Among those patients whose therapy was intensified, we investigated factors associated with triple therapy use by logistic regression. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for intensification to triple therapy in relation to various clinical and demographic factors were calculated. RESULTS: There were 24,576 patients with a mean ± SD age of 50.3 ± 12.3 years, and 78% were female. During the study period, treatment was intensified to biologic DMARDs in 2,739 patients (11.1%) compared to 181 patients (0.7%) whose treatment was intensified to triple therapy. There was no significant change in triple therapy use across calendar years. Patients whose treatment was intensified to triple therapy were more likely to receive glucocorticoids (HR 1.91 [95% CI 1.41-2.60]) compared to patients who did not use glucocorticoids and were more likely to use nonsteroidal antiinflammatory drugs (NSAIDs) (HR 1.48, 95% CI 1.10-1.99 versus no NSAID use). Among those patients whose treatment was intensified to triple therapy or biologic DMARDs, factors significantly associated with triple therapy use included older age, US region (with the highest odds for triple therapy use in the West and lowest odds for triple therapy use in the Northeast), glucocorticoid use, and lower number of outpatient visits within 180 days of initial nonbiologic DMARD prescription. CONCLUSION: Despite reports published during the study period suggesting equivalent efficacy of triple therapy and biologic DMARDs for RA, the use of triple therapy was infrequent and did not increase over time in this large nationwide study.
27917631 [15 years experience with biological therapy of inflammatory rheumatic diseases in Czech n 2016 Fall The publication is summarizing application of biological DMARDs in autoimmune inflammatory rheumatic diseases.Up to now conventional therapy, which for example in rheumatoid arthritis was application of methotrexate (MTx) in combination with glucocorticoids, was effective, but the remission as a target was achieved in small proportion of patients and also there was little effect on structural progression of diseases. Biological therapy was great advance because response was achieved in ¾ patients who failed MTx. At present time 8 biological drugs are available. 5 are inhibitors of TNFα and 3 have different move of action. In psoriatic arthritis are beside TNF blockers available blocker of IL 17 (secukinumab, ustekinumab, apremilast). For ankylosing spondylitis is registered secukinumab.Anti-TNF therapy is relative safe but rarely serious adverse events can occur. The most important are serious infections, opportunistic infections and tuberculosis. Other adverse event includes allergic reactions and local intolerance. Increase incidence of lymphomas was not confirmed. There is probably minimal increased risk of skin melanoma and non-melanoma tumors. Benefit/risk ratio is still very positive.National registry of biological therapy ATTRA was founded 15 years ago and includes patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis. In June 2016 over all 6800 patients with those diagnoses was included and actually 5194 have been treated. In registry patients are regularly followed for activity, efficacy of the drug and other events. Results of registry are sent payers for evaluations of pharmacologic parameters.
27523005 Other Iatrogenic Immunodeficiency-associated Lymphoproliferative Disorder Presenting as Pr 2016 Primary bone lymphoma (PBL) is a rare disorder. We herein present a case of other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD) presenting as PBL. A 63-year-old woman was diagnosed with rheumatoid arthritis and had been treated with methotrexate for seven years. Two months before admission, she suffered from pain in the limbs. Magnetic resonance imaging revealed multiple irregular lesions in the bones of the limbs, which showed an uptake of (18)F-FDG on positron emission tomography. A biopsy of the right radius revealed diffuse large B-cell lymphoma, leading to the diagnosis of OIIA-LPD. She received rituximab-containing regimens resulting in a complete response.
27428186 High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthri 2016 Jul OBJECTIVES: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). METHODS: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. RESULTS: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. CONCLUSIONS: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment.
