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ID PMID Title PublicationDate abstract
16251389 Immune-related conditions and immune-modulating medications as risk factors for non-Hodgki 2005 Dec 15 In immunosuppressed or autoimmune disease states, disordered immune responses may lead to non-Hodgkin's lymphoma (NHL). In a US population-based case-control study of NHL (1998-2000), the authors collected personal histories of immune-related conditions and use of immune-modulating therapies as well as family histories of autoimmune conditions. The study included 1,321 NHL cases and 1,057 controls; only half received some questionnaire components. NHL was associated with Sjögren's syndrome (odds ratio (OR) = 13, 95% confidence interval (CI): 1.7, 100) and lupus (OR = 4.2, 95% CI: 1.2, 15). Two specific NHL subtypes were strongly associated with Sjögren's syndrome: salivary gland (OR = 290, 95% CI: 33, 2600) and marginal zone (OR = 75, 95% CI: 9.1, 610). NHL was less convincingly associated with receipt of an organ transplant (OR = 2.0, 95% CI: 0.4, 11). Other autoimmune conditions were too rare to evaluate or not associated with NHL. Corticosteroid use was unrelated to NHL (OR = 1.0, 95% CI: 0.8, 1.2), but methotrexate use was marginally associated (OR = 2.3, 95% CI: 0.7, 7.5). Family history of dermatomyositis was associated with NHL (7 cases vs. 0 controls, OR = infinite; two-sided p = 0.02), but dermatomyositis was absent in cases themselves. Family history of remaining conditions was unrelated to NHL. Results suggest that disordered immunity in some immune-related conditions can lead to NHL.
17006270 Epstein-Barr virus associated Hodgkin lymphoma in a 9-year-old girl receiving long-term me 2006 Sep We describe a case of Hodgkin lymphoma developing in a 9-year-old girl with polyarticular, rheumatoid factor-positive juvenile idiopathic arthritis treated with methotrexate (MTX), prednisone, and naproxen for 5 years. Pathologic and molecular analyses revealed that the Hodgkin cells contained Epstein-Barr virus and the viral DNA was monoclonal. She achieved complete remission after MTX withdrawal, chemotherapy, and radiation. To the best of my knowledge, this is the sixth report of Hodgkin lymphoma in patients with juvenile idiopathic arthritis receiving low dose MTX therapy.
16700080 Changes in use of disease-modifying anti-rheumatic drugs in Australia over the period 1992 2006 Jul PURPOSE: Evidence is growing that early use of disease-modifying anti-rheumatic drugs (DMARDs) and combinations of these drugs provide optimal care for people with rheumatoid arthirits. The aim of this study was to describe objectively the pattern of consumption of DMARDs in the Australian community (community-based prescribing, specialist and general practitioner) 1992-2004, and to compare this with prescribing patterns reported in other countries. METHOD: Dispensing statistics from the Pharmaceutical Benefit Scheme (PBS-Australia's universal prescription subsidy scheme) were analysed and temporal trends evaluated. Drug consumption was calculated as the number of dispensed defined daily doses (DDD)/1000 inhabitants/day (WHO ATC/DDD classification 2005). RESULTS: The consumption of DMARDs in the Australian community increased steadily from 2.6 DDD/1000 inhabitants/day in 1992 to 5.5 DDD/1000 inhabitants/day. Over the period 1992-2004, methotrexate (MTX) was the most commonly used DMARD (from 0.6 to 3.0 DDD/1000 inhabitants/day). Consumption of gold (parenteral and oral) and penicillamine declined during this time. The inclusion of leflunomide on the PBS in 2000 contributed to the increase in DMARD usage. CONCLUSION: Use of DMARDs within the Australian community has increased in recent years, coinciding with the change in guidelines for therapy for rheumatoid arthritis (RA) to earlier use of DMARDs and the more common use of combinations. This study used DDD methodology to quantify trends for DMARD consumption and these trends are broadly consistent with international prescribing patterns assessed using different methodologies.
