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ID PMID Title PublicationDate abstract
26221616 DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of A 2015 We have previously demonstrated that semimature dendritic cell- (smDC-) based immunotherapy is effective for the treatment of collagen-induced arthritis (CIA) prior to disease onset. In the present study, we examined the efficacy of combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-) pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs. The effect of CII-smDCs alone was also comparable to the combination therapy. CD4(+)Foxp3(+) Treg populations and IL-10 secretion markedly increased, and CII-specific autoreactive T cells decreased in mice treated with CII-smDCs alone or in combination with MTX. Combination therapy reduced the secretion of interferon-γ (IFN-γ) and IL-17 with little influence on the IL-4 secretion in the mixed leukocyte reaction. These results imply that the combination therapy with low-dose MTX and smDCs is effective in controlling advanced CIA by enhancing Treg population and suppresses antigen-specific Th1/Th17 immunity, rather than initiating Th1 to Th2 immune deviation. Our findings provide a better understanding of the DC therapy in combination with MTX for the treatment of patients with rheumatoid arthritis (RA).
29160632 LGL leukemia and autoimmunity - the borderline between autoimmune disease and cancer is be 2016 Large granular lymphocyte (LGL) leukemia is a chronic hematological disease, in which the diseased cells consist of clonal large, mature T or NK cells. Major symptoms and findings of the disease include anemia, neutropenia and rheumatoid arthritis. Immunosuppressive treatments, such as methotrexate, usually relieve the symptoms in patients. In LGL leukemia, next-generation sequencing has recently revealed mutations in the STAT3 and STAT5B genes that lead to the activation of these proteins. Similar mutations have been detected in hereditary autoimmune diseases, disorders of bone marrow and malignancies of lymphocyte origin.
25739847 A qualitative analysis of methotrexate self-injection education videos on YouTube. 2016 May The aim of this study is to identify and evaluate the quality of videos for patients available on YouTube for learning to self-administer subcutaneous methotrexate. Using the search term "Methotrexate injection," two clinical reviewers analyzed the first 60 videos on YouTube. Source and search rank of video, audience interaction, video duration, and time since video was uploaded on YouTube were recorded. Videos were classified as useful, misleading, or a personal patient view. Videos were rated for reliability, comprehensiveness, and global quality scale (GQS). Reasons for misleading videos were documented, and patient videos were documented as being either positive or negative towards methotrexate (MTX) injection. Fifty-one English videos overlapped between the two geographic locations; 10 videos were classified as useful (19.6 %), 14 misleading (27.5 %), and 27 personal patient view (52.9 %). Total views of videos were 161,028: 19.2 % useful, 72.8 % patient, and 8.0 % misleading. Mean GQS: 4.2 (±1.0) useful, 1.6 (±1.1) misleading, and 2.0 (±0.9) for patient videos (p < 0.0001). Mean reliability: 3.3 (±0.6) useful, 0.9 (±1.2) misleading, and 1.0 (±0.7) for patient videos (p < 0.0001). Comprehensiveness: 2.2 (±1.9) useful, 0.1 (±0.3) misleading, and 1.5 (±1.5) for patient view videos (p = 0.0027). This study demonstrates a minority of videos are useful for teaching MTX injection. Further, video quality does not correlate with video views. While web video may be an additional educational tool available, clinicians need to be familiar with specific resources to help guide and educate their patients to ensure best outcomes.
