Browse

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

ID PMID Title PublicationDate abstract
15638077 Isolation and structural characterization of the photolysis products of etoricoxib. 2004 Dec Etoricoxib is a potent and novel selective inhibitor of cyclooxygenase-2 (COX-2) which has been developed for the treatment of osteoarthritis, rheumatoid arthritis and several other inflammatory conditions. To support clinical pharmacokinetics studies, a method for the determination of etoricoxib in human plasma was developed. During the development of the method it was found that highly fluorescent products were formed when etoricoxib was exposed to UV light (254 nm). The formation of highly fluorescent products was the basis for the development of a highly sensitive HPLC/fluorescent assay for the indirect determination of etoricoxib in human plasma; the limit of quantification (LOQ) was 1 ng/mL. To unequivocally determine the chemical structures of the photolysis products of etoricoxib, a series of studies was conducted. When etoricoxib was irradiated online in a photochemical reactor, three products were detected in an HPLC-UV system. These products were characterized by HPLC-UV-fluorescence and HPLC-MS/MS. Possible structures of these products were proposed based on these data. The major photolysis products of etoricoxib were further isolated and their structures were elucidated using NMR and HPLC-NMR. The results of these experiments indicate that etoricoxib undergoes a photocyclization reaction when irradiated with UV light (254 nm), leading to the formation of two major isomeric photocyclization products.
15301251 Ear-nose-throat manifestations of autoimmune rheumatic diseases. 2004 Jul Ear-nose-throat (ENT) manifestations of connective tissue disorders represent a diagnostic challenge for clinicians as they often constitute the initial sign of an otherwise asymptomatic autoimmune disease. Moreover, in patients with known autoimmune rheumatic diseases, ENT manifestations can be overlooked. Hearing disturbances may be seen in patients with systemic lupus erythematosus, Wegener's granulomatosis, relapsing polychondritis, polyarteritis nodosa, Cogan's syndrome, Sjögren's syndrome, and less frequently in Churg-Strauss syndrome and Adamantiades-Behçet's disease. Nose and paranasal sinuses are variably affected during the course of Wegener's granulomatosis, Churg-Strauss syndrome, relapsing polychondritis and sarcoidosis. Recurrent mucosal ulcerations are common in systemic lupus erythematosus and Adamantiades-Behçet's disease. Xerostomia is a common feature of primary and secondary Sjögren's syndrome; salivary gland enlargement may be also seen in these patients, as well as in patients with sarcoidosis. The cricoarytenoid joint can be involved during the course of rheumatoid arthritis, ankylosing spondylitis and gout; osteoarthritic changes have also been described. Motility disorders of the upper and/or the lower portions of the esophagus have been reported in patients with dermatomyositis/polymyositis, systemic sclerosis and systemic lupus erythematosus. Trigeminal nerve dysfunction may occur in patients with Sjögren's syndrome, systemic sclerosis, systemic lupus erythematosus and mixed connective tissue disease. Peripheral facial nerve palsy has been described to complicate the course of Sjögren's syndrome and sarcoidosis.
15241561 Adhesion dependent release of hepatocyte growth factor and interleukin-1 receptor antagoni 2004 Jul OBJECTIVE: Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads. METHODS: In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes beta2 integrin (CD18) on granulocyte adsorption to CA beads. RESULTS: Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads. CONCLUSIONS: Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.