16646003 A comparison of response criteria to evaluate therapeutic response in patients with juveni 2006 May OBJECTIVE: There are no validated criteria to evaluate clinical response in juvenile idiopathic arthritis (JIA). The purpose of this study was to compare 4 sets of criteria (2 from the American College of Rheumatology [ACR] and 2 from the European League Against Rheumatism [EULAR]) for clinical response evaluation in JIA patients treated with methotrexate and/or anti-tumor necrosis factor alpha drugs. METHODS: Seventy-five patients with JIA were evaluated at baseline and after 6 months of therapy with second-line drugs. Mean age at study onset was 12.8 years (range 2-32.9 years). Diagnoses were systemic JIA (n = 16), rheumatoid factor-positive JIA (n = 5), rheumatoid factor-negative JIA (n = 9), persistent oligoarticular JIA (n = 10), extended oligoarticular JIA (n = 33), and psoriatic arthritis (n = 2). Clinical response was evaluated with the ACR Pediatric 30 criteria and the ACR 20% response criteria (ACR20), and with the EULAR Disease Activity Score (DAS) and 28-joint DAS (DAS28). Patients with EULAR criteria responses of "good" or "moderate" were classified as responders. Responders and nonresponders according to the different criteria were then compared. RESULTS: For patients younger than 16 years, Cohen's kappa varied between 0.51 and 0.72, with a good-to-excellent reproducibility index for all comparisons, except for the DAS28/ACR20 comparison. The best agreement was obtained by comparing the DAS and the ACR Pediatric 30. For patients older than 16 years, the reproducibility index was good or excellent in only 2 cases, i.e., comparing the DAS and the ACR Pediatric 30 and comparing the DAS and the DAS28 (as expected). CONCLUSION: Our study shows a good agreement overall for the different criteria tested. The highest concordance was observed between the DAS and the ACR Pediatric 30, the lowest between the DAS28 and the ACR20. Our data suggest that the ACR Pediatric 30 criteria can be used also in adult patients affected by JIA, and that the original DAS can be an alternative to the ACR Pediatric 30 in both children and young adults with JIA.
15698518 Effect of varying types of anti-arthritic drugs on Th1 and Th2 immune responses in mice. 2005 Jan The present study was undertaken to study the effect of varying types of anti-arthritic drugs on Th1 and Th2 immune responses in mice. To immunize mice, ovalbumin (OVA) emulsified with complete Freund's adjuvant was injected s.c. at the base of the tail (day 0). Indomethacin (IND) as a non-steroidal antiinflammatory drug (NSAID), dexamethasone (DEX) as a steroidal antiinflammatory drug, methotrexate (MTX), auranofin (AUR), and D-penicillamine (D-PA) as an anti-rheumatic drugs were orally administrated daily from days 0 to 20. On day 21, anti-OVA IgG2a and interferon (IFN)-gamma as indicators of Th1 responses and anti-OVA IgG1 and interleukin (IL)-10 as those of Th2 responses were measured. Treatments with IND, DEX, MTX and AUR were followed by decreases in OVA-specific IgG and proliferation of spleen cells to the antigen. Treatments with IND, DEX, MTX and AUR inhibited both Th1 and Th2 immune responses, although the inhibitory effects of these drugs on the antigen-specific IgG2a and IFN-gamma production appeared to be greater than those on IgG1 and IL-10 production. D-PA failed to influence anti-OVA IgG, IgG2a and IgG1 production as well as IFN-gamma and IL-10 secretion. Administrations of all the drugs used resulted in suppression of antigen (OVA)-induced arthritis in mice which was associated with inhibition of anti-OVA IgG2a but not IgG1 production. These results suggest that anti-arthritic drugs including IND, DEX, MTX and AUR appear to suppress Th1 and, to a lesser extent, Th2 immune responses, and their anti-inflammatory effects on human rheumatoid arthritis might be at least in part explained by downregulation by these drugs of Th1 responses involved in the disease.
17101059 Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A3 ad 2006 Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A3 adenosine receptor (A3AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A3AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A3AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A3AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A3AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A3AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A2AAR and A3AR over-expression in paw cells from treated animals. Moreover, increased A3AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A3AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A3AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA.
