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ID PMID Title PublicationDate abstract
18211615 Treatment of pregnant and non-pregnant rheumatic patients: a survey among Dutch rheumatolo 2008 Feb BACKGROUND: The aim of this study was to explore, among Dutch rheumatologists, aspects such as attitude towards guidelines, pharmacotherapy and information needs in the treatment of pregnant as well as non-pregnant rheumatoid arthritis (RA) patients. METHODS: Fifteen rheumatologists from nine different hospitals were interviewed by means of a semi-structured interview. Questions addressing attitude towards guidelines, pharmacotherapy preferences and information needs with respect to the pregnant and non-pregnant patient were asked. The analysis will be based on descriptive statistics. RESULTS: Guidelines are used by almost half of the hospitals with respect to pregnant RA patients and by all hospitals for RA patients in general. With respect to pregnant women, nine respondents preferred stopping the medication as soon pregnancy is known. When treating RA patients, in general sulfasalazine and methotrexate would be drugs of first choice. Information is found in international and national books and guidelines. CONCLUSION: Dutch rheumatologists are of the view that there is sufficient information on the treatment of RA in pregnant women or women wishing to become pregnant, except for safe use of medication during pregnancy. In the future, pregnancy risk categorization should be updated and discussed regularly. This should be based on more recent literature and experience. A good monitoring system for following all young patients with a rheumatic disease should be set up as a first step to collect more information on the safe use of medication during pregnancy.
17429636 Eight versus 16-week re-evaluation period in rheumatoid arthritis patients treated with le 2007 Aug In a step-up approach of DMARD treatment of RA a fast response and an early DMARD switch in the case of non-response is important. Therefore, we performed an open trial in which we compared an 8-week and a 16-week observation period during treatment of RA with MTX or LEF, both given in intensified starting doses and accompanied by moderate dose prednisone. MTX and LEF naïve patients with RA (mean time since diagnosis: 2.3 years) were randomised to receive either LEF in a 3-day-loading dose of 100 mg/day followed by 20 mg/day (n = 19) or MTX intramuscularly in a dose of 25 mg once weekly (n = 21). All patients received concomitant treatment with oral prednisone in an initial dose of 20 mg/day with weekly dose reductions of 5 mg/day. The disease activity was re-evaluated 8 and 16 weeks after the start of the treatment. Mean DAS28 before the start of treatment was 5.36 +/- 0.8 for the MTX-group and 5.46 +/- 0.8 for the LEF-group. After 8 weeks of treatment the DAS28 in the MTX-group was 2.59 +/- 1.0 and 3.16 +/- 0.8 in the LEF group (difference not significant). The mean DAS28 at re-evaluation 16 weeks after the starting of treatment (2.58 +/- 1.5 for the MTX-group and 3.25 +/- 1.16 for the LEF-group) was significantly different neither in between the both treatment groups nor in comparison to the week 8 evaluation. Efficiency of RA treatment with MTX or LEF in intensified doses and in combination with moderate dose prednisone can be sufficiently judged 8 weeks after its initiation.
16934327 The changing maternal "self" hypothesis: a mechanism for maternal tolerance of the fetus. 2007 May Recent advances in placental biology and immunology lead us to propose a novel hypothesis for maternal tolerance of the semi-allogeneic fetus and amelioration of rheumatoid arthritis (RA) during pregnancy. The initial event in this hypothesis is extrusion of placental apoptotic syncytiotrophoblast debris recently identified to contain intracellular fetal HLA Class II molecules, into maternal blood. The second event is uptake of apoptotic syncytiotrophoblast by immature maternal dendritic cells and presentation of fetal HLA class II peptides. In addition to presenting foreign antigens, HLA molecules also present HLA self-peptides. In the setting of the non-inflammatory environment of pregnancy, this process is expected to induce peripheral tolerance of fetal antigens through T cell death, anergy or induction of regulatory T cells in the lymph nodes. This hypothesis suggests a mechanism by which the simultaneous presentation of fetal and self (RA-associated) HLA peptides by tolerogenic dendritic cells during pregnancy may explain the observed amelioration of RA as a secondary benefit of fetal tolerance. After delivery, apoptotic syncytiotrophoblast debris disappears from maternal blood, autoimmunity returns and RA recurs. Thus, during pregnancy maternal immunologic "self" includes fetal HLA Class II as a result of apoptotic syncytiotrophoblast uptake by maternal tolerogenic dendritic cells.
