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18480575 Clinical and radiological features of Pneumocystis pneumonia in patients with rheumatoid a 2008 OBJECTIVE: To elucidate the clinical and radiological features of Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA), compared with methotrexate (MTX) pneumonitis in RA and Pneumocystis pneumonia in acquired immunodeficiency syndrome (AIDS). SUBJECTS AND METHODS: Retrospective analysis of 14 PCP cases in RA (RA-PCP), 10 MTX pneumonitis cases in RA (MTX-P) and 11 PCP cases in AIDS (AIDS-PCP) from 9 centers in the Kanto area in the last 6 years. RESULTS: Compared with AIDS-PCP, both RA-PCP and MTX-P developed more rapidly, showing higher serum CRP and lower plasma beta-D-glucan levels, and more severe oxygenation impairment. In most of the RA-PCP cases, a high dose of corticosteroid was administered as adjunctive therapy, resulting in a favorable outcome. The mortality was 14% in RA-PCP, 0% in AIDS-PCP and 0% in MTX-P cases. In RA-PCP patients the CD4 cell count showed only mild suppression, not reaching the predisposing level for PCP in HIV infection, suggesting that there are risk factors for RA-PCP other than immunosuppression. Radiologic analysis revealed some characteristic patterns of each disease. In MTX-P, diffuse homogeneous ground glass opacity (GGO) with sharp demarcation by interlobular septa (type A GGO) was found in 70%, while in AIDS-PCP diffuse, homogeneous or nonhomogeneous GGO without interlobular septal boundaries (type B GGO) was predominant (91%). In RA-PCP, type A GGO was found in 6 cases and type B GGO in 5 cases, showing the complex nature of this disease. CONCLUSION: RA-PCP differed considerably from AIDS-PCP clinically and radiologically. Clinically it occurred without severe immunosuppression, and showed characteristic aspects, with more intense inflammation and less parasite burden. Radiologically it mimicked MTX-P in some cases sharing the conspicuous CT features of MTX-P, rendering the distinction of these two disorders difficult.
17417995 Switching to etanercept in patients with rheumatoid arthritis with no response to inflixim 2007 Jan TNF-alpha is thought to play a pivotal role in the initiation and perpetuation of the chronic inflammatory process in rheumatoid arthritis. TNF-alpha blockers such as infliximab and etanercept are currently used in the treatment of active rheumatoid arthritis (RA) when traditional DMARDs have failed and are effective in a significant proportion of patients. However, about one third are non-responders to anti-TNF-alpha. The aim of this study was to verify whether rheumatoid patients, after failing infliximab, can benefit from etanercept. We analysed 18 patients with active RA with no response to at least 3 DMARDs and where infliximab therapy had failed. The patients had received infliximab associated with methotrexate: eleven of them did not show any significant response, while seven patients, after a good response, relapsed. Etanercept was then started. EULAR criteria of response were used with calculation of activity index DAS28 at baseline, after 2 weeks, 3 months and every third month until last follow-up. A moderate or good response was achieved with etanercept in 13 out of 18 patients. From our experience, etanercept can be considered as a good alternative choice when infliximab has failed.