15195196 Drug-induced pulmonary fibrosis. 2004 Jun Pulmonary fibrosis is characterized by the accumulation of excessive connective tissue in the lungs. Its causes include chronic administration of some drugs for example bleomycin, cyclophosphamide, amiodarone, procainamide, penicillamine, gold and nitrofurantoin; exposure to certain environmental factors such as gases, asbestos and silica and bacterial or fungal infections. Some systemic diseases also predispose to the disease for example rheumatoid arthritis and systemic lupus erythematosus. The disease is associated with release of oxygen radicals and some mediators such as tumor necrosis factor-alpha TNF-alpha, transforming growth factor-beta TGF-beta, PDGF, IGF-I, ET-I and interleukins 1, 4, 8 and 13. The symptoms of the disease include dyspnea, non-productive cough, fever and damage to the lung cells. It is diagnosed with the aid of chest radiography, high resolution computed tomographic scanning and the result of pulmonary function tests. Drug-induced pulmonary fibrosis may involve release of free oxygen radicals and various cytokines for example IL-Ibeta and TNF-alpha via activation of nuclear transcription factor NF-beta as in the case of bleomycin and mitomycin or via release of TGF-beta as in case of tamoxifen or via inhibition of macrophages' and lymphocytes' phospholipases as in the case of amiodarone with the resultant accumulation of phospholipids and reduction of the immune system.
15063339 Plasma D-penicillamine redox state evaluation by capillary electrophoresis with laser-indu 2004 Apr 25 D-Penicillamine (D-Pen) is a thiol drug used in the treatment of Wilson's disease, rheumatoid arthritis, metal intoxication and cystinuria. We have recently described a new capillary electrophoresis (CE) method to measure physiological thiols, in which separation of total plasma homocysteine, cysteine, cysteinylglycine, glutathione is achieved using the organic base N-methyl-D-glucamine in the run buffer. In this paper, we present an improvement of our method that allows a baseline separation of total plasma D-Pen from the physiological thiols. Moreover, reduced, free and protein-bound forms of drug are measured by varying the order of disulfide reduction with tributylphosphine and proteins precipitation with 5-sulphosalicylic acid (SSA). After derivatization with 5-iodoacetamidofluorescein (5-IAF), samples are separated and measured by capillary electrophoresis with laser-induced fluorescence in an uncoated fused-silica capillary (57 x 75 microm i.d.) using a phosphate/borate run buffer pH 11.4. In these conditions, the migration time of D-Pen is about 7 min and the time required for each analysis is roughly 10 min. The proposed method has been utilized to measure the various forms of the drug in a D-Pen administered Wilson's disease patient.
15046611 Chemokine inhibition--why, when, where, which and how? 2004 Apr Chemokines are small chemoattractant cytokines that control a wide variety of biological and pathological processes, ranging from immunosurveillance to inflammation, and from viral infection to cancer. Genetic and pharmacological studies have shown that chemokines are responsible for the excessive recruitment of leucocytes to inflammatory sites and damaged tissue. In the present paper, we discuss the rationale behind interfering with the chemokine system and introduce various points for therapeutic intervention using either protein-based or small-molecule inhibitors. Unlike other cytokines, chemokines signal via seven-transmembrane GPCRs (G-protein-coupled receptors), which are favoured targets by the pharmaceutical industry, and, as such, they are the first cytokines for which small-molecule-receptor antagonists have been developed. In addition to the high-affinity receptor interaction, chemokines have an in vivo requirement to bind to GAGs (glycosaminoglycans) in order to mediate directional cell migration. Prevention of the GAG interaction has been shown to be a viable therapeutic strategy. Targeting chemokine intracellular signalling pathways offers an alternative small-molecule approach. One of the key signalling targets downstream of a variety of chemokine receptors identified to date is PI3Kgamma (phosphoinositide 3-kinase gamma), a member of the class I PI3K family. Thus the chemokine system offers many potential entry points for innovative anti-inflammatory therapies for autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and allergic contact dermatitis.
