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ID PMID Title PublicationDate abstract
20881757 Inadequate therapy behavior is associated to disease flares in patients with rheumatoid ar 2010 Oct OBJECTIVES: (1) To determine 6-month follow-up adherence and persistence with disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis with disease under control. (2) To compare disease flares across adherent, nonadherent, persistent and nonpersistent patients. (3) To identify differences in adherent and persistent rates among therapeutic regimens. (4) To identify baseline prognosticators of poor compliance. METHODS: Ninety-three patients (86% female) had 4 consecutive 2-month apart evaluations during which the 28-joint disease activity score and the Health Assessment Questionnaire were scored, comorbidities and treatment recorded and a compliance questionnaire and a drug record registry applied. Descriptive statistics, Student t and χ tests and logistic regression analysis were used. RESULTS: At the study entry, patients had mean ± standard deviation age of 40.8 ± 13.9 years, the 28-joint disease activity score of 2.1 ± 1.1, the Health Assessment Questionnaire of 0.09 ± 0.2, and 68 of them (73.1%) had remission. During follow-up, 47 patients (50.5%) were adherent and 51 (54.8%) persistent; 14 of 68 patients (20.6%) who achieved remission had a disease flare. Incidence rate and individual risk of a disease flare were significantly greater in nonadherent and nonpersistent patients. Compared with methotrexate monotherapy, therapeutic regimens with >3 disease-modifying antirheumatic drugs had increased risk of nonadherence and nonpersistence (P ≤ 0.02). Higher previous serial erythrocyte sedimentation rate was associated to nonadherence (as was a shorter follow-up at the Clinic) and to nonpersistence (odds ratio: 1.03; 95% confidence interval: 1.01-1.05 for both, P = 0.05 and P = 0.001, respectively). CONCLUSIONS: Therapy behavior of patients with rheumatoid arthritis with mild/no disease activity and disability was poor and translated into disease flares. Higher serologic activity was associated to poor compliance with therapy.
20798997 Effects of different medical treatments on serum copper, selenium and zinc levels in patie 2011 Sep The aim of the present study was to measure the changes in serum selenium, zinc, and copper in patients being treated for rheumatoid arthritis. Thirty-two patients and 52 healthy controls were included in the study. The copper level was higher and those of selenium and zinc were lower in the patients relative to controls. Treatment with methotrexate elevated the zinc levels, but not zinc and selenium. Treatments with salazopyrin, corticosteroids, chloroquine, and non-steroidal anti-inflammatory drugs did not change the levels of any of the elements studied. The decrease in zinc and selenium levels and elevation in copper levels observed in the patients probably resulted from the defense response of organism and are mediated by inflammatory-like substances.
20556817 Efficacy and safety of a selective estrogen receptor β agonist, ERB-041, in patients with 2010 Nov OBJECTIVE: Selective estrogen receptor β (ERβ) agonists have demonstrated relevant antiinflammatory effects in different animal models. This study aimed to compare the efficacy and safety of one of these agonists, ERB-041, in subjects with rheumatoid arthritis (RA). METHODS: A total of 291 patients with active RA receiving stable doses of methotrexate were randomized to receive 5, 25, or 75 mg of ERB-041 or placebo for 12 weeks. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) at 12 weeks. Secondary end points included the ACR 50% improvement criteria (ACR50) and the ACR 70% improvement criteria (ACR70) responses, health outcomes measures, C-reactive protein (CRP) levels, and potential exposure-response relationships. Medical history, physical examination, and laboratory values were obtained at screening, baseline, and weeks 2, 4, 8, and 12. RESULTS: No statistically significant difference for the ACR20 was found between the ERB-041 treatment and placebo groups (P = 0.518). Nor was a significant difference observed for ACR50 and ACR70 responses, health outcomes measures, CRP levels, and overall incidence of adverse events among all groups. Forty-four subjects (15.1%) discontinued the study and the rate of discontinuation was similar among the treatment groups. The most commonly reported treatment-emergent adverse events were headache (7.6%), nausea (6.2%), infection (4.8%), and bronchitis (4.1%). None of the adverse events was considered treatment related. CONCLUSION: Although well tolerated and safe, ERB-041 failed to demonstrate antiinflammatory efficacy in RA patients, despite evidence of strong activity in preclinical arthritis models. These results suggest that selective ERβ agonists would not have effects on regulating inflammatory response in RA. Nevertheless, further studies are warranted to establish their efficacy in inflammatory arthritis.
