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ID PMID Title PublicationDate abstract
26403330 Feeding transgenic plants that express a tolerogenic fusion protein effectively protects a 2016 Apr Although much explored, oral tolerance for treatment of autoimmune diseases still awaits the establishment of novel and effective vectors. We investigated whether the tolerogenic CTA1(R7K)-COL-DD fusion protein can be expressed in edible plants, to induce oral tolerance and protect against arthritis. The fusion protein was recombinantly expressed in Arabidopsis thaliana plants, which were fed to H-2(q) -restricted DBA/1 mice to assess the preventive effect on collagen-induced arthritis (CIA). The treatment resulted in fewer mice exhibiting disease and arthritis scores were significantly reduced. Immune suppression was evident in treated mice, and serum biomarkers for inflammation as well as anticollagen IgG responses were reduced. In spleen and draining lymph nodes, CD4(+) T-cell responses were reduced. Concomitant with a reduced effector T-cell activity with lower IFNγ, IL-13 and IL-17A production, we observed an increase in IL-10 production to recall antigen stimulation in vitro, suggesting reduced Th1, Th2 and Th17 activity subsequent to up-regulated IL-10 and regulatory T-cell (Treg) functions. This study shows that edible plants expressing a tolerogen were effective at stimulating CD4 T-cell tolerance and in protecting against CIA disease. Our study conveys optimism as to the potential of using edible plants for oral treatment of rheumatoid arthritis.
25863233 Expression of receptor activator of nuclear factor-κB ligand is related to sex difference 2015 Oct Osteoclasts are responsible for bone destruction in rheumatoid arthritis, and women show greater disease activity and functional disability than men. This study aimed to examine differences in the pathogenesis of collagen-induced arthritis and osteoclastogenesis between female and male mice in vivo and in vitro. Female mice exhibited worse disease progression and increased osteoclastogenesis, as measured by tartrate-resistant acid phosphatase (TRAP) staining than male mice. Significantly higher levels of CD11b(+) cells were detected in the bone marrow of female mice than that of male mice. Furthermore, the mRNA expression of receptor activator of nuclear factor-κB ligand was higher in female mice that were immunized with or without collagen II. These findings highlighted sex differences in arthritis morbidity and suggested that female mice are more likely to develop arthritis than male mice. Further studies are needed to investigate the mechanisms of sex differences in collagen-induced arthritis.
26472472 The joint in psoriatic arthritis. 2015 Sep Psoriatic arthritis (PsA), a chronic inflammatory joint disease associated with psoriasis, is notable for diversity in disease presentation, course and response to treatment. Equally varied are the types of musculoskeletal involvement which include peripheral and axial joint disease, dactylitis and enthesitis. In this review, we focus on the psoriatic joint and discuss pathways that underlie synovial, cartilage and bone inflammation and highlight key histopathologic features. The pivotal inflammatory mechanisms and pathobiology of PsA parallel findings in other forms of spondyloarthritis but are distinct from disease pathways described in rheumatoid synovitis and bone disease. The diagnosis of PsA from both a clinical and imaging perspective is also discussed.
27708408 PTEN ameliorates autoimmune arthritis through down-regulating STAT3 activation with recipr 2016 Oct 6 PTEN is a tyrosine phosphatase with significant function in inhibiting STAT3 activation. Recently, inactivation of STAT3 has been demonstrated as a therapeutic candidate for autoimmune arthritis. The expression of PTEN controlled by p53 regulates autoimmune arthritis through modulating the balance between Th17 and Treg. We hypothesized that PTEN regulated by p53 might reduce CIA severity and inflammatory response via inhibiting STAT3 activation. Our results revealed that PTEN could ameliorate experimental autoimmune arthritis by reducing STAT3 activity and Th17 differentiation. Systemic infusion of PTEN overexpression downregulated CIA severity. In addition, PTEN overexpression decreased the activation of T cells and modulated reciprocal differentiation of Th17 and Treg cells. We observed that PTEN expression downregulated by p53 deficiency induced the activation of STAT3. Loss of p53 exacerbated autoimmune arthritis and dysregulated the population of Th17 and Treg. These data suggest that induction of STAT3-modulatory activity of PTEN may be a therapeutic target for rheumatoid arthritis therapy.