16011443 Adalimumab: a review of side effects. 2005 Jul Adalimumab (Humira) is a human monoclonal TNF-alpha antibody that blocks the effects of TNF-alpha. It is administered by subcutaneous injection. It has been approved alone or in combination with methotrexate for the treatment of rheumatoid arthritis in the EU and US. Approval for its use for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis is expected in the near future. Its side effect profile is favourable when compared with traditional systemic treatments for these diseases. It does not require laboratory monitoring. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. There is a two-fold risk of serious infections with the use of adalimumab, as reported in the Premier trial. This risk should not be minimised in this way. It should not be used during periods of active infection. Its most notable infectious complication is the reactivation of tuberculosis. Tuberculosis screening should be according to country standards and may or may not include purified protein derivative test or chest X-ray. Deep fungal and other serious and atypical infection can also be promoted by adalimumab. It has been associated infrequently with skin rashes. Rare side effects include: worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis/neurological disease. There has been reported pancytopenia and elevated transamines with the use of adalimumab, which suggest that laboratory monitoring blood counts and liver functions, at least intermittently, are useful. In patients with any of the foregoing problems, its use should be extremely carefully considered. Adalimumab is a useful medication which can be safely used if its side effects are recognised.
16678646 Treatment of psoriatic arthritis with etanercept, methotrexate, and cyclosporin A. 2006 Feb BACKGROUND: Psoriatic arthritis (PsA) is seen in approximately 5% to 42% of individuals with psoriasis. CASE SUMMARY: A 37-year-old white male weighing 90 kg presented with erythrodermic psoriasis and PsA. The overall duration of PsA was 3 years. Serum levels of glucose, electrolytes, and tumor markers were normal, as were the results of tests of hepatic and renal function and urinalysis. The findings of posteroanterior radiographic examination of the chest were also normal. However, radiographic examination showed porosis and degeneration in the lumbar vertebrae; narrowing of the L2-L3, L3-L4, and L5-S1 spaces; degenerative changes and narrowing of the proximal interphalangeal and distal interphalangeal (DIP) joints; and osseous ankylosis of the DIP joints of the hands. The cutaneous eruption improved with cyclosporin A (CsA) 3.5 mg/kg p.o., but the severity of PsA did not change. Therefore, parenteral methotrexate (MTX) 15 mg/wk and an indomethacin suppository 100 mg/d were added to the regimen. CsA and MTX were continued for 3 months, during which the patient's PsA symptoms did not abate, based on tender and swollen joint counts, hand-to-floor distance, erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), antistreptolysin O, and rheumatoid factor. Therefore, etanercept 25 mg s.c. twice weekly was added to the regimen. Three weeks after the initiation of this combination, the patient's arthritis had improved. The visual analog scale score decreased from 9 to 4. Tender and swollen joint counts decreased from 28 and 24 to 15 and 10, respectively. The hand-to-floor distance decreased from 20 to 10 cm. The erythrocyte sedimentation rate and levels of CRP, antistreptolysin O, and rheumatoid factor decreased from 72 mm/h, 162 mg/L, 250 IU/mL, and 304 IU/mL at baseline to 23 mm/h, 64 mg/L, 48 IU/mL, and 56.1 IU/mL, respectively. No change was observed in radiographs of the patient's back, hands, and feet. Based on the American College of Rheumatology scoring system, the patient showed 50% improvement in disease severity. Etanercept was discontinued at the end of 4 weeks, and maintenance therapy was continued with MTX alone. No adverse events were reported during or after the completion of etanercept therapy. CONCLUSION: In this patient with PsA that was refractory to CsA and MTX, either alone or in combination, the severity of PsA was reduced after 4 weeks of the combined use of etanercept, CsA, and MTX.
15989010 [Unwanted reactions to modifying antirheumatic drugs]. 2005 AIM: To specify causes of discontinuation of the disease-modifying antirheumatic drugs (DMAD) used in rheumatoid arthritis (RA) by the results of special questionnaire survey. MATERIAL AND METHODS: The study included 298 RA patients treated in the Institute of Rheumatology (34 males and 264 females aged 18-82, mean age 54.6%, duration of the disease 1 to 38 years, mean 10.7 years) who responded to questioning. RESULTS: The following DMAD were used: metotrexate (n = 137), sulfasalasine (n = 49), aminoquinoline drugs (n = 33), chlorbutin (n = 19), azathioprin (n = 13), tauredon (n = 11), cyclophosphamide (n = 5). The drugs were discontinued due to unwanted effects in 50, 10, 46, 9, 4, 3, 3 (methotrexate, sulfasalasin, aminoquinolines, chlorbutin, azathioprin, Ag salts, cyclophosphamide, respectively). Cyclophosphamide and chlorbutin appeared most toxic, while sulfasalasine and aminoquinolines were found least effective. CONCLUSION: DMAD discontinuation rate ranges from 12.1% (aminoquinolines) to 60% (cyclophosphamide), mean 31.1%.
