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ID PMID Title PublicationDate abstract
29068606 Salivary lipids: A review. 2017 Sep Saliva is produced by both large and small salivary glands and may be considered one of the most important factors influencing the behavior of oral cavity homeostasis. Secretion of saliva plays an important role in numerous significant biological processes. Saliva facilitates chewing and bolus formation as well as performs protective functions and determines the buffering and antibacterial prosperities of the oral environment. Salivary lipids appear to be a very important component of saliva, as their qualitative and quantitative composition can be changed in various pathological states and human diseases. It has been shown that disturbances in salivary lipid homeostasis are involved in periodontal diseases as well as various systemic disorders (e.g. cystic fibrosis, diabetes and Sjögren's syndrome). However, little is known about the role and composition of salivary lipids and their interaction with other important ingredients of human saliva, including proteins, glycoproteins and salivary mucins. The purpose of this review paper is to present the latest knowledge on salivary lipids in healthy conditions and in oral and systemic diseases.
27726238 Use of T1ρMR imaging in Sjögren's syndrome with normal appearing parotid glands: Initial 2017 Apr PURPOSE: To explore the feasibility of parotid spin-lattice relaxation time in the rotating frame (T1ρ) MR imaging in the diagnosis of Sjögren's syndrome (SS) without morphological changes of the parotid glands. MATERIALS AND METHODS: The study enrolled 32 consecutive SS patients without morphological changes of parotid glands and 32 age- and gender-matched healthy volunteers who underwent parotid 3.0 Tesla MR imaging, including T1ρ sequences. Follow-up imaging was performed at 3 months. T1 signal intensities and T1ρ values of bilateral parotid glands were compared using paired samples t-test. Parotid T1 signal intensities and T1ρ values were compared using two independent samples t-test. Diagnostic performance of the parotid T1ρ values was evaluated by receiver operating characteristic analysis. The intraclass correlation coefficient (ICC) was calculated to evaluate the reproducibility of parotid T1ρ measurements. RESULTS: There were no significant differences of T1 signal intensities and T1ρ values between bilateral parotid glands in SS patients and healthy volunteers (P = 0.170, 0.886 and 0.942, 0.229). The parotid T1ρ values of SS patients (96.47 ± 15.38 ms) were significantly higher than those of healthy volunteers (84.25 ± 6.11 ms) (P < 0.001), while there were no significant differences of T1 signal intensities between SS patients and healthy volunteers (P = 0.655). With a cutoff value of 88.02 ms, the sensitivity and specificity of the parotid T1ρ value was 75.0% and 100.0% in the diagnosis of SS. The reproducibility of parotid T1ρ measurement was excellent (ICC: 0.934-0.995). CONCLUSION: Parotid T1ρ MR imaging held a potential role in diagnosing SS without morphological changes of parotid glands. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:1005-1012.
27380269 Staphylococcus aureus-Associated Musculoskeletal Infections. 2017 Musculoskeletal infections caused by Staphylococcus aureus are among the most difficult-to-treat infections. S. aureus osteomyelitis is associated with a tremendous disease burden through potential for long-term relapses and functional deficits. Although considerable advances have been achieved in diagnosis and treatment of osteomyelitis, the management remains challenging and impact on quality of life is still enormous. S. aureus acute arthritis is relatively seldom in general population, but the incidence is considerably higher in patients with predisposing conditions, particularly those with rheumatoid arthritis. Rapidly destructive course with high mortality and disability rates makes urgent diagnosis and treatment of acute arthritis essential. S. aureus pyomyositis is a common disease in tropical countries, but it is very seldom in temperate regions. Nevertheless, the cases have been increasingly reported also in non-tropical countries, and the physicians should be able to timely recognize this uncommon condition and initiate appropriate treatment. The optimal management of S. aureus-associated musculoskeletal infections requires a strong interdisciplinary collaboration between all involved specialists.