19771491 A meta-analysis of the efficacy and safety of using infliximab for the treatment of rheuma 2009 Dec Infliximab is a chimeric monoclonal antibody. Published studies indicate that its use in patients with rheumatoid arthritis can be efficient in providing long-term benefits. The aim of this study is to evaluate the efficacy and safety of using infliximab for the treatment of rheumatoid arthritis. A systematic review was performed to search for randomized clinical trials that compared intravenous administration of 3 mg/kg body weight infliximab or placebo in patients concomitantly using methotrexate. Only studies of moderate or high quality were included. A meta-analysis was conducted to assess the efficacy (based on changes of American College of Rheumatology (ACR) criteria) and the safety (based on serious adverse events, serious infections, malignancy, and deaths) of infliximab use. Withdrawals due to adverse events or lack of efficacy were also evaluated in both infliximab-treated and control groups. Seven trials met the inclusion criteria, comprising 2,129 patients. In the efficacy meta-analysis, a greater number of infliximab-treated patients relative to those in the placebo group achieved ACR20, ACR50, and ACR70 values from 14 weeks to 2 years of treatment. For safety analysis, there were no statistically significant differences between the groups. Withdrawals due to adverse events were higher in the infliximab group relative to the placebo group, and withdrawals due to lack of efficacy were higher in the placebo group relative to the infliximab-treated group. This meta-analysis shows a higher efficacy of infliximab relative to placebo without significant safety differences between the infliximab-treated and control groups.
18713784 Effects of infliximab therapy on biological markers of synovium activity and cartilage bre 2009 Jul BACKGROUND: Defining the remission criteria of rheumatoid arthritis (RA) remains a critical issue. Markers of synovium activity, urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and of cartilage destruction, urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II) have been shown to reflect disease activity and joint damage progression in RA. METHODS: The prospective study cohort comprised 66 RA patients treated with infliximab and methotrexate and 76 healthy controls. Measurements of urinary Glc-Gal-PYD and CTX-II were performed at baseline and at 1 year of infliximab therapy. RESULTS: At baseline, urinary Glc-Gal-PYD and CTX-II levels were increased in patients with RA and correlated with modified Sharp scores and progression of joint damage. Patients with more progressive joint destruction had higher Glc-Gly-PYD and CTX-II baseline levels. CONCLUSION: These markers reflected bone erosion evolution and might be useful for treatment monitoring and evaluation of RA. Markers remained high even in clinical responders after infliximab, suggesting persistence of synovitis.
19827168 Genetic polymorphisms in folate pathway enzymes as a possible marker for predicting the ou 2009 Jun BACKGROUND: Low-dose methotrexate (MTX) therapy is widely used in the treatment of rheumatoid arthritis (RA). Though the difference in response to MTX between patients with RA is large, the factors that contribute to this variability remain unclear. OBJECTIVE: We aimed to identify those factors with a particular emphasis on the pharmacogenetics of MTX. METHOD: We evaluated the association of possible factors, including genetic polymorphisms of folate metabolic pathway enzymes, with the cumulative value of C-reactive protein, an index of MTX anti-inflammatory efficacy, in 87 Japanese patients with RA. RESULTS: Polymorphisms of the reduced folate carrier gene (RFC) G80A and of the gamma-glutamylhydrolase gene (GGH) C-401T were more closely associated (beta = 2.1194, P = 0.0017) than other polymorphisms, with the anti-inflammatory response to MTX. CONCLUSION: Patients with RA having RFC 80A and GGH-401T alleles were less responsive to MTX than those with RFC 80A and without GGH-401T alleles. Thus, this data may be useful for guiding treatment of RA patients with MTX.