17113808 Polymyalgia rheumatica: diagnosis and treatment. 2006 Dec Polymyalgia rheumatica (PMR) typically manifests as inflammatory pain in the shoulder and/or pelvic girdles in a patient over 50 years of age. This condition was long underrecognized and therefore underdiagnosed. Today, however, overdiagnosis may occur. Physicians must be aware that many conditions may simulate PMR, including diseases that carry a grim prognosis or require urgent treatment. PMR may be the first manifestation of giant cell arteritis, and a painstaking search for other signs is mandatory. PMR may inaugurate other rheumatologic diseases such as rheumatoid arthritis, RS3PE syndrome, spondyloarthropathy, systemic lupus erythematosus (SLE), myopathy, vasculitis, and chondrocalcinosis. Finally, PMR may be the first manifestation of an endocrine disorder, a malignancy, or an infection. Failure to respond to glucocorticoid therapy should suggest giant cell arteritis, malignant disease, or infection. Ultrasonography may assist in the diagnosis by showing bilateral subdeltoid bursitis. Glucocorticoids are the mainstay of the treatment of PMR. Although the optimal starting dosage and tapering schedule are not agreed on, a low starting dosage and slow tapering may decrease the relapse rate. Methotrexate is probably useful when glucocorticoid dependency develops. In contrast, TNF-alpha antagonists are probably ineffective.
17110316 Malignancies and soluble tumor antigens in rheumatic diseases. 2006 Nov Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Recognition of paraneoplastic syndromes is important, as it may lead to an early diagnosis of cancer. There is some evidence that systemic inflammatory diseases, such as rheumatoid arthritis (RA), lupus, scleroderma or dermatomyositis may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. However, reports are somewhat controversial. Immunosuppressive and cytotoxic drugs used in antirheumatic therapy, such as methotrexate, cyclophosphamide, azathioprine or anti-TNF biologicals may also lead to the development of such tumors. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in RA and other autoimmune diseases.
16229202 Psoriatic arthritis: a retrospective study of 162 patients. 2005 Sep AIM: The aim of our study was to determine the prevalence of psoriatic arthritis in the patients with psoriasis and to analyze retrospectively the results of a 34-year multidisciplinary management of the patients with psoriatic arthritis. METHODS: The study included 162 out of 183 treated patients with psoriatic arthritis, aged 48 +/- 15 years. All the patients satisfied the current diagnostic criteria for psoriasis and psoriatic arthritis according to the American College of Rheumatology. RESULTS: Psoriatic arthritis developed in 183 (9.3%) out of 1976 patients with psoriasis. Time interval for establishing the diagnosis was 4 years. A positive family history of the disease had 15.0% of the studied patients. Its onset was most often at 42 years of age in 70.4% of the cases, and 2 months to 59 years after the appearance of psoriasis. Psoriatic arthritis without psoriasis appeared in 1.8% of the patients. A severe form of arthritis had 64.2% of the patients, mainly the patients with scalp psoriasis (chi2 = 3.2; p < 0.05). Nail changes had 35% of the patients. Distal interphalangeal joints were involved in 63.6%, axial skeleton in 36.4%, oligoarthritis in 45.0%, polyarthritis in 55.0%, and mutilating form in 6.8% of the patients. Elevated Erythrocyte Sedimentation Rate was reveald in 61.7% of the patients. Immunoglobulin M (IgM) rheumatoid factor was altered in 4.3% of the patients. The human leukocyte antigen (HLA) typing in the 28 patients were: A2 32.0%, A3 18.0%, Al and A9 14.0%, A28 and A29 3.5%, B8 and B16 14.0%, B5 and B12 11.0%, B13, B15, B18, B27 and B35 7.0%. Radiologic changes were most often in hand and foot joints, less frequently in the knees and quite infrequently in hips and shoulders joints. Sacroiliitis was found in 46.4% of the patients. Psoriasis was treated with topical corticosteroids and salicylic ointments in all the patients, ultraviolet (PUVA therapy) in 5.6% and retinoids in 4.3% of them. Artrithis was treated with nonsteroidal anti-inflammatory drugs, with systemic corticosteroids 41.3% and with disease modified antirheumatic drugs, most frequently methotrexate, 59.9% of the patients. Radionuclide synovectomy was performed in 6.8%, surgery in 6.2% and physical therapy in all the patients. CONCLUSION: Psoriatic arthritis developed in 9.3% of the psoriatic patients. Time interval for establishing the diagnosis was long, and there were no specific laboratory findings. All the synovial joints could be involved in the psoriatic process. Scintigraphy should be used only in case of early suspected sacroiliitis. The treatment of psoriatic arthritis was the teamwork between the dermatologist, rheumatologist, physiatrist and orthopedic surgeon.