28673789 Efficacy and safety of biological DMARDs modulating B cells in primary Sjögren's syndrome 2018 Jan OBJECTIVE: In this review, we summarise the clinical efficacy and safety of B-cell targeted therapies for primary Sjögren's syndrome (pSS). METHODS: A systematic literature review was conducted using databases including MEDLINE, EMBASE and Cochrane. Only articles reporting controlled or prospective studies of b-DMARDs modulating B cells in treatment of pSS were selected. The highest-quality studies were selected for meta-analysis. The primary outcome of interest was clinical efficacy at week 24 on fatigue, dryness, Schirmer test, salivary flow rate and the full ESSDAI score including biological domain. For the efficacy criteria used, the difference between rituximab and placebo groups was expressed as mean difference (MD). RESULTS: Eighteen articles (13 of rituximab, 3 of belimumab, 1 of epratuzumab and 1 of baminercept) were identified for detailed evaluation. 4 controlled randomised trials of rituximab treatment vs. placebo involving 300 patients were included for quantitative analysis. No significant differences were observed between groups in the meta-analysis of mean improvements between baseline and week 24 in fatigue VAS [MD -3,24 95% CI (-30,21 to 23,72)], oral dryness VAS [MD -8,41 95% CI (-35,06 to 18,24)], salivary flow rate [MD 0,04 95% CI (-0,03 to 0,11)] and Schirmer test [MD 0,35 95% CI (-2,13 to 2,82)]. Rituximab was relatively safe compared to placebo. CONCLUSION: Our review shows that rituximab is not effective in pSS with the designs and outcomes proposed in the trials. Controlled randomised trials are needed to prove the efficacy of belimumab and epratuzumab in this indication. The randomised controlled trial evaluating baminercept failed to achieve its primary endpoint.
27900604 Assessment of interstitial lung disease in Sjögren's syndrome by lung ultrasound: a pilot 2017 Apr The background of this study is to assess the accuracy of lung ultrasound (LUS) to diagnose interstitial lung disease (ILD) in Sjögren's syndrome (Sjs), in patients who have any alterations in pulmonary function tests (PFT) or respiratory symptoms. LUS was correlated with chest tomography (hrCT), considering it as the imaging gold standard technique to diagnose ILD. This is a pilot, multicenter, cross-sectional, and consecutive-case study. The inclusion criteria are ≥18 years old, Signs and symptoms: according to ACEG 2002 criteria, respiratory symptoms (dyspnea, cough), or any alterations in PFR. LUS was done following the International Consensus Conference on Lung Ultrasound protocol for interstitial syndrome (B pattern). Of the 50 patients in follow-up, 13 (26%) met the inclusion criteria. All were women with age 63.62 years (range 39-88). 78.6% of the cases had primary Sjs (SLE, RA, n = 2). The intra-rater reliability k is 1, according to Gwet's Ac1 and GI index (probability to concordance-e(K)-, by Cohen, of 0.52). LUS has a sensitivity of 1 (95% CI 0.398-1.0), specificity of 0.89 (95% CI 0.518-0.997), and a positive probability reason of 9.00 (95% CI 7.1-11.3) to detect ILD. The correlation of Pearson is r = 0.84 (p < 0.001). To check the accuracy of LUS to diagnose ILD, a completely bilateral criterion of yes/no for interstitial pattern was chosen, AUC reaches significance, 0.94 (0.07) (95% CI 0.81-1.0, p = 0.014). LUS reaches an excellent correlation to hrCT in Sjs affected with ILD, and might be a useful technique in daily clinical practice for the assessment of pulmonary disease in the sicca syndrome.
29297564 Oral Nodular Lesions in Patients with Sjögren's Syndrome: Unusual Oral Implications of a 2017 May Sjögren's syndrome (SS) is a systemic chronic autoimmune disorder affecting the lacrimal and salivary glands. SS may manifest as primary SS (pSS) or secondary SS (sSS), the latter occurring in the context of another autoimmune disorder. In both cases, the dry eyes and mouth affect the patient's quality of life. Late complications may include blindness, dental tissue destruction, oral candidiasis and lymphoma. This paper reports two cases of SS, each of them presenting unusual oral nodular lesion diagnosed as relapsed MALT lymphoma and mucocele. The importance of the diagnosis, treatment and management of the oral lesions by a dentist during the care of SS patients is emphasized, as the oral manifestations of SS may compromise the patient's quality of life.
28583168 Mesenchymal stem cells for treating autoimmune dacryoadenitis. 2017 Jun 5 Autoimmune dacryoadenitis, such as Sjögren syndrome, comprises multifactorial and complex diseases. Inflammation of the lacrimal gland plays a key role in the pathogenesis of diseases. Unfortunately, current treatment strategies, including artificial tears, anti-inflammatory drugs, punctual occlusion, and immunosuppressive drugs, are only palliative, and long-term administration of these strategies is associated with adverse effects that limit their utility. Hence, an effective and safe treatment for autoimmune dacryoadenitis is urgently needed. Mesenchymal stem cells (MSCs) have emerged as a promising tool for treating autoimmune dacryoadenitis, owing to their immunosuppressive properties, tissue repair functions, and powerful differentiation capabilities. A large number of studies have focused on the effect of MSCs on autoimmune diseases, such as autoimmune uveitis, inflammatory bowel disease, and collagen-induced arthritis, but few studies have, to date, unequivocally established the efficacy of MSCs for treating autoimmune dacryoadenitis. In this review, we discuss recent advances in MSC treatment for autoimmune dacryoadenitis.
