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ID PMID Title PublicationDate abstract
21894442 IL-17 receptor and its functional significance in psoriatic arthritis. 2012 Jan To delineate the functional significance of IL-17 Receptor (IL-17RA) and characterize the IL-17 producing T cell (Th17) subpopulation in psoriatic arthritis (PsA). Mononuclear cells from blood and synovial fluid (SF) were obtained from PsA (n=20), rheumatoid arthritis (RA, n=20) and osteoarthritis (OA, n=20) patients. Synoviocytes (FLS) were isolated from the synovium of RA (n=5), PsA (n=5) and OA (n=5) patients. IL-17RA expression in FLS was identified by western blotting (WB) and flowcytometry. T lymphocytes derived from the SF of these patients were studied to identify and phenotype the Th17 cells. The functional significance of IL-17RA was determined by evaluating its regulatory role on the production of proinflammatory cytokines and endopeptidase. IL-17RA expression was found to be significantly higher in FLS of RA (15.7%±4.9) and PsA (4.5%±0.9) in comparison to OA (1.14%±0.9). Western blot analyses showed that the relative intensity (RI) of IL-17RA protein was higher in RA and PsA compared to OA (Fisher exact, P<0.01). A significant enrichment of IL-17-producing CD4+ T cells (7.9%±2.8) was observed in the SF of PsA patients compared to that of OA patients (P<.001). Compared to OA-FLS, recombinant IL-17 induced higher levels of IL-6, IL-8, and MMP-3 production in PsA-FLS. Blockage of IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and MMP-3. This is the first report to demonstrate the functional significance of IL-17RA in PsA. Results of this study support the hypothesis that IL-17RA blocking antibodies have the potential to be a therapeutic option for psoriatic arthritis.
21062853 The extent of the anti-citrullinated protein antibody repertoire is associated with arthri 2011 Jan OBJECTIVES: To determine the fine specificity of anti-citrullinated protein antibodies (ACPA) in the early phase of arthritis development, the ACPA repertoire in arthralgia patients and the association with arthritis development were studied. METHODS: A total of 244 patients with arthralgia positive for anti-cyclic citrullinated peptide antibodies (aCCPs) and/or IgM rheumatoid factor (IgM-RF), without arthritis were included. Development of arthritis was defined as presence of one or more swollen joints at clinical examination during follow-up. Sera were tested at baseline for reactivity to five citrullinated peptides derived from fibrinogen (three), vimentin (one) and α-enolase (one) and five corresponding arginine peptides in an ELISA. RESULTS: In all, 69 patients (28%) developed arthritis in a median of 3 joints after a median follow-up of 11 (IQR 5-20) months. Reactivity to each peptide was significantly associated with arthritis development (p<0.001). The ACPA repertoire did not differ between patients who did or did not develop arthritis. Among aCCP-positive patients, patients recognising two or more additional citrullinated peptides developed arthritis more often (p=0.04). The number of recognised peptides was positively associated with the aCCP level (p<0.001). Crossreactivity between different peptides was minimal. CONCLUSIONS: Arthritis development is not associated with recognition of a specific citrullinated peptide once joint complaints are present. The ACPA repertoire in some patients with arthralgia is expanded. High aCCP levels are associated with a qualitatively broad ACPA repertoire. Patients with an extended ACPA repertoire have a higher risk of developing arthritis.
21483874 A 4-year follow-up of two complete mandibular implant-supported removable prostheses in a 2011 Mar Rheumatoid polyarthritis is a systemic autoimmune disease characterized by chronic synovitis and bone damage associated with significant functional disability and morbidity. This case report describes a 4-year follow-up of a 56-year-old female receiving polymedication for severe rheumatoid polyarthritis and osteoporosis with a fully edentulous maxilla treated with two osseointegrated implants supporting a removable mandibular prosthesis. No practitioner wanted to use implants to stabilize her mandibular prosthesis because of the health risks involved. This report encourages the dental practitioner to be familiar with the symptoms and oral manifestations of rheumatoid polyarthritis in order to help manage this disease when patients lose all of their teeth.