26773117 Longterm Efficacy of an Antipneumococcal Polysaccharide Vaccine among Patients with Autoim 2016 Feb OBJECTIVE: To estimate the longterm humoral response of an antipneumococcal polysaccharide vaccine (PPSV23) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or inflammatory bowel disease (IBD)-associated spondyloarthropathy (SpA), and the effect of demographic and clinical factors and treatment on the longterm efficacy of the vaccine. METHODS: A total of 145 consecutive patients treated with biologics [tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) receptor inhibitors] or methotrexate (MTX) participated in this study. Fifteen were excluded because of absent information regarding their vaccination status (n = 9) or because of technical problems in obtaining their serum sample (n = 6). They were diagnosed with RA (n = 63, 48.5%), PsA (n = 29, 22.3%), AS (n = 28, 21.5%), or IBD-associated SpA (n = 3, 2.3%). Their mean age was 54.6 years, and 61.5% were women. Data were collected on the timing of vaccination, demographic and clinical characteristics, and treatment, and patients' serum antipneumococcal antibody levels were tested. RESULTS: Two-thirds of the patients (67.7%) had received PPSV23 45 months (mean) earlier. Treatment included TNF-α inhibitors (73.9%), IL-6 receptor inhibitors (13.1%), or MTX without a biological treatment (13%). The uptake of vaccination was significantly higher in the older population (> 65 yrs). Vaccinated patients had significantly higher antibody levels compared with vaccine-naive patients. The antibody levels had been preserved after 10 years. MTX use, but not biologics, was associated with significantly lower antibody levels. CONCLUSION: The longterm efficacy of the PPSV23 vaccination seems to be preserved among patients with RA, PsA, AS, and IBD-associated SpA for at least 10 years. Efficacy is slightly impaired by MTX, but it is not affected by biologics. These findings suggest that revaccination after 5 years might not be needed for all, and testing the antibody titers should be considered to identify those who may benefit from revaccination.
27307501 Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. 2017 Jan OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs. METHODS: We report patients evaluated in the Johns Hopkins Rheumatology clinics from 2012 to 2016 identified as having new rheumatological symptoms in the context of treatment with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) for solid tumours. RESULTS: We identified 13 patients who received ICIs and developed rheumatological IRAEs. Mean age was 58.7 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer and renal cell carcinoma. ICI regimens included nivolumab or ipilimumab as monotherapy (n=5), or combination nivolumab and ipilimumab (n=8). Nine of 13 patients developed an inflammatory arthritis, 4 with synovitis confirmed on imaging (3 ultrasound, 1 MRI) and 4 with inflammatory synovial fluid. Four patients developed sicca syndrome with severe salivary hypofunction. Other IRAEs included: pneumonitis, colitis, interstitial nephritis and thyroiditis. Antinuclear antibodies were positive in 5 out of 13 patients. All 13 patients were treated with corticosteroids with varying response. Two patients were treated with methotrexate and antitumor necrosis factor therapy for inflammatory arthritis. CONCLUSIONS: As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs are likely to emerge. Further research is required to understand mechanisms, determine risk factors and develop management algorithms for rheumatic IRAEs.
26071217 Selective inhibition of extracellular oxidants liberated from human neutrophils--A new mec 2015 Sep Hydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis. In human neutrophils, extra- and intracellular formation of oxidants, mobilisation of intracellular calcium and the phosphorylation of proteins regulating NADPH oxidase assembly were analysed. Administration of hydroxychloroquine decreased the concentration of oxidants in blood of arthritic rats. The inhibition was comparable with the reference drug methotrexate, yet it was not accompanied by a reduction in neutrophil count. When both drugs were co-applied, the effect became more pronounced. In isolated human neutrophils, treatment with hydroxychloroquine resulted in reduced mobilisation of intracellular calcium, diminished concentration of external oxidants and in decreased phosphorylation of Ca(2+)-dependent protein kinase C isoforms PKCα and PKCβII, which regulate activation of NADPH oxidase on plasma membrane. On the other hand, no reduction was observed in intracellular oxidants or in the phosphorylation of p40(phox) and PKCδ, two proteins directing the oxidase assembly to intracellular membranes. Hydroxychloroquine reduced neutrophil-derived oxidants potentially involved in tissue damage and protected those capable to suppress inflammation. The observed effects may represent a new mechanism involved in the anti-inflammatory activity of this drug.
