Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
15760927 Impact of age and comorbidities on the criteria for remission and response in rheumatoid a 2005 Sep OBJECTIVE: To determine to what extent health status impairment in rheumatoid arthritis (RA) measured by self report of pain, global assessment, and functional disability is attributable to age and other comorbid conditions as opposed to the disease itself. METHODS: Pain, global assessment, and Health Assessment Questionnaire Disability Index (HAQ-DI) were measured in a random sample of 1530 adults in the Central Finland District, Finland. Median regressions were used for multivariable analyses. RESULTS: The mean age was 55.4 years and 72% were women. A large majority of the population reported some pain (76%) and less than perfect general health (83%). The overall mean values of pain, HAQ-DI, and general health were 20 mm, 0.25 units, and 21 mm, respectively. The most common self reported musculoskeletal comorbidities were osteoarthritis (24%) and chronic back pain (25%). Age and number of comorbidities were the only statistically significant correlates of pain and general health in multivariable analyses. CONCLUSIONS: Self reported disability, pain, and poor health were widely prevalent in the general population and are related to age and comorbid conditions. This needs to be taken into account when interpreting remission and response rates using current criteria and for future development of definitions for these end points in RA and other rheumatic diseases.
16508927 Development of antiinfliximab antibodies and relationship to clinical response in patients 2006 Mar OBJECTIVE: Treatment of patients with infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, may result in the formation of infliximab-specific IgG antibodies. This study evaluated the clinical significance of these antibodies in patients with rheumatoid arthritis (RA). METHODS: Antiinfliximab antibodies were measured using a newly developed radioimmunoassay in a cohort of 51 consecutive patients with RA treated with infliximab, with a followup of 1 year. In addition, serum infliximab levels were determined by enzyme-linked immunosorbent assay. The results were analyzed in relation to the clinical response to treatment according to the European League Against Rheumatism criteria. RESULTS: Antibodies against infliximab were detected in 22 patients (43%). Patients without detectable antiinfliximab antibodies (n = 29 [57%]) were significantly more often classified as responders (20 of 29 [69%]) compared with patients with detectable antiinfliximab antibodies (8 of 22 [36%]; P = 0.04). Three patients had an infusion-related allergic reaction, all of whom had detectable antiinfliximab antibodies. CONCLUSION: In this study, nearly half of the RA patients treated with infliximab developed antiinfliximab antibodies within the first year of treatment. This seems to be clinically relevant, since development of antiinfliximab antibodies is associated with a reduced response to treatment.
16891923 Panniculitis: an unusual cutaneous manifestation of rheumatoid arthritis. 2006 Aug Specific and nonspecific panniculitis may occur during the course of connective tissue diseases. However, association of panniculitis and rheumatoid arthritis has only rarely been described, and with so few reports, it is difficult to know the significance of this unusual association. We describe 2 patients with rheumatoid arthritis and features of Sjögren syndrome in whom panniculitis developed during the course of the disease. Histologic confirmation of septal panniculitis was established in one case and the panniculitis in this case improved as the arthritis resolved.
15838509 A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid 2005 May Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here we identify a SNP in the promoter region of FCRL3, a member of the Fc receptor-like family, that is associated with susceptibility to rheumatoid arthritis (odds ratio = 2.15, P = 0.00000085). This polymorphism alters the binding affinity of nuclear factor-kappaB and regulates FCRL3 expression. We observed high FCRL3 expression on B cells and augmented autoantibody production in individuals with the disease-susceptible genotype. We also found associations between the SNP and susceptibility to autoimmune thyroid disease and systemic lupus erythematosus. FCRL3 may therefore have a pivotal role in autoimmunity.