20473501 Antibodies against cyclic citrullinated peptide don't decrease after 6 months of inflixima 2011 Nov Anti-citrullinated peptide antibodies (ACPA) and the rheumatoid factor (RF) are well-established serological markers for rheumatoid arthritis (RA). ACPA are very useful in the diagnosis of RA, especially at the early stages of the disease when ACPA have a greater diagnostic value than RF. The aim of the study was to assess the influence of infliximab treatment on RF IgM and ACPA serum levels and RA activity during 6 months of treatment. Thirty-two patients with refractory RA were treated with infliximab during a 6-month period. At baseline, 3 and 6 months of treatment the patients were examined for the number swollen and tender joints out of 28 (SJC, TJC) and the visual analogue scale of arthritis activity according to the patient (VAS). Serum samples were tested for erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP), ACPA and RF IgM. The disease activity score (DAS-28) parameter was also calculated at the same time. During the course of our study, we observed statistically significant improvement in ESR, CRP, TJC, SJC, VAS DAS-28, and RF IgM after 3 and 6 months of infliximab treatment when compared to the baseline, whereas the ACPA level remained unchanged after 3 and 6 months of treatment (P = 0.96 and P = 0.85). The changes in the ACPA level are not a factor for evaluation of successful infliximab treatment but the changes in RF IgM are. According to different behavior of these antibodies during infliximab treatment, we suggest that the roles of ACPA and RF in the pathogenesis of RA are different.
22606051 Vascular function and handgrip strength in rheumatoid arthritis patients. 2012 OBJECTIVE: To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. METHODS: Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. RESULTS: The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r = 0.5; P = 0.0001), and inversely related to RVR (r = -0.3; P = 0.009) and RHVR (r = -0.3; P = 0.007). CONCLUSION: The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals.
21128999 Phenotypic diversity of peripheral blood plasma cells in primary Sjögren's syndrome. 2011 Jan Production of autoantibodies is one of the main features of primary Sjögren's syndrome (pSS). Long-lived plasma cells (PC) can produce autoantibodies for prolonged period of times without being affected by immunosuppressive therapies. As of today, little is known about the long-lived PC subset and their contribution to autoimmunity. We have characterized the phenotypic and migratory properties of peripheral blood PC isolated from pSS patients (grouped by focus score, FS) and compared them to PC from rheumatoid arthritis (RA) patients and normal non-autoimmune subjects. We observed two populations of PC in all study groups, CD19+ PC and CD19- PC. Interestingly, the CD19- PC subset was most prominent in autoimmune patients (pSS and RA) compared to normal controls. Further investigation of the PC phenotype revealed that a high percentage of both CD19+ and CD19- PC isolated from pSS and RA patients did not express the CD27 marker, which is normally highly expressed on all types of PC. Differences in the expression of markers such as IgM, IgG, CD95 and CXCR3 in the group with high FS compared to FS = 1, underscore the heterogeneity of pSS patient group and demonstrate that phenotypic pattern of circulating PC associates with the severity of inflammation in the salivary glands of these patients. Our migration experiments show that addition of CXCL12 to PC in vitro, do not alter the migration potential of PC in any group tested. However, we observed an overall higher spontaneous migration of PC from pSS compared to both RA and normal controls.
23070992 Hospitalizations of patients treated with anti-tumor necrosis factor-α agents -- a retros 2013 Jan OBJECTIVE: To assess the association between treatment with anti-tumor necrosis factor-α (TNF-α) agents and the occurrence of hospitalizations, their causes and complications, compared to treatment with traditional disease-modifying antirheumatic drugs in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). METHODS: A retrospective cohort study was conducted of patients with RA, AS, and PsA treated with anti-TNF-α agents between April 2002 and December 2007. Patients were assessed during the period of anti-TNF-α treatment (Group B) and compared to an equivalent period before initiation of anti-TNF-α therapy (Group A). All hospitalization charts were reviewed and diagnoses, comorbidities, concomitant medications, and clinical course were analyzed. Statistical analysis was performed using multivariate mixed Poisson regression. RESULTS: In the study period of 57 months, 735 hospitalization events of 327 patients were analyzed. Statistically significant decreases were seen in the total number of hospitalization events as well as hospitalizations due to exacerbation of rheumatic diseases in Group B compared to Group A (44.4 vs 74.2 and 21.9 vs 47.5 per 100 patient-years, respectively; p < 0.0001). More infectious events (7.4 in Group B compared to 4.6 per 100 patient-years in Group A; p = 0.043) were associated with anti-TNF-α treatment, older age, and underlying disease, because patients with RA had higher rates of infections compared to patients with PsA and patients with AS. CONCLUSION: The overall effect of anti-TNF-α therapy was a significant decline in total hospitalization events. The decrease was more prominent in patients with RA than in patients with AS and patients with PsA, and reflected the significant decrease in hospitalizations due to rheumatic disease exacerbation. The decrease was more pronounced than the observed increase in infectious events.