25045858 Rapidly Fatal Internal Carotid Artery Mycotic Aneurysm Rupture in a Rheumatoid Patient Tak 2015 May OBJECT: Tumor necrosis factor (TNF)-α inhibitors are effective at treating certain inflammatory and autoimmune disorders. They are generally safe; potential adverse events include infections (bacterial, fungal, and viral), congestive heart failure exacerbations, and the potential for demyelinating diseases and possibly certain malignancies. We present the first documented case of fungal internal carotid artery (ICA) mycotic aneurysm in a patient being treated with a TNF-α inhibitor. We also review the literature on infections with TNF-α inhibition and the management of previously reported fungal ICA mycotic aneurysm cases. CASE DESCRIPTION: A 76-year-old woman with rheumatoid arthritis, treated with etanercept and methotrexate, presented with a 2-week history of left temporal headaches. She was treated empirically for giant cell arteritis (GCA) with oral prednisone, which provided no symptom relief. She was subsequently hospitalized for a superficial temporal artery biopsy, which was negative for GCA. She returned 2 weeks later after experiencing a left thromboembolic ischemic stroke. She had an acute neurologic decline, and a head computed tomography scan showed diffuse subarachnoid hemorrhage from a ruptured left fusiform paraclinoid ICA aneurysm. She was taken emergently for a craniotomy for clip-wrapping of the aneurysm, but intraoperative ultrasound revealed poor flow in the left anterior cerebral circulation and a complete infarct of the left-sided anterior circulation. The family withdrew care and the patient died. Postmortem analysis demonstrated fungi consistent with Aspergillus invading the necrotic left ICA. CONCLUSIONS: Although fungal mycotic aneurysms of the ICA are rare, their incidence may increase with the expanded use of immunosuppressive medications. Patients with rheumatoid arthritis who take potent immunosuppression regimens may be prime candidates for mycotic aneurysms because they often have two favoring conditions: atherosclerosis and immunosuppression. These ICA aneurysms carry a high mortality rate, so early diagnosis and aggressive therapy, potentially by endovascular trapping/vessel occlusion coupled with long-term antifungal therapy, is essential.
27934678 Incidence of hepatitis B virus reactivation in patients with resolved infection on immunos 2017 Jun BACKGROUND: Although the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial. OBJECTIVES: To investigate the incidence and risk factors for HBV reactivation in patients with RD. METHODS: We performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded. RESULTS: Among 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3-182 months; median, 66 months). CONCLUSIONS: The incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.
25925313 Reduced levels of circulating progenitor cells in juvenile idiopathic arthritis are counte 2015 Apr 30 BACKGROUND: Endothelial progenitor cells (EPC) promote angiogenesis and vascular repair. Though reduced EPC levels have been shown in rheumatoid arthritis, no study has so far evaluated EPCs in children with juvenile idiopathic arthritis (JIA). We aimed to study circulating EPCs in children with JIA, their relation to disease activity, and effects of anti TNF-α treatment. METHODS: Circulating EPCs were quantified by flow cytometry based on CD34, CD133 and KDR expression in peripheral blood of 22 patients with oligoarticular JIA and 29 age-matched controls. EPCs were re-assessed in children with methotrexate-resistant oligo-extended JIA before and up to 12 month after initiation of anti-TNF-alpha therapy. Plasma concentrations of inflammatory and EPC-regulating factors were measured using a multiplex array. Confocal immunofluorescence was used to demonstrate EPCs in synovial tissues. RESULTS: Children with active JIA showed a significant reduction of relative and absolute counts of circulating progenitor cells and EPCs compared to age-matched healthy controls. CD34(+) cell levels were modestly and inversely correlated to disease activity. A strong inverse correlation was found between serum TNF-α and EPC levels. In 8 patients treated with anti TNF-α agents, the number of EPCs rose to values similar to healthy controls. CD34(+)KDR(+) EPCs were found in the synovial tissue of JIA children, but not in control. CONCLUSIONS: Children with JIA have reduced levels of the vasculoprotective and proangiogenic EPCs. While EPCs may contribute to synovial tissue remodelling, EPC pauperization may indicate an excess cardiovascular risk if projected later in life.
