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ID PMID Title PublicationDate abstract
21794647 [Anti-TNF drugs: New results on efficacy]. 2009 Apr Anti-TNF drugs have represented a great advancement in the treatment of rheumatoid arthritis since their introduction in the late 1990s. The development of these products has been very similar for etanercept, infliximab and adalimumab, the 3 approved TNF blockers for the treatment of RA. The first studies centered their attention on patients with active disease and refractory to several disease modifying treatments, finding very significant differences when compared to placebo or methotrexate in the ACR improvement scores. Trials in patients who had not been previously treated with methotrexate show less differences between anti-TNF and methotrexate, but becomes more significant when the two drugs are used combined. In this manuscript we analyze the results of the registry of anti-TNF studies with regard to other improvement indexes such as quality of life, reduction in cardiovascular risk, maintained efficacy through time and progression of joint erosions. We also contemplate the possibility of using lower doses than those authorized for rheumatoid arthritis and analyze factors related to a poor prognosis in patients refractory to methotrexate, which is currently the indication for the use of anti-TNF in RA accordiong to the SER consensus.
21794643 [Management of difficult clinical situations in patients with rheumatoid arthritis: Pregna 2009 Apr Rheumatoid arthritis does not produce special damaging effects on pregnancy and/or fetal health, without taking into account the different risks the diverse medications to which these patients are normally exposed. Globally, non-steroidal anti-inflammatory drugs (NSAID) do not seem to produce fetal alterations when taken during the first part of pregnancy, but their use in the third trimester is contraindicated because of the possibility of an early closure of the arteriovenous ductus. Steroids, such as prednisone, barely cross the placental barrier and can be used safely during pregnancy. With regard to the use of DMARDs during pregnancy, both methotrexate and leflunomide are contraindicated, although experience accumulated through involuntary pregnancies in rheumatic patients exposed to these drugs has not shown an increase in teratogenicity at the doses commonly employed for these diseases. Sulphasalazine or hidroxycloroquine can be used safely in pregnant patients and azathioprine and cyclosporin A do not seem to be teratogenic either, although the use of azathioprine is not recommended due to its mechanism of action. With respect to the use of biologic therapy during pregnancy, available data currently is limited to anti-TNF agents and does not seem to show noxious effects on the fetus nor on the progression of pregnancy. However, experience is still limited and the current recommendation is to avoid pregnancy while under treatment with these drugs.
20643120 Nimesulide improves the disease modifying anti-rheumatic profile of methotrexate in mice w 2010 Oct 10 Methotrexate is a disease modifying anti-rheumatic drug that is widely used for the treatment of rheumatoid arthritis. Nimesulide is a non-steroidal anti-inflammatory drug which is frequently used as adjuvant therapy for symptomatic alleviation of rheumatoid arthritis. In this study, we have evaluated the potential influence of nimesulide on the disease modifying anti-rheumatic properties of methotrexate using the collagen-induced arthritis model. Mice were immunized with collagen type II for the induction of arthritis and treated with methotrexate (2.5mg/kg) twice a week, nimesulide (20mg/kg) every other day or a combination of both drugs. Treatment started one week after the onset of arthritis until day 40. An arthritic index was used to compare the severity of arthritis between different treatments. In addition, articular hyperalgesia, joint stiffness, radiological deterioration and intra-articular leucocytic infiltration were evaluated. Methotrexate alone showed modest but significant analgesic and anti-inflammatory effects, and the effects of nimesulide were comparable. On the other hand, nimesulide significantly improved the disease modifying anti-rheumatic profile of methotrexate in terms of arthritic index and joint mobility. Furthermore, although nimesulide failed to show any radiological evidence of articular protection, it significantly improved methotrexate-induced joint protection as judged by X-ray analysis.
20033412 Clarithromycin in adult-onset Still's disease: a study of 6 cases. 2010 Feb Adult-onset Still's disease (AOSD) is a rare rheumatological condition characterized by an acute systemic involvement. There are no treatment guidelines. Glucocorticoids (GC), methotrexate (MTX), cyclosporin A and biologic agents have been successfully used, often in association. We treated six cases of AOSD with clarithromycin (CM) in combination with low-mild dose of GC and MTX. Four of them were not responsive to high-dose GC added to DMARDs, while two of them were treated with low-mild dose of GC added to CM from the beginning. CM, 500 mg b.i.d., was added to a mild-low dose of GC and to MTX. The dose of the drugs was reduced (and stopped where possible) following clinical and laboratory parameters. ACR criteria were used to assess clinical improvement. At 6 months 5 patients reached ACR 70% and could stop any therapy in 6-18 months; 1 continued chronic therapy with low-dose GC added to CM and MTX to maintain ACR 50%. CM can be a useful drug for the treatment of AOSD, even in patients not responsive to high-dose GC and DMARDs. No definitive conclusion can be drawn based on the present study.