26523061 Disease-modifying Antirheumatic Drugs (DMARD) and Combination Therapy of Conventional DMAR 2015 Nov Treatment with nonsteroidal antiinflammatory drugs (NSAID) is the recommended first-line therapy in patients with axial spondyloarthritis (axSpA); and for those patients who have persistently active disease, the introduction of tumor necrosis factor-α (TNF-α) inhibitors is indicated. Conventional nonbiological disease-modifying antirheumatic drugs (DMARD), although effective and used in clinical practice for peripheral arthritis, are not recommended. Few studies have been conducted with the aim of evaluating the effect of conventional DMARD, either alone or in combination, in axSpA. As for psoriatic arthritis (PsA), DMARD are widely used, but few trials are available about their effects on axial involvement, which is not often assessed as a primary outcome in clinical trials. In rheumatoid arthritis, combination therapy of 2 or more conventional DMARD appears to confer better response than methotrexate monotherapy, and may even be a viable alternative to TNF-α inhibitors. In peripheral PsA, combination therapy can be used after treatment failure with 1 DMARD, but few studies have been conducted. However, available evidence for the combination of conventional DMARD indicates a lack of any significant benefit on axial symptoms; thus this treatment approach does not represent an effective alternative to anti-TNF-α therapy.
26075259 Designation of a novel DKK1 multiepitope DNA vaccine and inhibition of bone loss in collag 2015 Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases. Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1. In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopes in vitro and in vivo assays. Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA. High level expression of the designed vaccine was measured in supernatant of COS7 cells. In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1 in vivo. Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice. These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion.
27385219 Circulating cartilage oligomeric matrix protein in juvenile idiopathic arthritis. 2017 May OBJECTIVES: Raised serum cartilage oligomeric matrix protein (sCOMP) has been reported to predict erosive disease in early rheumatoid arthritis (RA). In juvenile idiopathic arthritis (JIA), subnormal sCOMP levels have been associated with ongoing inflammation and growth retardation. In this study we aimed to assess sCOMP, C-reactive protein (CRP), and insulin-like growth factor (IGF)-1 in children/adolescents with JIA and in referents. METHOD: We enrolled 52 JIA patients at planned outpatient visits and 54 inpatients with ongoing infection ('infection referents'). A total of 120 referents testing negative for immunoglobulin (Ig)E-mediated allergy ('IgE referents') served as controls. All serum samples were analysed for COMP, IGF-1, and CRP. RESULTS: The average sCOMP level was highest among the IgE referents and lowest among the infection referents. In the JIA patients, the level of sCOMP was not associated with the level of CRP or with clinical signs of disease activity. CONCLUSIONS: The results of this study do not support routine clinical analysis of sCOMP levels in patients with JIA.
27126942 [Sonic hedgehog (SHH) promotes the proliferation of synovial fibroblasts of rats with coll 2016 May OBJECTIVE: To investigate the effect of sonic hedgehog (SHH) on the proliferation of synovial fibroblasts (SFs). METHODS: The serum samples were collected from 30 rheumatoid arthritis (RA) patients, 30 systemic lupus erythematosus (SLE) patients, 30 ankylosing spondylitis (AS) patients and 30 healthy subjects. The concentrations of serum SHH were detected by ELISA. Collagen induced arthritis (CIA) were developed by type 2 collagen in Sprague-Dawley rats. The SFs were isolated from knee synovial tissues of CIA rats, and then identified by the detection of vimentin by immunofluorescence technique. Before and 72 hours after blocking SHH-glioma-associated oncogene 1 (Gli-1) signaling pathway with GANT61, the expression level of SHH in SFs was detected by Western blotting, and the proliferation of SFs was examined with CCK-8 assay. RESULTS: The level of serum SHH in the RA patients was remarkably higher than that in the SLE, AS patients and the healthy controls. In the CIA rats, the expression of SHH in SFs in vitro was higher than that in the healthy control rats. After 72-hour treatment of GANT61 to block SHH-Gli-1 signaling pathway, the expression level of SHH protein in SFs from CIA rats was reduced, and meanwhile the proliferation of the SFs was inhibited. CONCLUSION: SHH plays an important role in the proliferation of SFs and could be used as a potential therapeutic target for RA.