26295143 Folate Receptor-Targeted Dendrimer-Methotrexate Conjugate for Inflammatory Arthritis. 2015 Aug Generation 5 (G5) poly(amidoamide) (PAMAM) dendrimers are synthetic polymers that have been broadly applied as drug delivery carriers. Methotrexate (MTX), an anti-folate metabolite, has been successfully used as an anti-inflammatory drug to treat rheumatoid arthritis (RA) in the clinic. In this study, we examine the therapeutic efficacy of G5 PAMAM dendrimer methotrexate conjugates (G5-MTX) that also have folic acid (FA) conjugated to the G5-MTX (G5-FA-MTX) to target inflammation-activated folate receptors overexpressing macrophages. These cells are thought to play an important role in the development of RA. With G5 serving as a control, the in vitro binding affinities of G5-FA-MTX and G5-MTX to activated macrophages were assessed in RAW264.7, NR8383 and primary rat peritoneal macrophages. The results indicated that the binding of either conjugate to macrophages was concentration- and temperature-dependent and could be blocked by the presence of 6.25 mM free FA (p < 0.005). The preventive effects of G5-MTX and G5-FA-MTX conjugates on the development of arthritis were explored on an adjuvant-induced inflammatory arthritis model and had similar preventive effects in inflammatory arthritis at a MTX equivalent dose of 4.95 μmol/kg. These studies indicated that when multiples of MTX are conjugated on dendritic polymers, they specifically bind to folate receptor overexpressing macrophages and have comparable anti-inflammatory effects to folate targeted MTX conjugated polymers.
32263177 Activated macrophage-targeted dextran-methotrexate/folate conjugate prevents deterioration 2016 Mar 28 Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, leading to articular synovial hyperplasia, cartilage destruction, and bone erosion. In RA pathophysiology, the activated macrophages contribute to the initiation and maintenance of the disease. Folate receptor, an overexpressed receptor on the activated macrophages, becomes a promising target site for RA treatment. In this work, the folate-modified dextran-methotrexate conjugate (noted as Dex-g-MTX/FA) was synthesized with an untargeted dextran-methotrexate prodrug (referred as Dex-g-MTX) as the control. The two prodrugs self-assembled into spherical micelles with both scales of about 90 nm and exhibited sustained MTX release. Dex-g-MTX/FA exhibited more superior cellular uptake mediated by the folate receptor and higher cytotoxicity toward macrophages activated by lipopolysaccharide (LPS) compared with Dex-g-MTX. Moreover, Dex-g-MTX/FA possessed improved biodistribution at the lesion site and stronger remission of RA through the inhibition of proinflammatory cytokines in comparison with both Dex-g-MTX and free MTX. These results demonstrated that the folate-targeted prodrug, i.e., Dex-g-MTX/FA, is a potential strategy for activated macrophage-targeted therapy of RA.