16395747 Anti-infliximab antibodies in patients with rheumatoid arthritis who require higher doses 2006 Jan OBJECTIVE: To determine whether the need to use doses of infliximab greater than 3 mg/kg every 8 weeks to achieve or maintain clinical response in patients with rheumatoid arthritis (RA) is associated with differences in baseline clinical characteristics or anti-infliximab antibodies. METHODS: Baseline clinical characteristics and anti-infliximab levels were evaluated retrospectively in a cohort of 51 consecutive patients with RA treated with infliximab at a single center. Patients were divided into 2 groups for comparison: Group 1 patients achieved and maintained clinical responses with infliximab 3 mg/kg every 8 weeks; Group 2 patients required higher doses. RESULTS: Thirty-two (63%) patients required infliximab dose escalation (Group 2). There were no statistically significant differences in baseline or clinical characteristics between Group 1 and Group 2 patients. Anti-infliximab antibodies occurred in 47% of Group 2 versus 27% of Group 1 patients, with higher anti-infliximab antibody concentrations in Group 2 patients (mean +/- SD: 18.3 +/- 8.9 g/ml vs 7.5 +/- 4.8 g/ml; p = 0.02). Patients who developed anti-infliximab antibodies were younger and receiving less prednisone at the time of infliximab initiation than patients who did not. CONCLUSION: Finding higher anti-infliximab antibody concentrations in patients who needed dose escalation of infliximab to achieve or maintain clinical responses with lower serum trough levels of infliximab suggests that development of anti-infliximab antibodies may reduce clinical efficacy of infliximab in some patients with RA.
16263777 Safety of tacrolimus, an immunosuppressive agent, in the treatment of rheumatoid arthritis 2006 Apr OBJECTIVE: To prospectively evaluate the safety of tacrolimus in active rheumatoid arthritis (RA) in elderly patients with insufficient response to disease-modifying antirheumatic drugs (DMARDs). METHODS: Fifty-seven patients aged > or =65 yr with RA for > or =6 months were enrolled in an open-label, non-controlled study. All DMARDs were discontinued and tacrolimus was administered orally once daily after the evening meal for 28 weeks. Tacrolimus, initiated at 1.5 mg/day, was increased to 3 mg/day after 6 weeks if no abnormal changes developed. Existing NSAID and oral corticosteroid (< or =7.5 mg/day prednisolone equivalent) therapy could be continued during the study. Safety was evaluated as clinical symptoms, abnormal changes in laboratory values and the development of infection. Treatment response was determined using the American College of Rheumatology (ACR) criteria for improvement. Whole blood concentrations of tacrolimus 12 h after administration were measured by high-performance liquid chromatography and tandem mass spectrometry. RESULTS: Clinical adverse events developed in 25 patients (46.3%). Abnormal changes in laboratory values occurred in 25 patients (46.3%). Ten patients (18.5%) developed infection. An ACR20 response was achieved by 50.0% of efficacy-evaluable patients and ACR20 success rates (the proportion of patients achieving ACR20 response and completing the study) was 46.3%. The ACR50 response rate was 18.5% of evaluable patients. Mean blood concentration of tacrolimus was 3.3 and 5.3 ng/ml in patients receiving 1.5 and 3.0 mg daily, respectively. No relationship between its concentration and adverse reactions was observed. CONCLUSION: In elderly patients with insufficient response to DMARD therapy, tacrolimus at 1.5-3.0 mg/day is safe and well-tolerated and provides clinical benefit.
15876399 The role of cathepsins in osteoporosis and arthritis: rationale for the design of new ther 2005 May 25 Human cysteine proteases of the papain family have been recognized as potential drug targets for musculoskeletal diseases. Most of the interest is focused on cathepsins S and K, which display selective expression in cells of the immune system and cells capable to efficiently degrade extracellular matrix proteins, in particular collagens. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel anti-resorptive drugs in osteoporosis whereas cathepsin S appears to be an attractive drug target candidate for various inflammatory diseases including rheumatoid arthritis. Since rheumatoid arthritis is at the same time an inflammatory and joint destructive disorder, the combined inhibition of both cathepsins S and K should be beneficial. This review will outline the rationale and recent progress for targeting cathepsins in arthritis and osteoporosis.