26271978 [Up-regulated expressions of HIF-1α, VEGF and CD34 promote synovial angiogenesis in rats 2015 Aug OBJECTIVE: To observe the alterations of hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and CD34 in synovial tissues in rats with adjuvant arthritis and explore the mechanism of angiogenesis in rheumatoid arthritis. METHODS: Thirty SD rats were randomly divided into normal control and model groups. Adjuvant arthritis was induced using Freund's complete adjuvant in the rats of the model group. Nineteen days after the modeling, the expressions of HIF-1α, VEGF and CD34 were detected using immunohistochemistry. The mRNA and protein levels of HIF-1α and VEGF were detected by reverse transcription PCR and Western blotting, respectively. RESULTS: Compared with the normal control group, the model group showed paw swelling, increased arthritic index, and significantly up-regulated expressions of VEGF, HIF-1α, CD34 in synovial tissue. VEGF mRNA was positively correlated with paw swelling degree, HIF-1α protein was positively correlated with the arthritis index, and VEGF mRNA and HIF-1α protein were positively correlated with CD34. CONCLUSION: The synovial angiogenesis is associated with the over-expressions of VEGF, HIF-1α and CD34 in rats with adjuvant arthritis.
26311320 Which Factors Influence Self-Efficacy in Patients with Chronic Inflammatory Polyarthritis? 2016 Jun OBJECTIVES: Patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or unspecified polyarthritis (UA) deal with several symptoms such as joint stiffness, pain, physical limitations and fatigue. Self-efficacy is about patients' beliefs and abilities to handle the symptoms and implications of having arthritis. Patients' self-efficacy is also a phenomenon that nurses may affect through patient education. Therefore, the aim of the present study was to investigate the factors that predict self-efficacy in patients with chronic inflammatory polyarthritis. METHODS: The participants (n = 132) were recruited from St Olavs University Hospital in central Norway from 2008 to 2010, and consisted of adult patients with RA, PsA or UA. We performed secondary analyses on data collected in a randomized controlled trial studying the long-term effects of nurse-led patient education. We carried out bivariate and multivariate linear regression analyses. The predictor variables consisted of baseline data on demographics, disease characteristics (diagnosis, disease duration, disease activity, use of disease-modifying anti-rheumatic drugs, pain and tiredness) and psychological variables (well-being, psychological distress and patient activation). The dependent variables were self-efficacy over other symptoms and self-efficacy over for pain after one year. RESULTS: The analyses showed that female gender and patient activation predicted higher self-efficacy over other symptoms, whereas female gender and better well-being predicted higher self-efficacy over pain. CONCLUSION: To strengthen arthritis patients' self-efficacy, nurses need to focus on patients' well-being and activation. Nurses also need to be aware of possible gender differences regarding patients' self-efficacy. Copyright © 2015 John Wiley & Sons, Ltd.