17037265 Bayesian optimal designs for a quantal dose-response study with potentially missing observ 2006 In a dose-response study, there are frequently multiple goals and not all planned observations are realized at the end of the study. Subjects drop out and the initial design can be quite different from the final design. Consequently, the final design can be inefficient. Single- and multiple-objective Bayesian optimal designs that account for potentially missing observations in quantal response models were recently proposed in Baek (2005). In this work, we investigate the efficiencies of the conventional optimal designs that do not incorporate potential missing information relative to our proposed designs. Furthermore, we examine the impact of restricted dose range on the resulting optimal designs. As an application, we used missing data information from a study by Yocum et al. (2003) to design a study for estimating dose levels of tacrolimus that will result in a certain percentage of rheumatoid arthritis patients having an ACR20 response at 6 months.
18514883 Erysipelothrix rhusiopathiae infection of a total knee arthroplasty an occupational hazard 2008 Jun A 76-year-old man with a medical history of rheumatoid arthritis, lupus intersititial nephritis, and steroid therapy was found at first-stage revision total knee arthroplasty to have Erysipelothrix rhusiopathiae (a zoonotic pathogen normally associated with pigs and fish) infection of the arthroplasty. He had a history of potential occupational exposure to the organism. On literature review, we found only 3 other case reports of E rhusiopathiae linked to septic arthritis in humans. This unique case of an infected joint arthroplasty further illustrates the pathogenicity of E rhusiopathiae in humans.
18092260 The number needed to treat for adalimumab, etanercept, and infliximab based on ACR50 respo 2007 Nov OBJECTIVE: To compare the efficacy of adalimumab, etanercept, and infliximab in patients with established rheumatoid arthritis (RA) taking concomitant methotrexate (MTX) by calculating the number needed to treat (NNT) using three different methods. METHODS: A systematic literature search of the Cochrane Library, MEDLINE, and EMBASE was conducted from inception to 30 June 2006. Two pairs of investigators, a Danish and a Swedish pair, independently conducted a structured literature review. The reviewers selected any published randomized, double-blind, MTX controlled study of adalimumab, etanercept, and infliximab, presenting the American College of Rheumatology 50% response (ACR50) after 12 months in RA patients with a mean disease duration of at least 5 years. The two review groups independently extracted the estimates necessary to calculate the NNT. RESULTS: The reviewers consistently selected the same three randomized, controlled trials (RCTs), one for each of the drugs, and extracted equal data for the number of patients completing the 12-month intervention, and the corresponding number of ACR50 responding patients after therapy. Some baseline differences were noted: patients in the etanercept trial had a shorter disease duration and did not receive MTX prior to inclusion; patients in the adalimumab study had lower Health Assessment Questionnaire (HAQ) scores. The calculated NNTs varied slightly depending on the method used. The fully adjusted NNTs (95% confidence intervals) for adalimumab, etanercept, infliximab standard dosage and infliximab double dosage were 4 (3-6), 4 (3-6), 8 (4-66), and 4 (3-11) patients, respectively. CONCLUSION: This study indicates equal efficacy of the three anti-tumour necrosis factor (TNF) therapies.
17451848 [Pancytopenia related to low-dose methotrexate: study of five cases and review of the lite 2007 Sep PURPOSE: The aim of this study is to report personal experience of pancytopenia related to low-dose methotrexate and to review the literature. METHODS: We included retrospectively all cases of pancytopenia related to low-dose methotrexate (<25 mg/week), followed between January 1997 and December 2006, in the university hospital of Strasbourg, France. RESULTS: Five women, mean age 75.6 years, were included in the present study. Clinical manifestations included: symptomatic anemia (n=4), infection (n=3) and hemorrhagic manifestations (n=2); one patient had no feature. Mean hemoglobin concentration was 8,8 g/dl; mean white cell and platelet counts were 1,500 /mm(3) and 16,000 /mm(3), respectively. Potential risk factors were identified in all patients: renal failure and low serum albumin levels (n=5), anti-inflammatory drug intake (n=2), folate deficiency (n=4) and cobalamin deficiency (n=1). One patient died of septic and hemorrhagic cerebral complications. CONCLUSION: Pancytopenia related to tow-dose methotrexate is a rare but life-threatening disorder. Search and prevention of potential risk factors are required in all patients; determination of MTHFR genotype may be of several interests as folate supplementation.