21516741 [Pharmacogenetic criteria for the efficacy of basic anti-inflammatory therapy for rheumato 2010 AIM: To analyze the prognostic value of detection of allelic variants of the promoter regions of cytokine genes in patients with rheumatoid arthritis (RA) with varying efficiency of basic anti-inflammatory therapy (BAIT). SUBJECTS AND METHODS: Eighty-nine patients with a valid diagnosis of RA, of them there were 79 females and 10 males (mean age 52.5 +/- 13.1 years), were examined. The patients received BAIT with methotrexate in a dose of 10.0-17.5 mg/week (77.5%) or with sulfasalazine in a dose of 2.0 g/day (22.5%) for 24 weeks. The efficiency of BAIT was evaluated using the European League Against Rheumatism (EULAR) criteria (DAS28) following 24 weeks. A high therapeutic effect was stated when DAS28 decreased by more than 1.2 scores. Changes in DAS28 by less than 0.6 scores were regarded as ineffective BAIT. Cytokine gene polymorphisms were studied by restriction analysis of amplification products. The following polymorphic sites in the interleukin genes: FNOA at positions C-863A, G-308A, G-238A, IL-1BT-31C, IL-4 C-590T, IL-6 G-174C, and IL-10 C-592A, were explored. RESULTS: The IL-6 G-174G genotype associated with the high production of this proinflammatory cytokine and the IL-IB C-31C genotype associated with the low production of interleukin-1beta (IL-1beta) were most frequently encountered in a group of patients with the high efficiency of BAIT (22 and 24.7%). At the same time the C allele associated with the low production of IL-6 and the IL1B T-31C genotype associated with the high production of this cytokine were most frequently detected at position of G-174C of the promoter regions in the IL-6 gene in patients unresponsive to BAIT (32 and 36%). CONCLUSION: The allelic variants of the promoter regions of the IL-6 G-174G, IL-1B C-31C, IL-4 C-590T, and IL-10 C-592A can be genetically prognostic factors of formation of the high efficiency of BAIT.
20979550 Certolizumab pegol: a new biologic targeting rheumatoid arthritis. 2010 Nov The past decade has been an exciting period for clinical research and patient care in rheumatoid arthritis. This is mostly due to targeted biologic agents that have changed the outcome of this disease. Certolizumab pegol (Cimzia(®), UCB Inc., GA, USA), which targets TNF-α with a different mechanism of action than widely used biologics, was initially investigated for Crohn's disease but has now been shown to be effective for rheumatoid arthritis. There have been three significant clinical trials demonstrating the efficacy of certolizumab pegol in active rheumatoid arthritis; two with combination methotrexate and one with monotherapy. This article will summarize the data from those trials and compare some of the characteristics of certolizumab pegol to conventional disease-modifying antirheumatic drugs and other biologic agents. Treatment recommendations are beyond the scope of this review; however, with many options available, there will be annotations on current trends in the care of this chronic disease.