15692989 Reduction of joint damage in severe rheumatoid arthritis by high-dose chemotherapy and aut 2005 Feb OBJECTIVE: To examine the influence of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) on joint damage in patients with rheumatoid arthritis. METHODS: Eight patients with active, refractory, progressively erosive RA were treated. The conditioning regimen consisted of intravenous administration of high doses of cyclophosphamide (totaling 200 mg/kg), with subsequent reinfusion of the positively selected graft. Radiographs of hands and feet were obtained before, and at 1 and 2 years after transplantation. All radiographs of hands and feet obtained up to 6 years before transplantation were also collected to compare radiographic progression before and after HDC + ASCT. Scoring of all radiographs was performed according to the Larsen scale by a trained investigator who was blinded with regard to the clinical data. RESULTS: Radiographic assessment by the Larsen scale showed a decreased progression of joint damage. Before transplantation, the mean Larsen score increased at a rate of 8.9 points per year. During the 2 years after transplantation, the mean rate of progression in the Larsen score decreased to 2.7 points per year (P = 0.023 by paired t-test). CONCLUSION: The results of the present analysis demonstrate major beneficial effects of HDC + ASCT on the rate of joint destruction during the first 2 years of followup after treatment.
15998631 The 158V polymorphism of Fc gamma receptor type IIIA in early rheumatoid arthritis: increa 2005 Oct OBJECTIVES: To evaluate the influence of Fcgamma receptor IIIA (FcgammaRIIIA) 158V/F polymorphism on susceptibility and disease severity in early rheumatoid arthritis (RA). METHODS: In 181 Swedish patients (128 women, 53 men) with RA of recent onset, disease and disability variables such as erythrocyte sedimentation rate, 28-joint disease activity score (DAS28) and health assessment questionnaire (HAQ) scores were monitored regularly during 3 yr. Three hundred and sixty-two controls were recruited from the same geographical area as the patients. FcgammaRIIIA genotyping was performed using denaturing high-performance liquid chromatography. RESULTS: In all RA patients, FcgammaRIIIA-158VV was significantly over-represented compared with controls [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.01-3.5, P<0.05]. After stratifying for sex, the difference remained in the male population (OR 3.2, 95%CI 1.03-11, P<0.05) but disappeared among women (OR 1.4, 95%CI 0.7-3.1, P=0.4). In addition, 158VV patients were more likely to exhibit early joint erosions (OR 6.1, 95%CI 1.4-28, P<0.01). At baseline, patients with different FcgammaRIIIA genotypes did not differ with respect to measures of disease activity or functional ability. Thereafter, in male patients with at least one V allele the mean DAS28 and HAQ scores were higher compared with 158FF. In contrast, female patients with at least one 158V allele displayed lower mean DAS28 and HAQ scores compared with those with 158FF. CONCLUSIONS: In a male population, the FcgammaRIIIA-158VV genotype is associated with an increased risk of developing RA, and the 158V allele with more severe disease in early RA.
16542505 Conventional radiography requires a MRI-estimated bone volume loss of 20% to 30% to allow 2006 The aim of this study was to demonstrate the ability of conventional radiography to detect bone erosions of different sizes in metacarpophalangeal (MCP) joints of rheumatoid arthritis (RA) patients using magnetic resonance imaging (MRI) as the standard reference. A 0.2 T Esaote dedicated extremity MRI unit was used to obtain axial and coronal T1-weighted gradient echo images of the dominant 2nd to 5th MCP joints of 69 RA patients. MR images were obtained and evaluated for bone erosions according to the OMERACT recommendations. Conventional radiographs of the 2nd to 5th MCP joints were obtained in posterior-anterior projection and evaluated for bone erosions. The MRI and radiography readers were blinded to each other's assessments. Grade 1 MRI erosions (1% to 10% of bone volume eroded) were detected by radiography in 20%, 4%, 7% and 13% in the 2nd, 3rd, 4th and 5th MCP joint, respectively. Corresponding results for grade 2 erosions (11% to 20% of bone volume eroded) were 42%, 10%, 60% and 24%, and for grade 3 erosions (21% to 30% of bone volume eroded) 75%, 67%, 75% and 100%. All grade 4 (and above) erosions were detected on radiographs. Conventional radiography required a MRI-estimated bone erosion volume of 20% to 30% to allow a certain detection, indicating that MRI is a better method for detection and grading of minor erosive changes in RA MCP joints.