18691998 Treatment persistence with adalimumab, etanercept, or infliximab in combination with metho 2008 Jul BACKGROUND: Anti-tumor necrosis factor (TNF) biologic agents are effective in treating rheumatoid arthritis (RA). Information on patient persistence with biologic anti-TNF therapies is limited, and the effects of persistence on the costs of therapy are unknown. OBJECTIVES: The aims of this study were to compare treatment persistence with adalimumab, etanercept, or infliximab in combination withmethotrexate (MTX) and evaluate the effects of persistence on overall health care costs. METHODS: This retrospective study used data from the PharMetrics managed care administrative claims database. Data from patients with RA who received combination treatment with an anti-TNF agent plus MTX and had > or = 24 months of continuous plan eligibility were collected. The 3 anti-TNF cohorts were adalimumab + MTX (adalimumab group), etanercept + MTX (etanercept group), and infliximab + MTX (infliximab group). Treatment persistence was defined as the number of days between the first and last anti-TNF treatment and was reported as a percentage of the 1-year period after treatment initiation. Costs were compared between patients with treatment persistence rates > or = 80% or <80%. Demographics, comorbidities, disease severity, and RA-related costs were assessed using descriptive statistics. Univariate and multivariate analyses were applied to identify differences in mean persistence between the 3 cohorts. RESULTS: Data from 1242 patients were included (77.7% female; mean age, 50.0 years). The mean persistence rate in the overall population was 74.6%, and the mean treatment time was 272.3 days. The infliximab group had a higher persistence rate compared with the etanercept and adalimumab groups (78.0% vs 72.8% and 70.8%, respectively; P < 0.005). In all patients combined, those with treatment persistence > or = 80% had higher mean total health care costs compared with those with treatment persistence <80% ($19,271.52 vs $15,598.46; P < 0.001), largely due to higher pharmacy costs. However, nonpharmacy costs were lower in the > or = 80% persistence cohort ($3091 vs $4601; P = 0.015). CONCLUSIONS: In this population of patients with RA, overall treatment persistence was high, with patients treated with infliximab + MTX having significantly higher persistence compared with those treated with adalimumab + MTX or etanercept + MTX. While pharmacy costs were higher in patients with > or = 80% persistence, nonpharmacy costs were lower.
18617467 [The pulmonological manifestations of rheumatoid arthritis]. 2008 Jul 20 In their review article the authors overview the primary and secondary pulmonary complications of rheumatoid arthritis with the help of bibliographic data. They emphasize the pulmonological complications of disease modifying antirheumatic drugs used for the pharmaceutical therapy of rheumatoid arthritis, of which they discuss the methotrexate induced pulmonary diseases. Methotrexate participates nearly in all of additive double and triple--O'Dell-scheme--combined disease modifying antirheumatic drugs therapy. Because of that, the early detection of drug-induced pulmonological complications is important. For rheumatologists the treatment of methotrexate resistant rheumatoid arthritis is always getting a higher and higher challenge. Biological therapeutical drugs act as cytokine antagonists, by blocking TNF-alpha and, compared to disease modifying antirheumatic drugs, they can more effectively inhibit the progression of the disease. These are the biological response modifiers. Their main representatives are infliximab, adalimumab, and etanercept. At the end, the authors discuss secondary pulmonary complications caused by biological response modifiers, e.g. the biological response modifiers associated pulmonary tuberculosis, bacterial tracheobronchitis, bacterial pneumonia, bronchiectasia, pulmonary oedema, rapid fibrosing alveolitis, and coccidioidomycosis. At 3% of patients with rheumatoid arthritis, treated with biological response modifiers, who live in Arizona, California, Nevada, pulmonary and systemic mycosis--coccidioidomycosis can appear with a 15% of mortality. As a consequence of frequent earthquakes, the spores getting into the air from the ground infect immunosuppressed patients treated with biological response modifiers. The authors draw attention to the fact that patients who receive biological therapy and travel to the above-mentioned endemic or earthquake-active regions, have a potential high risk, so it is indispensable that they are informed by the doctor. Testing and use of newer and newer groups of biological response modifiers are expected in the near future in the therapy of rheumatoid arthritis. Nowadays--in patients, who are non-reactive for TNF-alpha inhibitor treatment--the use of B-lymphocyte inhibitor rituximab, characteristic in non-Hodgkin lymphoma therapy is possible. The pulmonary complications of rheumatoid arthritis therapy of that cytokine are not known yet. Today, antirheumatic therapy results in a significant improvement of patients' life-quality, whilst the more and more modern therapeutical methods cause more complications.
17762459 Reactivation of pulmonary tuberculosis in a patient with rheumatoid arthritis during treat 2007 Aug This single case report describes reactivation of previous pulmonary tuberculosis (TBC) after 23 months of treatment with the IL-1 receptor antagonist anakinra. This patient had severe acute rheumatoid arthritis (Disease Activity Score >6). Initially, he received treatment with 10 mg prednisolone daily along with oral methotrexate 15 mg weekly. Methotrexate was discontinued after 3 months because of repeated liver enzyme elevation. After the disease became more active, he was treated with the IL-1 receptor antagonist along with 10 mg prednisolone daily. One month later, the patient improved significantly, and prednisolone was decreased to 5 mg on alternate days and discontinued after another 3 months. After 23 months of anakinra monotherapy, the patient developed pulmonary TBC and was put on quadruple anti-TBC treatment, which resulted in excellent recovery. Six years before, the patient had pulmonary TBC and received triple anti-TBC treatment for 9 months with complete clinical and radiologic remission. We believe this is the first reported case of TBC reactivation during anakinra treatment.