20704609 A case of refractory adult-onset Still's disease treated with anakinra. 2010 Aug Adult-onset Still's disease (AOSD) often presents both a diagnostic and a therapeutic challenge. We report a 40-year-old Chinese woman, in whom multiple adjustments of drug combinations were required before successful control of the patient's disabling symptoms. The patient failed multiple therapies including non-steroidal anti-inflammatory drugs, glucocorticoid, methotrexate (MTX), cyclosporine, leflunomide and infliximab. Treatment was complicated by hyperglycemia, glucocorticoid-induced osteoporosis, worsening hypertension and vaginal candidiasis. She suffered recurrent hospitalisation for active disease, developed carpal joint erosions and lost her employment over the course of 1 year. In view of refractoriness to multiple conventional therapies, anakinra was initiated in combination with MTX with a rapid and sustained improvement in clinical and laboratory parameters over 12 months. However, radiographic damage ensued despite aggressive therapies.
20827446 Combined methotrexate and coenzyme Q₁₀ therapy in adjuvant-induced arthritis evaluated 2010 Rheumatoid arthritis is a common severe joint disease that affects all age groups, it is thus of great importance to develop new strategies for its treatment. The aim of the present study was to examine the combined effect of coenzyme Q₁₀ (CoQ₁₀) and methotrexate (MTX) on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritis (AA) was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experiments included healthy animals, arthritic animals not treated, arthritic animals treated with CoQ₁₀, with methotrexate, and with a combination of CoQ₁₀ and methotrexate. The two latter groups received a daily oral dose of 20 mg/kg b.w. of CoQ₁₀, either alone or with methotrexate in an oral dose of 0.3 mg/kg b.w. twice a week. We found that CoQ₁₀ potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect of methotrexate on the level of oxidation of proteins (suppression of protein carbonyl level in plasma) as well as lipoperoxidation (suppression of levels of HNE-adducts and MDA-adducts to plasma proteins). The same effect was observed for plasmatic levels of CoQ₉ and IL-1α, and partially also for γ-glutamyltransferase activity assessed in joints and spleen. Moreover, the combination therapy improved the functionality of peripheral blood neutrophils in AA, with a balancing effect on the immunosuppression caused by MTX monotherapy. In summary, combined administration of CoQ₁₀ and methotrexate suppressed arthritic progression in rats more effectively than did MTX alone. This finding may help improve treatment of rheumatoid arthritis.
19893395 Type two or localized endobronchial non-Hodgkin lymphoma. 2009 Oct We present chest x-ray, chest CT, and FDG PET images of a patient diagnosed with endobronchial lymphoma. The commonly involved thoracic structures in non-Hodgkin lymphoma are mediastinal lymph nodes. Non-Hodgkin lymphoma involving the tracheobronchial tree is rare. Localized primary endobronchial lymphoma confined to the tracheobronchial tree with no dissemination classified as type-2 is extremely rare. This is a report describing the type-2 endobronchial DLBCL. The patient also had a history of rheumatoid arthritis and was treated with methotrexate for 10 years. The other interesting aspect of this case is its association with rheumatoid arthritis and methotrexate treatment. Although there are reports documenting this type of association in the literature, there is almost no documented evidence of this association specifically with type-2 endobronchial non-Hodgkin lymphoma.
21044454 Use of methotrexate in adult-onset Still's disease. 2010 Sep Adult-onset Still's disease, a febrile, multisystem rheumatic disease, has variable outcomes. Some patients experience remission after a single or multiple inflammatory episodes, while others progress to a chronic course with substantial joint destruction. Although no controlled clinical trials with immunosuppressive agents in this disease have been reported, a number of small uncontrolled studies and case reports describe the use of methotrexate therapy. Methotrexate has shown efficacy for the control of systemic and articular symptoms and its favourable safety profile appears similar to that seen in other rheumatic diseases, when for this indication. The combination of methotrexate and corticosteroids has, over the years, become the first step in the standard of care in adult-onset Still's disease. If the response to this treatment is incomplete, additional therapies, such as biologic agents may be appropriate.
