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ID PMID Title PublicationDate abstract
22021998 Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuva 2011 Sep OBJECTIVE: To evaluate the concomitant administration of methotrexate and curcumin for antiarthiritic activity in rats. MATERIALS AND METHODS: Arthritis was induced in rats following a single subplantar injection of Freund's complete adjuvant (0.1 ml). Rats were divided into six groups of six animals each. Group I and II were control injected with saline and Freund's complete adjuvant (0.1 ml), respectively. Group III arthritic rats were treated with curcumin (100 mg/kg, i.p.) on alternate days. Group IV received methotrexate (MTX) (2 mg/kg, i.p.) once in a week. Group-V and VI were treated with MTX (1 mg/kg, i.p.) once in a week and after 30 min received curcumin (30 mg/kg and 100 mg/kg, thrice a week, i.p.) from 10(th) to 45(th) days, respectively. Body weight and the paw volume was measured on 9(th), 16(th), 23(rd), 30(th), 37(th), and 45(th) days. Determination of complete blood cell counts, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration was determined on the 46(th) day. RESULTS: An improvement in body weight and a significant (P < 0.05) reduction in arthritis was observed with the combination treatment as compared to the positive control. A significant improvement in the hematological profile was also observed in rats treated with curcumin and methotrexate. CONCLUSION: The study showed a significant anti-arthritic action and protection from hematological toxicity with the combination treatment of methotrexate and curcumin.
22124545 The rapid efficacy of abatacept in a patient with rheumatoid vasculitis. 2012 Aug We report a case of rheumatoid vasculitis (RV) that responded well to abatacept, a cytotoxic T lymphocyte-associated antigen 4 (CTLA4)-immunoglobulin fusion protein. A 38-year-old woman developed RV despite treatment with methotrexate and tumor necrosis factor (TNF) inhibitors. The effects of steroid therapy, immunoabsorption plasmapheresis, and interleukin-6 inhibitor were insufficient, however, administration of abatacept rapidly improved her clinical symptoms with almost normalization of the immunological findings. This is the first published case report of the successful treatment of RV with abatacept.
20340022 Good clinical response to methotrexate treatment in a patient with fibroblastic rheumatism 2012 Jun Fibroblastic rheumatism (FR) is a rare disease first described by Chaouat (in Rev Rhum Mal Osteoartic 47:345-351, 1980) and is characterized by a combination of rheumatologic and dermatological manifestations. Rheumatologic features are symmetrical polyarthralgias with joint stiffness, associated with cutaneous nodules and sclerodactyly. Histology shows an increased number of fibroblasts and a marked dermal fibrosis. A large number of treatments have been tried, but all of them have shown an unpredictable effect on FR. We report a Brazilian case of FR showing a good clinical response to methotrexate treatment. This drug may be considered an effective treatment in FR.
22221757 Anti-arthritis activity of roots of Hemidesmus indicus R.Br. (Anantmul) in rats. 2012 Feb OBJECTIVE: To investigate the protective effects of hydroalcoholic and its fractions from roots of Hemidesmus indicus on arthritis in in vitro models of rodents. METHODS: Preliminary phytochemical analysis and thin-layer chromoatography were performed to analyze constituents of hydroalcoholic extract and its three fraction namely ethyl acetate fraction, chloroform fraction and residual fraction of root of Hemidesmus indicus. Arthritis rats models were established by Complete Freund's Adjuvant. The parameters including paw edema, body weight, arthritic index, erythrocyte sedimentation rate, serum rheumatoid factor, serum C-reactive protein, serum nitrite level, and histopathology of synovial joints were observed. Methotrexate was taken as positive control. RESULTS: Rats treated with hydroalcoholic extract (450 mg/kg, p.o.), ethyl acetate (75 mg/kg, p.o.), chloroform (60 mg/kg, p.o) and residual fractions (270 mg/kg, p.o.), showed significant decrease in physical and biochemical parameters compared with arthritic model rats. Hydroalcoholic extract and its ethyl acetate fraction of Hemidesmus indicus showed significantly higher anti-arthritic activity than chloroform and residual fraction. Histopathological analysis demonstrated that both of hydroalcoholic extract and its ethyl acetate fraction had comparable anti-arthritic activity with methotrexates. CONCLUSIONS: The present study suggests that Hemidesmus indicus has protective activity against arthritis and the activity might be attributed to presence of terpenoid in hydroalcoholic extract, as well as in ethyl acetate fraction.