27853859 Hemophagocytic lymphohistiocytosis in a patient with Sjögren's syndrome: case report and 2017 Apr Hemophagocytic lymphohistiocytosis (HLH) is a very rare syndrome with a mortality up to 95% of cases if not treated. It is characterised by an excessive activation of the immune system that leads to a disproportionate and destructive inflammatory response. The high mortality rates are in part due to a delay in the diagnosis, and therefore clinicians must maintain a high index of suspicion. When the treatment is started early, the survival rate reaches around 55% of cases. HLH usually presents with persistent fever, pancytopenia, and organomegaly and is associated with very high levels of serum ferritin. In this manuscript, we present the case of a patient with primary Sjögren's syndrome who developed HLH after an acute infection by Cytomegalovirus. We will describe and discuss the pathogenesis, differential diagnosis and a pragmatic approach to the treatment for this critically important and, when diagnosed early, potentially curable syndrome.
28321568 Gastrointestinal and liver lesions in primary childhood Sjögren syndrome. 2017 Jun Sjögren syndrome (SS) is characterized by lymphocytic infiltration of exocrine glands, mainly the lacrimal and salivary glands, leading to keratoconjunctivitis sicca and xerostomia. SS is one of the most common autoimmune rheumatic diseases in adults; however, few cases of primary childhood SS with gastrointestinal and liver lesions have been reported in the literature. We report five cases of primary childhood SS with gastrointestinal and liver lesions. Multiple gastric biopsies in four cases revealed atrophic gastritis in the antrum of the stomach or chronic gastritis. Liver biopsies in two cases revealed nonalcoholic steatohepatitis. Careful clinical approach and follow-up for gastrointestinal and liver lesions are required.
27659405 Cystic lung disease in Sjögren's syndrome: An observational study. 2017 May OBJECTIVES: To analyze the prevalence, characteristics and outcome of cystic lung disease associated with Sjögren's syndrome (SS). METHODS: From June 2010 to February 2015, 90 consecutive SS patients [60.1±14.8years; 88 (97.8%) female, 75 (83.3%) primary SS] had a systematic chest CT-scan. The presence of thin-walled cysts was analyzed by one experienced radiologist. Demographic data, clinical history, laboratory findings, and pulmonary function tests were extracted retrospectively from medical records. RESULTS: Twenty-one (23.3%) patients had cysts on CT scan performed 40.5±54.5months after SS diagnosis. Cysts number ranged from 1 to 25 were often bilateral (52.4%) and mostly located in the middle lung zone (76.2%). Cysts were isolated (n=6, 28.6%) or associated with other lesions, including bronchiectasis (n=5, 23.8%), micronodules (n=5, 23.8%), ground-glass opacity (n=4, 19%) and/or air trapping (n=3, 14.3%). Most patients with cysts (57.1%) had no respiratory symptoms. When comparing SS patients with and without cysts, patients with cysts tended to be older (65.3±15.3 versus 58.5±14.4years, P=0.06). Smoking habits were similar in both groups. Anti-SSB antibodies were more frequently detected in patients with cysts (57.1% vs. 26.1%, P=0.02). Pulmonary function tests were normal or displayed only mild small airways obstruction and reduced diffusion capacity to carbon monoxide. Four (19%) patients with cysts had a past history of associated pulmonary disease, including interstitial lung disease. During follow-up (25.1±17.7months), no patient developed specific lung disease or lymphoproliferative disorders. CONCLUSIONS: Cystic lung disease is frequent, benign, associated with anti-SSB/La antibodies and has no impact on outcome in SS.