24297383 Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in 2015 Feb OBJECTIVE: To investigate if erythrocyte-methotrexate-polyglutamate (MTX-PG) concentrations in patients with rheumatoid arthritis (RA) are associated with disease activity or adverse events. METHODS: We used a longitudinal study design with two cohorts. The derivation cohort included 102 and the validation cohort included 285 patients with RA on MTX. We measured erythrocyte-MTX-PG with 1-5 glutamate residues at 3 months, 6 months and 9 months after MTX start with a liquid chromatography (LC)-mass spectrometry (MS)/MS assay. Outcomes were disease activity score in 28 joints (DAS28) and adverse events. Longitudinal associations of MTX-PG concentrations after 3 months, 6 months and 9 months with DAS28 were tested with a linear mixed model adjusted for age, gender, baseline DAS28, MTX dose and comedication. RESULTS: In the derivation cohort, mean DAS28 decreased from 4.26 (SE=0.14) at baseline to 2.72 (SE=0.13) after 9 months. Thirty per cent of patients in the derivation cohort experienced more than three adverse events after 3 months, which decreased to 18% after 9 months. In the validation cohort, DAS28 and adverse events were comparable with the derivation cohort. In the derivation cohort, MTX-PG1 (ß=-0.005), MTX-PG2 (ß=-0.022), MTX-PG3 (β=-0.007) and total MTX-PG (ß=-0.004) were associated (p<0.05) with lower DAS28 over 9 months. In the validation cohort, MTX-PG2 (ß=-0.015), MTX-PG3 (ß=-0.010), MTX-PG4 (ß=-0.008) and total MTX-PG (ß=-0.003) were associated with lower DAS28 over 9 months. None of the MTX-PGs was associated with adverse events. CONCLUSIONS: In this first longitudinal study, we showed that an increase in erythrocyte-MTX-PG concentration was associated with a decreased DAS28 over 9 months in two cohorts, and is therefore a potential tool for therapeutic drug monitoring of MTX in RA.
27523007 MYC/BCL2 Double-hit Lymphoma in a Patient with Rheumatoid Arthritis Associated with Methot 2016 Several reports have suggested an increased risk of malignant lymphoma in patients with rheumatoid arthritis treated with methotrexate (MTX). We herein describe the case of a 71-year-old woman with rheumatoid arthritis who developed MYC/BCL2 double-hit lymphoma associated with MTX therapy. She developed a fever and lymphadenopathies over a 2-week period and had elevated levels of soluble IL-2 receptor. Inguinal lymph node and bone marrow biopsies showed diffuse large B cell lymphoma. Fluorescent in situ hybridization revealed MYC and BCL2 gene rearrangements in her lymphoma cells. Accordingly, a diagnosis of MYC/BCL2 double-hit lymphoma was made. This is the first reported case of a double-hit lymphoma associated with MTX therapy.
27102806 Methotrexate monotherapy and methotrexate combination therapy with traditional and biologi 2016 Apr 21 OBJECTIVE: To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate. DESIGN: Systematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate used alone or in combination with other conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients with rheumatoid arthritis. DATA SOURCES: Trials were identified from Medline, Embase, and Central databases from inception to 19 January 2016; abstracts from two major rheumatology meetings from 2009 to 2015; two trial registers; and hand searches of Cochrane reviews. STUDY SELECTION CRITERIA: Randomized or quasi-randomized trials that compared methotrexate with any other DMARD or combination of DMARDs and contributed to the network of evidence between the treatments of interest. MAIN OUTCOMES: American College of Rheumatology (ACR) 50 response (major clinical improvement), radiographic progression, and withdrawals due to adverse events. A comparison between two treatments was considered statistically significant if its credible interval excluded the null effect, indicating >97.5% probability that one treatment was superior. RESULTS: 158 trials were included, with between 10 and 53 trials available for each outcome. In methotrexate naive patients, several treatments were statistically superior to oral methotrexate for ACR50 response: sulfasalazine and hydroxychloroquine ("triple therapy"), several biologics (abatacept, adalimumab, etanercept, infliximab, rituximab, tocilizumab), and tofacitinib. The estimated probability of ACR50 response was similar between these treatments (range 56-67%), compared with 41% with methotrexate. Methotrexate combined with adalimumab, etanercept, certolizumab, or infliximab was statistically superior to oral methotrexate for inhibiting radiographic progression, but the estimated mean change over one year with all treatments was less than the minimal clinically important difference of 5 units on the Sharp-van der Heijde scale. Triple therapy had statistically fewer withdrawals due to adverse events than methotrexate plus infliximab. After an inadequate response to methotrexate, several treatments were statistically superior to oral methotrexate for ACR50 response: triple therapy, methotrexate plus hydroxychloroquine, methotrexate plus leflunomide, methotrexate plus intramuscular gold, methotrexate plus most biologics, and methotrexate plus tofacitinib. The probability of response was 61% with triple therapy and ranged widely (27-70%) with other treatments. No treatment was statistically superior to oral methotrexate for inhibiting radiographic progression. Methotrexate plus abatacept had a statistically lower rate of withdrawals due to adverse events than several treatments. CONCLUSIONS: Triple therapy (methotrexate plus sulfasalazine plus hydroxychloroquine) and most regimens combining biologic DMARDs with methotrexate were effective in controlling disease activity, and all were generally well tolerated in both methotrexate naive and methotrexate exposed patients.