22701193 Stabilization of bilateral progressive rheumatoid corneal melt with infliximab. 2012 Purpose. To report the use of infliximab in the rapid stabilization of a case of progressive, bilateral rheumatoid peripheral ulcerative keratitis (PUK) that failed to respond to conventional immunosuppressive therapy. Methods. A single interventional case report. Results. A patient with rheumatoid arthritis presented with bilateral PUK following a 2-month history of ocular discomfort and redness. His systemic prednisolone (PDN) and methotrexate (MTX) were increased and, despite an initial favorable response, bilateral recurrent corneal perforations ensued. Both eyes underwent cyanoacrylate glue repair, amniotic membrane transplantation (AMT), and penetrating keratoplasty (PKP). Recurrence of the disease and bilateral perforations of the second PKP in both eyes prompted administration of intravenous infliximab immediately after the fourth PKP. The disease activity rapidly settled in both eyes, and at eighteen-month followup, after 12 infliximab infusions, the PUK remains quiescent with no further graft thinning or perforation. Conclusion. Infliximab can be used to arrest the progression of severe bilateral rheumatoid PUK in cases that are refractory to conventional treatment.
21723947 The road forward: the scientific basis for tetracycline treatment of arthritic disorders. 2011 Dec The potential role of a collagenase inhibitor for treatment of arthritis was recognized almost immediately after the discovery of vertebrate collagenase. Yet despite vast efforts from the pharmaceutical industry, no such drug has been approved for such use by a regulatory agency. Although two semisynthetic antimicrobial tetracyclines, viz. minocycline and doxycycline, have been shown to have modest clinical benefits in over a dozen trials in rheumatoid arthritis, neither drug is in widespread use. The almost universal use of methotrexate and the rapid development of potent biologic agents have eclipsed the potential usage of TETs for RA. Ironically, it is in osteoarthritis, where there has only been one clinical trial which essentially failed, that the best potential exists for use of an MMP-inhibiting TET.
31643544 Methotrexate. 2012 Methotrexate is an antineoplastic and immunosuppressive agent widely used in the therapy of leukemia, lymphoma, solid tumors, psoriasis and rheumatoid arthritis. When given in high intravenous doses, methotrexate can cause acute elevations in serum enzymes, and long term methotrexate therapy has been associated with frequent but mild elevations in serum liver enzymes and, more importantly, with development of chronic liver injury, progressive fibrosis, cirrhosis and portal hypertension.
22751600 Adalimumab in psoriatic arthritis. 2012 Jul Open prospective studies and randomized controlled trials (RCT) have shown the short-term efficacy of adalimumab (ADA) in psoriatic arthritis (PsA) and psoriasis. ADA effectively treated all varied musculoskeletal manifestations characteristic of PsA, including peripheral arthritis, spinal disease, enthesitis, and dactylitis. ADA significantly inhibited structural changes on radiographs, lessened disability, and improved quality of life in patients with active PsA. One study showed the efficacy of 24-week ADA therapy on bone marrow edema and erosions, as measured by magnetic resonance imaging. The clinical and radiographic efficacy of ADA demonstrated during short-term treatment was sustained during longterm treatment. ADA was generally well tolerated and its safety profile was similar to that reported in studies of ADA in rheumatoid arthritis. Overall, ADA has a favorable risk-benefit profile in PsA. The combination of ADA and cyclosporine seems to be more effective than ADA monotherapy in patients with active PsA and inadequate response to methotrexate; however, this observation must be confirmed in RCT.