17075823 Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observatio 2006 Nov OBJECTIVE: Randomized clinical trials (RCTs) evaluate the efficacy of treatments in selected groups of patients defined by strict inclusion criteria. The value of these trials in predicting therapeutic effectiveness in "real world" patients is limited. This observational cohort study was designed to complement the knowledge obtained in RCTs by evaluating the effectiveness of tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) according to their eligibility for the major trials. METHODS: Using the data from the German biologics register Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT [in German]), we investigated how many of the RA patients who were treated with a TNF inhibitor (infliximab, etanercept, or adalimumab) would have been eligible for the major clinical trials that led to approval of the drugs. In addition, therapeutic effectiveness was compared in the eligible and ineligible patients using the American College of Rheumatology 20% (ACR20) and 50% (ACR50) improvement response criteria. RESULTS: Only 21-33% of the patients in the RABBIT register would have been eligible for the major trials. In these patients, the ACR20 and ACR50 improvement responses, indicating therapeutic effectiveness, were comparable with the response rates in the published trials. ACR response rates were lower in those patients considered ineligible for the trials; however, absolute improvement was similar to that in eligible patients. Ineligible patients had lower baseline disease activity, more comorbidity, and lower functional status. CONCLUSION: RCT cohorts reflect only a minor proportion of the patients treated with biologic agents in routine care. In the clinic setting, the indications for treatment with biologic agents are not identical to the inclusion criteria for trials. Despite the smaller relative improvement achieved in these patients with longstanding, severe RA who would not fulfill the inclusion criteria of a major trial, the majority of such patients would nevertheless benefit from biologic therapy.
17167996 Automatic quantification of changes in bone in serial MR images of joints. 2006 Dec Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions.
16889662 Robust computational reconstitution - a new method for the comparative analysis of gene ex 2006 Aug 4 BACKGROUND: Biological tissues consist of various cell types that differentially contribute to physiological and pathophysiological processes. Determining and analyzing cell type-specific gene expression under diverse conditions is therefore a central aim of biomedical research. The present study compares gene expression profiles in whole tissues and isolated cell fractions purified from these tissues in patients with rheumatoid arthritis and osteoarthritis. RESULTS: The expression profiles of the whole tissues were compared to computationally reconstituted expression profiles that combine the expression profiles of the isolated cell fractions (macrophages, fibroblasts, and non-adherent cells) according to their relative mRNA proportions in the tissue. The mRNA proportions were determined by trimmed robust regression using only the most robustly-expressed genes (1/3 to 1/2 of all measured genes), i.e. those showing the most similar expression in tissue and isolated cell fractions. The relative mRNA proportions were determined using several different chip evaluation methods, among which the MAS 5.0 signal algorithm appeared to be most robust. The computed mRNA proportions agreed well with the cell proportions determined by immunohistochemistry except for a minor number of outliers. Genes that were either regulated (i.e. differentially-expressed in tissue and isolated cell fractions) or robustly-expressed in all patients were identified using different test statistics. CONCLUSION: Robust Computational Reconstitution uses an intermediate number of robustly-expressed genes to estimate the relative mRNA proportions. This avoids both the exclusive dependence on the robust expression of individual, highly cell type-specific marker genes and the bias towards an equal distribution upon inclusion of all genes for computation.