16540551 Reactive haemophagocytic syndrome in adult-onset Still's disease: a report of six patients 2006 Dec OBJECTIVE: To examine the prevalence and characteristics of patients with reactive haemophagocytic syndrome (RHS) complicating adult-onset Still's disease (AOSD). METHODS: Of 50 patients with AOSD fulfilling Yamaguchi and Fautrel criteria followed in our department, clinical and laboratory data, course and treatment of six patients with histologically proven RHS and without any obvious cause other than AOSD were retrospectively recorded. RESULTS: RHS led to AOSD in two cases, whereas it appeared after a mean duration of 3.5 years from onset of AOSD in the other cases. The main symptoms were fever (n = 6), polyarthralgias or myalgias (n = 4), lymphadenopathy or splenomegaly (n = 3), pharyngitis (n = 3), rash (n = 3), pleuritis (n = 3), hepatomegaly (n = 1), normal or low leucocyte count (n = 4), anaemia (n = 6), lymphocytopenia (n = 6), thrombocytopenia (n = 4), hyperbasophilic lymphocytes (n = 2), abnormal liver function tests (n = 6) and increased serum triglyceride level (n = 6). Serum ferritin concentration was constantly increased (>10,000 microg/l in five cases, with <5-35% in glycosylated form). Two patients presented with coagulopathy. Treatment comprised corticosteroids (n = 4) and intravenous immunoglobulins (n = 3), whereas prednisone was unchanged in one case. One death due to pneumonia occurred 15 days after RHS. With a follow-up ranging from 2 to 7.5 years, the other patients were in remission with prednisone plus etanercept (n = 1), prednisone plus methotrexate (n = 1), low-dose prednisone (n = 2) or without treatment (n = 1). CONCLUSION: RHS is not uncommon in AOSD. It should be evoked in a patient with AOSD in the absence of hyperleucocytosis, thrombocytopenia, lymphopenia and coagulopathy, or in the presence of high serum ferritin and triglyceride levels.
16750873 [Evolution and prognosis of adult onset Still's disease. A monocentric study of 17 patient 2006 Sep Adult-Onset Still's disease (AOSD) is a rare condition of unknown origin with various presentations and unpredictable outcome. The aim of this study was to analyse clinical and biological presentation, and outcome of patients admitted to an internal medicine service. METHOD: A retrospective cohort design with prospective follow-up was used. All the patients admitted to our internal medicine service for AOSD between January 1998 and March 2004 were included. RESULTS: According to Yamaguchi's classification criteria, 17 patients were analysed with a mean age at onset of 37.3 years and a 2.4 sex-ratio (female/male). Mean follow-up length was 52.1 months. Eight patients developed a monocyclic systemic form, 8 a polycyclic systemic form and 1 a chronic articular form. Arthralgia (87%) and arthritis (53%) were less frequent than in other series. Sixteen patients were treated: 14 by corticosteroids, 6 by non-steroid anti-inflammatory drugs, 5 by methotrexate, 2 intravenous polyglobulin and one by anti-TNF drug. Patients with a corticodependant or corticoresistant form had more polyarthritis at the onset of the disease (3/6 vs 0/11, P=0.029). DISCUSSION: In internal medicine activity, AOSD without oligo- or polyarthritis may be more frequent than expected according to the literature. Corticotherapy alone is often efficient in these AOSD form without synovitis, and methotrexate use is uncommon.