23253241 Adult onset Still's disease: experience from a tertiary care rheumatology unit. 2012 Dec BACKGROUND: Adult-onset Still's disease (AOSD) is a rare chronic inflammatory disorder presenting with prolonged fever and polyarthritis. METHODS: Retrospective study of patients with AOSD, seen between 1992 and 2009 at a large tertiary care hospital. RESULTS: Twenty-nine patients (18 female) with median age at onset of 28 (17-58) years were seen. The clinical features included fever in 29, inflammatory polyarthritis in 26, sore throat in eight and typical rash in 13. Lymphadenopathy was present in 15, hepatomegaly in 15, splenomegaly in 13 and serositis in five patients. Anemia was present in 22, neutrophilic leukocytosis in 28 and thrombocytosis in 13 patients. Acute phase reactants were elevated in all. Fifteen patients had transaminitis. Low titer antinuclear antibodies were present in 6/28 patients. On median follow-up (25 patients) of 23.7 months (range: 3-84) one patient had self-limited or monocyclic pattern, eight had polycyclic and 16 had chronic articular pattern. All patients received non-steroidal anti-inflammatory drugs and 25 received methotrexate and/or prednisolone. During the course 14 patients had remission and of these six were in remission on drugs at last follow-up. One patient received tociliziumab and was in clinical remission. One patient developed macrophage activation syndrome and one had atlanto-axial dislocation. Three patients developed tuberculosis and two died of infection associated with immunosuppression. CONCLUSION: AOSD is an uncommon disorder with 1-2 patients seen at a large tertiary care rheumatology unit. Overall AOSD has a fair outcome with significant morbidity and most needing long-term therapy with steroids and methotrexate.
22896026 The Canadian Early Arthritis Cohort (CATCH): patients with new-onset synovitis meeting the 2012 Nov OBJECTIVE: Our objective was to describe characteristics of Canadian patients with early arthritis and examine differences between those fulfilling 1987 and 2010 rheumatoid arthritis (RA) classification criteria. METHODS: The Canadian Early Arthritis Cohort (CATCH) is a national, multicenter, observational, prospective cohort of patients with early inflammatory arthritis, receiving usual care, recruited since 2007. Inclusion criteria include age > 16 years; symptom duration 6-52 weeks; swelling of ≥ 2 joints or ≥ 1 metacarpophalangeal/proximal interphalangeal joint; and 1 of rheumatoid factor ≥ 20 IU, positive anticitrullinated protein antibodies (ACPA), morning stiffness ≥ 45 min, response to nonsteroidal antiinflammatory drug, or positive metatarsophalangeal joint squeeze test. Data from patients enrolled to March 15, 2011, were analyzed. RESULTS: In total, 1450 patients met the eligibility criteria (1187 were followed). At baseline, mean age was 53 ± 15 years, symptom duration was 6.1 ± 3.2 months, Disease Activity Score (DAS28) was 4.9 ± 1.6, Health Assessment Questionnaire-Disability Index was 1.0 ± 0.7. Forty-one percent (n = 450) of patients had moderate (3.2 < DAS28 ≤ 5.1) and 46% (n = 505) had high (DAS28 > 5.1) disease activity; 28% of those with baseline radiographs (n = 250/908) had radiographic evidence of erosions. ACPA status was available for 70% (n = 831) of patients; 55% (n = 453) tested positive. Sixty percent (n = 718) of patients were treated with methotrexate (MTX) initially. Of 612 patients without erosions, 63% and 83% fulfilled 1987 and 2010 RA classification criteria, respectively. Seventy-three percent (n = 166) of those who did not fulfill 1987 criteria were newly identified by the 2010 criteria. These patients had less severe disease and more were MTX-naive compared to those satisfying the 1987 criteria. Forty-seven percent of all patients achieved remission at 1 year. CONCLUSION: Patients with early RA present with moderate high disease activity; < 50% achieve remission at 1 year, despite MTX treatment in the majority. The 2010 RA classification criteria identify more patients with RA who would previously have been designated as having undifferentiated disease. However, these patients have lower disease activity at the time of identification.