20843910 Canadian variation by province in rheumatoid arthritis initiating anti-tumor necrosis fact 2010 Dec OBJECTIVE: We compared variations among Canadian provinces in rheumatoid arthritis (RA) initiating anti-tumor necrosis factor (TNF) therapy. METHODS: Data were obtained from the Optimization of Humira trial (OH) and from the Ontario Biologics Research Initiative (OBRI). Baseline characteristics were compared between regions: Ontario (ON), Quebec (QC), and other provinces (OTH). We compared Ontario OH to OBRI patients who were initiating anti-TNF therapy. RESULTS: In 300 OH patients, mean age was 54.8 years (13.3). There were 151 (50.3%) ON patients, 57 from QC (19%), and 92 from OTH (30.7%). Regional differences were seen in the number of disease-modifying antirheumatic drugs (DMARD) ever taken (ON: 3.8 ± 1.4, QC: 3.1 ± 1.1, OTH: 3.3 ± 1.4; p < 0.001); swollen joint count (SJC; ON: 10.9 ± 5.9, QC: 9.0 ± 4.4, OTH: 11.3 ± 5.6; p = 0.033); tender joint count (TJC; ON: 12.2 ± 7.5, QC: 10.3 ± 5.7, OTH: 14.4 ± 7.6; p = 0.003); 28-joint Disease Activity Score (DAS28; ON: 5.8 ± 1.2, QC: 5.6 ± 1.0, OTH: 6.0 ± 1.1; p = 0.076); and Health Assessment Questionnaire (ON: 1.4 ± 0.7, QC: 1.7 ± 0.7, OTH: 1.5 ± 0.7; p = 0.060). DMARD-ever use differed: methotrexate (ON: 94.7%, QC: 93%, OTH: 84.8%; p = 0.025); leflunomide (ON: 74.8%, QC: 21.1%, OTH: 51.1%; p < 0.001); sulfasalazine (ON: 51%, QC: 38.6%, OTH: 25%; p < 0.001); myochrysine (ON: 9.3%, QC: 0%, OTH: 15.2%; p = 0.008); and hydroxychloroquine (ON: 67.5%, QC: 86%, OTH: 66.3%; p = 0.018). In comparison to ON OH patients, 95 OBRI patients initiating first anti-TNF had lower SJC (p = 0.017), TJC (p = 0.008), and DAS28 (p = 0.05). CONCLUSION: In Quebec, where access to anti-TNF is less restrictive, patients had lower SJC and TJC. ON used more DMARD, especially leflunomide, as mandated by the provincial government. Both provincial funding criteria and prescribing habits may contribute to differences. Canadian rheumatologists may vary in treatment decisions, but patients generally have similar DAS28 when initiating anti-TNF therapy.
19300372 Oral bisphosphonates-associated osteonecrosis in rheumatoid arthritis. 2009 Jun 1 Adverse effects associated with the use of bisphosphonates are infrequent and consist of pyrexia, renal function impairment, and hypocalcemia. Bisphosphonates-associated osteonecrosis of the jaws is an uncommon but potentially serious complication of intravenous bisphosphonate therapy in cancer patients. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate, is uncertain and warrants careful monitoring. Oral bisphosphonates-associated osteonecrosis can occur in patients with rheumatoid arthritis. We report a case of mandibular osteonecrosis in a patient who received alendronate for 3.8 years. The pathology improved after bisphosphonate therapy discontinuation and sequestrectomy. To our knowledge there are only three cases published in the literature relating bisphosphonates-associated osteonecrosis of the jaws in patients with rheumatoid arthritis. All the cases published, including our case, have reported association between methotrexate, prednisone and alendronate sodium (Fosamax) therapy. Corticosteroid therapy and dental surgery could increase the risk of developing bisphosphonates-associated osteonecrosis of the jaws in these patients.
19365268 Clinical value of blocking IL-6 receptor. 2009 May PURPOSE OF REVIEW: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates inflammatory response and immune reaction. Overproduction of IL-6 is pathologically involved in inflammatory autoimmune diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis, and therefore, blocking IL-6 activity is one of therapeutic options for these diseases. Tocilizumab is a humanized anti-IL-6 receptor (IL-6R) antibody and inhibits IL-6 activity. There is now accumulating evidence that tocilizumab is therapeutically effective for patients with RA and other inflammatory autoimmune diseases. This article reviews the clinical value of blocking IL-6R. RECENT FINDINGS: Tocilizumab, as monotherapy and in combination with methotrexate, has been shown to be effective for RA patients with insufficient efficacy to methotrexate or other disease-modifying antirheumatic drugs. These findings of tocilizumab have been expanded to patients refractory to tumor necrosis factor inhibitors. Tocilizumab also retards the progression of structural joint damage. Furthermore, a 5-year long-term safety and efficacy has been shown. Tocilizumab is also a promising therapeutic option for other rheumatic diseases such as systemic-onset juvenile idiopathic arthritis, adult-onset Still's disease, and Takayasu arteritis. SUMMARY: Blocking IL-6R with tocilizumab represents a promising new treatment for RA and other inflammatory diseases. Large registry data will warrant the safety profile of tocilizumab.