24420724 Prescription patterns and trends in anti-rheumatic drug use based on a large-scale claims 2015 May This drug utilization study aimed to investigate prescription patterns and trends for anti-rheumatic drug use in Japanese patients with rheumatoid arthritis (RA), clarifying if patients with RA in Japan are being treated according to EULAR recommendations and ACR guidelines. We used a large-scale claims database consisting of the medical claims of employee health insurance recipients, which included approximately one million insured people. The claims data for incident 5,126 patients with diagnosis codes of RA between January 1, 2005 and October 31, 2011 were analyzed. The number of patients who received disease modifying anti-rheumatic drugs (DMARDs) including biologics as initial therapy was 629 (12.3 %), while the others received non-DMARD therapy only. During the study period, use of methotrexate (MTX) and biologics as first-line drugs increased from 1.9 to 8.0 % and from 0 to 1.6 %, respectively (p < 0.001 for both), while that of non-steroidal anti-inflammatory drugs (NSAIDs) decreased (p = 0.004). Time from first RA diagnosis to the start of treatment with DMARDs decreased significantly from 2005 to 2010. These findings suggest that many early RA patients in Japan do not yet receive aggressive treatment, albeit that this prescribing practice has gradually changed to better comply with clinical recommendations. The current, obsolete Japanese RA guidelines require urgent updating to reflect the most recent knowledge and care with effective treatment modalities.
25775147 Comparison of efficacy and safety of tacrolimus and methotrexate in combination with abata 2015 OBJECTIVES: Tacrolimus (TAC) and abatacept (ABT) inhibit T-cells via different mechanisms and, in combination, may be effective against rheumatoid arthritis. However, they may also disrupt normal immune functions. We compared the efficacy and safety of ABT administered to patients in combination with TAC, methotrexate (MTX), or other drugs. METHODS: This was a retrospective multicenter study conducted to compare the efficacy and safety of ABT in 211 patients: the drug was administered together with TAC (ABT+ TAC group; 22 patients), MTX (ABT+ MTX group; 102 patients), or patients treated without concomitant MTX or TAC (ABT mono group; 87 patients). The disease activity, treatment continuation rate, and reason for discontinuation of treatment were investigated. RESULTS: The retention rate at Week 24 was similar in the three groups. There were no cases of discontinuation related to the appearance of adverse events in the ABT+ TAC group. At Week 24, according to the European League Against Rheumatism response criteria, the "good" response rates were 33.3%, 13.4%, and 13.4% in the ABT+ TAC, ABT+ MTX, and ABT mono groups, respectively. Statistically significant decreases in various disease activity scores/indices were observed in all the groups as early as Week 4. CONCLUSIONS: Although the sample size was small, the results of this retrospective study suggest that the ABT+ TAC combination therapy has at least comparable safety and efficacy to those of the ABT+ MTX combination, and that it can thus be a useful option for patients who cannot take MTX.