27751863 Impact of genetic variants of ATP binding cassette B1, AICAR transformylase/IMP cyclohydro 2017 Nov OBJECTIVE: To analyze the effect of single nucleotide polymorphisms (SNPs) with well-known functional impact of methylenetetrahydrofolatereductase (MTHFR; rs1801131 and rs1801133), the membrane transporter ABCB1 (rs1045642), the AICAR transformylase/IMP cyclohydrolase (ATIC; rs2372536) and folyl-polyglutamatesynthetase (FPGS; rs1544105), on liver and bone marrow toxicity of methotrexate (MTX). PATIENTS AND METHODS: We analyzed 1415 visits from 350 patients of the PEARL (Princesa Early Arthritis Register Longitudinal) study: (732 with MTX, 683 without MTX). The different SNPs were genotyped using specific TaqMan probes (Applied Biosystems). Multivariate analyzes were performed using generalized linear models in which the dependent variables were the levels of serum alanine aminotransferase (liver toxicity), leukocytes, platelets or hemoglobin (hematologic toxicity) and adjusted for clinical variables (disease activity, etc.), analytical (renal function, etc.), sociodemographic (age, sex, etc.) and genetic variants of MTHFR, ABCB1, ATIC and FPGS. The effect of these variables on the MTX doses prescribed throughout follow-up was also analyzed through multivariate analysis nested by visit and patient. RESULTS: When taking MTX, those patients carrying the CC genotype of rs1045642 in ABCB1 showed significantly higher GPT levels (7.1±2.0 U/L; P<.001). Carrying at least one G allele of rs1544105 in FPGS was associated with lower leukocyte (-0.67±0.32; 0.038), hemoglobin (-0.34±0.11g/dL; P=.002), and platelet (-11.8±4.7; P=.012) levels. The presence of the G allele of rs1544105 in FPGS, and the T allele of rs1801133 in MTHFR, was significantly associated with the use of lower doses of MTX. DISCUSSION: Our data suggest that genotyping functional variants in FGPS and MTHFR enzymes and the transporter ABCB1 could help to identify patients with increased risk of MTX toxicity.
26490030 Cytomegalovirus as an Insidious Pathogen Causing Duodenitis. 2015 A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion;however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathological features of CMV-related duodenitis, likely due to its low prevalence. CMV infection in the upper gastrointestinal tract should be considered as a differential diagnosis in high-risk individuals, particularly those with symptoms relating to the digestive system. Biopsy examinations are preferable for the definitive diagnosis of CMV gastrointestinal infection, even without specific endoscopic features.
25163736 Predicting toxicity: biomarkers and the value of the patient's opinion. 2015 Safety is usually a secondary endpoint in clinical trials, and most observational studies on predictors focus on response, not toxicity. Research is clearly biased towards efficacy rather than safety, probably because of the difficulty in measuring toxicity arising from lack of standardization, low statistical power, missing data, misinterpretation, and confounding variables. An extensive search revealed very few studies on toxicity markers for the drugs used to treat rheumatoid arthritis. The literature contains many studies on predictors of the safety of methotrexate. Most analyze genetic markers, which are difficult to apply in daily practice. We found few studies on markers of toxicity for biologics. As many adverse events are related to patient characteristics, we recommend that clinicians understand the risk factors for the most common adverse events, especially infections and cancer, and manage risk on an individual basis. Moreover, patient involvement in monitoring safety is crucial.
26124700 Cost-utility analysis of certolizumab pegol versus alternative tumour necrosis factor inhi 2015 BACKGROUND: Certolizumab pegol, a PEGylated tumour necrosis factor (TNF)-inhibitor, improves the clinical signs and symptoms of rheumatoid arthritis (RA) when used in combination with methotrexate or as monotherapy. This study evaluatedthe cost-utility of certolizumab pegol versusTNF-inhibitors plus methotrexate in the treatment of moderate-to-severe RA in Spain. METHODS: A Markov cohort health state transition model was developed to evaluate the cost-utility (costs and quality-adjusted life years [QALYs]) of certolizumab pegol versus other TNF-inhibitors licensed in Spain in 2009. Efficacy was measured using the American College of Rheumatology (ACR) responses at 6 months, based on adjusted indirect comparisons from published clinical trials. Utilities were derived from EQ-5D data from certolizumab pegol RA clinical trials. Clinical history and resource use data came from published literature. Unit costs were taken from Spanish databases or published data (cost year 2009). Base case analyses were conducted from the payer perspective, with a lifetime horizon, 3.5 % annual discounting rates for costs and outcomes, and 3 % inflation rate for 2009 onwards. One-way sensitivity analyses were conducted. RESULTS: The average lifetime costs for certolizumab pegol, etanercept, adalimumab (every 2 weeks and weekly) and infliximab (3 mg/kg and 5 mg/kg) in combination with methotrexate were €140,971, €141,197, €139,148, €164,741, €136,961 and €152,561, respectively. The QALYs gained were 6.578, 6.462, 6.430 (for both adalimumab doses), 6.430, and 6.318 (for both infliximab doses), respectively. At a €30,000/QALY willingness-to-pay threshold, certolizumab pegol plus methotrexate dominated adalimumab weekly, etanercept, and infliximab 5 mg/kg, and was cost-effective versus adalimumab every 2 weeks and infliximab 3 mg/kg (all with methotrexate), with estimated ICERs of €12,346/QALY and €15,414/QALY, respectively. Certolizumab pegol monotherapy was more cost-effective versus adalimumab, and less expensive with similar health gains versus etanercept (6.416 QALYs vs 6.492). Univariate analysis showed ICERs to be sensitive to changes in time horizon, ACR response time point, baseline Heath Assessment Questionnaire (HAQ) score, and rate of HAQ-disability index deterioration after discontinuing treatment. CONCLUSIONS: This analysis shows that certolizumab pegol is cost-effective compared with other TNF-inhibitors recommended in Spain for the treatment of RA.
