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ID PMID Title PublicationDate abstract
23075462 Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical, mi 2012 Oct 17 INTRODUCTION: The association between rheumatoid arthritis (RA) and periodontitis is suggested to be linked to the periodontal pathogen Porphyromonas gingivalis. Colonization of P. gingivalis in the oral cavity of RA patients has been scarcely considered. To further explore whether the association between periodontitis and RA is dependent on P. gingivalis, we compared host immune responses in RA patients with and without periodontitis in relation to presence of cultivable P. gingivalis in subgingival plaque. METHODS: In 95 RA patients, the periodontal condition was examined using the Dutch Periodontal Screening Index for treatment needs. Subgingival plaque samples were tested for presence of P. gingivalis by anaerobic culture technique. IgA, IgG and IgM antibody titers to P. gingivalis were measured by ELISA. Serum and subgingival plaque measures were compared to a matched control group of non-RA subjects. RESULTS: A higher prevalence of severe periodontitis was observed in RA patients in comparison to matched non-RA controls (27% versus 12%, p < 0.001). RA patients with severe periodontitis had higher DAS28 scores than RA patients with no or moderate periodontitis (p < 0.001), while no differences were seen in IgM-RF or ACPA reactivity. Furthermore, RA patients with severe periodontitis had higher IgG- and IgM-anti P. gingivalis titers than non-RA controls with severe periodontitis (p < 0.01 resp. p < 0.05), although subgingival occurrence of P. gingivalis was not different. CONCLUSIONS: Severity of periodontitis is related to severity of RA. RA patients with severe periodontitis have a more robust antibody response against P. gingivalis than non-RA controls, but not all RA patients have cultivable P. gingivalis.
22718267 Incremental expenditure of biologic disease modifying antirheumatic treatment using instru 2013 Jul In health care, decision makers are generally interested in simultaneous comparisons among multiple treatments or interventions available as treatment choices in real-world clinical setting. The lack of random assignment to treatment in real-world clinical settings leads to selection-bias issues when evaluating the marginal benefits of treatment. The application of instrumental variables (IV) estimation to mitigate selection bias has traditionally been limited to comparing only two treatments/interventions concurrently. Using the case of biologic treatment in rheumatoid arthritis, we describe a generalized method of moments (GMM)-based panel data IV (IV-GMM) framework, to simultaneously estimate multiple treatment effects in the presence of time-varying selection bias and time-invariant heterogeneity. To satisfy the order and rank conditions for identification with multiple endogeneity, we propose lagged values of each treatment as excluded instruments. We evaluate the validity of the IV estimation assumptions on instrument relevance and exogeneity. Results indicate that the IV-GMM model offers enhanced control over selection bias and heterogeneity, and more importantly the panel data framework can provide valid excluded instruments that satisfy the order and rank conditions for identification when dealing with multiple endogenous variables. The approach outlined in this article has broad application for comparative effectiveness and health technology assessment involving multiple treatments/interventions using real-world nonexperimental data.
22685272 Economic benefits of optimizing anchor therapy for rheumatoid arthritis. 2012 Jun The total cost of RA is substantial, particularly in patients with high levels of disability. There are considerable differences in cost between countries, driven in part by differences in the use of biologic therapies. Economic evaluations are needed to assess the extra cost of using these treatments and the benefits obtained, to ensure appropriate allocation of limited health care resources. The BeSt trial, evaluating four treatment strategies, found comparable medium-term efficacy but substantially higher costs with early biologic therapy. A systematic review of such cost-effectiveness analyses concluded that biologic therapy should be used after therapy has failed with less costly alternatives such as synthetic DMARDs and glucocorticoids. Optimizing such relatively low-cost therapy to improve outcomes may delay the need for biologic therapy, thereby saving costs. A simple model has confirmed the value of this approach. The addition of modified-release prednisone 5 mg/day to existing synthetic DMARD therapy in patients with active disease resulted in improvement in DAS-28 to below the threshold level for initiation of reimbursed biologic therapy in 28-34% of patients. On a conservative estimate (i.e. assuming no further benefits beyond the 12 weeks of the study and a 12-week wait-and-see approach to starting biologic therapy), cost savings amounted to nearly € 400 per patient. While treatment decisions should never be based only on cost considerations, prolonging disease control by optimizing the use of non-biologic treatments may bring benefits to patients and also economic benefits by delaying the need for biologic treatments.