16645972 Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. 2006 May OBJECTIVE: Spontaneous reports of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with leflunomide, a disease-modifying antirheumatic drug (DMARD), have been appearing recently. To assess this risk, we conducted a population-based epidemiologic study. METHODS: A cohort of 62,734 patients with RA to whom a DMARD had been dispensed between September 1, 1998 and December 31, 2003 was formed using the PharMetrics claims database. A nested case-control design was used, in which each case of serious ILD requiring hospitalization was matched to 100 controls according to age (calendar time) and equal or greater duration of followup, to estimate adjusted rate ratios (RRs) of serious ILD associated with DMARD use. RESULTS: There were 74 cases of serious ILD, which corresponds to a rate of 8.1 per 10,000 patients per year. The risk of ILD was increased with the use of leflunomide (adjusted RR 1.9 [95% confidence interval (95% CI) 1.1-3.6]). Among subjects with no previous methotrexate use and no history of ILD, the risk associated with leflunomide treatment was not elevated (RR 1.2 [95% CI 0.4-3.1]), but it was elevated among the remaining subjects (RR 2.6 [95% CI 1.2-5.6]). Patients with a history of ILD were twice as likely to have been prescribed leflunomide as any other DMARD. CONCLUSION: The reports of ILD associated with leflunomide use are likely the result of channeling of high-risk patients to leflunomide treatment, particularly those with a history of methotrexate use or preexisting ILD. Patients with no history of ILD and no previous methotrexate use show no excess risk of developing ILD with leflunomide treatment.
19062243 [Pneumocystis pneumonia among patients with systemic diseases]. 2009 Feb The termPneumocystis carinii is now reserved for the animal form of the disease, for humans Pneumocystis jiroveci is appropriated. Incidence of pneumocystis pneumonia (PCP) among patients with systemic rheumatic diseases varies from 0.2% for rheumatoid arthritis to up 12% for Wegener's granulomatosis. Clinical and radiological presentation of pneumocystis pneumonia among non-VIH patients is often difficult to diagnose and the installation can be abrupt. Most of cases of PCP occur during the first 3 months following the beginning of immunosuppressant agents. Mortality during PCP is high with an average of 40% of death, rising 60% in case of mechanical ventilation. Prophylaxis of PCP is needed (without support by randomised studies) for patients with Wegener's granulomatosis, in case of cyclophosphamide or high-dose of methotrexate use except for rheumatoid patients, if a simultaneous treatment by corticosteroids and immunosuppressant agent is required, if a prolonged corticosteroid treatment (> 2 months) is used with dose of prednisone-equivalent > 16mg per day or > 20mg per day > 1month associated with one or more risk factors of PCP among advanced age, denutrition or deep lymphopenia. The best prophylaxis of PCP is cotrimoxazole.
18318257 [Case of malignant lymphoma associated with rheumatoid arthritis]. 2008 Feb A 72-year-old woman was admitted to our hospital with exacerbation of dyspnea. She had a history of rheumatoid arthritis (RA) for 26 years, and had been taking methotrexate and prednisolone. Chest radiograph and chest CT revealed marked mediastinal and right axillary lymph node swelling, interstitial shadows and bilateral pleural effusion. A biopsy of the right axillary lymph node for histopathological examination revealed diffuse large B cell lymphoma. The patient achieved complete remission, following 7 cycles of chemotherapy (R-EPOCH). As RA is associated with an increased risk of developing lymphoma, malignant lymphoma must be considered as a possible cause of the mediastinal swelling in a patient with RA.