22354754 Lysophosphatidic acid receptor 1 suppression sensitizes rheumatoid fibroblast-like synovio 2012 Aug OBJECTIVE: To investigate the role of lysophosphatidic acid (LPA) receptors in the proliferation and apoptosis of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHODS: Expression of LPA receptors 1-3 was analyzed by real-time polymerase chain reaction (PCR). LPAR1 and LPAR2 were suppressed in RA FLS by small interfering RNA (siRNA) transfection. Proliferation of RA FLS after tumor necrosis factor (TNF) and LPA stimulation was determined with a luminescent cell viability assay. Apoptosis was analyzed by quantification of nucleosome release and measurement of activated caspase 3/7. Genes involved in the apoptotic response were identified with a human apoptosis PCR array and validated with Western blot assays. The requirement of these genes for apoptosis sensitization was assessed by siRNA transfection. Secretion of mediators of inflammation was analyzed by enzyme-linked immunosorbent assay. RESULTS: Only LPAR1 and LPAR2 were expressed by RA FLS, and their levels were higher than those in osteoarthritis (OA) FLS. Suppression of LPAR1 abrogated TNF-induced proliferation and sensitized the RA FLS, but not the OA FLS, to TNF-induced apoptosis. These changes occurred despite an increased early inflammatory response to TNF. Sensitization to apoptosis was associated with changes in expression of multiple apoptosis-related genes. Three of the up-regulated proapoptotic genes were further studied to confirm their involvement. In contrast, suppression of LPAR2 showed no effect in any of these analyses. CONCLUSION: LPA(1) is an important receptor in RA FLS. Its suppression is accompanied by a global increase in the response to TNF that is ultimately dominated by sensitization to apoptosis.
22649468 Increased frequency of circulating follicular helper T cells in patients with rheumatoid a 2012 Follicular helper T (Tfh) cells are recognized as a distinct CD4(+) helper T-cell subset, which provides for B-cell activation and production of specific antibody responses, and play a critical role in the development of autoimmune disease. So far, only one study investigated the circulating Tfh cells increased in a subset of SLE patients. Since relatively little is known about the Tfh cells in rheumatoid arthritis (RA) patients, in this study, Tfh-cell frequency, related cytokine IL-21, and transcription factor Bcl-6 were investigated in 53 patients with RA and 31 health controls. Firstly, we found that the frequency of CD4(+)CXCR5(+)ICOS(high) Tfh cells was increased significantly in the peripheral blood of RA patients, compared with that in healthy controls. It is known that Tfh cells are critical for directing the development of an antibody response by germinal centers B cells; secondly, we observed that the Tfh-cell frequency is accompanied by the level of anti-CCP antibody in RA patients. Furthermore, expression of Bcl-6 mRNA and plasma IL-21 concentrations in RA patients was increased. Taken together, these findings have shown that the increased frequency of circulating Tfh cells is correlated with elevated levels of anti-CCP antibody, indicating the possible involvement of Tfh cells in the disease progression of RA.
22176821 [Pregnancy outcomes before and after the onset of rheumatoid arthritis]. 2011 Nov OBJECTIVE: to compare the obstetric prognosis before and after the onset of rheumatoid arthritis (RA). METHODS: a survey in RA women patients who become sexually active before disease onset, and who tried or got pregnant after diagnosis was performed. Obstetrical features such as: number of pregnancies, threat of abortion, abortion, early natal death, congenital abnormalities and preeclampsia-eclampsia syndrome, before and after RA onset were compared. RESULTS: only 47 women were eligible (age: 40.5 ± 11.0 years; time of evolution: 15.9 ± 11.5 years; positive rheumatoid factor: 93.6 %) from 700 screened. After RA onset there were 63 gestations in 36 patients who got pregnant (secondary infertility rate: 21.3 %). A significant increase in frequency and number of cesarean deliveries, besides a higher number of pregnancies with preeclampsia, were found after RA onset. Additionally, four newborns with congenital anomalies were reported after the disease onset compared to none before RA onset. CONCLUSIONS: compared to pre-RA obstetric events, a higher frequency and number of adverse outcomes was found in pregnancies that occurred after RA onset.