26762160 Involvement of the multidisciplinary team and outcomes in inpatient rehabilitation among p 2016 Jan 13 BACKGROUND: The last decades have for patients with inflammatory rheumatic diseases seen a shift towards more physically active rehabilitation programs, often provided as out-patients with less use of inpatient facilities. There is little research on which effect the multidisciplinary team has on health outcomes for patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and connective tissue disease. This study examined patient reported outcomes for patients with inflammatory rheumatic diseases receiving rehabilitation care as inpatients in departments of rheumatology, and studied how number of consultations with the multidisciplinary team affected these clinical outcomes. METHODS: Patients with inflammatory rheumatic diseases were included in a multi-center prospective observational study if rehabilitation was considered a focus during an inpatient stay at four departments of rheumatology. At admission, discharge, and after 3 and 6 months, 317 patients were assessed with patients reported outcomes (PRO) including health assessment questionnaire (HAQ), short-form 36 (SF-36), pain, fatigue, patient global assessment of disease activity, self-efficacy scales, rheumatoid arthritis disease activity index (RADAI), and SF-6D utility. Patients stated consultations with the multidisciplinary team. RESULTS: Improvements were short-lived, and at 6 months follow-up period only mental health, pain and utility remained improved with small effect sizes. Extensive involvement of health professionals was not associated with improved outcomes. CONCLUSIONS: Patients with inflammatory rheumatic disease receiving inpatient multidisciplinary rehabilitation had small and mainly short-term improvements in most PROs. High use of the multidisciplinary team did not enhance or preserve rehabilitation outcomes in inflammatory rheumatic conditions when admitted as inpatients.
27803949 Usability and Workflow Evaluation of "RhEumAtic Disease activitY" (READY). A Mobile Applic 2016 Nov 2 BACKGROUND: RhEumAtic Disease activitY (READY) is a mobile health (mHealth) application that aims to create a shared platform integrating data from both patients and physicians, with a particular emphasis on arthritis disease activity. METHODS: We made READY available on an iPad and pilot implemented it at a rheumatology outpatient clinic. We conducted 1) a usability evaluation study to explore patients' and physicians' interactions with READY, and 2) a time motion study (TMS) to observe the clinical workflow before and after the implementation. RESULTS: A total of 33 patients and 15 physicians participated in the usability evaluation. We found usability problems in navigation, data entry, pain assessment, documentation, and instructions along with error messages. Despite these issues, 25 (75,76%) patients reported they liked READY. Physicians provided mixed feedback because they were concerned about the impact of READY on clinical workflow. Six physicians participated in the TMS. We observed 47 patient visits (44.72 hours) in the pre-implementation phase, and 42 patient visits (37.82 hours) in the post-implementation phase. We found that patients spent more time on READY than paper (4.39mins vs. 2.26mins), but overall, READY did not delay the workflow (pre = 52.08 mins vs. post = 45.46 mins). This time difference may be compensated with READY eliminating a workflow step for the staff. CONCLUSION: Patients preferred READY to paper documents. Many found it easier to input information because of the larger font size and the ease of 'tapping' rather than writing-out or circling answers. Even though patients spent more time on READY than using paper documents, the longer usage of READY was mainly due to when troubleshooting was needed. Most patients did not have problems after receiving initial support from the staff. This study not only enabled improvements to the software but also serves as good reference for other researchers or institutional decision makers who are interested in implementing such a technology.
26684871 Inflammatory but not apoptotic death of granulocytes citrullinates fibrinogen. 2015 Dec 17 BACKGROUND: Neutrophil activation induces citrullination of intracellular targets of anticitrullinated peptide antibodies (ACPA), which are specific for rheumatoid arthritis (RA). Citrullinated fibrinogen is bound by ACPA but it is less well understood how extracellular proteins are citrullinated. The cells that produce fibrinogen, hepatocytes, do not express peptidyl arginine deiminase (PAD) enzymes nor do PAD enzymes include N-terminal signal peptides to direct them into the secretory pathway. We hypothesized that dying neutrophils release PAD in the extracellular space, and that this could cause citrullination of target extracellular antigens relevant to RA such as fibrinogen. METHODS: HL60 cells were differentiated into neutrophil-like cells by treatment with all-trans retinoic acid (ATRA). Differentiation was confirmed by CD11b staining, PAD4, PAD2 and myeloperoxidase expression, cell division, and nuclear morphology. Death was induced with various stimuli, including freeze-thaw to induce necrosis, Ionomycin and PMA to induce NETosis, and UV-B to induce apoptosis. Death markers were assessed by immunohistochemistry and flow cytometry. To quantify extracellular citrullination, dying ATRA-differentiated HL60 cells were cultured with fibrinogen for 24 hours and supernatants were probed for fibrinogen citrullination, PAD2 and PAD4 by western blot. RESULTS: While both NETotic and necrotic ATRA differentiated HL60 cells citrullinated fibrinogen, apoptotic cells did not citrullinate fibrinogen, even when allowed to undergo secondary necrosis. Incubation of necrotic neutrophil lysates with fibrinogen also causes fibrinogen citrullination. PAD2 and PAD4 were detected by western blot of supernatants of ATRA-differentiated HL60 cells undergoing necrotic and NETotic death, but not apoptotic or secondarily necrotic cell death. CONCLUSION: We implicate granulocytes undergoing inflammatory cell death as a mechanism for altering extracellular self-proteins that may be targets of autoimmunity linked to inflammatory diseases such as rheumatoid arthritis.