16634363 The world of biologics. 2006 In March 2002 the National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of anti-TNF therapy for patients with rheumatoid arthritis (RA). The guidelines recommended that all RA patients treated with these drugs should be enrolled on a national register which had been established by the British Society for Rheumatology (the BSRBR). A comparison cohort of RA patients treated with traditional disease modifying drugs (DMARDs) is also being recruited. The main role of the BSRBR is to study the long-term safety of biologic drugs. Up to the end of March 2005, 9508 patients with RA had been enrolled on the BSRBR. Four thousand, three-hundred and six had been treated with etanercept, 3561 with infliximab, 1500 with adalimumab and 141 with anakinra. With regards to anti-TNF drugs, 79% remained on their original drug at six months, 65% of whom could be classified as responders. Co-prescription with methotrexate was associated with a 70% response rate. Patients with a high baseline level of disability were less likely to respond. Overall the rates of serious infection were not increased in the anti-TNF versus the comparison cohort. However the rates of skin and soft tissue infection and of intracellular infections (eg, salmonella, listeria, legionella) were increased. There were 11 cases of tuberculosis (seven extra-pulmonary). There was concern about the high mortality rates among patients with baseline pulmonary fibrosis treated with anti-TNF therapy. It is unclear whether this is related to the drug or to the underlying disease. The rates of malignancy and mortality were not increased compared to the DMARD treated group in the short term. Further follow-up is needed to determine the long term safety of these drugs.
18848647 Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid 2009 Jan Antibody titers to P. gingivalis are increased in patients with rheumatoid arthritis and are associated with disease-specific autoimmunity. BACKGROUND: Periodontitis (PD) has been implicated as a risk factor for rheumatoid arthritis (RA). We sought to characterize antibody titers to P. gingivalis (a pathogen in PD) in subjects with RA, PD, and in healthy controls and to examine their relationship with disease autoantibodies. METHODS: P. gingivalis antibody was measured in subjects with RA (n=78), PD (n=39), and in controls (n=40). Group frequencies of bacterial titer elevations were compared using the Chi-square test and antibody titers were compared using non-parametric tests. Correlations of P. gingivalis titer with C-reactive protein (CRP), antibody to cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were examined in those with RA while CRP and autoantibody concentrations were compared based on seropositivity to P. gingivalis. RESULTS: Antibody titers to P. gingivalis were highest in PD, lowest in controls, and intermediate in RA (p=0.0003). Elevations in P. gingivalis (titer> or =800) were more common in RA and PD (67% and 77%, respectively) than in controls (40%) (p=0.002). In RA, there were significant correlations with P. gingivalis titer with CRP, anti-CCP-IgM, and -IgG-2. CRP (p=0.006), anti-CCP-IgM (p=0.01) and -IgG2 (p=0.04) concentrations were higher in RA cases with P. gingivalis titers > or =800 compared to cases with titers <800. CONCLUSION: Antibodies to P. gingivalis are more common in RA subjects than controls, although lower than that in PD. Associations of P. gingivalis titers with RA-related autoantibody and CRP concentrations suggests that infection with this organism plays a role in disease risk and progression in RA.
18328142 Maintenance and tolerability of infliximab in a cohort of 152 patients with rheumatoid art 2008 Jan OBJECTIVE: To determine the maintenance, tolerability and safety of infliximab in an unselected cohort of patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: One hundred and fifty-two RA patients receiving at least one course of infliximab between 2000 and 2003 were included in this study. Response to treatment and safety were assessed through recording adverse events, physical examinations and standard laboratory tests. The dosage of infliximab was patient specifically modified, when therapeutic response was judged inadequate by the assessment of a physician. RESULTS: The mean duration of follow-up was 401 days (85-1221). One hundred and twenty-two patients (78%) continued to receive infliximab after one year. 40 patients (26.3%) stopped infliximab therapy: 14 (9.2%) for inefficacy, 21 (13.8%) for adverse events. Fifty nine patients (38.8%) required an increase of the dosage (n=23, 15%) or a shortening of the interval between the infusions (n=20, 13.2%), or both (n=16, 10.5%) for symptomatic control. Infliximab discontinuation tended to be more frequent in smokers (p=0.055). Ninety-four patients (62%) reported at least one adverse event during the study: 64 infections (43%), 35 infusion reaction events (23%) which led to a discontinuation for 10 patients. Infusion reactions were more frequent in patients with a history of allergy. Three cases of tuberculosis and 1 breast carcinoma were reported during the study. CONCLUSIONS: Adjustments in the treatment of RA patients treated with recommended doses of infliximab were common (38.8% of the treated patients). Furthermore, the observed rate of infections (43%), including three cases of tuberculosis, should alert physicians to be vigilant in the routine care of patients treated with infliximab.