26345159 The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats. 2015 BACKGROUND: Rheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1) examining the therapeutic effect of CM administered via intravenous (iv) injection on RA and 2) formulating the drug into oil-water nanoemulsions (Ns) to overcome the low oral bioavailability of CM and achieve oral delivery of the drug. METHODS: The effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI) fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high performance liquid chromatography method and the pharmacokinetic parameters were calculated based on a statistical moment theory was also performed in rats. RESULTS: CM administered via iv injection had a therapeutic effect on RA similar to methotrexate. CM-Ns with a diameter of approximately 150 nm were successfully prepared, and the drug was well encapsulated into the Ns without degradation in simulated GI conditions. The area under the curve (AUC) and Cmax for the CM-Ns were more than threefold greater than those for the suspensions; moreover, similar decreases in the levels of TNF-α and interleukin-1β in both synovial fluid and blood serum were obtained from oral administration of CM-Ns and iv injection. CONCLUSION: CM was an effective antiarthritic agent, and the present N formulation appeared to be a promising system that allowed RA therapy with CM to be converted from iv to oral administration.
26203828 Efficacy and Safety of Rituximab in Systemic Lupus Erythematosus and Sjögren Syndrome Pat 2015 Aug OBJECTIVE: Recent studies suggested a potential of rituximab (RTX) in treating autoimmune thrombocytopenia (AITP) secondary to autoimmune diseases. In this study, we retrospectively evaluated the efficacy and safety of RTX therapy in patients with refractory AITP secondary to systemic lupus erythematosus (SLE) and Sjögren syndrome (SS). METHODS: Twenty-one SLE and/or SS patients with treatment-resistant AITP were treated once or repeatedly with RTX at the Rheumatology Clinic Renji Hospital, during the period March 2012 to June 2014. Clinical and laboratory variables recorded at every follow-up visit were analyzed. RESULTS: The median age of all patients was 37.05 ± 3.15 years (range, 13-67 years; 20 female and 1 male). The median AITP duration before RTX treatment was 5.46 years. Previous treatments of 21 patients included immunosuppressive agents such as corticosteroids (n = 19), cyclosporine (n = 9), mycophenolate mofetil (n = 2), methotrexate (n = 3), cyclophosphamide (n = 2), vincristine (n = 3), and hydroxychloroquine (n = 15), and 7 patients received concomitantly intravenous immunoglobulin therapy. Two patients had undergone splenectomy without improvement. Seventeen patients (80.95%) were treated repeatedly with RTX during the follow-up period. The overall response rate to RTX treatment (including complete response, 52.38%; partial response, 28.57%) was 80.95%. A significant increase (P < 0.05) of platelet counts was seen after 1 month (median, 32.24 × 10/mL vs 66.53 × 10/mL). Relapses occurred mostly during the first 9 months, and maintaining duration of response was 10.27 months (range, 2-17 months) on average after the first RTX infusion. Antiplatelet antibodies, especially IgG isotype, decreased significantly (P < 0.05) after RTX treatment. No adverse effects were observed among 15 patients (71.4%); however, 2 cases died of severe pneumonia, and another developed lymphoma. CONCLUSIONS: Rituximab is an additional potent therapeutic treatment option for SLE and SS patients with AITP refractory to conventional immunosuppressive treatments. For most patients, RTX was safe and well tolerated.