26153840 Isolated herpes simplex in the adult larynx as a rare complication of methotrexate-induced 2015 Jul OBJECTIVE: This report describes the clinical presentation and management of a rare case of herpes simplex virus infection in the larynx of a patient treated with methotrexate. CASE REPORT: We report a case of a clinically suspicious laryngeal lesion in an 82-year-old woman who started methotrexate treatment for rheumatoid arthritis. Shortly afterwards she developed dysphonia, which worsened over four months. On microlaryngoscopy, there was bilateral erythema and ulceration of the vocal folds. No other mucocutaneous lesions or systemic features were present. Biopsies revealed herpes simplex virus infection of the vocal folds; there was complete resolution with oral aciclovir. A brief literature review for this rare entity is presented and the diagnostic challenges arising from under-recognition of atypical presentations are discussed. CONCLUSION: To our knowledge, this is the first report of a rare complication of herpes simplex virus infection in the context of methotrexate-induced immunosuppression. It may present therapeutic challenges for conditions which rely on immunosuppressive treatments.
26834213 Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis R 2016 Mar OBJECTIVE: To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). METHODS: This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. RESULTS: A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. CONCLUSION: In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).
27414105 Effectiveness and safety of tocilizumab in achieving clinical and functional remission, an 2017 Mar OBJECTIVE: To evaluate effectiveness and safety of tocilizumab (TCZ) in biologic-naive Japanese patients with rheumatoid arthritis (RA) in real-world settings, and to analyze the relationship between disease duration and clinical outcomes. METHODS: The FIRST Bio study was a postmarketing surveillance study of intravenous TCZ in biologics-naive patients who had a prior inadequate response or were intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Effectiveness, safety, and concomitant csDMARD administration were assessed. RESULTS: Of the 839 patients analyzed, 72.3% completed 52 weeks of treatment. The Clinical Disease Activity Index (CDAI) remission rate at week 52 was 36.8%. Contributing factors for CDAI remission were younger age, early disease stage, and no comorbidities. Health Assessment Questionnaire Disability Index ≤0.5 was achieved in 65.1% of patients, and was significantly associated with disease duration. Discontinuation of concomitant methotrexate (MTX) and glucocorticoids (GCs) was possible in 19.3% and 34.1% of patients, respectively, without decreasing remission rate. The incidence (events/100 patient-years) of serious adverse events was 18.09, the most common being infection. CONCLUSION: These data validate the importance of TCZ treatment in the early stages of RA in biologic-naive patients to achieve increased effectiveness. The safety profile of TCZ was reconfirmed. Furthermore, TCZ therapy may allow discontinuation of concomitant MTX and GCs without affecting remission.
27307531 Longterm Retention Rate and Risk Factors for Adalimumab Discontinuation Due To Efficacy an 2016 Aug OBJECTIVE: To evaluate the rates of retention and discontinuation of adalimumab (ADA) due to efficacy and safety in Japanese patients with rheumatoid arthritis (RA). METHODS: All patients with RA (n = 476) who were treated with ADA in the Tsurumai Biologics Communication Registry were enrolled. RESULTS: The retention rate of ADA was 46% at 5 years. When focusing on insufficient efficacy, previous biologics use and high baseline disease activity were significant risk factors for up to 1 year. Methotrexate (MTX) use was a significantly low risk factor after 1 year of treatment. CONCLUSION: Concomitant MTX contributes to the longterm efficacy of ADA therapy.
24842477 Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patie 2015 Mar Abstract Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA.
26494588 Severe apoptotic enteropathy caused by methotrexate treatment for rheumatoid arthritis. 2016 Mar The folic acid antagonist methotrexate is a cornerstone treatment of rheumatoid arthritis. Its use is limited chiefly by gastrointestinal toxicity, which is among the main reasons for methotrexate discontinuation. Here, we report the case of a 40-year-old man on chronic methotrexate therapy in whom life-threatening apoptotic enteropathy with watery diarrhea and hypovolemic shock developed after he was switched from the oral to the intramuscular route, with no change in dosage. Colonic biopsies suggested drug-induced colitis, showing a nonspecific, mildly inflammatory infiltrate of lymphocytes and plasma cells, dilated damaged crypts, and a marked increase in basal crypt apoptosis (>20 apoptotic bodies/100 crypts). Clinicians should be aware that methotrexate can cause life-threatening apoptotic enteropathy. Increased basal crypt apoptosis in colonic biopsies with more than 5 apoptotic bodies/100 crypts should routinely suggest drug-induced enteropathy.