20460033 Decreased recent thymus emigrant number in rheumatoid factor-negative polyarticular juveni 2010 May OBJECTIVES: To determine TCR excision circle (TREC) levels, a marker of recent thymic emigrants, in the peripheral lymphocyte pool of rheumatoid factor-negative (RFØ) polyarticular juvenile idiopathic arthritis (JIA) children. METHODS: We studied TREC levels in peripheral blood mononuclear cells (PBMC) in 30 RFØ polyarticular JIA children with active disease and in 30 age- and gender-matched healthy controls. Signal-joint TREC concentration was determined by real-time quantitative-PCR as the number of TREC copies/microg PBMC DNA gauged by a standard curve with known number of TREC-containing plasmids. RESULTS: TREC levels in PBMC were significantly lower in JIA (4.90 +/- 3.86 x 104 TRECs/microg DNA) as compared to controls (10.45 +/- 8.45 x 104 TRECs/microg DNA, p=0.001). There was an inverse correlation between age and TREC levels in healthy children (r=-0.438, p=0.016) but not in JIA. No clinical association was observed between TREC levels and disease activity and use of oral steroids and methotrexate. CONCLUSIONS: The finding of decreased PBMC TREC levels in RFØ polyarticular JIA children is consistent with a low proportion of recent thymus emigrants. This may interfere with the equilibrium between populations of polyclonal and naïve T cells versus oligoclonal memory auto-reactive T cells and, therefore, may hinder the maintenance of immune tolerance in this disease.
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.
21044444 Use of methotrexate in undifferentiated arthritis. 2010 Sep The prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA and based on the safety profile of a course of methotrexate for 30-90 days, many clinicians consider using methotrexate in this patient category using the "n of 1" trial principle. During the last few years, more data on interventions in UA have become available that provide guidance in the prescription of drugs to UA patients.
20346888 Cotton wool spots as an indicator of methotrexate-induced blood dyscrasia. 2010 Apr BACKGROUND: The disease-modifying antirheumatic drug methotrexate (MTX) is the treatment of choice for many patients with rheumatoid arthritis. Systemic toxicity in MTX use is well documented. Side effects such as pancytopenia, myelosuppression, hepatotoxicity, and pulmonary toxicity may be life-threatening. Various ocular effects with methotrexate use have been reported; however, to the best of our knowledge, this is the first case documenting cotton wool spots as the presenting feature of systemic MTX toxicity. CASE REPORT: A 52-year-old woman presented for a routine ocular examination. Medical history was significant for rheumatoid arthritis and treatment with methotrexate for 11 years. She reported missing her most recent rheumatology follow-up examination. Fundus examinations found progressive cotton wool spots in both eyes. Systemic blood workup found severe pancytopenia (reduced white blood cell, red blood cell, and platelet counts). The MTX was tapered, cotton wool spots resolved, and the blood results normalized. CONCLUSION: Patients using MTX typically are monitored for adverse effects at scheduled intervals by their prescribing physician. Patients taking MTX and presenting with ischemic retinal findings warrant investigation for pancytopenia. Prompt workup and communication with the patient's prescribing doctor may be life-saving.
21794638 [Biologics as first line therapy in the treatment of rheumatoid arthritis. A posture a fav 2009 Apr Changes in diagnosis and treatment of rheumatoid arthritis oblige us to question clinical practice. Evidence demonstrates that the combination of biologics and methotrexate in rapid increments leads to larger remission rates than methotrexate alone. The combination has a faster clinical response in activity, physical function, quality of life, fatigue and sleep. But the most significant effect of biologics is on radiographic progression. The reduction in radiological damage has a spectrum that goes from anti-TNF+methotrexate to anti-TNF monotherapy, being less with methotrexate, and independent from improvement in activity; it occurs with all of the anti-TNF drugs and with other targets with different mechanisms of action (anti-CD20, T cell costimulation inhibitors and anti IL-6). The clinical significance of this finding will be seen in the future, when more is known of its impact on the poor outcomes of RA patients. Because methotrexate is an excellent drug, it seems madness to say that all patients should receive biologics+methotrexate, but it is reasonable to consider that a subgroup must receive them from the start. The American College of Rheumatology recommends their use in patients with RA of less than 6 months since onset, with no previous exposure to methotrexate, persistent and elevated activity (<3 months) and poor prognostic factors or those with persistent and elevated activity (3-6 months) independent of poor prognostic factors, and if the patient "has insurance". A final thought would be: Is there a new treatment pyramid which has cost at its base now?