21441054 Distinct serum and synovial fluid interleukin (IL)-33 levels in rheumatoid arthritis, psor 2012 Jan OBJECTIVES: Recent evidence suggests a role for interleukin (IL)-33 and its receptor ST2 in arthritis. In this study, we quantified IL-33 and soluble (s)ST2 levels in serum and synovial fluid (SF), and assessed synovial IL-33 expression levels and pattern in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or osteoarthritis (OA). METHODS: Serum and SF IL-33 and sST2 levels were assessed by ELISA. IL-33 mRNA was quantified by RT-qPCR. Synovial IL-33 protein expression pattern was examined by immunohistochemistry. RESULTS: Serum and SF IL-33 levels tended to be higher in RA than in OA patients. In contrast to RA, IL-33 was not detectable in PsA serum and SF. Serum sST2 levels were higher in RA than in OA. There was a wide variation of synovial tissue IL-33 mRNA expression within each disease group and IL-33 mRNA levels were not significantly different between the groups. A similar IL-33 protein expression pattern was observed in RA, PsA and OA synovium, with strong nuclear expression of IL-33 in endothelial cells and, in a subset of RA, PsA and OA patients, in cells morphologically consistent with synovial fibroblasts. DISCUSSION/CONCLUSIONS: This study confirms increased circulating IL-33 levels in RA. In addition, we report that IL-33 is undetectable in the serum or SF of PsA patients. Local expression of IL-33 in the synovium was observed at similar variable levels in RA, PsA and OA, suggesting that inflamed joints do not represent the primary source of elevated serum and SF levels of IL-33 in RA.
23070360 Proximal rotational closing-wedge osteotomy of the first metatarsal in rheumatoid arthriti 2013 Sep OBJECTIVES: The introduction of powerful antirheumatic drugs has dramatically improved the treatment of rheumatoid arthritis (RA), leading clinicians to reconsider the benefits of joint preservation for rheumatoid forefoot deformities. We have employed joint-preserving forefoot surgeries, including rotational closing-wedge osteotomy of the first metatarsal. The aim of our study is to assess the short-term results of this procedure. METHODS: From January 2011 through December 2011, 35 feet were treated with this procedure. Subjective, functional, and radiographic outcomes were surveyed. RESULTS: The mean Japanese Society for Surgery of the Foot improved from a preoperative level of 52.6 to 68.7 postoperatively. The average hallux valgus and intermetatarsal angles improved from 47.3° preoperatively to 17.5° postoperatively, and from 16.7° preoperatively to 9.0° postoperatively, respectively. To assess the repositioning of pronation deformities of the first metatarsal, the position of the medial sesamoid was also surveyed according to the measurement system proposed by Hardy and Clapham. All feet except two were classified as grade V or higher preoperatively; 25 of these were grade IV or lower at the latest follow-up. CONCLUSIONS: Rotational closing-wedge osteotomy of the first metatarsal was beneficial for correcting forefoot deformities in RA over the short term.
23815015 [Medical and economic aspects of rheumatoid arthritis]. 2012 Oct Rheumatoid arthritis (RA) is a chronic disabling disease that induces substantial costs in terms of healthcare resources (direct costs) and lost productivity (indirect costs). The main cost drivers used to be disability and hospitalization. Recently, however, the cost of new and expensive therapies has exceeded that of hospitalization. These effective treatments have lowered RA-related use of healthcare resources, especially totaljoint replacement, as well as sick leave. In contrast, they have not yet been shown to reduce the number of patients who become disabled, and their cost-effectiveness ratio thus tends to be unfavorable.