18024284 [Association of interleukin-6 and interleukin-18 gene polymorphism with rheumatoid arthrit 2007 Nov OBJECTIVE: To investigate the single-nucleotide polymorphisms (SNPs) at positions -572 and -174 in the promoter region of interleukin-6 (IL-6) gene and at -607 and -137 in the promoter region of interleukin-18 (IL-18) gene for their association with rheumatoid arthritis (RA) in the Chinese Han population in Guangdong Province. METHODS: SNPs of IL-6 and IL-18 genes were detected in 120 patients with RA and 168 normal subjects using polymerase chain reaction with sequence-specific primers (PCR-SSP). RESULTS: SNPs at -572 and -174 of IL-6 gene and at -607 and -137 of IL-18 gene were detected in this population. There was a significant difference in the genotype and allele frequency at -572 and -174 of IL-6 gene and -607 of IL-18 gene (P<0.001), but not in the distribution of genotype frequencies at -137 of IL-18 gene between the RA patients and healthy subjects (P=0.141). A significant difference was found, however, in the allele frequency at -137 of IL-18 (P=0.024). Logistic regression analysis revealed significant association of age, gender, IL-6 gene -572, -174 and IL-18 gene -137 SNPs with RA (P<0.05). CONCLUSIONS: The polymorphisms of the promoter region of IL-6 gene at positions -572 and -174 is probably associated with RA, and further study is needed to understand the relation of the polymorphisms of IL-18 gene at positions -607C/A and-137G/C with RA.
18069009 Shoulder and elbow arthroplasty: one-stage or two-stage. 2008 Jan Multiple joint replacement in 1 operative session is frequently performed in the lower extremity but less often in the upper extremity. The purpose of the present study is to determine whether a 1-stage arthroplasty of the ipsilateral shoulder and elbow affects the clinical outcome. Replacement of the ipsilateral shoulder and elbow was performed in 34 rheumatoid patients (42 upper extremities). In 11 patients (13 upper limbs), the shoulder and elbow arthroplasty was a 1-stage procedure. The average follow-up of the whole group was 4.5 years (range, 2-12 years). The patients were in a prospective study and evaluated clinically and radiographically. With a 1-stage procedure, the hospitalization time was shorter. The overall Hospital for Special Surgery shoulder score and its items (pain, function, and strength) were similar at follow-up in the 2 groups, and only the motion score showed more improvement in the 1-stage group. The clinical outcome of elbow arthroplasty was similar in both groups, regardless of the sequence of surgery. From this study, it may be concluded that a 1-stage procedure for shoulder and elbow arthroplasty will reduce the hospitalization time and does not adversely affect the clinical outcome.
18208329 Analysis and application of European genetic substructure using 300 K SNP information. 2008 Jan European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA) showed the largest division/principal component (PC) differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA) analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.
17878395 Intramuscular methotrexate-induced aseptic meningitis. 2007 Nov OBJECTIVE: To report a case of aseptic meningitis induced by intramuscularly administered methotrexate in a patient with rheumatoid arthritis. CASE SUMMARY: A 62-year-old male presented on 3 separate occasions with symptoms consistent with aseptic meningitis: 2 required hospitalization and 1 was noted during a subsequent ambulatory care visit. Prior to the first episode, the methotrexate dose ranged between 17.5 mg and 20 mg given once weekly over 5 years, 11 months. One month before the patient's first admission, the dose was increased to 22.5 mg. Symptoms on presentation included headache, neck stiffness, and fever. Cerebrospinal fluid testing indicated pleocytosis and low glucose level. Methotrexate was discontinued but was restarted 2 weeks after hospital discharge at the same dose and resulted in a second hospitalization for aseptic meningitis. Upon discharge from the second hospitalization, methotrexate was withheld. After a 2 month withdrawal period and rechallenge, the symptoms returned within 3 days. The drug was then discontinued. DISCUSSION: Methotrexate-induced aseptic meningitis has been reported in the literature; however, in those cases, the effect occurred only when methotrexate was given via the intrathecal route. We identified 7 relevant articles via a search of MEDLINE, International Pharmaceutical Abstracts, and EMBASE (1970-August 3, 2007): 3 were review articles, 2 were case series, and 2 were case reports. All of the series and reports involved patients with leukemia. The available literature suggests that aseptic meningitis is associated with long-term use of methotrexate or recent dose escalation. A definitive mechanism for methotrexate-induced aseptic meningitis is not known. The Naranjo probability scale indicates a probable relationship between the development of the condition and the methotrexate use in our patient. CONCLUSIONS: Aseptic meningitis has been previously associated with intrathecal use of methotrexate. Our report describes the first case of aseptic meningitis that occurred in a patient being treated with intramuscular methotrexate.