23018897 Chronopharmacology of mizoribine in collagen-induced arthritis rats. 2012 We previously reported that higher therapeutic effects were obtained in rheumatoid arthritis (RA) patients and RA model animals when the dosing-times of methotrexate and tacrolimus were chosen according to the 24-h rhythms of the inflammatory response. Mizoribine (MZR) is an immunosuppressive agent and is used against RA in the same manner as methotrexate and tacrolimus. In this study, we examined whether a dosing-time dependency of the therapeutic effect of MZR could be detected in collagen-induced arthritis (CIA) rats. To measure C-reactive protein (CRP) and tumor necrosis factor (TNF)-α levels, blood was collected from CIA rats at different times. MZR was administered at two different dosing-times based on these findings and its effects and toxicity were examined. CRP and TNF-α concentrations in blood showed significant 24-h rhythms. The exacerbation of arthritis and excessive increase in leukocytes in CIA rats were markedly lower in the group treated with MZR at the dark phase than those of the group treated with MZR at the light phase. These findings suggest that the therapeutic index of RA therapy may be improved by administering MZR at a time in the day when the inflammatory reaction begins to activate.
22264340 The balance of expression of PTPN22 splice forms is significantly different in rheumatoid 2012 Jan 20 BACKGROUND: The R620W variant in protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with rheumatoid arthritis (RA). The PTPN22 gene has alternatively spliced transcripts and at least two of the splice forms have been confirmed to encode different PTPN22 (LYP) proteins, but detailed information regarding expression of these is lacking, especially with regard to autoimmune diseases. METHODS: We have investigated the mRNA expression of known PTPN22 splice forms with TaqMan real-time PCR in relation to ZNF592 as an endogenous reference in peripheral blood cells from three independent cohorts with RA patients (n = 139) and controls (n = 111) of Caucasian origin. Polymorphisms in the PTPN22 locus (25 SNPs) and phenotypic data (gender, disease activity, ACPA and RF status) were used for analysis. Additionally, we addressed possible effects of methotrexate treatment on PTPN22 expression. RESULTS: We found consistent differences in the expression of the PTPN22 splice forms in unstimulated peripheral blood mononuclear cells between RA patients and normal controls. This difference was more pronounced when comparing the ratio of splice forms and was not affected by methotrexate treatment. CONCLUSIONS: Our data show that RA patients and healthy controls have a shift in balance of expression of splice forms derived from the PTPN22 gene. This balance seems not to be caused by treatment and may be of importance during immune response due to great structural differences in the encoded PTPN22 proteins.
22143415 Methylene tetrahydrofolate reductase gene polymorphisms and their association with methotr 2012 Feb OBJECTIVE: A systematic review and a meta-analysis were conducted, to investigate the possible association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with adverse effects related to methotrexate (MTX). METHODS: A systematic literature search in PubMed retrieved a total of 44 studies (42 unique articles). Two polymorphisms were included in the meta-analysis: C677T and A1298C. Random effect models were used in the analysis. Odds ratios along with their 95% confidence intervals were computed to compare the distribution of alleles and genotypes between cases and controls. RESULTS: The analysis highlighted a significant association of C677T polymorphism with overall MTX toxicity, hepatotoxicity, hematological toxicity, and neurotoxicity. It also revealed an association with MTX toxicity in patients with rheumatoid arthritis. In contrast, a protective effect of C677T MTHFR polymorphism on acute graft-versus-host disease and on patients treated with hematopoietic cell transplantation was found. As for the A1298C polymorphism, a statistically significant association with overall MTX toxicity and a protective role of the polymorphism in rheumatoid arthritis patients was detected. CONCLUSION: These results indicate the association of MTHFR polymorphisms with MTX toxicity. However, further studies are needed to reveal the underlying biological mechanism of the association.