15927997 Adsorptive granulocyte/monocyte apheresis for the treatment of refractory rheumatoid arthr 2005 Sep OBJECTIVE: To assess the efficacy and safety of adsorptive granulocyte and monocyte apheresis (GCAP) in patients with refractory rheumatoid arthritis (RA). METHODS: Patients with active and refractory RA were treated with weekly GCAP sessions using a column filled with acetate beads (Adacolumn) over five consecutive weeks. Clinical assessments and response to therapy were analysed at weeks 5, 7, 12 and 20 in an open multicentre trial. The primary outcome measure of clinical response was 20% improvement in the American College of Rheumatology criteria (ACR20) at week 20. EULAR (European League Against Rheumatism) response criteria, based on the disease activity score for 28 joints (DAS28) and disability using the Health Assessment Questionnaire (HAQ), were also assessed. RESULTS: Of 27 patients, 81.5% were women with mean disease duration of 14.4 yr. The mean number of previous disease-modifying antirheumatic drugs (DMARDs) was 3.7, and 48.1% of patients had previously failed on biologicals. On an intention-to-treat basis, 40.7% of patients achieved an ACR20 and 44.4% a therapeutic EULAR response at week 20. These percentages were 50 and 54.5% in 22 patients who completed the trial. In the 10 completers who had previously failed on biologicals, an ACR response was achieved in four patients (ACR20, two; ACR50, one; ACR70, one). A significant decrease was recorded in different ACR response components, including the tender joint and swollen joint counts, pain score and patient and physician global disease assessments, as well as the DAS28 index; most of them improved after week 5. ESR and CRP, but not the HAQ score, had decreased significantly at week 20. The treatment was well tolerated and only one serious adverse event related to the study procedure was documented (sepsis due to a catheter infection). CONCLUSIONS: GCAP treatment led to significant clinical improvement in a subset of patients with RA who had failed to respond to DMARDs or biologicals. Further large, placebo-controlled studies are warranted to fully assess the therapeutic value of GCAP for refractory RA.
16973113 Gene therapy works in animal models of rheumatoid arthritis...so what! 2006 Oct Rheumatoid arthritis (RA) is a systemic disease with polyarticular manifestation of chronic inflammation in the knees and small joints of hand and feet. The current systemic anti-tumor necrosis factor (TNF)-alpha therapies with biologics ameliorate disease in 60% to 70% of RA patients. However, biologics must be given systemically in relatively high dosages to achieve constant therapeutic levels in the joints, and side effects have been reported. To this end, local gene delivery can provide an alternative approach to achieve high, long-term expression of biologics, optimizing the therapeutic efficacy and minimizing systemic exposure. Evidence from animal models convincingly supports the application of local gene therapy in rheumatoid arthritis, but preclinical studies remain necessary to evaluate the merge of cell-specific targeting, viral vector development, and disease-regulated transgene expression to optimize efficacy and safety.
16273310 Evaluating the Korean version of the Multidimensional Health Assessment Questionnaire in p 2006 May Although the Health Assessment Questionnaire (HAQ) and the Modified Health Assessment Questionnaire are useful tools for assessing and monitoring patients with rheumatic diseases, they have a "floor effect" and do not fully reflect the psychological status of patients. Recently, the Multidimensional Health Assessment Questionnaire (MDHAQ) was developed to overcome these shortcomings. We translated the MDHAQ into the Korean language and evaluated its reliability and validity for use with Korean-speaking patients with rheumatoid arthritis (RA). The questionnaire was translated into the Korean language by three translators, who were aware of its objectives, and it was translated back into the English language by three different translators. One question was modified to reflect Korean culture, and imperial measures were changed to metric measures because most Koreans use the metric system. The Korean MDHAQ was administered to 136 patients with RA who were attending the outpatient rheumatology clinic at the Chonnam National University Hospital (Gwangju, South Korea). Test-retest reliability was assessed in 101 patients after 1 week. To assess criterion validity, we compared MDHAQ scores with HAQ scores and the American College of Rheumatology (ACR) functional class. To test construct validity, the MDHAQ was compared to ACR core criteria (tender and swollen joint count, pain, patient's global assessment, physician's global assessment, erythrocyte sedimentation rate, and C-reactive protein), the Beck Depression Inventory (BDI), and the State-Trait Anxiety Inventory (STAI). The test-retest reliability was analyzed by computing kappa statistics, which ranged from 0.60 to 0.76. Cronbach's alpha coefficient ranged from 0.892 to 0.938. The MDHAQ was significantly correlated with the HAQ and ACR functional class (all p<0.001). The correlations between the MDHAQ scores and the ACR core set, BDI, and STAI were all high and statistically significant. The Korean version of the MDHAQ is a reliable, valid tool for assessing Korean patients with RA.