19493332 Locomotion and muscle mass measures in a murine model of collagen-induced arthritis. 2009 Jun 3 BACKGROUND: Rheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and can in part be explained by a decreased physical activity. The murine collagen induced arthritis (CIA) model has been proven to be a useful model in RA research since it shares many immunological and pathological features with human RA. The present study explored the interactions between arthritis development, locomotion and muscle mass in the CIA model. METHODS: CIA was induced in male DBA/1 mice. Locomotion was registered at different time points by a camera and evaluated by a computerized tracing system. Arthritis severity was detected by the traditionally used semi-quantitative clinical scores. The muscle mass of the hind-legs was detected at the end of the study by weighing. A methotrexate (MTX) intervention group was included to study the applicability of the locomotion and muscle mass for testing effectiveness of interventions in more detail. RESULTS: There is a strong correlation between clinical arthritis and locomotion. The correlations between muscle mass and locomotion or clinical arthritis were less pronounced. MTX intervention resulted in an improvement of disease severity accompanied by an increase in locomotion and muscle mass. CONCLUSION: The present data demonstrate that registration of locomotion followed by a computerized evaluation of the movements is a simple non invasive quantitative method to define disease severity and evaluate effectiveness of therapeutic agents in the CIA model.
20137605 [Characteristics of patients with primary Sjögren's syndrome and non-Hodgkin's lymphoma: 2009 Oct 27 OBJECTIVE: To characterize the clinical patterns of expression, laboratory serologic parameters and lymphomatous histological characteristics in patients with primary Sjögren's syndrome (pSS) who subsequently developed non-Hodgkin's lymphoma (NHL). METHODS: The authors analyzed 9 pSS patients (8 females, 1 male) who developed NHL. Five patients had received glucocorticoids, four of whom had received at least one immunosuppressive drugs (methotrexate, glucosidorum tripterygll totorum, cyclophosphamide and imuran). A protocol form was used to record the main characteristics of pSS and NHL. RESULTS: Eight patients fulfilled the American-European Consensus Criteria (AECC). The main SS manifestations were painless parotid enlargement (n = 7), six of whom were unilateral; the main immunologic features were positive rheumatoid factor (RF) in all examined patients and hyperimmunoglobulinemia (n = 7). The main manifestations of NHL were splenomegaly (n = 7) and lymphadenopathy (n = 5). The main histological subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma (n = 4) and diffuse large B cell lymphoma (n = 2). None of the patients with MALT lymphoma had a nodal primary location. Eight patients had an extranodal primary location, most frequently in salivary gland (n = 4) and lung (n = 4). CONCLUSION: Patients with pSS and NHL are clinically characterized by a high frequency of painless unilateral parotid enlargement, splenomegaly, lymphadenopathy, an immunologic pattern dominated by the presence of high-titer RF and hyperimmunoglobulinemia, a predominance of MALT lymphomas and an elevated frequency of primary extranodal involvement.
20492818 Diffuse large B-cell lymphoma with lung involvement in a psoriatic arthritis patient treat 2010 May 15 Non-Hodgkin lymphoma (NHL) occurs in the setting of methotrexate (MTX) therapy for rheumatoid arthritis. However, it has been very rarely reported in subjects with psoriatic arthritis treated with MTX. We report here a case of a 70-year-old woman with psoriatic arthritis who presented with bilateral lung infiltrates, pleural effusion, splenomegaly, and inguinal lymphadenopathy during treatment with MTX. The diagnosis of diffuse large B-cell lymphoma was made by analysis of the pleural fluid via thoracentesis and biopsy of an enlarged inguinal lymph node. Clinicians should consider the possibility of a NHL complicating psoriasis and with MTX therapy in order to prevent treatment delays.