20601897 Infliximab reduces the frequency of interleukin 17-producing cells and the amounts of inte 2010 Oct BACKGROUND: To detect frequency changes in interleukin 17 (IL-17)(+) CD4(+) T cells and the amounts of IL-17 in supernatants between baseline and 30 weeks after Infliximab combined with methotrexate (MTX) or MTX-alone therapy. METHODS: Flow cytometry was used to analyze the frequency of IL-17(+) CD4(+) T cells in rheumatoid arthritis (RA) patients and control subjects at baseline and 30 weeks after therapy. Secretion of IL-17 by peripheral blood mononuclear cells was measured by enzyme-linked immunosorbent assay. RESULTS: The percentages of IL-17(+) CD4(+)T cells were increased in the peripheral blood mononuclear cells of patients with RA compared with healthy subjects. The percentages of IL-17(+) CD4(+)T cells were correlated with the number of swelling joints and C-reactive protein of RA patients. Likewise, concentrations of IL-17 in supernatants from patients with RA were significantly higher compared with those from control subjects. After infliximab combined with MTX or MTX-alone therapy, the number of swelling joints, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and Disease Activity Score 28 decreased significantly compared with baseline. Only in the infliximab + MTX group that the frequency of T(H)17 cells and concentration of IL-17 decreased. CONCLUSIONS: These data support the hypothesis that infliximab therapy can have an effect on T(H)17 cells and decrease disease activity.
20975633 Tocilizumab - a new step in rheumatoid arthritis treatment. 2010 Jul Rheumatoid Arthritis is a chronic systemic inflammatory disease characterized by joint pain, stiffness and swelling, with progressive destruction of small joints of the hands and feet. Methotrexate remains the most commonly used therapy and has been the recommended standard against which new drugs should be evaluated and, to date, there is limited evidence that monotherapy with other treatments is superior to MTX. The introduction of biologic agents, such as TNFα-antagonists, represented an advance in the treatment of RA. However, there are still patients with no or inadequate response, patients in whom responsiveness to treatment is lost over time, and patients in whom safety issues may develop. Thus, patients may benefit from treatment with newer biologic agents with a different mechanism of action. Tocilizumab is an IL-6 receptor inhibitor which shows significant (and rapid) clinical efficacy in the treatment of Rheumatoid Arthritis patients, as assessed by ACR responses and DAS remission rates, with an acceptable safety profile.
19252250 [Effect of disease modifying anti-rheumatic drugs on radiographic progression in rheumatoi 2009 Mar Because of a paradigm shift in the therapeutic strategy of RA by biologics, the goal of RA therapy became not only the clinical remission, but also the imaging remission. From the results of randomized controlled clinical trials of disease modifying anti-rheumatic drugs (DMARDs), decreased radiographic progression has been documented. In particular, methotrexate (MTX) is described as "anchor drug" of RA therapy because inhibitory effects of MTX on radiographic progression are proved by many clinical trials. Although DMARDs can slow down the radiographic progression with the achievement of clinical remission in RA, some patients still have subclinical synovitis detected by imaging technique. Such subclinical inflammation may explain the observed discrepancy between disease activity and radiographic progression in RA during DMARD therapy.