16534538 [Productivity costs of rheumatoid arthritis in Germany. Cost composition and prediction of 2006 Oct OBJECTIVE: Identification of predictors for the productivity cost components: (1) sick leave, and (2) work disability in gainfully employed and (3) impaired household productivity in unemployed patients with rheumatoid arthritis (RA) from the societal perspective. METHODS: Investigation of productivity costs was linked to a multicenter, randomized, controlled trial evaluating the effectiveness of clinical quality management in 338 patients with RA. The productivity losses were assessed according to the German Guidelines on Health Economic Evaluation. By means of multivariate logistic regression analyses, predictors of sick leave, work disability (employed patients, n=96), and for days confined to bed in unemployed patient (n=242) were determined. RESULTS: Mean annual costs of 970 EUR arose per person taking into consideration all patients (453 EUR sick leave, 63 EUR work disability, 454 EUR impaired productivity of unemployed patients). Disease activity, disease severity, and impaired physical function were global predictors for all of the cost components investigated. Sick leave costs were predicted by prior sick leave periods and the vocational status blue collar worker, work disability costs by sociodemographic variables (marital status, schooling), and the productivity costs of unemployed patients by impaired mental health and impaired physical functions. CONCLUSIONS: Interventions such as reduction in disease progression and control of disease activity, early vocational rehabilitation measures and vocational retraining in patients at risk of quitting working life, and self-management programs to learn coping strategies might decrease future RA-related productivity costs.
16765715 Bronchiectasis in rheumatoid arthritis: report of four cases and a review of the literatur 2006 Jun OBJECTIVE: To describe patients with rheumatoid arthritis (RA) who subsequently developed bronchiectasis (BR) and to review the literature on biologic response modifiers (BRM) in relation to infectious complications in the management of these patients. METHODS: We describe 4 patients with RA who were diagnosed with BR out of a cohort of 170 patients. We then performed a comprehensive review of the English language literature on the major clinical trials for RA that involved the BRMs etanercept, infliximab, anakinra, and adalimumab. We focused on inclusion/exclusion criteria involving pulmonary disease and infectious complications in these trials. RESULTS: Of the 4 patients we describe, all developed BR after the diagnosis of RA was established, had positive cyclic citrullinated peptide antibodies, had extra-articular manifestations, and had clinical courses complicated by pneumonia. Management strategies were influenced by these factors in all of the patients described. Of the 16 clinical trials on BRMs reviewed, few studies mentioned BR as an exclusion criteria or reported pneumonia as a specific infectious complication. CONCLUSIONS: BR may be considered as an extra-articular pulmonary manifestation of RA. The infectious complications associated with BR in these patients underscore the management challenge, especially in choosing whether or not to treat with BRMs. Further studies are needed to analyze the infectious complications in RA trials with BRMs, specifically, to assess the risk of patients with BR. Risk stratification in these patients may require screening them for the presence of underlying BR.