17075191 [Multi-drug resistance in the treatments of autoimmune diseases]. 2006 Oct Although corticosteroids and immunosuppressants are widely used for the treatments of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), we often experience patients who are resistant to these treatments. P-glycoprotein (P-gp) of membrane transporters, a product of the multiple drug resistance (MDR)-1 gene, plays a pivotal role in the acquisition of drug resistance. However, the relevance of MDR-1 and P-gp to resting and activated lymphocyte, major targets of the treatments in autoimmune diseases, remains unclear. We found that peripheral lymphocytes in patients with SLE and RA express P-gp on the surface and its expression is highly correlated with disease activity. P-gp on lymphocytes is induced by activation with cytokines such as IL-2, IL-4 and TNF-alpha, resulting in active efflux of corticosteroids from cytoplasm of lymphocytes, which mechanisms could lead to drug-resistance and high disease activity. However, the addition of P-gp antagonists such as ciclosporin A and inhibitors of P-gp synthesis successfully reduce efflux of corticosteroids from lymphocytes in vitro and these results imply that P-gp antagonists and P-gp synthesis inhibitors could work in order to overcome drug-resistance in vivo. Therefore, we propose that measurement of P-gp on lymphocytes is useful marker to indicate drug resistance and requirement of antagonists and/or intensive treatments to overcome drug resistance in active SLE and RA patients.
18173917 Adalimumab plus methotrexate or standard therapy is more effective than methotrexate or st 2007 Nov OBJECTIVES: Fatigue is an important systemic symptom of rheumatoid arthritis (RA) but has rarely been evaluated consistently after initiation of treatment in RA patients. This study examined the effects of adalimumab (HUMIRA, Abbott Laboratories, Abbott Park, IL, USA), a fully human, anti-tumor necrosis factor (anti-TNF) monoclonal antibody, on reducing fatigue in patients with RA. METHODS: A total of 1526 patients with RA were enrolled in 3 randomized, placebo-controlled clinical trials of adalimumab versus placebo plus methotrexate (MTX) or placebo plus standard antirheumatic therapies. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale questionnaire (which has been validated in RA) at baseline, mid-study, and at the end of the study. Logistic regression models were constructed using baseline demographic variables to test for treatment effect. In addition, sensitivity analyses were performed to determine the robustness of the data. RESULTS: At baseline in the 3 trials, patients' fatigue ranged from 27.9-29.7, representing considerable fatigue on the FACIT fatigue scale. Fatigue was significantly and consistently reduced in adalimumab-treated patients in the 3 clinical trials. Relative to placebo plus MTX, the adalimumab 40-mg-every-other-week dosage group reported statistically significantly less fatigue at all time points post-baseline. Improvements between adalimumab and placebo ranged from 3-7 points across all 3 trials, with a 3-4-point change representing a minimum clinically important difference. CONCLUSION: Adalimumab treatment was shown to significantly reduce fatigue in patients with moderate to severe RA. Changes in fatigue in all 3 trials were found to be clinically important.
17580555 [Pharmacotherapy in pregnancy and lactation in rheumatic diseases]. 2006 The specific pharmacotherapy in pregnant women is of great importance in chronic inflammatory rheumatic diseases. Before every potential pregnancy or afterwards the knowledge of pregnancy of women with inflammatory rheumatic disease, it is necessary to evaluate the pregnancy risk for patient and child. The purpose of this review is to give concise informations about the most frequent used drugs in rheumatology and their use in pregnancy and lactation.