25907010 Lycium barbarum polysaccharide attenuates type II collagen-induced arthritis in mice. 2015 No curative treatment is yet available for rheumatoid arthritis (RA), wherein chronic synovitis progresses to cartilage and bone destruction. Considering the recently recognized anti-inflammatory properties of Lycium barbarum polysaccharide (LBP; a derivative of the goji berry), we established the collagen type II-induced arthritis (CIA) mouse model to investigate the potential therapeutic effects and mechanisms of LBP. The CIA-induced changes and LBP-related effects were assessed by micro-computed tomography measurement of bone volume/tissue volume and by ELISA and western blotting detection of inflammatory mediators and matrix metalloproteinases (MMPs). The CIA mice showed substantial bone damage, bone loss, and increased concentrations of TNF-α, IL-6, IL-17, PGE2, MIP-1, anti-type II collagen IgG, MMP-1, and MMP-3. LBP treatments produced significant dose-dependent improvements in CIA-induced bone damage and bone loss, and significantly reduced CIA-stimulated expression of the inflammatory mediators and MMPs. Thus, LBP therapy can preserve bone integrity in CIA mice, possibly through down-regulation of inflammatory mediators.
28352356 Investigation of the effect of phlomisoside F on complete Freund's adjuvant-induced arthri 2017 Feb Phlomis younghusbandii Mukerjee (Labiatae) has been reported to be effective in the treatment of rheumatoid arthritis (RA). In the present study, the anti-inflammatory and anti-arthritic effects of phlomisoside F (PF), isolated from P. younghusbandii Mukerjee (Labiatae), were investigated in male Wistar rats subjected to carrageen-induced paw edema and complete Freund's adjuvant (CFA)-induced arthritis. Arthritis scores were evaluated by a 5-point ordinal scale (scores 0-4). Expression levels of TNF-α, IL-1β, IL-6, IL-10, COX-2 and 5-LOX were determined via ELISA and western blot assays. Subsequent to establishing the edema and arthritis models, oral administration of PF (5, 10 and 20 mg/kg) significantly inhibited mean edema rate, compared with the control group in carrageenan-induced paw edema assay. In addition, administration of PF (5, 10 and 20 mg/kg/day) for 28 days markedly exhibited an anti-arthritic activity by offsetting the body weight loss, inhibiting the paw edema, reducing the arthritis scores and the indices of thymus and spleen, inhibiting the expression levels of TNF-α, IL-1β, IL-6, COX-2 and 5-LOX, and increasing the expression of IL-10, when compared with the respective control group in CFA-induced arthritis assay. In conclusion, PF is a valuable anti-arthritic constituent of P. younghusbandii, and the present study results suggest that this herb may be used in the treatment of RA.