19771179 Epstein-Barr-Virus-Infected CD15 (Lewis X)-Positive Hodgkin-Lymphoma-Like B Cells in Patie 2009 Sep 7 Patients with rheumatoid arthritis (RA), especially those who are treated with methotrexate (MTX), might have an increased risk of Hodgkin lymphoma (HL), a malignancy that is associated with Epstein-Barr virus (EBV). Here we describe a monoclonal EBV-infected B-lymphoblastoid cell line (LCL) called TKS-1 that was established from cells that spontaneously converted from an MTX-treated RA patient. TKS-1 has properties similar to HL cells and it is distinctly different from control LCLs established from normal individuals. TKS-1 cells express the HL -associated surface markers CD15 and CD30 (Takei et al. 1989). Like Hodgkin Reed-Sternberg (H-RS) cells of EBV-positive HL, TKS-1 cells express EBNA1 mRNA transcribed from the Qp promoter of the virus, whereas control LCLs use the Cp or Wp promoter to transcribe mRNA. TKS-1 cells can proliferate in an anchorage-independent manner and possess a cloning efficiency comparable to that of the Burkitt lymphoma (BL) line Raji. In addition, two EBV-positive LCLs established by cocultivated CD34+ cells isolated from the bone marrow of patients with RA and peripheral blood B lymphocytes from a healthy EBV-seronegative individual also expressed CD15. These results indicate that EBV-infected B-lymphoblastoid cells from patients with RA tend to acquire properties similar to HL cells.
20734215 A case of refractory adult-onset Still's disease successfully controlled with tocilizumab 2010 Dec Adult-onset Still's disease (AOSD) is an uncommon systemic inflammatory disease of unknown aetiology. Up to 80% of AOSD cases can be controlled with corticosteroids; however, reports on those unresponsive to corticosteroids, conventional disease modifying drugs and biological agents, including anti-IL1 inhibitors, are emerging. We present a case of AOSD with severe poylarthritis unresponsive to corticosteroids, methotrexate, anakinra and etanercept, but successfully stabilised with a humanized monoclonal anti-IL-6 receptor antibody, tocilizumab, administered once monthly. Thereafter, we compare our case with case reports available in the literature and suggest that for anakinra refractive AOSD patients with arthritis, tocilizumab could be the drug of choice.
19826925 Treatment of adjuvant-induced arthritis with the combination of methotrexate and probiotic 2009 A certain relationship was observed between the gastrointestinal system, arthritis and immune system. Patients with rheumatoid arthritis have an altered microflora composition and disturbed intestinal defensive barrier. Effect of probiotic bacteria (Colinfant; COL) with known favorable effect on intestinal microflora was determined on the methotrexate (MTX) treatment of adjuvant arthritis. Rats with adjuvant arthritis were administered methotrexate 0.5 mg/kg body mass 2-times weekly per os, COL 1 mL/kg body mass every second day per os, and a combination of MTX+COL for a period of 28 d from the immunization. Levels of serum albumin, body mass, changes in hind paw swelling, and arthrogram score were estimated in rats as variables of inflammation and destructive arthritis-associated changes. Treatment with MTX, as well as with the combination treatment with MTX+COL significantly inhibited both inflammation and destructive arthritis-associated changes. The combination treatment inhibited both the hind paw swelling and arthrogram score more remarkably than MTX alone; on the other hand, the difference between combination treatment and MTX alone was not significant. Treatment with COL alone had no effect on adjuvant arthritis in rats. Colinfant can increase the preventive effect of MTX treatment in rat adjuvant arthritis by improving its antiarthritic effects.
21794714 [Pharmacoeconomic analysis of Metoject(®) in the treatment of rheumatoid arthritis in Spa 2010 Jul OBJECTIVES: The aim of this study was to compare the clinical and economic consequences of using subcutaneous methotrexate (Metoject(®)) with respect to oral methotrexate in the management of rheumatoid arthritis (RA) in Spain. METHODS: A cost-effectiveness analysis was performed to compare early treatment of RA using a Markov model. The model allowed us to estimate long term efficacy of RA treatment based on data from the literature and expert opinion, and to combine this data with costs of managing RA in Spain. The perspective of the study was from the National Health System point of view, using a time horizon of 5 years and patient lifetime. All costs were expressed in 2009 euros and a 3% discount rate was applied. RESULTS: The cost (only pharmacologic costs) per quality-adjusted life year (QALY) gained with Metoject(®) went from 25,173 to 35,807€ at 5 years and from 19,056 to 25,351€ for patient lifetime. When direct costs in RA treatment were considered, it was observed that cost-effectiveness at 5 years went from 29,682 to 42,175€/QALY gained, and for patient lifetime from 22,514 to 29,848€/ QALY gained. CONCLUSIONS: Additional costs of Metoject(®) with respect to oral methotrexate would be offset by their improved effectiveness, expressed in QALY, showing that Metoject(®) could be a cost-effective treatment option for RA in the Spanish Health System assuming a spanish threshold.