22275154 Bone marrow-derived and synovium-derived mesenchymal cells promote Th17 cell expansion and 2012 Jul OBJECTIVE: Th17 cells have been implicated in rheumatoid arthritis (RA). We hypothesized that the interaction of T cells with bone marrow-derived mesenchymal stem cells (BM-MSCs) or with fibroblast- like synoviocytes (FLS) might, with the help of T cell-secreted inflammatory cytokines (i.e., interleukin-17A [IL-17A], tumor necrosis factor α [TNFα], and/or interferon-γ [IFNγ]), promote Th17 cell expansion and activation. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy blood donors were cocultured with BM-MSCs or FLS from RA patients or osteoarthritis (OA) patients. Cocultures were exposed to phytohemagglutinin with or without IL-17A, TNFα, or IFNγ. Quantitative reverse transcription-polymerase chain reaction analysis, enzyme-linked immunosorbent assay, and cytofluorometry were used to measure IL-17A production. RESULTS: Interaction of PBMCs with BM-MSCs inhibited Th1 and Th2 responses, but promoted Th17 cell expansion, as early as 24 hours, as demonstrated by increases in retinoic acid receptor-related orphan nuclear receptor γ or IL-17A messenger RNA (mRNA) levels, IL-17A secretion levels, and IL-17A-secreting cell frequency, as well as by T cell switching to the Th17 pathway after 2 rounds of stimulation with MSCs. IL-17A production was also increased in PBMCs stimulated with anti-CD3 plus anti-CD28 or in isolated CD3+ or CD45RO+ T cells, thus demonstrating the role of T cell activation. Levels of mRNA for IL-6, IL-8, and IL-1β were further amplified when T cell-secreted inflammatory cytokines were added. Interestingly, OA FLS or RA FLS also enhanced IL-17A and IL-6 production, but only RA FLS enhanced IFNγ and IL-1β production. We further demonstrated that MSC-mediated Th17 promotion requires caspase 1 activation by using an inhibitory peptide and measuring its activity. CONCLUSION: We found that the interaction of MSCs or FLS with T cells promotes the activation and expansion of Th17 cells through caspase 1 activation. Since proinflammatory and T cell-secreted inflammatory cytokines are also amplified, this mechanism may participate in the chronicity of RA.
23149905 New-onset multiple sclerosis associated with adalimumab treatment in rheumatoid arthritis: 2013 Feb Tumor necrosis factor (TNF) antagonists have brought about a significant advancement in treatment for autoimmune diseases such as rheumatoid arthritis (RA) and Crohn's disease; however, they are accompanied with a risk of severe adverse effects. We report the case of a 68-year-old female with a 33-year history of RA that developed multiple sclerosis (MS) during adalimumab (ADM) treatment at 22 months after the initial administration. Her first neurological symptom was mild dizziness, which progressed to severe dizziness with gait disturbance within 2 weeks. Fortunately, when she had this neurological disorder, ADM treatment was being transiently stopped because she was in the perioperative period. Repeated magnetic resonance imaging examinations revealed multiple demyelinating lesions in her brain, leading to the diagnosis of MS. The patient completely recovered spontaneously from the symptoms in several days. A review of the literature revealed another 15 cases of MS associated with anti-TNF-α treatment, emphasizing the importance of detecting neurological symptoms and discontinuing the anti-TNF-α therapy.