16736164 Leflunomide increases the risk of early healing complications in patients with rheumatoid 2006 Oct The aim of this object is to study whether treatment with biological or leflunomide increases the risk of wound-healing complications after elective orthopedic surgery. Between March 2002 and September 2003, 201 patients participated in this study with the following inclusion criteria: (a) Rheumatoid arthritis (RA) or psoriatic arthritis (psA), (b) therapy with: MTX, leflunomide, etanercept, infliximab, adalimumab, anakinra, (c) undergoing elective orthopedic surgery. The incidence of early postoperative wound-healing complications was compared among the different groups. In comparison with patients who received MTX therapy (n = 59), the risk of postoperative wound-healing complications in patients undergoing leflunomide therapy (n = 32) was significantly higher: 13.6% in the MTX group, 40.6% in the leflunomide group (P = 0.01). It is recommended that leflunomide medication for patients with RA undergoing elective orthopedic surgical procedure is interrupted preoperatively to reduce the risk of early wound-healing complications or infections.
16397736 Peripheral bone status in rheumatoid arthritis evaluated by digital X-ray radiogrammetry a 2006 Jan The development of secondary osteoporosis in rheumatoid arthritis (RA) has recently become well recognized, characterized by demineralization at axial and in particular periarticular peripheral bone sites. Our aim was to evaluate multisite quantitative ultrasound (QUS) compared to digital X-ray radiogrammetry (DXR) by the quantification of cortical bone loss dependent on the severity of RA. Fifty-three patients with verified RA underwent QUS measurements (Sunlight Omnisense 7000) with estimation of the speed of sound (QUS-SOS) at the distal radius and at the phalanx of the third digit. Also, bone mineral density (DXR-BMD) and metacarpal index (DXR-MCI) were estimated on metacarpals II-IV using DXR technology. Additionally, Larsen score and Steinbroker stage were assessed. Disease activity of RA was estimated by disease activity score 28 (DAS 28). For the group with minor disease activity (3.2 5.1), QUS-SOS of the radius revealed a significant correlation to DXR-BMD (R = 0.71) and DXR-MCI (R = 0.84), whereas for QUS-SOS (phalanx) no significant association to the DXR parameters was shown. The DXR parameters and, to a lesser extent, the QUS data also demonstrated pronounced declines in the case of accentuated disease activity (DAS > 5.1). Both DXR-BMD (-25.9 %, P < 0.01) and DXR-MCI (-38.6 %, P < 0.01) revealed a notable reduction dependent on the severity of RA. Otherwise, QUS-SOS marginally decreased, with -2.6% (radius) and -3.9% (phalanx). DXR revealed a significant reduction of DXR-BMD as well as DXR-MCI dependent on the severity of RA and surpassed multisite QUS as a promising diagnostic tool.
16395746 Evolution of antinuclear antibodies and clinical patterns in patients with active rheumato 2006 Jan OBJECTIVE: To investigate the effect of longterm infliximab therapy on serum levels of fluorescent antinuclear and anti-double and single-stranded DNA antibodies (FANA, anti-dsDNA, anti-ssDNA) in patients with rheumatoid arthritis (RA), and their possible association with clinical evolution. METHODS: Sera from 58 RA patients, treated for one to 3 years with infliximab, were retrospectively analyzed. Matched control groups were RA patients treated with corticosteroids or methotrexate. FANA were tested using HEp-2 cells, and anti-dsDNA and anti-ssDNA IgG by ELISA. After 28 months of infliximab therapy, clinical status was evaluated in 43/58 patients with uninterrupted therapy and associations with autoantibody levels were investigated. Data were documented for patients who discontinued infliximab. RESULTS: Over the 3 year period, significant increases in FANA and anti-ssDNA IgG levels were observed in infliximab treated patients (p < 0.001 and p < 0.01, respectively). In 43 patients with an uninterrupted infliximab regimen, association was found between high FANA (>or= 1/1280) and lower age (p = 0.048) and patient's assessment of infliximab's efficacy (p = 0.014). Three patients developed anti-dsDNA IgG, preceded by high anti-ssDNA IgG levels, and one of them developed a lupus-like syndrome. Neither the initial presence of high FANA levels nor their increase >or= 1/1280 was significantly associated with discontinuation of infliximab. In contrast, at baseline (p = 0.0012) and at the time of infliximab discontinuation (p = 0.0078), anti-ssDNA IgG (>or= 500 arbitrary units) were more frequent in 7 patients who stopped infliximab due to skin or systemic anaphylactoid reactions. CONCLUSION: Monitoring of serum FANA, anti-dsDNA, and anti-ssDNA IgG antibodies provided predictors of lupus-like symptoms and/or anaphylactoid reactions in patients with RA.