19505397 Imaging progression despite clinical remission in early rheumatoid arthritis patients afte 2009 Apr The aim of this preliminary study is to evaluate clinical and imaging response in twenty patients with early Rheumatoid Arthritits (eRA) treated with Etanercept (Etn) + Methotrexate (Mtx) and to investigate whether clinical and MRI remission may be maintained after biological therapy interruption. Assessment included: radiography, Visser score and anti-CCP antibodies at baseline; disease activity score in 44 joints (DAS44), rheumatoid factor (RF), Magnetic Resonance Imaging (MRI) of hands and wrists at baseline (T0), 12 (T1), and 24 months (T2). MRI was scored for synovitis, bone oedema and erosions (OMERACT study); patients who reached clinical and imaging remission at T1 were considered eligible for interrupting Etn. At T1 8/20 (40 percent) patients showed a total remission, DAS44 from 5 (T0) to 1.4 (T1); p<0.02, whereas the other 12/20 (60 percent) showed an improvement, without complete remission, DAS44 from 4.8 (T0) to 2.8 (T1); p<0.05. Etn was therefore interrupted in the first group of patients (group A), whereas it was continued in the other group (group B). At T2, group A maintained clinical remission and group B showed further not significant DAS44 reduction from T1. At T1, a significant reduction in synovitis, bone oedema and total score (p<0.01) was observed both in group A and in group B. At T2, group A showed an increase in all the MRI scores that was significant for the synovitis and total score, whereas group B exhibited a further not significant reduction. This preliminary study reports an excellent clinical and imaging response in eRA patients treated with Etn with total remission in 40 percent of them after a 1-year therapy period. However, it indicates that joint damage may progress, despite a sustained clinical remission, after Etn suspension.
19504146 Persistent low grade synovitis without erosive progression in magnetic resonance imaging o 2009 Oct Disease remission is only reached by a minority of rheumatoid arthritis (RA) patients treated with infliximab. Radiological assessment reported in clinical trials support the view that even under persistent inflammatory activity there is no further structural damage. Magnetic resonance imaging (MRI) allows a highly accurate detection of synovitis, bone edema, and erosions, constituting the ideal instrument for the evaluation of treatment response. The goal of this study was to evaluate MRI changes over 1 year in RA patients treated with infliximab. Four RA patients refractory to methotrexate (MTX) therapy were treated with infliximab 3 mg/kg 8/8 weeks and followed up for 1 year. Disease Activity Score (DAS28) was measured in the day of each infliximab administration. MRI was performed at baseline, 3 months, and 1 year. A simplified OMERACT RA MRI scoring (RAMRIS) was applied to the dominant wrist: synovitis (0-3) was measured in the intercarpal-carpometacarpal joints (CMTJ); bone edema (0-39) and erosions (0-130) in the base of the metacarpal and wrist bones. Baseline DAS28 was superior to 3.2 in all patients (ranging from 4.8 up to 6.2). At 14 weeks, DAS28 was still superior to 3.2 (ranging from 3.5 up to 4.6) and at 46 weeks all patients have responded, however without having achieved clinical remission, as DAS28 was still above 2.6 (ranging from 2.6 up to 3.4). MRI showed that synovitis was reduced in all patients to a score of 1, bone edema was slightly reduced (10% reduction), and erosive score was unchanged (baseline values ranging from 2 up to 20). Despite persistent low disease activity, these four RA patients treated with infliximab had stable simplified RAMRIS erosive scores over 1 year. These results support the view that there might be an uncoupling process between inflammation and bone erosions when tumor necrosis factor alpha is targeted in RA.
20969545 T-cell agents in the treatment of rheumatoid arthritis. 2010 T cells play a prominent role in the pathogenesis of rheumatoid arthritis. Abatacept is the first FDA approved agent for rheumatoid arthritis that blocks the activation of T cells by interrupting the interaction between the CD28 ligand on the T cell and the CD80/86 ligand on the antigen presenting cell. Inhibition of T cell activation has pleotropic effects that lowers the downstream production of multiple cytokines. In clinical trials, abatacept is effective in treating the signs and symptoms of rheumatoid arthritis as well as in inhibiting structural damage. It has a favorable safety profile and can be used in patients who may have comorbidities that preclude the use of anti-TNF agents. While no direct head to head trials exist, a study in which both abatacept and infiximab were compared to an identical control population, suggested that the efficacy of the two drugs was similar but that there were fewer adverse effects with abatacept than with infiximab. Abatacept is an important addition to the therapeutic repertoire available to treat rheumatoid arthritis. Available data support its use as a first line agent to treat patients who have had and inadequate response to methotrexate.