28357074 TRAF6 regulates the effects of polarized maturation of tolerability: Marrow-derived dendri 2017 Feb The study aimed to investigate the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and a differentially mature dendritic cell (mDC) in collagen-induced arthritis (CIA) mice and to determine whether or not TRAF6 regulates the activation of an immature dendritic cell (iDC) and inhibits iDC maturation to induce immune tolerance. The mouse bone marrow stem cells were induced with recombinant granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and recombinant interleukin-4 (rmIL-4) to differentiate immature dendritic cells (DCs), which were divided into four groups with different maturation states: rmGM-CSF, rmIL-4; TNF-α; LPS; and FK506 group. The levels of the cell surfaces of CD80, CD86, and MHI-II were analyzed by flow cytometry to prove DCs at different levels of maturity. The expression of IL-12 in DCs at different maturation states was detected by enzyme-linked immunosorbent assay (ELISA). The expression of TRAF6 mRNA and protein in each group of DCs was detected by a reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. The results revealed that the differentiation of bone marrow cells into iDCs was significantly induced by cytokines (rmGM-CSF, IL-4). CD80, CD86, MHC-II were expressed in the four groups, and the difference between them was statistically significant (P<0.05). A higher degree of DC differentiation led to a gradual increase of IL-12 secretion in the four groups. The difference was statistically significant (P<0.05) for this secretion (group D, 10,620.73±276.73 pg/ml). The expression levels of TRAF6 mRNA were significantly higher in group D than those in the other three groups (P<0.01). Although there was no significant difference in the expression levels of TRAF6 mRNA between groups B and C, the expression levels of TRAF6 mRNA between groups B and C were higher than those of the control group. The TRAF6 protein expression was higher in group D than that in the other three groups (P<0.01), and the difference was statistically significant. There was a statistically significant difference in the TRAF6 protein expression between group A and groups B and C, but the expression in group C was higher than that in group B (P<0.01). In conclusion, the expression of co-stimulatory molecules gradually increased in the DCs of different maturation states, and the expression of IL-12, TRAF6 mRNA, and TRAF6 protein positively correlated with the degree of DC maturation. TRAF6 is important in iDC polarity and maturation.
28333965 Worm infestations and development of autoimmunity in children - The ABIS study. 2017 Worm infestations influence the immune system and may therefore decrease the risk for autoimmune diseases. The aim of the study was to determine whether children who have developed autoimmune disease were less likely to have had worm infestations in childhood. The ABIS-study is a prospective population-based cohort study of children born in southeast Sweden 1997/99. 17.055 children participated. As of June 2014 116 individuals had developed Type 1 diabetes, 181 celiac disease, and 53 Juvenile Rheumatoid Arthritis. The parents answered questions on worm infestations when the children were 1, 5 and 8 years of age. The ABIS registry was connected to the National Registry of Drug Prescriptions, and national registries for diagnosis of the studied diseases. We found no differences in incidence of worm infestations at 1, 5 or 8 years of age between children who developed autoimmune disease(s) or healthy controls. At 8 years in total 20.0% of the general child population had experienced a worm infestation; children who developed Type 1 diabetes, 21,3%, celiac disease 19,5% and JRA 18,8%. There was no difference in prescriptions of drugs for treatment of worm infestations between those who had and who had not developed Type 1 diabetes, celiac disease, Juvenile Rheumatoid Arthritis. We found no associations indicating that worm infestations in childhood does not play a role in the development of autoimmune diseases in Sweden.
28324118 Early onset polymyalgia rheumatica: two rare cases under age of 50. 2017 Jun Polymyalgia rheumatica (PMR) is almost an exclusive disease of adults over the age of 50, and only a few cases have been reported. Two 46-year-old females visited our locomotor pain clinic with multiple joint pain with increased acute phase reactants. Rheumatologic markers, and HLA-B27 were checked. Serum protein electrophoresis and serum immunofixation electrophoresis, imaging studies including plane image, sonography, and magnetic resonance image was done. (18)F-Fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed characteristic findings of PMR, without evidences of sacroiliitis. Since PMR can develop in mid 40s, a high index of suspicion is necessary in younger patients presenting the bilateral pain in shoulders, hips, and back, with elevated acute phase reactants. Furthermore, in addition to the previous case reports, FDG-PET/CT is helpful in making early differential diagnosis of PMR in patients under the age of 50. Here we present two cases of PMR onset in the mid-40s emphasizing the importance of diagnostic imaging for early differential diagnosis in PMR.