21448644 Fatigue and severity of rheumatoid arthritis in Moroccan patients. 2012 Jul The aim of this study was to assess fatigue aspects in Moroccan patients with rheumatoid arthritis (RA) and its relationships with disease-specific variables especially parameters of functional and structural severity. A total of 248 patients with RA were included. Patients' and disease characteristics were identified. Disease activity was measured clinically using physical examination, biologically and by the disease activity scores (DAS28). Radiographs were evaluated by using Sharp's method as modified by van der Heijde. Functional disability was measured by using the Moroccan version of Health Assessment Questionnaire (HAQ). Immunological abnormalities and treatment (doses and duration) were identified. Fatigue was evaluated by using a 0-100 visual analogue scale (VAS fatigue) and the multidimensional assessment of fatigue (MAF). Quality of life (QoL) was assessed using the Arabic version of the generic instrument SF-36. The mean age of patients was 47.5 ± 11.7 years [25-72]; 37.5% of patients had a high activity of disease and 11.3% were in remission. The mean Sharp score was 107.13 ± 91, and the mean score of HAQ was 1.40 ± 0.63. All domains of QoL were deteriorated; 89.51% of our patients experienced fatigue. The mean total score of MAF was 30.21 ± 11.32. A low level of education, low socioeconomic status, atlantoaxial subluxation, hip involvement, the presence of a Sjögren syndrome, and cigarette smoking had a negative impact on fatigue scores. The severity of fatigue was correlated with the duration of RA, the intensity of joint pain, the activity of disease, the importance of structural damage, the degree of functional impairment, and the rate of anti-cyclic citrullinated protein (CCP) antibodies (P < 0.05). Patients receiving methotrexate had better scores of fatigue. Also, severity of fatigue was correlated with the deterioration of all domains of QoL. Fatigue is a major issue for our patients with RA and must be included in the routine assessment of patients. In our sample, fatigue appears to be related to disease activity, functional disability, structural damage, and immunological status and had a negative impact on QoL.
21149243 Cost of illness in rheumatoid arthritis in Germany in 1997-98 and 2002: cost drivers and c 2011 Apr OBJECTIVE: Comparison of overall RA-related costs and of relative contribution of single-cost domains before and after the introduction of TNF-blocking agents in Germany. METHODS: Two cohorts of RA outpatients (ACR '87 criteria) with long-standing disease are assessed in terms of disease-related costs and cost composition (n = 106 patients in 1997-98 and n = 180 patients in 2002 with similar patient characteristics). Full-cost analyses are performed including direct disease-related costs (medical and non-medical) and productivity costs as collected by patient questionnaires. Absolute costs (€/patient/year) are compared and the impact of single-cost domains on overall costing in RA is estimated (relative proportions of cost components within samples). RESULTS: Overall costs are comparable (1997-98: €4280; 2002: €3830; not significant). Differences can be observed in medication (1997-98: €550; 2002: €1580; P < 0.001) and hospitalization costs (1997-98: €1240; 2002: €500; P < 0.001). Productivity costs are significantly lower (€1480 vs €850; P < 0.05) in 2002. The impact of medication costs is outstanding in the 2002 sample (42 vs 12%), the proportion of hospitalization costs is substantially lower (29 vs 13%). Costs for DMARDs in 2002 are mostly driven by TNF blockers (37%). The number of DMARDs per patient is higher in 2002 as are costs for osteoporosis medication and gastroprotective treatment. CONCLUSION: Although overall costs before and after the introduction of TNF blockers are comparable, the decrease in hospitalization and productivity costs is promising in terms of future long-term cost savings. The development of these aspects and of the increasing medication costs will have to be evaluated with longer time frames.
21908880 Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid ar 2011 Nov OBJECTIVES: To compare glucose tolerance and parameters of insulin sensitivity and β-cell function between chronic glucocorticoid (GC)-using and GC-naive patients with rheumatoid arthritis (RA). METHODS: Frequently sampled 75 g oral glucose tolerance tests were performed in 58 chronic GC-using and 82 GC-naive patients with RA with established disease, with no known type 2 diabetes mellitus (T2DM), and 50 control subjects of comparable age with normal glucose tolerance. The associations between cumulative GC dose and disease characteristics and glucose tolerance state, insulin sensitivity and β-cell function were tested using multivariate linear and logistic regression models, correcting for patient characteristics. RESULTS: Glucose tolerance state, insulin sensitivity and β-cell function did not differ between the two RA populations; de novo T2DM was detected in 11% and impaired glucose metabolism in 35% of patients with RA. In patients with RA, cumulative GC dose was associated with T2DM, which seemed mostly driven by the effects of cumulative GC dose on insulin resistance; however, the association decreased when corrected for current disease activity. Patients with RA had decreased insulin sensitivity and impaired β-cell function compared with controls, and multivariate regression analyses showed a negative association between the presence of RA and insulin sensitivity. CONCLUSIONS: GC-using and GC-naive patients with RA had comparable metabolic parameters, and had decreased insulin sensitivity and β-cell function as compared with healthy controls. Although cumulative GC dose was shown to have a negative impact on glucose tolerance state and insulin sensitivity, confounding by indication remains the main challenge in this cross-sectional analysis.