22906004 Management of temporomandibular joint arthritis in adult rheumatology practices: a survey 2012 Aug 20 BACKGROUND: The temporomandibular (TMJ) is frequently involved in juvenile idiopathic arthritis (JIA), however little is known about management of this joint once a patient transitions from pediatric to adult care and about how rheumatologists approach TMJ involvement in rheumatoid arthritis (RA). The objective of this project was to describe adult rheumatologists' approaches to the diagnosis and treatment of TMJ arthritis in adults with JIA or RA. FINDINGS: One hundred and eighteen rheumatologists responded to an online survey of adult rheumatologists in the United States and Canada. Respondents estimated that 1-25% of their patients with RA or JIA had TMJ arthritis. Respondents reported lower rates of MRI use (19%) and higher rates of use of splinting/functional devices (50%) than anticipated. Approximately 80% of respondents reported that their practice had a standardized approach to the evaluation of patients with TMJ arthritis. The most commonly used medical therapies were non-steroid anti-inflammatory drugs, anti-tumor necrosis factor alpha medications, and methotrexate. CONCLUSIONS: Despite the majority of respondents stating that their practices had a standardized approach to the diagnosis and treatment of TMJ disease, there nevertheless appeared to be a range of practices reported. Standardizing the evaluation and treatment of TMJ arthritis across practices may benefit both adult and pediatric patients.
22844292 Markers of treatment response to methotrexate in rheumatoid arthritis: where do we stand? 2012 Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, despite its efficacy and affordability, additional DMARDs or biologic agents are often required in order to achieve the recommended goals of low disease activity or remission. Although well tolerated by most, some patients develop important side effects such as cytopenias, gastrointestinal adverse events (stomatitis, nausea), or abnormal liver function tests, which may limit its use and may result in additional health care costs. Given the clinical implications of widespread use of MTX in RA, various studies have evaluated the role of potential biomarkers in predicting treatment effectiveness of MTX. These biomarkers include RBC MTX polyglutamate (PG) levels; genetic variation in genes from relevant biological and metabolic pathways; gene expression profiles; serum proteins. This paper provides an update on the current data regarding biomarkers of treatment response to MTX.
21677004 Bone health in adult men and women with a history of juvenile idiopathic arthritis. 2011 Aug OBJECTIVE: Our aim was to determine areal bone mineral density (BMD(a)) and disease-related factors linked with BMD(a) in adults with a history of juvenile idiopathic arthritis (JIA). METHODS: Men and women with a history of JIA attending a young adult rheumatology clinic in Newcastle, UK, underwent dual energy x-ray absorptiometry (DEXA) of the lumbar spine and total hip. Information was obtained about disease duration and subtype, previous treatment including corticosteroid and methotrexate therapy, and large-joint replacement. Subjects completed the modified Health Assessment Questionnaire (HAQ). Blood was taken for assessment of C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor (RF). RESULTS: Seventy-one women and 16 men, mean age 28.7 and 31.4 years, and mean disease duration 20.6 and 24.0 years, respectively, were studied. Mean BMD(a) was 0.982 (Z-score = -0.328; 95% CI -0.657, 0.001) and 1.028 g/cm(2) (Z-score = -0.251; 95% CI -1.266, 0.764) in women and men, respectively, at the spine and 0.817 (Z-score = -0.542; 95% CI -0.975, -0.109) and 0.857 g/cm(2) (Z-score = -0.176; 95% CI -2.323, 1.971) at the hip. After adjusting for age and sex, increasing HAQ score was associated with both lower spine BMD(a) and hip BMD(a). Compared with patients with oligoarticular disease, those with enthesitis-related arthritis had higher BMD(a) at the spine, while those with extended oligoarticular and polyarticular RF-negative disease had lower hip BMD(a). Oral corticosteroids and the presence of a large-joint replacement were associated with lower BMD(a) at both the spine and hip. CONCLUSION: There was a trend toward low BMD(a) in women with a history of JIA. These patients may be at risk of the complications of osteoporosis including fragility fractures and should be considered for targeted preventive measures.