17185324 Efficacy of infliximab on MRI-determined bone oedema in psoriatic arthritis. 2007 Jun BACKGROUND: Psoriatic arthritis (PsA) is commonly associated with bone pathology, including entheseal new bone formation and osteolysis. On MRI, areas of active clinical involvement are represented by bone oedema and synovitis. AIM: To assess the impact of infliximab on bone oedema in PsA as shown by MRI. METHODS: 18 patients with joint swelling, psoriasis and seronegativity for rheumatoid factor received four infusions of infliximab, 3 mg/kg, in combination with methotrexate. MRI of the affected hand (12 patients) or knee joints (6 patients) was performed before and after treatment. The primary outcome was the assessment of bone oedema and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the American College of Rheumatology (ACR) response criteria, psoriasis skin scores (Psoriasis Area and Severity Index (PASI)) and a quality of life measure (Psoriatic Arthritis Quality of Life (PsAQoL)). RESULTS: At baseline, bone oedema was seen in 50% of patients (seven hands and two knees) in 30% of scanned joints, and this improved or resolved in all cases in the hand joints (p = 0.018) and in one knee joint at 20 weeks. Synovitis was found to be reduced in 90% of cases on MRI. Likewise, a significant improvement in all clinical outcomes, including PASI (p = 0.003) and PsAQoL (p = 0.006) was seen at week 20. 65% (n = 11) of the patients achieved an ACR response, of whom 45% had ACR70 or above and 54% had ACR20 or ACR50. CONCLUSIONS: Infliximab treatment is associated with dramatic improvements in MRI-determined bone oedema in PsA in the short term. It remains to be determined whether infliiximib treatment is the cause for prevention of new bone formation, bone fusion or osteolysis in PsA as shown by radiography.
16947627 Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Resul 2006 Sep OBJECTIVE: To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population. METHODS: We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Randomized Evaluation of Long-Term Efficacy of Rituximab in RA (REFLEX) Trial, a 2-year, multicenter, randomized, double-blind, placebo-controlled, phase III study of rituximab therapy. Patients with active RA and an inadequate response to 1 or more anti-TNF agents were randomized to receive intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each) or placebo, both with background MTX. The primary efficacy end point was a response on the American College of Rheumatology 20% improvement criteria (ACR20) at 24 weeks. Secondary end points were responses on the ACR50 and ACR70 improvement criteria, the Disease Activity Score in 28 joints, and the European League against Rheumatism (EULAR) response criteria at 24 weeks. Additional end points included scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) Disability Index (DI), and Short Form 36 (SF-36) instruments, as well as Genant-modified Sharp radiographic scores at 24 weeks. RESULTS: Patients assigned to placebo (n = 209) and rituximab (n = 311) had active, longstanding RA. At week 24, significantly more (P < 0.0001) rituximab-treated patients than placebo-treated patients demonstrated ACR20 (51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and moderate-to-good EULAR responses (65% versus 22%). All ACR response parameters were significantly improved in rituximab-treated patients, who also had clinically meaningful improvements in fatigue, disability, and health-related quality of life (demonstrated by FACIT-F, HAQ DI, and SF-36 scores, respectively) and showed a trend toward less progression in radiographic end points. Rituximab depleted peripheral CD20+ B cells, but the mean immunoglobulin levels (IgG, IgM, and IgA) remained within normal ranges. Most adverse events occurred with the first rituximab infusion and were of mild-to-moderate severity. The rate of serious infections was 5.2 per 100 patient-years in the rituximab group and 3.7 per 100 patient-years in the placebo group. CONCLUSION: At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti-TNF therapies.
17040588 Etanercept, a tumour necrosis factor alpha receptor antagonist, and methotrexate in acute 2006 Dec Patients with autoimmune inner-ear disease (AIED) are treated with high doses of steroids in the short term when suffering an acute hearing loss. As a consequence, substances such as methotrexate have been employed in the role of steroid-sparing agents. Additionally, it is known that tumour necrosis factor alpha (TNFalpha) is an important mediator of the inflammatory process, inhibition of which may be of benefit in AIED. This case report illustrates the use of a TNFalpha inhibitor in combination with methotrexate, which is known to be an effective combination in rheumatoid arthritis but has yet to be described for sensorineural hearing loss. We conclude that progressive AIED may respond well to TNFalpha inhibition, whilst more difficult cases, such as this example, could benefit from combining such therapy with methotrexate.