23157225 Distribution of regulatory T cells and interaction with dendritic cells in the synovium of 2012 OBJECTIVES: The aim of this study was to investigate the tissue distribution of regulatory T cells (Treg cells) and their interaction with dendritic cells (DCs) in synovium from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: Immunohistochemical staining was used to investigate the distribution of Treg cells and the interaction between Treg cells and DCs in RA (n = 30) and OA synovium (n = 8). mRNA levels were measured by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Large numbers of Treg cells were observed in lymphoid aggregates and perivenular infiltration areas in the RA synovium. Specific cellular markers for Treg cells (Foxp3, CD39, LAG-3, and Nrp-1) were found in lymphoid aggregates, perivenular infiltration, and scattered in lining layer areas. As molecular markers for DCs, DC-LAMP, DEC-205, CD80/86, and CD83 were also detected in the lymphoid aggregates and perivenular infiltration areas in RA. Furthermore, the co-localization of Treg cells and DCs was confined mainly in the lymphoid aggregation areas. The number of DCs increased significantly more than the number of Treg cells with inflammatory progression in RA. mRNA expression of the cellular markers for Treg cells (Foxp3, LAG-3, and Nrp-1) and the molecular markers for DCs (DC-LAMP and DEC-205) was increased in RA compared with OA synovium. CONCLUSIONS: Our results indicate that DCs play a dominant role in regulating the activation and progression of immune responses in RA, even though the number of Treg cells was upregulated at the same time. This suggests that Treg cells do not function normally to suppress the maturation of DCs in the RA synovium.
21486979 Development of antidrug antibodies against adalimumab and association with disease activit 2011 Apr 13 CONTEXT: Short-term data on the immunogenicity of monoclonal antibodies showed associations between the development of antidrug antibodies and diminished serum drug levels, and a diminished treatment response. Little is known about the clinical relevance of antidrug antibodies against these drugs during long-term follow-up. OBJECTIVE: To examine the course of antidrug antibody formation against fully human monoclonal antibody adalimumab and its clinical relevance during long-term (3-year) follow-up of patients with rheumatoid arthritis (RA). DESIGN, SETTING, AND PATIENTS: Prospective cohort study February 2004-September 2008; end of follow-up was September 2010. All 272 patients were diagnosed with RA and started treatment with adalimumab in an outpatient clinic. MAIN OUTCOME MEASURES: Disease activity was monitored and trough serum samples were obtained at baseline and 8 time points to 156 weeks. Serum adalimumab concentrations and antiadalimumab antibody titers were determined after follow-up. Treatment discontinuation, minimal disease activity, and clinical remission were compared for patients with and without antiadalimumab antibodies. RESULTS: After 3 years, 76 of 272 patients (28%) developed antiadalimumab antibodies--51 of these (67%) during the first 28 weeks of treatment. Patients without antiadalimumab antibodies had much higher adalimumab concentrations (median, 12 mg/L; IQR, 9-16 mg/L) compared with patients with antibody titers from 13 to 100 AU/mL (median, 5 mg/L; IQR, 3-9 mg/L; regression coefficient, -4.5; 95% CI, -6.0 to -2.9; P < .001) and also those greater than 100 AU/mL (median, 0 mg/L; IQR, 0-3 mg/L; regression coefficient, -7.1; 95% CI, -8.4 to -5.8; P < .001). Patients with antiadalimumab antibodies more often discontinued participation due to treatment failure (n = 29 [38%]; hazard ratio [HR], 3.0; 95% CI, 1.6-5.5; P < .001) compared with antiadalimumab antibody-negative ones (n = 28 [14%]). Ninety-five of 196 patients (48%) without antiadalimumab antibodies had minimal disease activity vs 10 of 76 patients (13%) with antiadalimumab antibodies; patients with antiadalimumab antibodies less often had sustained minimal disease activity score in 28 joints (DAS28) (< 3.2; HR, 3.6; 95% CI, 1.8-7.2; P < .001) compared with antiadalimumab antibody-negative ones. Three of 76 patients (4%) with antiadalimumab antibodies achieved sustained remission compared with 67 of 196 (34%) antiadalimumab antibody-negative ones; patients with antiadalimumab antibodies less often achieved remission (DAS28 < 2.6; HR, 7.1; 95% CI, 2.1-23.4; P < .001) compared with antiadalimumab antibody-negative ones. CONCLUSION: Among outpatients with RA in whom adalimumab was started over 3 years, the development of antidrug antibodies was associated with lower adalimumab concentration and lower likelihood of minimal disease activity or clinical remission.