28925305 Pneumocystis jirovecii pneumonia associated with etanercept treatment in patients with rhe 2012 Nov Objectives The association of anti-tumor necrosis factor therapy with opportunistic infections in rheumatoid arthritis (RA) patients has been reported. The goal of this study was to clarify the clinical characteristics and the risk factors of RA patients who developed Pneumocystis jirovecii pneumonia (PCP) during etanercept therapy. Methods We conducted a multicenter, case-control study in which 15 RA patients who developed PCP were compared with 74 RA patients who did not develop PCP during etanercept therapy. Results PCP developed within 26 weeks following the first injection of etanercept in 86.7% of the patients. All PCP patients presented with a rapid and severe clinical course and the overall mortality was 6.7%. Independent risk factors were identified using multivariate analysis and included age ≥ 65 years [hazard ratio (HR) 3.35, p = 0.037], coexisting lung disease (HR 4.48, p = 0.009), and concomitant methotrexate treatment (HR 4.68, p = 0.005). In patients having a larger number of risk factors, the cumulative probability of developing PCP was significantly higher (p < 0.001 for patients with two or more risk factors vs. those with no risk factor, and p = 0.001 for patients with one risk factor vs. those with no risk factor). Conclusion Physicians must consider the possibility of PCP developing during etanercept therapy in RA patients, particularly if one or more risk factors are present.
22751597 The actual role of therapy with traditional disease-modifying antirheumatic drugs in psori 2012 Jul Although several reviews and metaanalyses have shown lack of evidence of efficacy of traditional disease-modifying antirheumatic drugs (DMARD) in psoriatic arthritis (PsA), these drugs are very often used and are recommended by treatment guidelines around the world as first-line therapy for most patients with PsA. Some new investigations showed that higher doses of methotrexate (MTX) are more beneficial for patients with PsA with peripheral involvement. Also, observational studies have shown that retention of MTX for patients with PsA is comparable to that of patients with rheumatoid arthritis (RA), and that with MTX, remission is achievable by around 20% of patients with PsA. Sulfasalazine, leflunomide, and cyclosporine have also been shown to be effective in a small number of patients, although the overall effect on disease activity for these drugs is small. Although combination of anti-tumor necrosis factor agents with traditional DMARD is not mandatory in PsA as it is in RA, there is evidence that some extra benefit might be achieved when combinations are used, not only for the joints but for the skin. There is still room for the use of traditional DMARD in PsA, and for the time being, DMARD should still be considered as first-line therapy for most patients with PsA.
21786602 [Biological therapy in pediatric rheumatology]. 2011 This article presents the unique experience of Research Centre of Children's Health in the treatment of 438 children with juvenile rheumatoid arthritis using biological preparations, viz. infliximab (270), adalimumab (55), ethanercept (25), rituximab (74), and tocilizumab (34). It is shown that differential biological therapy, unlike treatment with classical immunodepressants (methotrexate, cyclosporine, leflunomide, etc.), permits to achieve clinico-laboratory remission in 70% and markedly decrease activity of the disease in 20% of the patients within 1 year after the onset. It is concluded that treatment with gene-engineered drugs improves the quality of life of the children and their families, normal growth and development of the patients and affects prognosis of this formerly incurable chronic autoimmune disease.
22690387 Psoriatic arthritis: treatment strategies using anti-inflammatory drugs and classical DMAR 2012 Jun 5 Psoriatic Arthritis (PsA) is a chronic inflammatory disease typically characterized by arthritis and psoriasis variably associated with other extra-articular manifestations. PsA has been considered a milder and less disabling disease compared with rheumatoid arthritis (RA), even if some studies showed that PsA had joint erosions and damage. In addition, about 20-40% of PsA patients have axial skeleton involvement that may lead to functional limitation and deformity. The treatment of PsA ranged from initial treatment with non-steroidal anti-inflammatory drugs (NSAIDs) to one or more disease-modifying anti-rheumatic agents (DMARDs) for the suppression of inflammation in patients with recalcitrant peripheral joint disease. In clinical practice, the most widely used DMARDs are methotrexate (level of evidence B), sulfasalazine (level of evidence A), leflunomide (level of evidence A), and ciclosporin (level of evidence B). However, the efficacy of these agents in inhibiting joint erosions has not been assessed in controlled studies. Finally, the effectiveness of DMARDs in treating enthesitis and dactylitis is controversial. The present paper revised the evidence-based results on treatment with "conventional" therapy for PsA. The revision was based on all the subsets of the diseases, namely the various manifestations of the articular involvement (peripheral, axial, enthesitis, dactylitis) as well as the skin and nail involvement.