15855185 Rheumatological manifestations of hepatitis C: incidence in a rheumatology and non-rheumat 2005 Aug OBJECTIVES: To evaluate hepatitis C virus (HCV)-positive patients followed in a rheumatology department and to compare them with a similar population of HCV-positive patients who had never seen a rheumatologist, in order to describe the rheumatological symptoms present and the effects of methotrexate and interferon-alpha therapy. METHODS: We performed a retrospective study of clinical, radiological and biological data on 21 rheumatology patients (Group I) presenting symptoms consistent with a chronic inflammatory arthritis with a known HCV infection and compared them with 41 members of an HCV support association (Group II). RESULTS: Symptoms of myalgia, sicca syndrome, Raynaud's phenomenon or paraesthesias were similarly frequent in the two groups. However, inflammatory joint pain and joint swelling were more common in Group I. In this group rheumatoid factor was positive in 48%, antinuclear antibodies in 26%, cryoglobulin in 44% and a reduced complement level in 63%. The majority of patients from Group I treated with methotrexate demonstrated an amelioration of the rheumatological symptoms with few negative outcomes. Regarding interferon-alpha therapy and rheumatological symptoms-in Groups I and II respectively 50 and 66% demonstrated a deterioration, 33 and 30% showed no change and 17 and 4% showed an amelioration. CONCLUSION: Rheumatological symptoms are common in patients chronically infected with HCV. It is essential to individualize the role of treatment with interferon-alpha and to consider the use of methotrexate for difficult cases.
16011450 Methotrexate pulmonary toxicity. 2005 Jul Methotrexate is a commonly prescribed antineoplastic and immune modulating compound that has gained wide acceptance in the management of rheumatoid arthritis, psoriasis, sarcoidosis and a number of neoplastic disorders. Although generally considered safe and easy to use, methotrexate has been associated with a number of adverse reactions. Pulmonary toxicity has been well-described and may take a variety of forms. Pulmonary infiltrates are the most commonly encountered form of methotrexate pulmonary toxicity and these infiltrates resemble hypersensitivity lung disease. This discussion focuses primarily on low-dose methotrexate pulmonary toxicity and will discuss the diagnosis using clinical, pulmonary function, radiographical and pathological manifestations. Suggestions for clinical monitoring to detect adverse effects are given. In addition, management of pulmonary toxicity through discontinuation of the methotrexate, support and possibly the administration of corticosteroids is discussed.
16047265 Effect of drugs on homocysteine concentrations. 2005 May Many studies conducted over the last two decades have shown that drug treatment for common medical conditions may have an adverse effect on plasma total homocysteine (tHcy) concentrations. The mechanism for the effects of individual drugs on tHcy concentrations is frequently unknown, as the mechanism of action of the drug may not be established, or the drug is typically administered in combination with other drugs. Some drugs are believed to alter tHcy concentrations by interfering in the metabolism of folate or vitamins B (12) or B (6) or by altering renal function, but the underlying mechanisms for the effects on tHcy concentrations of many drugs remains to be discovered. Several widely used drugs, such as lipid-lowering drugs (like fibrates and niacin) or oral hypoglycemic drugs (like metformin), insulin, drugs used in rheumatoid arthritis, and anticonvulsants cause elevated tHcy concentrations. Sex hormones have variable effects on tHcy levels, and N-acetylcysteine lowers tHcy. The mechanisms of action of drugs on tHcy concentrations and strategies to avoid tHcy elevation have been studied. Assuming that the association of tHcy with cardiovascular disease is causal, this article focuses on the adverse effect on tHcy levels of fibrates, statins and niacin, antihypertensive drugs, metformin, methotrexate and sulfasalazine, anticonvulsant drugs, and levodopa and reviews strategies to avoid such effects. The clinical significance, if any, of these adverse effects on plasma tHcy concentrations remains to be determined.