28669429 Hybrid Photoacoustic/Ultrasound Tomograph for Real-Time Finger Imaging. 2017 Oct We report a target-enclosing, hybrid tomograph with a total of 768 elements based on capacitive micromachined ultrasound transducer technology and providing fast, high-resolution 2-D/3-D photoacoustic and ultrasound tomography tailored to finger imaging. A freely programmable ultrasound beamforming platform sampling data at 80 MHz was developed to realize plane wave transmission under multiple angles. A multiplexing unit enables the connection and control of a large number of elements. Fast image reconstruction is provided by GPU processing. The tomograph is composed of four independent and fully automated movable arc-shaped transducers, allowing imaging of all three finger joints. The system benefits from photoacoustics, yielding high optical contrast and enabling visualization of finger vascularization, and ultrasound provides morphologic information on joints and surrounding tissue. A diode-pumped, Q-switched Nd:YAG laser and an optical parametric oscillator are used to broaden the spectrum of emitted wavelengths to provide multispectral imaging. Custom-made optical fiber bundles enable illumination of the region of interest in the plane of acoustic detection. Precision in positioning of the probe in motion is ensured by use of a motor-driven guide slide. The current position of the probe is encoded by the stage and used to relate ultrasound and photoacoustic signals to the corresponding region of interest of the suspicious finger joint. The system is characterized in phantoms and a healthy human finger in vivo. The results obtained promise to provide new opportunities in finger diagnostics and establish photoacoustic/ultrasound-tomography in medical routine.
28947151 Discovery and structure-based design of 4,6-diaminonicotinamides as potent and selective I 2017 Nov 1 The identification of small molecule inhibitors of IRAK4 for the treatment of autoimmune diseases has been an area of intense research. We discovered novel 4,6-diaminonicotinamides which potently inhibit IRAK4. Optimization efforts were aided by X-ray crystal structures of inhibitors bound to IRAK4. Structure activity relationship (SAR) studies led to the identification of compound 29 which exhibited sub-micromolar potency in a LTA stimulated cellular assay.
28928840 A cytokine signal inhibitor for rheumatoid arthritis enhances cancer metastasis via deplet 2017 Sep Current therapy for rheumatoid arthritis (RA) relies on global suppression of the immune response or specific blockade of inflammatory cytokines. However, it is unclear how immunosuppressants affect patients with cancer. Therefore, in the present study, the effect of three biological agents, tofacitinib, anti-mouse IL-6 receptor antibody (MR16-1) and etanercept, which are used for the treatment of RA diseases, on a tumor-bearing mouse model was investigated. The effect of the three agents was examined using a mouse lung-metastasis model with the murine colon 26 cancer cell line. Lymphocyte subsets and natural killer (NK) cells in peripheral blood and spleen were analyzed using fluorescence-activated cell sorting, and the number of lung surface nodules was examined. In the continuous tofacitinib administration (15 mg/kg/day) group, the number of lung surface nodules was significantly increased compared with that of the vehicle-treated group (vehicle, 1.20±0.58; tofacitinib, 35.6±10.81; P<0.01). NK cell number in the blood and spleen of tofacitinib-treated mice was decreased 10-fold, and the percentage of cluster of differentiation (CD)11(+)CD27(-) NK cells was significantly reduced. MR16-1 [8 mg/mouse; once a week; intraperitoneal (i.p.)] or etanercept (1 mg/mouse; 3 times a week; i.p.) treatment did not affect the number of NK cells or lung metastasis. In the present study, immunosuppressants that target cytokines, including tofacitinib, were demonstrated to inhibit the proliferation and differentiation of NK cells, and exhibit the potential to promote cancer metastasis using a mouse model of lung metastasis.
28553086 Adherence to systemic therapies for immune-mediated inflammatory diseases in Lebanon: a ph 2017 BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are chronic conditions that may cause tissue damage and disability, reduced quality of life and increased mortality. Various treatments have been developed for IMIDs, including immune modulators and targeted biologic agents. However, adherence remains suboptimal. METHODS: An adherence survey was used to evaluate physicians' beliefs about adherence to medication in IMID and to evaluate if and how they manage adherence. The survey was distributed to 100 randomly selected physicians from three different specialties. Results were analyzed by four academic experts commissioned to develop an action plan to address practical and perceptual barriers to adherence, integrating it into treatment goals to maximize outcomes in IMID, thereby elevating local standards of care. RESULTS: Eighty-two physicians participated in this study and completed the questionnaire. Most defined adherence as compliance with prescribed treatment. Although the majority of surveyed physicians (74%) did not systematically measure adherence in their practice, 54% identified adherence as a treatment goal of equal or greater importance to therapeutic endpoints. Lack of time and specialized nursing support was reported as an important barrier to measuring adherence. The expert panel identified four key areas for action: 360° education (patient-nurse-physician), patient-physician communication, patient perception and concerns, and market access/cost. An action plan was developed centered on education and awareness, enhanced benefit-risk communication, development of adherence assessment tools and promotion of patient support programs. CONCLUSION: Nonadherence to medication is a commonly underestimated problem with important consequences. A customized target-based strategy to address the root causes of non-adherence is essential in the management of chronic immune-mediated diseases.