18383415 Comparison of employability outcomes among patients with early or long-standing rheumatoid 2008 Apr 15 OBJECTIVE: To compare employability between patients with early and long-standing rheumatoid arthritis (RA) and examine the relationships between improvement in employability and disease stage after adjustment for demographic characteristics, disease activity, physical functioning, and response to therapy. METHODS: We evaluated the employability data from 2 double-blind, randomized, placebo-controlled studies of infliximab plus methotrexate (MTX) in patients with RA. Patients were incomplete responders to MTX in 1 study and had never taken MTX in the other study. Patients age <65 years were categorized as having early RA (< or =3 years disease duration) or long-standing RA (>3 years disease duration). Physical functioning was assessed using the Health Assessment Questionnaire (HAQ) and clinical response was determined based on the American College of Rheumatology 20% improvement criteria (ACR20). RESULTS: Patients with early RA were more likely to be employable at baseline than those with long-standing RA, even after adjusting for baseline HAQ scores. Among patients who were not employable at baseline but achieved an ACR20 response after 1 year of treatment, after adjusting for baseline HAQ score, the patients with early RA who had never taken MTX were 3 times more likely to become employable compared with those with long-standing RA who had an incomplete response to MTX at baseline. CONCLUSION: In 2 clinical trials, patients with early RA were more likely to show improved employment outcomes after treatment than those with long-standing RA, suggesting intervention as early as possible in the disease course maximizes an individual patient's employment potential.
17134602 [Rituximab (MabThera) as treatment of active rheumatoid arthritis]. 2006 Nov 20 Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with a two-week interval and in combination with methotrexate. Mild to moderate side-effects are frequent, particularly during the first infusion, but long-term side-effects are generally rare, although pulmonary events and reactivation of viral infections of the liver is of concern.
18537774 Utilization of biologic agents in rheumatoid arthritis in the United States: analysis of p 2008 BACKGROUND: Treatment of rheumatoid arthritis (RA) has shifted toward earlier and more aggressive therapy with tra- ditional disease-modifying antirheumatic drugs (DMARDs) and biologics. However, the extent to which these agents are used in current clinical practice in the United States (U.S.) has not been systematically evaluated. MATERIALS AND METHODS: This analysis of a large claims database assessed patterns of use of biologics within clinical practice in a broad U.S. population with RA. We identifed two cohorts of adults with RA using Thomson Healthcare MarketScan Research databases. Patients newly diagnosed with RA between 1999 and 2004 with 12 months or more of continuous enrollment prior to diagnosis and with 24 months or more post-diagnosis were included in one cohort. The second cohort included RA patients who appeared to be newly treated with biologic therapy and had continu- ous enrollment for 12 months or more prior to frst use of a biologic agent and 18 months or more following initial treatment. A total of 16,752 patients, newly diagnosed with RA, and 8218, new to biologics therapy, were included. RESULTS: Utilization of biologics increased from 3% of patients in 1999 to 26% in 2006. Patients initiated biolog- ics both as monotherapy (30%) and in combination with methotrexate (36%). Regimen modifcations were frequent, with a large percentage of patients requiring addition or subtraction of methotrexate. CONCLUSIONS: The use of biologics to treat RA is increas- ing, either as monotherapy or in combination with another DMARD. Modifcations to drug regimens are frequent and episodes are often of comparatively short duration.
16126800 An open label, single dose study to evaluate the safety, efficacy, and effects on CD25 exp 2006 Apr OBJECTIVE: To explore the safety, efficacy, and lymphocyte activation of a triple therapeutic regimen with infliximab, methotrexate (MTX), and ciclosporin A (CsA) by an open label, pilot study. PATIENTS AND METHODS: 19 patients (mean age 52.9 years) with active rheumatoid arthritis (mean DAS28 7.3) after a mean of 16.8 infliximab infusions and dose adjustments of both infliximab and MTX were enrolled. CsA was added to a stable therapeutic regimen. Disease activity was evaluated by the DAS28. Lymphocyte activation was evaluated by assessing CD25 expression on peripheral blood mononuclear cells (PBMCs). Primary end points were safety and efficacy according to the EULAR response criteria at 24 weeks. RESULTS: Eight patients (42%) discontinued treatment: adverse events (3), inefficacy (2) or non-compliance (2). One patient had a stroke and died. 5/11 (45%) patients who completed 24 weeks' treatment were moderate responders. CD25 expression, both on unstimulated and phytohaemagglutinin stimulated PBMCs in five patients assessed, was reduced (mean (SD) values from 37 (34)% to 15 (10)% and from 50 (15)% to 29 (20)%, respectively). CONCLUSION: In this group of patients with refractory, highly active disease, addition of CsA reduced lymphocyte activation, and resulted in a modest response and a high rate of discontinuation. In such patients, other new approaches need to be explored.