27059799 The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a P 2016 Sep OBJECTIVE: To evaluate the efficacy of clazakizumab, a monoclonal antibody with high affinity and specificity for the interleukin-6 (IL-6) cytokine, in psoriatic arthritis (PsA). METHODS: In this randomized, double-blind, placebo-controlled, dose-ranging study (ClinicalTrials. gov identifier: NCT01490450), patients with active PsA and an inadequate response to nonsteroidal antiinflammatory drugs were randomized (1:1:1:1) to receive subcutaneous placebo or clazakizumab 25 mg, 100 mg, or 200 mg every 4 weeks, with or without methotrexate. The primary end point was the response rate according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 16, with secondary efficacy end points at weeks 16 and 24. RESULTS: A total of 165 patients were randomized. At week 16, the ACR20 response rate was significantly higher with clazakizumab 100 mg versus placebo (52.4% versus 29.3%; P = 0.039). ACR20 response rates at week 16 were 46.3% with clazakizumab 25 mg (P = 0.101 versus placebo) and 39.0% with clazakizumab 200 mg (P = 0.178 versus placebo). ACR50/ACR70 response rates were numerically higher with clazakizumab versus placebo at weeks 16 and 24. Compared with placebo, clazakizumab treatment significantly improved musculoskeletal manifestations (joint signs and symptoms, enthesitis, and dactylitis), with minimal improvements in skin disease, without clear evidence of a dose response. Clazakizumab was well tolerated. CONCLUSION: This is the first clinical trial of an IL-6-targeted therapy in PsA. Clazakizumab may be an effective treatment option for musculoskeletal aspects of PsA, but because of the lack of a dose response in this study, further studies are required to confirm the appropriate dose. The safety profile is consistent with the pharmacology of IL-6 blockade and prior clinical experience with this antibody in rheumatoid arthritis.
27381347 Methotrexate induced pneumatosis intestinalis under hemodialysis patient. 2017 Jan Pneumatosis intestinalis (PI) is a rare disorder characterized by the gas within the intestinal mucosa. This is the first report methotrexate (MTX) induced PI under hemodialysis (HD) patient. A 46-year-old man suffered rheumatoid arthritis and underwent HD at local HD center. After the initial induction of MTX, the patient showed epigastralgia and diarrhea. He was referred to our hospital and abdominal computed tomography showed significant large intestinal edema and free intraperitoneal air consistent with PI. Physicians should aware that MTX is contraindication drug for chronic kidney disease and high-flux HD may decrease MTX toxicity and oxidative stress, improving PI.
27867742 Dermoscopic appearance of an amelanotic mucosal melanoma. 2016 Oct BACKGROUND: Hypomelanotic or amelanotic melanomas are challenging to identify, especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal melanomas have been reported to be structureless zones with the presence of blue, gray, or white colors. CASE: A female in her seventies noted a new lesion on the inside of her right labia that first appeared two months prior. Her past medical history was significant for rheumatoid arthritis requiring ongoing treatment with methotrexate for 20 years and adalimumab for 10 years. After no response to two weeks of local treatment for suspected herpes simplex infection, her gynecologist performed a skin biopsy. Based on the histopathological diagnosis of an amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to dermatology for further assessment. Polarized dermoscopy revealed a distinct asymmetric, sharply demarcated homogenous white papule (4 × 5 mm) as well as polymorphous vessels. CONCLUSION: Dermoscopy may aid in the diagnosis of amelanotic mucosal melanomas. Our case revealed a structureless white area and polymorphous vessels. Additional clues to the diagnosis were the advanced age of the patient and the clinical presentation of a new lesion.