21468143 C-reactive protein in rheumatology: biology and genetics. 2011 May Measurement of serum C-reactive protein (CRP) level is in widespread clinical use as a sensitive marker of inflammation. CRP has a role in the clearance of bacteria and of dying and altered cells, and might also have more complex immunomodulatory functions. Impaired clearance of apoptotic cells is important in the pathogenesis of systemic lupus erythematosus (SLE), raising the possibility that CRP dysregulation plays a part in this process. We review the available functional and genetic evidence supporting a role for CRP in the pathogenesis of SLE, but recognize that inconsistencies in the existing data mean that conclusions have to be interpreted with caution. More consistent is the evidence that the genetic variants influencing basal CRP level also influence the magnitude of the acute-phase rise in CRP level in active inflammation. Initial reports suggest that these genetic effects might be large enough to directly influence clinical decision-making processes that are based on an interpretation of CRP thresholds. This concept is explored further in this article, particularly in relation to the use of the CRP-based disease activity score in the evaluation of rheumatoid arthritis, where a systematic under-scoring or over-scoring of disease activity could result from a failure to consider the genetic influences on CRP level.
23178208 A prediction rule for the development of arthritis in seropositive arthralgia patients. 2013 Dec OBJECTIVE: To predict the development of arthritis in anticyclic citrullinated peptide antibodies and/or IgM rheumatoid factor positive (seropositive) arthralgia patients. METHODS: A prediction rule was developed using a prospective cohort of 374 seropositive arthralgia patients, followed for the development of arthritis. The model was created with backward stepwise Cox regression with 18 variables. RESULTS: 131 patients (35%) developed arthritis after a median of 12 months. The prediction model consisted of nine variables: Rheumatoid Arthritis in a first degree family member, alcohol non-use, duration of symptoms <12 months, presence of intermittent symptoms, arthralgia in upper and lower extremities, visual analogue scale pain ≥50, presence of morning stiffness ≥1 h, history of swollen joints as reported by the patient and antibody status. A simplified prediction rule was made ranging from 0 to 13 points. The area under the curve value (95% CI) of this prediction rule was 0.82 (0.75-0.89) after 5 years. Harrell's C (95% CI) was 0.78 (0.73-0.84). Patients could be categorised in three risk groups: low (0-4 points), intermediate (5-6 points) and high risk (7-13 points). With the low risk group as a reference, the intermediate risk group had a hazard ratio (HR; 95% CI) of 4.52 (2.42-8.77) and the high risk group had a HR of 14.86 (8.40-28.32). CONCLUSIONS: In patients presenting with seropositive arthralgia, the risk of developing arthritis can be predicted. The prediction rule that was made in this patient group can help (1) to inform patients and (2) to select high-risk patients for intervention studies before clinical arthritis occurs.
22018189 Rheumatoid arthritis and glucocorticoids; the contribution of a literature search to the d 2011 Sep In 2010 the EULAR recommendations on the treatment of rheumatoid arthritis (RA) was published. The search for evidence for treatment of rheumatoid arthritis with glucocorticoids and the development of a EULAR Task Force Guideline on this subject is described in this paper.
21671414 Racial and ethnic disparities in disease activity and function among persons with rheumato 2011 Sep OBJECTIVE: Health outcomes in rheumatoid arthritis (RA) have improved significantly over the past 2 decades. However, research suggests that disparities exist by race/ethnicity and socioeconomic status, with certain vulnerable populations remaining understudied. Our objective was to assess disparities in disease activity and function by race/ethnicity and explore the impact of language and immigrant status at clinics serving diverse populations. METHODS: We examined a cross-sectional study of 498 adults with confirmed RA at 2 rheumatology clinics: a university hospital clinic and a public county hospital clinic. Outcomes included the Disease Activity Score in 28 joints (DAS28) and its components, and the Health Assessment Questionnaire (HAQ), a measure of function. We estimated multivariable linear regression models including interaction terms for race/ethnicity and clinic site. RESULTS: After adjusting for age, sex, education, disease duration, rheumatoid factor status, and medication use, clinically meaningful and statistically significant differences in DAS28 and HAQ scores were seen by race/ethnicity, language, and immigrant status. Lower disease activity and better function was observed among whites compared to nonwhites at the university hospital. This same pattern was observed for disease activity by language (English compared to non-English) and immigrant status (US-born compared to immigrant) at the university clinic. No significant differences in outcomes were found at the county clinic. CONCLUSION: The relationship between social determinants and RA disease activity varied significantly across clinic setting with pronounced variation at the university, but not at the county clinic. These disparities may be a result of events that preceded access to subspecialty care, poor adherence, or health care delivery system differences.