27432105 Cytomegalovirus Reactivation Induced Acute Hepatitis and Gastric Erosions in a Patient wit 2016 Tocilizumab, an anti-human interleukin 6 receptor (IL-6R) monoclonal antibody, is widely used to treat rheumatoid arthritis (RA) and is expected to exhibit clinical efficacy when used to treat other autoimmune diseases. However, a risk of opportunistic infection is occasionally recognized. A 54-year-old woman had received an oral corticosteroid and methotrexate to treat RA. Despite receiving these treatments, she received additional treatment with tocilizumab due to poor control of the disease activity. She presented at our hospital with a high fever and epigastralgia 19 days after receiving this treatment. A laboratory evaluation revealed liver injury and cytomegalovirus (CMV) viremia. Abdominal ultrasonography and computed tomography (CT) revealed hepatosplenomegaly, but no ascites. Upper gastrointestinal endoscopy revealed gastric erosions induced by CMV, which were confirmed immunohistochemically. Hence, we diagnosed the patient with CMV reactivation-induced acute hepatitis and gastric erosions under tocilizumab treatment. She received an anti-cytomegalovirus drug, ganciclovir, for 14 days due to her viremia and impaired general condition, which was suggestive of a severe infection. Her general condition subsequently improved, the liver function test results normalized, and the gastric erosions disappeared. In conclusion, although tocilizumab is very useful for treating certain autoimmune and inflammatory diseases, and will be prescribed more widely in the future, associated CMV infections must be closely monitored, as these can be lethal.
26510317 Enhancing Methotrexate Tolerance with Folate Tagged Liposomes in Arthritic Mice. 2015 Dec Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor β present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor β was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor β. These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance.
27301524 Methotrexate-associated Intravascular Large B-cell Lymphoma in a Patient with Rheumatoid A 2016 Intravascular large B-cell lymphoma (IVLBCL) is a rare and clinically aggressive lymphoma with an unfavorable prognosis. We report the case of a 50-year-old woman who was diagnosed with IVLBCL during treatment with methotrexate (MTX) and biologic agents for rheumatoid arthritis. The symptoms showed partial improvement only after the cessation of both treatments. She subsequently received chemotherapy and achieved a complete remission and has remained free of recurrence for 2 years without any further treatment. We herein describe a rare case of IVLBCL which presented with the features of an MTX-associated lymphoproliferative disorder.
24810700 Rheumatoid myositis leading to acute lower extremity compartment syndrome: a case-based re 2015 Oct Muscle pain and weakness in a rheumatoid arthritis (RA) patient has a broad differential, and myositis should be considered early in the disease course as serious limb and life-threatening sequelae may occur. A 55-year-old woman with a past medical history of methotrexate-controlled RA presented with right leg pain for 4 days. The patient suffered sensory loss in the right foot and decreased strength in the toes. Lab tests revealed elevated creatine kinase, ESR, and anti-rheumatoid factor antibody titers. CT scan revealed myositis of posterior compartment muscles. Progressive edema, pain, and neuromuscular deficits persisted despite steroid and antibiotic therapy, so the patient was taken for urgent fasciotomy for acute compartment syndrome. The muscle biopsy showed diffuse mononuclear cell infiltration as well as perivascular and perineural involvement consistent with rheumatoid myositis (RM). The patient did well post-op on a prednisone taper. This case underlines the systemic nature of RA and exemplifies the severity of inflammation that may lead to grave consequences such as compartment syndrome. The histopathology is diagnostic when there is evidence of mononuclear cell infiltration; however, this is not entirely specific. Early, aggressive therapy with immunosuppressives is warranted in such patients. RM has not, to our knowledge, been recorded to cause acute compartment syndrome. Clinicians should be aware of this uncommon manifestation of RA keeping the various presentations of rheumatoid disease in mind when faced with these patients.