22621287 Evidence-based knee injections for the management of arthritis. 2012 Jun OBJECTIVE: Arthritis of the knee affects 46 million Americans. We aimed to determine the level of evidence of intraarticular knee injections in the management of arthritic knee pain. METHODS: We systematically searched PUBMED/MEDLINE and the Cochrane databases for articles published on knee injections and evaluated their level of evidence and recommendations according to established criteria. RESULTS: The evidence supports the use of intraarticular corticosteroid injections for rheumatoid arthritis (1A+ Level), osteoarthritis (1A+ Level), and juvenile idiopathic arthritis (2C+ Level). Pain relief and functional improvement are significant for months up to 1 year after the injection. Triamcinolone hexacetonide offers an advantage over triamcinolone acetonide and should be the intraarticular steroid of choice (2B+ Level). Intraarticular injection of hyaluronate may provide longer pain relief than steroid injection in osteoarthritis (2B+ Level). It can also be effective for rheumatoid arthritis knee pain (1A+ Level). However, it is only recommended for patients with significant surgical risk factors and for patients with mild radiographic disease in whom conservative treatment has failed (2B± Level). Botulinum toxin type A injection is effective in reducing arthritic knee pain (2B+ Level), and so is tropisetron (2B+ Level) and tanezumab (2B+ Level). The new agents, such as rAAV2-TNFR:Fc, SB-210396/CE 9.1, and various radioisotopes have provided various degrees of success, but their long-term safety and efficacy remains to be determined. CONCLUSIONS: We conclude that strong evidence supports the use of intraarticular knee injection as a valuable intervention in the continuum of management of arthritis between conservative treatment and knee surgeries.
22422487 Time-dependent increased risk for serious infection from continuous use of tumor necrosis 2012 Aug OBJECTIVE: To investigate associations between continuous treatments with tumor necrosis factor (TNF) antagonists and risk for developing serious infections (SIs) over 3 years in Japanese patients with rheumatoid arthritis (RA) enrolled in the Registry of Japanese RA Patients for Long-Term Safety (REAL) database. METHODS: We analyzed 727 RA patients who had started either infliximab or etanercept (the anti-TNF group; 1,480.1 patient-years [PY]) and 571 RA patients who had started conventional nonbiologic disease-modifying antirheumatic drugs (the unexposed group; 1,104.1 PY) at the time of enrollment in the REAL. We assessed the occurrence of SIs within a 3-year observation period, including the period after switching to other TNF antagonists, and all SIs, unlimited to the first one in each patient as reported in other studies, to evaluate the real safety of TNF antagonists in daily practice. RESULTS: The incidence rate of SIs per 100 PY was 5.54 (95% confidence interval [95% CI] 4.44-6.84) in the anti-TNF group and 2.72 (95% CI 1.87-3.83) in the unexposed group. Poisson regression analysis revealed that the relative risk (RR) of continuous use of TNF antagonists for SIs after adjusting for baseline and time-dependent covariates was significantly elevated both overall (1.97, 95% CI 1.25-3.19) and for the first year (2.40, 95% CI 1.20-5.03), but not for the second and third years combined (1.38, 95% CI 0.80-2.43). The adjusted RR for SIs of etanercept compared to infliximab was not significantly elevated. CONCLUSION: Continuous anti-TNF therapy was significantly associated with increased risks for developing SIs during, but not after, the first year.
22954150 Adalimumab in the treatment of rheumatoid arthritis. 2012 Dec Adalimumab (ADA), a fully human monoclonal antibody against TNF-α is indicated for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohn's disease, ulcerative colitis and psoriasis. In RA, it may be prescribed in combination with methotrexate or other disease-modifying antirheumatic drugs or as monotherapy. Studies comparing ADA with other TNF-α inhibitors are limited and are based mainly on meta-analyses of randomised controlled trials and large observational cohorts. In this study, the effectiveness and safety of ADA is compared with that of etanercept and infliximab.