19386610 Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate 2009 Dec OBJECTIVE: To examine the effect of infliximab plus methotrexate (MTX) compared with placebo plus MTX on bone loss in patients with early rheumatoid arthritis (RA) in a double-blind randomised study design. Further, to explore the associations between bone loss and markers of RA disease. METHODS: All 20 patients with RA (10 patients in each treatment group) had active, early RA. Bone mineral density (BMD) was assessed at the hand, lumbar spine (L2-4) and hip by dual energy x-ray absorptiometry at baseline and 12 months' follow-up. Clinical data were collected at regular visits. RESULTS: BMD loss was significantly reduced in the infliximab group compared with the placebo group at the femoral neck (-0.35% vs -3.43%, p = 0.01) and total hip (-0.23% vs -2.62%, p = 0.03) but not at the hand (-2.09% vs -2.82%, p = 0.82) and spine (-0.75% vs -1.77%, p = 0.71). Measures of disease process and joint damage were found to be independently associated with bone loss. CONCLUSIONS: This study provides strong evidence of a causal link between inflammation and bone loss in RA. The anti-inflammatory effect of infliximab was potent enough to arrest inflammatory bone loss at the hip but not at the spine and hand.
20012622 Rituximab and concomitant leflunomide for the treatment of rheumatoid arthritis. 2010 Mar Rituximab has only been approved in combination with methotrexate for the treatment of rheumatoid arthritis. As some patients have intolerance to methotrexate, alternative co-therapies are needed. This method involved retrospective analysis of ten patients treated with a combination of rituximab and leflunomide. Primary outcome measures were the DAS28 response at month 6 and the time to relapse. The median initial DAS 28 of 5.7 (3.2-7.2) was reduced to 3.5 (1.9-6.1) at month 6. 70% of the patients achieved a good or moderate response, whereas 30% showed no response. Two patients had to stop leflunomide due to adverse effects. Two patients had to reduce the leflunomide dose to 10 mg/day. 5/8 patients experienced a relapse after a median of 10 (6-30) months and were successfully re-treated with rituximab. This small case series suggests that leflunomide might offer an alternative DMARD combination option for the treatment of RA with rituximab.
19060002 Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a syst 2009 Jul OBJECTIVE: To perform a systematic literature review of the long-term safety of methotrexate (MTX) monotherapy in rheumatoid arthritis (RA). METHODS: A search was performed in Medline, Cochrane and EMBASE. Adults with RA who had received MTX monotherapy for more than 2 years were studied. RESULTS: 88 published studies were included. Over 12 years of treatment, the termination rate of MTX due to toxicity was less than for sulfasalazine, gold, d-penicillamine and higher than for hydroxychloroquine (level of evidence 2a-2b). Long-term use of MTX does not appear to be a risk factor for serious infections, including herpes zoster (2b-4), and could provide a survival benefit by reducing cardiovascular mortality (2b). The prevalence of raised liver enzymes (more than twice the upper limit of normal) is close to 13% of patients; 3.7% of patients stopped MTX permanently owing to liver toxicity (2b). Data on the risk for liver fibrosis/cirrhosis are conflicting: a meta-analysis showed an incidence of fibrosis of 2.7% after 4 years of MTX (2a). However, two other studies on sequential liver biopsies did not show evidence for developing severe damage (2b). Insufficient data are available to fully assess the risk of lymphoma and malignancies, although there is no strong evidence of increased risk (2b-4). CONCLUSION: This systematic literature search on MTX monotherapy with relatively low-dose use during at least 2 years shows favourable long-term safety.