27873281 Generation and Analysis of Humanized Mouse Model of EBV Infection. 2017 The recent development of severely immunodeficient mouse strains enabled the production of new-generation humanized mice, in which major components of the human immune system are reconstituted. These new-generation humanized mice can be infected with human pathogenic viruses that do not infect regular mice and target cells of the hematoimmune system. Here we describe the method for preparing humanized mice, infecting them with EBV, and for their virological and immunological analyses. The results obtained from our own mouse models are briefly described.
29209219 Differential Effects of Inhibitor Combinations on Lysophosphatidic Acid-Mediated Chemokine 2017 Lysophosphatidic acid (LPA) is a pleiotropic bioactive lysophospholipid involved in inflammatory mediator synthesis. Signaling through p38MAPK, ERK, Rho kinase, and MSK-CREB contributes to LPA-mediated IL-8 production in fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. The study was undertaken to investigate how LPA activates MSKs and how signaling crosstalk between TNFα and LPA contributes to the super-production of cytokines/chemokines. RAFLS pretreated or not with TNFα were stimulated with LPA. Immunoblotting with phospho-antibodies monitored MSK activation. Cytokine/chemokine production was measured using ELISA and multiplex immunoassays. LPA induced MSK activation by signaling through ERK whereas p38MAPK, Rho kinase, NF-κB or PI3K contribute to IL-8 synthesis mainly via MSK-independent pathways. Priming with TNFα enhanced LPA-mediated MSK phosphorylation and cytokine/chemokine production. After priming with TNFα, inhibition of ERK or MSK failed to attenuate LPA-mediated IL-8 synthesis even if the MSK-CREB signaling axis was completely or partially inhibited. In TNFα-primed cells, inhibition of LPA-mediated cytokine/chemokine synthesis required a specific combination of inhibitors such as p38MAPK and ERK for IL-8 and IL-6, and Rho kinase and NF-κB for MCP-1. The ability of the signaling inhibitors to block LPA induced cytokine/chemokine synthesis is dependent on the inflammatory cytokinic environment. In TNFα-primed RAFLS the super-production of IL-8 and IL-6 induced by LPA occurs mainly via MSK-independent pathways, and simultaneous inhibition of at least two MAPK signaling pathways was required to block their synthesis. Since simultaneous inhibition of both the p38MAPK and ERK-MSK-CREB pathways are required to significantly reduce LPA-mediated IL-8 and IL-6 production in TNFα-preconditioned RAFLS, drug combinations targeting these two pathways are potential new strategies to treat rheumatoid arthritis.
28861167 Can rheumatoid arthritis ever cease to exist: a review of various therapeutic modalities t 2017 Therapies for rheumatoid arthritis (RA) were mostly aimed at reducing the pain, stiffness and further progression of joint destruction. However, with the advent of biologic agents that act against specific inflammatory cytokines contributing to RA pathogenesis (treat-to-target strategy), the degree of remission achieved has been remarkably impressive. In particular, inhibition of tumor necrosis factor α (TNFα), interleukins-1 and -6 and receptor-activator of nuclear kappa B ligand by neutralizing antibodies in early diagnosed RA patients has resulted in lowering of disease activity to levels that enable them to function as in the pre-disease stage. There are other biologic approaches such as depletion of B cells and blocking T-cell co-stimulators that have been included successfully in RA therapy under the class of disease-modifying anti-rheumatic drugs (DMARD). Given the excellent clinical outcomes of biologic DMARDs when initiated early in RA, discontinuation or dose tapering is practised. Because biologic DMARDs are expensive and also known to make users vulnerable to viral infections, dose reduction and drug holiday are reasonable steps when sustained good clinical response has been achieved. Majority clinical studies have been done with TNF inhibitors and data suggest that sustained remission of RA is achieved in several multi-centric studies carried out worldwide. However, high flare rate and reappearance of disease has been reported in several cases. This review critically discusses response predictors of biologic DMARDs, the case for treatment relaxation, strategizing drug tapering considering patient eligibility and timing in light of available clinical practice guidelines of RA.