22380578 Inhibiting citrullination in rheumatoid arthritis: taking fuel from the fire. 2012 Feb 29 Citrullination is a post-translational modification catalysed by peptidylarginine deiminase and is a common feature of inflammation. The presence of anti-citrullinated protein/peptide antibodies (ACPA), however, is unique to rheumatoid arthritis. Several lines of evidence suggest that ACPA are important in the pathogenesis of rheumatoid arthritis. A popular hypothesis for this pathogenesis is a two-hit model. The first hit gives rise to ACPA, and the second hit, an unrelated episode of synovial inflammation accompanied by citrullination, is perpetuated by the pre-existing antibodies. This model suggests that reducing citrullination might ameliorate disease. Recent findings indicate that citrullination closely correlates with inflammation, and that glucocorticoids decrease peptidylarginine deiminase expression independent of their other anti-inflammatory effects.
22773376 Racial and ethnic disparities in rheumatoid arthritis. 2012 Oct Racial and ethnic health disparities are a national health issue. They are well described in other chronic diseases, but in rheumatoid arthritis (RA), research into their causes, outcomes, and elimination is in its early stages. Health disparities occur in a complex milieu, with system-level, provider-level, and individual-level factors playing roles. Dissecting the overlapping aspects of race/ethnicity, socioeconomic variables, and how their individual components combine to explain the magnitude of disparities in RA can be challenging. Recent research has focused on the extent to which treatment preferences, adherence, trust in physicians, patient-physician communication, health literacy, and depression have contributed to observed disparities in RA. Practicing evidence-based medicine, improving patient-physician communication skills, reducing language and literacy barriers, improving adherence to therapies, raising awareness of racial/ethnic disparities, and recognizing comorbidities such as depression are steps clinicians may take to help eliminate racial/ethnic disparities in RA.
22277625 The effect of an educational programme consisting of group and individual arthritis educat 2012 Jul OBJECTIVE: The aim of this study was to investigate the effect of an educational programme for patients with polyarthritis compared to usual care. METHODS: Patients with rheumatoid arthritis, psoriatic arthritis and unspecified polyarthritis were randomised to the intervention (n=71) or usual care (n=70). The intervention consisted of three group educational sessions followed by one individual educational session. The primary outcomes were a patient's global well-being and arthritis self-efficacy. Secondary outcomes were patient activation, physical and psychological health status, educational needs and disease activity. RESULTS: After four months the intervention group had significantly better global well-being, 95% CI (2.3-14.1), p=0.01, and self-efficacy, 95% CI (0.2-8.1), p=0.04, than the control group. There were also trends for improved disease activity, and a statistically significant improvement in patient activation and pain in the intervention group. CONCLUSION: This patient educational programme consisting of group sessions and nurse-delivered individual education has statistically significant benefits for global well-being and maintaining a level of self-efficacy in managing other symptoms in patients with polyarthritis. PRACTICE IMPLICATIONS: This educational programme allows patients to learn from each other in addition to addressing individual educational needs.
22576809 Development and validation of a risk score for serious infection in patients with rheumato 2012 Sep OBJECTIVE: Infection risk is increased in patients with rheumatoid arthritis (RA), and accurate assessment of the risk of infection could inform clinical decision-making. This study was undertaken to develop and validate a score to predict the 1-year risk of serious infection in patients with RA. METHODS: We studied a population-based cohort of Olmsted County, Minnesota residents with incident RA ascertained in 1955-1994 whose members were followed up longitudinally, via complete medical records, until January 2000. The validation cohort included residents with incident RA ascertained in 1995-2007. The outcome measure included all serious infections (requiring hospitalization or intravenous antibiotics). Potential predictors were examined using multivariable Cox models. The risk score was estimated directly from the multivariable model, and performance was assessed in the validation cohort using Harrell's C statistic. RESULTS: Among the 584 RA patients in the original cohort (72% female; mean age 57.5 years), who were followed up for a median of 9.9 years, 252 had ≥ 1 serious infection (646 total infections). Components of the risk score included age, previous serious infection, corticosteroid use, elevated erythrocyte sedimentation rate, extraarticular manifestations of RA, and comorbidities (coronary heart disease, heart failure, peripheral vascular disease, chronic lung disease, diabetes mellitus, alcoholism). Validation analysis revealed good discrimination (C statistic 0.80). CONCLUSION: RA disease characteristics and comorbidities can be used to accurately assess the risk of serious infection in patients with RA. Knowledge of risk of serious infection in RA patients can influence clinical decision making and inform strategies to reduce and prevent the occurrence of these infections.