17985420 Treatment of recent-onset rheumatoid arthritis: lessons from the BeSt study. 2007 Nov OBJECTIVE: To determine the efficacy, toxicity, utilities, and costs of 4 treatment strategies for patients with recent-onset rheumatoid arthritis (RA). METHODS: 508 patients with recent-onset active RA [mean Disease Activity Score (DAS) 4.4, mean Health Assessment Questionnaire score 1.4] were randomized into 4 strategy groups: (1) sequential monotherapy; (2) step-up to combination therapy [both starting with methotrexate (MTX)]; (3) initial combination therapy with MTX, sulfasalazine, and prednisone; (4) initial combination therapy with MTX and infliximab. Treatment adjustments were based on 3-monthly calculations of the DAS (target DAS ? 2.4), by research nurses who were blinded to the strategy group. They also collected data on treatment toxicity, functional ability, costs, and utilities. Yearly anonymized radiographs of hands and feet were scored in random order by 2 independent physicians, using the Sharp/van der Heijde score. RESULTS: Functional ability improved significantly earlier in Groups 3 and 4 than in Groups 1 and 2, but was comparable among the groups at the end of the first year of treatment. Radiographic joint damage progression was significantly lower in Groups 3 and 4 than in Groups 1 and 2, but low in all groups compared to other RA populations, probably due to DAS-driven treatment adjustments in all groups. More patients in Groups 3 and 4 than in Groups 1 and 2 achieved clinical remission (DAS 1.6), and patients who achieved early continued remission in Groups 3 and 4 had significantly less joint damage progression than those who achieved the same in Groups 1 and 2. More patients could taper and stop all antirheumatic drugs and still retained remission in Group 4 (17% at t = 3 years) than in the other groups (10%, 5%, 9%, respectively). Toxicity was comparable between groups. Quality of life measures were significantly higher in Group 4 than in the other groups, but costs of treatment were also the highest in Group 4. Depending on the method used, higher productivity in Group 4 compensated for the higher medical costs. CONCLUSION: In patients with recent-onset RA, initial combination therapy including prednisone or infliximab results in earlier clinical improvement and less joint damage progression than initial monotherapy. Initial treatment with infliximab resulted in the highest quality of life, highest productivity, and highest medical costs. DAS-driven treatment adjustments were effective to suppress disease activity and damage progression in all groups.
19102090 [Undesirable effects of methothrexate during treatment of rheumatoid arthritis]. 2007 INTRODUCTION: Methotrexate used as antimetabolite since 40 years in cancerology, is curretly pointed out at weak dose in the treatment of rheumatoid arthitis. However, the intervening of undesirable effects is currently the principal factor limiting its use. The main of our study was evaluate the nature and the frequency of undesirable effects during treatement of rhumatoid arthritis by methotrexate in a prospective study in the department of internal medecine of A.L.D hospital. MATERIAL AND METHODS: Fifty patients were included in the study, they were 43 female and 7 male (sex ratio of 0.161).The mean age were 40.8 years, ranging from 18 to 68. The mean last of MTX treatment was 16.58 months, ranging from 1 to 64. RESULTS: Twenty seven patients (54%) had at least one undesirable effect. Undesirable effect appeared early in 74.1%. they were 61.5% when MTX was associated with others drugs versus 27.3% when MTX was used alone. Undesirable effects mostly were digestives (38%), general (30%), mucouscutaneous (8%) and hepatics (2%).for patients undesirable effects had involved. They were responsable of definitive stopping treatment in two cases of pulmonary tuberculosis.