21899592 Etanercept-induced cutaneous and pulmonary sarcoid-like granulomas resolving with adalimum 2012 Feb A 59-year-old female with rheumatoid arthritis on etanercept therapy presented with a 7-cm-large subcutaneous forearm mass. Multiple smaller nodules subsequently developed on the upper and lower extremities. Except for a new cough, the patient was systemically well. Biopsy of the mass showed sarcoidal type granulomatous inflammation with nodular aggregations of non-necrotizing epithelioid histiocytes in the subcutis. A chest computed tomography (CT) scan showed mediastinal adenopathy consistent with pulmonary sarcoidosis. Etanercept was discontinued, and the patient was started on adalimumab for rheumatoid arthritis control. The cutaneous nodules fully resolved in 6 months with no additional treatment. A 4-month follow-up CT scan showed significant regression of mediastinal adenopathy. The patient has since been maintained on adalimumab therapy for 2 years with no recurrence of sarcoid-like manifestations. Biologic response modifiers targeting tumor necrosis factor alpha (TNFα) are effective treatments of chronic inflammatory conditions such as rheumatoid arthritis and psoriasis. TNFα represents a major cytokine in granuloma formation, and TNFα inhibitors are sometimes efficacious in the treatment of sarcoidosis. Paradoxically, there is a small volume of literature implicating TNFα inhibitors in the development of sarcoid-like disease. We present this case to promote the recognition of TNFα inhibitor-induced sarcoidosis and to illustrate the wide clinicopathologic differential of sarcoidal type granulomas.
22555877 Association of vitamin D with cardiometabolic risk factors in rheumatoid arthritis. 2012 Oct OBJECTIVE: Individuals with rheumatoid arthritis (RA) are at a greater risk for cardiovascular disease (CVD). Vitamin D deficiency is a potential risk factor for CVD and metabolic syndrome. Since patients with RA have a high prevalence of vitamin D deficiency, we investigated the association of vitamin D levels with cardiometabolic risk factors in a cohort of RA patients with no prior history of CVD. METHODS: Serum 25-hydroxyvitamin D (25[OH]D) levels were measured among RA patients enrolled in a cohort study of subclinical CVD. The cross-sectional associations of 25(OH)D levels with traditional CVD risk factors such as insulin resistance (IR; estimated using the homeostatic model assessment [HOMA]), adipokines, markers of systemic inflammation, and endothelial activation were explored, adjusting for pertinent sociodemographic, lifestyle, and RA characteristics. RESULTS: Among 179 RA patients, 73 (41%) had a 25(OH)D level <30 ng/ml. Only 23 patients (13%) had a 25(OH)D level ≥45 ng/ml. After adjusting for demographics and body mass index (BMI), 25(OH)D remained significantly associated with high-density lipoprotein (HDL) cholesterol and inversely associated with HOMA-IR, fibrinogen, E-selectin, and soluble intercellular adhesion molecule 1 (sICAM-1). Significant associations with HDL cholesterol, E-selectin, and sICAM-1 were maintained after adjusting for the Disease Activity Score in 28 joints (DAS28) and autoantibody status. These associations were similar between the groups subdivided by sex, ethnicity, BMI, DAS28 level, and autoantibody status. CONCLUSION: These data suggest that vitamin D deficiency is common in RA and may be independently associated with several cardiometabolic intermediates in this population.
22665343 Anti-cyclic citrullinated peptide antibodies and joint involvement in Behçet's disease. 2012 Jul 1 PURPOSE: We aimed to determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in a large group of Korean patients with Behçet's disease (BD), with and without joint involvement, and to compare these findings with the prevalences of anti-CCP antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). MATERIALS AND METHODS: We tested 189 patients with BD, 105 with RA, and 36 with SLE for anti-CCP antibodies and IgM rheumatoid factor in serum. We reviewed the medical records of patients with BD to investigate their personal and clinical characteristics as well as their laboratory test results. RESULTS: Anti-CCP antibodies were detected in seven of the 189 BD patients (3.7%), at a mean titer of 30.6±44.4 U/mL, in 86 of the 105 RA patients (81.9%) with a mean titer of 198.8±205.7 U/mL, and in nine of the 36 SLE patients (25%) with a mean titer of 180.4±113.9 U/mL. One of the seven anti-CCP-positive BD patients fulfilled the diagnostic criteria for both BD and RA. Five of the seven anti-CCP-positive BD patients (71.4%) had polyarticular joint involvement, and the other two patients (28.6%) had oligoarticular involvement. CONCLUSION: We determined the prevalence of anti-CCP antibodies in a large group of Korean BD patients with and without joint involvement. Negative anti-CCP test in patients with BD may help to differentiate BD from RA and SLE, all of which present with similar clinical features.