26254734 Auto-reactions, autoimmunity and psoriatic arthritis. 2015 Dec Evidence from the literature suggests that autoimmune processes may drive features of psoriatic arthritis (PsA). Such hypothesis is supported by the evidence that class I major histocompatibility complex (MHC) genes are associated with susceptibility to develop PsA and auto-reactive cells, such as CD8 T cells, T helper (h) 17 and plasma cells, have been demonstrated in PsA. However, no autoantigens have ever been demonstrated in PsA. The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA) patients. These autoantibodies have been associated with a worse disease progression independent of anti-citrulline antibodies (ACPA). In PsA, anti-CarP antibodies have not been evaluated yet. We aimed at analyzing, for the first time, the anti-CarP antibodies in sera of patients with active PsA who were negative for ACPA in order to explore both their presence and their relationship with disease activity. A total of 70 individuals, 30 patients with diagnosis of PsA (according to CASPAR criteria) and 40 healthy controls (HC) were enrolled. We found significantly increased levels of anti-CarP antibodies in PsA patients compared with HC (P<0.0001). Our findings indicate that anti-CarP antibodies are detectable with high specificity and sensibility in PsA patients suggesting an autoimmune background of PsA. Anti-CarP antibodies can be useful in improving the diagnosis of PsA and are correlated with disease activity.
25966322 Cumulative therapeutic effects of phytochemicals in Arnica montana flower extract alleviat 2016 Mar 30 BACKGROUND: The plant Arnica montana is used in folk medicine to alleviate pain, inflammation and swelling of muscles and joints associated with rheumatoid arthritis and other inflammatory conditions. The present study aimed to investigate the therapeutic effects and mechanism of action of A. montana flower methanol extract (AMME) against both inflammation and oxidative stress in a collagen-induced arthritis (CIA) rat model. RESULTS: Oral administration of AMME was found to reduce clinical signs and improve the histological and radiological status of the hind limb joints. AMME-treated rats had lower expression levels of nitric oxide, tumor necrosis factor-α, interleukins (IL-1β, IL-6 and IL-12) and titer of anti-type II collagen antibody compared with untreated CIA rats. Furthermore, by inhibiting these mediators, AMME also contributed towards the reversal of disturbed antioxidant levels and peroxidative damage. CONCLUSION: The alleviation of arthritis in rats was very likely due to the combined action of phenolic and flavonoid compounds, the major constituents identified by gas chromatography/mass spectrometry (GC/MS) analysis. The study also shed some light on mechanisms involved in diminution of inflammatory mediators and free radical-generating toxicants and enhancement of the antioxidant armory, thereby preventing further tissue damage, injury and synovial hyperproliferation in arthritis.
26312870 Clinical utility of random anti-tumour necrosis factor drug testing and measurement of ant 2015 Feb 26 BACKGROUND: Up to 40% of patients with rheumatoid arthritis treated with anti-tumour necrosis factor (TNF) drugs do not respond because of primary inefficacy or loss of response. Although one explanation is that immunogenicity leads to the development of anti-drug antibodies and low drug concentrations, the clinical usefulness of pharmacological monitoring is debated. Our aim was to assess whether the presence of anti-drug antibodies and non-trough drug concentrations could predict treatment response in patients with rheumatoid arthritis treated with anti-TNF drugs. METHODS: 331 patients were selected from a multicentre prospective cohort (160 treated with adalimumab, 171 etanercept). Serum samples were collected at 3, 6, and 12 months after treatment initiation. Anti-drug antibodies were measured with RIA, drug concentrations with ELISAs, and Disease Activity Score in 28 joints (DAS28) at each timepoint. Linear and logistic regression, generalised estimating equation (GEE), and receiver operating characteristic curves were used to test the association and predictive value of anti-drug antibodies and non-trough drug concentrations on treatment response (ΔDAS28). FINDINGS: 835 serial samples were tested (414 adalimumab, 421 etanercept). Anti-adalimumab antibodies were detected in 31 (24·8%) of 125 patients who had completed 12 month follow-up and none of the etanercept patients. The presence of anti-drug antibodies was associated with lower adalimumab concentrations (Spearman r=-0·66, p=0·0041). At 3 months, anti-drug antibody formation and low adalimumab concentrations were significant predictors of poor treatment response at 12 months (area under curve [AUC] 0·68, 95% CI 0·54-0·81, and 0·66, 0·55-0·77, respectively; and both combined 0·71, 0·57-0·85). Adalimumab concentration was the most significant independent predictor of ΔDAS28 after adjustment for confounders (regression coefficient 0·12, 95% CI 0·06-0·18; p=0·003). High etanercept concentrations were associated with better treatment response (p=0·01), but low concentrations at 3 months were not a significant predictor of poor treatment response at 12 months (AUC 0·58, 95% CI 0·46-0·70). In the combined GEE model including adalimumab and etanercept, a body-mass index of 30 kg/m(2) or more was associated with low drug concentrations (regression coefficient 0·78, 95% CI 0·37-1·18; p<0·0001). INTERPRETATION: Pharmacological testing in anti-TNF initiated patients is clinically useful even in the absence of trough levels. At 3 months, presence of anti-drug antibodies and low adalimumab concentrations are a significant predictor for poor treatment response at 12 months. Strengths of this study include a large, prospective cohort and use of RIA to measure antibodies (less prone to drug interference). Although non-trough concentrations might have underestimated the frequency of antibodies, their presence still predicted response. FUNDING: MJ is a MRC Clinical Training Fellow supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the UK Medical Research Council (grant number G1000417/94909), ICON, GlaxoSmithKline, AstraZeneca, and the Medical Evaluation Unit. Arthritis Research UK (grant ref 20385).