18581158 Sinusitis: a possible link with adalimumab. 2008 Sep The experience with anti-TNF agents is relatively short; and with time, we are learning more about the frequency of occurrence of different adverse events as the original trials were either too small or too brief. We report a case series of four patients who suffered from chronic inflammatory arthritis [rheumatoid arthritis (n = 3) and psoriatic arthritis (n = 1)]. Their inflammatory arthritis remained refractory to increasing doses of methotrexate up to 20 mg weekly and required an advance in treatment to TNF antagonists. However, within a few weeks of commencing these patients on adalimumab, they developed newly diagnosed recurring sinusitis. All these patients were assessed by otorhinolaryngologists, and had clinically confirmed diagnosis. The sinusitis remained refractory to standard medications; however, it resolved after the discontinuation of adalimumab. Although FDA and Irish Pharmaceutical Health Association describe that adalimumab use increases the risk of non-serious infections marginally and most of the patients continued on Humira (adalimumab) after the infection was resolved, however, our recent observation raises the concern of probable higher incidence.
18463945 Efficacy of low-dose tacrolimus added to methotrexate in patients with rheumatoid arthriti 2008 The aim of this study was to assess if low-dose tacrolimus is efficacious for the treatment of rheumatoid arthritis (RA) when combined with methotrexate (MTX). The clinical courses of 32 RA patients who received tacrolimus plus MTX were analyzed retrospectively. Disease activity and clinical response were evaluated by DAS28 (disease activity score of 28 joints) and EULAR (European League Against Rheumatism) response criteria. Tacrolimus was started at 1 mg/day in five patients, 1.5 mg/day in 24 patients, and three mg/day in 3 patients. At six months, tacrolimus was continued at 1-2 mg/day in 27 of 32 patients, but was discontinued in five cases who showed no or inadequate response. Of the 32 patients, 47% were evaluated as having a moderate or good response at one month of tacrolimus therapy, and 72% at six months. No serious adverse events were observed. Our results suggest that the addition of tacrolimus at low dose to MTX for the treatment of patients with moderately active RA appears to be highly efficacious. Further studies are required for the appropriate use of this expensive immunosuppressant in the treatment of RA.
17564786 Methotrexate pneumonia lacking dyspnea and radiographic interstitial patterns during treat 2007 Methotrexate (MTX) pneumonia is an unpredictable and sometimes life-threatening adverse effect occurring in the treatment of rheumatoid arthritis (RA). We present a case of MTX pneumonia lacking severe respiratory symptoms and typical radiographic findings. A 66-year-old man with early RA presented with intermittent fever and nonproductive cough during the MTX therapy, but neither hypoxemia nor dyspnea was a complaint. His chest X-ray films revealed multiple bilateral consolidations, but interstitial infiltrates were not observed. High-resolution computed tomography showed no ground-glass opacities. In contrast, the histological findings of transbronchial lung biopsy (TBLB) samples were characterized by the interstitial infiltration of mononuclear cells and hyperplasia of type II alveolar cells, which are the main features of drug-induced interstitial inflammation. Special stains for microorganisms were negative for the TBLB samples. Although cultures of bronchoalveolar lavage (BAL) fluids were slightly positive for Haemophilus influenzae, intensive antibiotic therapy was ineffective. A discontinuation of MTX followed by steroid therapy induced the patient's dramatic recovery. A new treatment with tacrolimus was started for RA. We would like to emphasize that the histological examinations and microbiological studies using BAL and TBLB are useful for the exclusion of other causes and the diagnosis of MTX pneumonia, especially in a case without typical respiratory symptoms and radiographic patterns.