22451025 Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis. 2013 Feb YKL-40, also known as human cartilage glycoprotein 39, is a member of the "mammalian chitinase-like proteins" family without chitinase activity. Increased serum concentrations are associated with inflammatory processes and several types of cancer. In this study, we evaluated YKL-40 levels in serum and synovial fluid of patients with rheumatoid arthritis in comparison with the ultrasonographic findings. YKL-40 levels were measured by enzyme-linked immunosorbent assay in 25 patients with active rheumatoid arthritis and in 40 healthy subjects. B mode and power Doppler were performed to determine synovial thickening and vascularization. Serum YKL-40 level in patients was significantly higher than the concentration in healthy controls (P < 0.01). In patients with rheumatoid arthritis, the level of the glycoprotein in synovial fluid was remarkably elevated compared to the serum level (P = 0.003). The B mode and power Doppler scores correlated to YKL-40 in serum and synovial fluid (P = 0.07). Serum YKL-40 levels were related positively to serum markers of inflammation such as C-reactive protein (P = 0.004) and erythrocyte sedimentation rate (P = 0.003). This study is the first to demonstrate a relationship between YKL-40 levels and ultrasonographic examinations in Bulgarian patients with rheumatoid arthritis. The findings suggest that YKL-40 might be implicated in the pathogenesis of the disease and could indicate the level of joint inflammation.
21173018 Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice. 2011 May OBJECTIVES: Increasing evidence suggests that oxidative stress may play a key role in joint destruction due to rheumatoid arthritis (RA). The aim of this study was to elucidate the role of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that maintains the cellular defence against oxidative stress, in RA. METHODS: The activation status of Nrf2 was assessed in synovial tissue from patients with RA using immunohistochemistry. Antibody-induced arthritis (AIA) was induced in Nrf2-knockout and Nrf2-wild-type control mice. The severity of cartilage destruction was evaluated using a damage score. The extent of oxidative stress, the activation state of Nrf2 and the expression level of Nrf2 target genes were analysed by immunhistological staining. The expression of vascular endothelial growth factor (VEGF)-A was examined on mRNA and protein using the Luminex technique. A Xenogen imaging system was used to measure Nrf2 activity in an antioxidant response element-luciferase transgenic mouse during AIA. RESULTS: Nrf2 was activated in the joints of arthritic mice and of patients with RA. Nrf2-knockout mice had more severe cartilage injuries and more oxidative damage, and the expression of Nrf2 target genes was enhanced in Nrf2-wild-type but not in knockout mice during AIA. Both VEGF-A mRNA and protein expression was upregulated in Nrf2-knockout mice during AIA. An unexpected finding was the number of spontaneously fractured bones in Nrf2-knockout mice with AIA. CONCLUSION: These results provide strong evidence that oxidative stress is significantly involved in cartilage degradation in experimental arthritis, and indicate that the presence of a functional Nrf2 gene is a major requirement for limiting cartilage destruction.
21569921 [Rituximab in rheumatoid arthritis-associated peripheral ulcerative keratitis]. 2011 Apr CLINICAL CASE: We report two cases of patients affected by longstanding rheumatoid arthritis who developed a severe form of peripheral ulcerative keratitis (PUK). Neither of them had an optimal biological and clinical control of their systemic illness despite being treated with several disease-modifying antirheumatic drugs (DMARDs) and biologic therapy. High-dose systemic corticosteroids were given to treat the PUK without any success. Rituximab resulted in a favourable response with resolution of the corneal lesions and optimal control of their systemic illness. DISCUSSION: Rituximab may be an additional tool to arrest progressive rheumatoid arthritis-associated PUK that is refractory to other drugs.