26273164 Erythrodermic Psoriasis Treated with Golimumab: A Case Report. 2015 Aug Erythrodermic psoriasis (EP) is a very severe variant of psoriasis whose management poses a challenge to physicians, as currently available therapies often provide unsatisfactory results. Many biologics have been used to treat chronic plaque psoriasis, the most common form of psoriasis; however, their effectiveness for EP is poorly understood. A recently developed biologic, golimumab, has been extensively studied for the treatment of moderate-to-severe active rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis, and chronic plaque psoriasis. However, no clinical trials have been performed for EP. Here, we report the case of a 32-year-old man who presented with severe psoriasis that previously failed to respond satisfactorily to methotrexate, cyclosporine, retinoid, narrow-band ultraviolet B phototherapy, and topical agents (i.e., steroids and calcipotriol). Skin lesions worsened progressively and developed into erythroderma. Psoriatic arthritis was also detected. Conventional therapies lacked efficacy. Therefore, we administered golimumab 50 mg. The skin lesions improved significantly according to the Psoriasis Area and Severity Index score after the first administration; lesions improved further throughout the treatment course. Although additional studies are required to fully evaluate the efficacy and safety of golimumab, this agent may be an alternative treatment strategy for some patients with recalcitrant EP.
26811933 Active immunisation targeting soluble murine tumour necrosis factor alpha is safe and effe 2016 Mar OBJECTIVES: TNF-α has been proved to be an effective target in rheumatoid arthritis treatment. So far, all the commercialised TNF-α antagonists function as passive immunotherapy. The aim of this study was to design a complex which can trigger active immunisation and overcome self-tolerance to elicit antibodies against murine TNF-α. METHODS: The complex (KLH-TNF) was chemically synthesised by linking a selected peptide TNFα(4-23) from murine soluble TNF-α to a carrier protein, keyhole limpet haemocyanin (KLH). We evaluated its safety and antibody eliciting performance. We also evaluated its disease-regulating ability on collagen-induced arthritis models. Furthermore, the immune cells responses were analysed by T cell proliferation assay and B cell memory experiments. RESULTS: The complex was safe without cytotoxity. The anti-mTNF-α antibody titers of the KLH-TNF group were 400 times greater than the control groups (p<0.0001). The elicited antibodies could combine with soluble TNF-α. The antibody response was independent of autologous TNF-α and could be reinforced by booster immunisation. Moreover, the complex did not trigger T cell activation and B cell memory response against native TNF-α. In animal experiments, KLH-TNF immunized mice showed a lower arthritis score (p<0.001) and better weight gain (p<0.01). Histological evaluations showed milder inflammation and cartilage depletion. CONCLUSIONS: Active immunotherapy against cytokine TNF-α is feasible by conjugating cytokine peptide with carrier protein. The elicited antibodies could combine with the native TNF-α and inhibit its activity. Importantly, the antibody response is reversible and independent of autologous TNF-α.