17655372 Clinical pharmacokinetics and use of infliximab. 2007 Tumor necrosis factor-alpha (TNFalpha) is a key proinflammatory cytokine involved in chronic inflammatory diseases. Infliximab, a chimeric (human-murine) monoclonal IgG1 anti-TNFalpha antibody, is used in the treatment of Crohn's disease (including fistulising disease) and rheumatoid arthritis (in combination with methotrexate) if standard treatments have failed. The indications for infliximab have recently been expanded to include ankylosing spondylitis, psoriatic arthritis, psoriasis and ulcerative colitis. The biological agent infliximab is given by multiple intravenous infusions in a dosage of 3-5 mg/kg (initially at weeks 0, 2 and 6; subsequently in intervals of 4-8 weeks). In controlled trials, clinical response rates of 20-40% have been achieved with such regimens in Crohn's disease and rheumatoid arthritis. However, the therapeutic benefits must be balanced against the risks of a variety of severe adverse events (e.g. severe infections including tuberculosis, hepatotoxicity, infusion reactions, serum sickness-like disease and lymphoma). Following single and multiple infusions of infliximab, no relevant differences in median concentration-time profiles have been observed between patients with Crohn's disease, patients with rheumatoid arthritis and patients with psoriasis. The apparent volume of distribution of the high-molecular-weight infliximab (149.1 kDa) is low (3-6L) and represents the intravascular space. The long persistence in this compartment (elimination half-life 7-12 days, mean residence time 12-17 days) is due to the very low systemic clearance of about 11-15 mL/hour (0.18-0.25 mL/minute). Elimination of infliximab is most probably accomplished through degradation by unspecific proteases. During multiple infusions (every 4-8 weeks), no accumulation was observed, and serum concentrations and the area under the plasma concentration-time curve of infliximab increased in proportion to the infused dose, indicating linear pharmacokinetics. Co-medication with methotrexate delayed the decline in the serum concentrations of infliximab. When relating serum concentrations to the clinical response in patients with rheumatoid arthritis and patients with Crohn's disease, it can be assumed that trough concentrations above 1 microg/mL could be used as a kind of therapeutic target. In the future, identification of biomarkers for (non-)response and risk factors for adverse drug reactions would be very helpful. Furthermore, combined biological, pharmacokinetic, pharmacogenomic and clinical studies have not yet been performed and are needed to optimise the therapeutic potential of infliximab, which is currently established as a rescue treatment in refractory patients.
17293364 Limited efficacy of conventional DMARDs after initial methotrexate failure in patients wit 2007 Oct OBJECTIVES: To determine the efficacy of subsequent disease modifying antirheumatic drug (DMARD) therapies after initial methotrexate (MTX) failure in patients with recent onset rheumatoid arthritis (RA), treated according to the DAS for 2 years. METHODS: In groups 1 and 2 of the BeSt study, 244 RA patients were initially treated with MTX 15-25 mg/week. Patients who discontinued MTX because of insufficient clinical response (disease activity score, DAS >2.4) or toxicity were classified as "MTX failures." In group 1, these patients switched to sulfasalazine (SSA), then leflunomide and finally to MTX + infliximab (IFX). In group 2, "MTX failures" added SSA to MTX, then hydroxychloroquine (HCQ), then prednisone, and eventually switched to MTX + IFX. "MTX successes" were patients who achieved a DAS
17521223 Etanercept: a review of its use in the management of rheumatoid arthritis. 2007 Etanercept (Enbrel), a soluble fusion protein that binds specifically to the cytokine human tumour necrosis factor (TNF), is approved for subcutaneous use in the treatment of patients with moderate to severe active rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing arthritis and plaque psoriasis in the US, Italy, the rest of the EU and other countries worldwide. Subcutaneous etanercept was efficacious and generally well tolerated in several large, well designed, clinical trials and in the clinical-practice setting in adult patients with rheumatoid arthritis, including methotrexate-naive patients with early disease and those with long-standing, treatment-resistant active disease. Etanercept plus methotrexate combination therapy was generally superior to either monotherapy in reducing disease activity and structural joint damage, as well as improving health-related quality of life (HR-QOL). Furthermore, etanercept monotherapy was superior to placebo and at least as effective as methotrexate therapy in reducing disease activity and improving HR-QOL in patients with early or refractory disease. The beneficial effects of etanercept monotherapy or combination therapy were sustained in the long term (< or =9 years). Some pharmaco-economic analyses suggest that etanercept is a cost-effective option in the treatment of patients with rheumatoid arthritis. Direct head-to-head comparisons with other biological agents would help to definitively position etanercept with respect to these agents. Nevertheless, extensive clinical experience indicates that etanercept is a valuable treatment option in adult patients with long-standing moderate to severe active rheumatoid arthritis and an emerging option in those with early disease.