16870097 Effectiveness of different cryotherapies on pain and disease activity in active rheumatoid 2006 May OBJECTIVE: Local cryotherapy is used to relieve pain and inflammation in injuries and inflammatory conditions. Whole-body cryotherapy is an extreme method administered at -110 degrees C for 2 to 3 minutes. The aim of the study was to compare the effect of cryotherapies on pain and inflammation in patients with rheumatoid arthritis (RA). METHODS: Sixty patients with active seropositive RA were recruited in a randomised controlled single-blinded study to receive whole-body cryotherapy at -110 degrees C, whole-body cryotherapy at -60 degrees C, application of local cold air at -30 degrees C and the use of cold packs locally. In the final analysis, the last 2 groups were pooled. The patients had 2-3 cryotherapy sessions daily for one week plus conventional physiotherapy. Clinical and laboratory variables and patient's and physician's global assessments were used to assess the outcome. Disease activity was calculated by DAS. RESULTS: Pain decreased in all treatment groups, most markedly in the whole-body cryotherapy (-110 degrees C) group. DAS decreased slightly with no statistically significant differences between the groups. No serious or permanent adverse effects were detected. Six of 40 patients (15%) discontinued the whole-body cryotherapy. CONCLUSION: Pain seemed to decrease more in patients in the whole-body cryotherapy at -110 degrees C than during other cryotherapies, but there were no significant differences in the disease activity between the groups. However, cryotherapy at -110 degrees C is expensive and available only in special centres and may have minor adverse effects. Based on our results, whole-body cryotherapy at -110 degrees C is not superior to local cryotherapy commonly used in RA patients for pain relief and as an adjunct to physiotherapy.
16886894 IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein pla 2006 Jul OBJECTIVES: To analyze the association of interleukin (IL-1) gene polymorphisms with susceptibility to, and severity of, rheumatoid arthritis (RA) patients, comparing them with the genotype distribution in healthy controls. Also, to assess the influence of IL1-B and IL1RN gene polymorphism on IL-1beta/IL-1Ra plasma levels and response to therapy. PATIENTS AND METHODS: We tested the allelic distribution of IL-1B (-511 and +3953) and IL-1RN (variable number of tandem repeats) gene polymorphism in 126 RA patients and 178 healthy blood donors (HBDs). The patients were categorized into two subgroups in relation to the response to methotrexate (MTX) therapy. Group A included 70 RA patients in stable partial remission after 6 months of MTX treatment (MTX-R). Group B included 56 RA patients with active disease despite MTX therapy. This group received antitumor necrosis factor (TNF) biological drugs and were defined MTX-nonresponders (MTX-NR). RESULTS: None of the two IL-1B (-511 and +3953) gene polymorphisms were significantly different in frequency between RA patients and healthy controls. We observed an increased frequency of the rare allele IL1RN*3 in RA patients with active disease, not responding to MTX therapy (MTX-NR) (4.5%) vs MTX-R (3.6%) and healthy controls (0.8%). Interestingly, RA patients whose genotypes included the IL1RN*long allele (haplotype long-C-T) showed the worse response to MTX. HBDs harboring the IL1RN*2/2 genotype showed significantly lower levels of plasma IL1-Ra, but comparable levels of IL-1beta with regard to subjects with the presence of the IL1RN* long allele. Furthermore, the presence of the TT IL-1B +3953 genotype was associated with lower plasma levels of IL1-Ra, both in HBDs and in RA patients. Carriers of the IL1RN*2 allele responded better to infliximab therapy. CONCLUSIONS: The results of this study provide evidence of an association between the IL1RN*long allele and RA, the strongest association being observed in RA patients with an aggressive disease resistant to MTX treatment.