15009335 Rheumatology: a study of patient satisfaction with follow-up monitoring care. 2004 Mar BACKGROUND: This paper reports the findings of a quantitative study to determine the satisfaction of rheumatology patients receiving follow-up monitoring care within primary and secondary locations. AIMS AND OBJECTIVES: The aim of the study was to compare and contrast the satisfaction of patients with rheumatoid arthritis following two different routes of care. The objective was to explore the dimensions of care identified in an earlier qualitative study. DESIGN: A convenience sample of 80 participants was used; 40 from each care location. METHODS: Data were collected using the Leeds Satisfaction Questionnaire, which explores the dimensions of satisfaction previously identified as being important to this group of patients. RESULTS: The secondary care group showed significantly higher levels of satisfaction in respect of general satisfaction, provision of information and continuity of care and a significant difference in relation to empathy, technical ability and attitude to the patient. CONCLUSIONS: While patients from both locations were satisfied with the care they received, those receiving specialist nursing care in the secondary location were more satisfied. RELEVANCE TO CLINICAL PRACTICE: Increased emphasis on care in the community and the evolution of nurse specialist roles indicate the need for further qualitative work to inform the future planning of care provision for rheumatology patients in this area.
14992290 Toxicity of selected cationic drugs in retinoblastomal cultures and in cocultures of retin 2004 Jan Tamoxifen and toremifene are antiestrogenic drugs successfully used in the therapy of breast cancer. Rheumatoid arthritis and malaria have been treated with chloroquine for decades. Unfortunately, tamoxifen and chloroquine are reported to induce retinal changes as a side effect. We now studied the effects of tamoxifen, toremifene, and chloroquine on the viability of the human retinoblastomal cell line Y79, using the WST-1 test or measurement of the cellular ATP content. The studies were made on Y79 cell cultures and on cocultures of Y79 cells and retinal pigment epithelial cell line ARPE-19. The cocultures were used to clarify the effect of retinal pigment epithelium on toxicity to Y79 cells. In the coculture, the drugs were applied to ARPE-19 cells growing in the culture inserts on top of Y79 cells and the viability of ARPE-19 and Y79 cells was assessed separately. Tamoxifen, toremifene, and chloroquine reduced dose-dependently the viability of Y79 cells after 24-h exposure. The ARPE-19 cells proved to be protective after chloroquine exposure in the coculture. The results shed light on the toxicity of tamoxifen and chloroquine in Y79 cells in vitro. With the coculture we were able to simulate the in vivo route of chloroquine to the retina via the retinal pigment epithelium.
14751012 Working memory deficits in chronic fatigue syndrome: differentiating between speed and acc 2004 Jan To examine the relative influence of speed of information processing versus working memory ability, CFS participants with psychiatric comorbidity (CFS-Psych) and CFS without a psychiatric history (CFS-noPsych) were examined on tests of visual and auditory processing speed and visual and auditory working memory. Compared to healthy controls (HC) and a group of participants with rheumatoid arthritis (RA), the CFS-noPsych group displayed significantly reduced performance on tests of information processing speed, but not on tests of working memory. No significant differences were observed between the CFS-Psych group and any other group in the study. The implications of group heterogeneity on the understanding of cognitive impairment in CFS are discussed.
14686489 Immunology of B7-H1 and its roles in human diseases. 2003 Nov B7-H1 was originally identified by homology analysis in comparison with B7-1 and B7-2, two molecules with important immunoregulatory functions. B7-H1, however, was broadly induced in the majority of peripheral tissues as well as hematopoietic cells. Upon binding to an as yet unidentified costimulatory receptor on primed T-cells, B7-H1 costimulates T-cell proliferation and preferentially induces interleukin 10 and interferon gamma. The costimulatory function of B7-H1 may be critical for enhancing maturation and differentiation of T-cells in lymphoid organs. Conversely, by binding to programmed death 1 receptors on activated T-cells and B-cells, B7-H1 may inhibit ongoing T-cell responses in peripheral tissues by inducing apoptosis and arresting cell-cycle progression. Although a positive regulatory role of B7-H1 has been demonstrated in vitro and in various animal models, a negative regulatory role of B7-H1 has also been documented in human diseases, including cancer, rheumatoid arthritis, and human immunodeficiency virus infection. Delineation of the complex interactions between B7-H1 and its receptors as well as its interplay with other ligands is critical for understanding this new immunoregulatory system. Precise manipulation of B7-H1 and its receptors may provide unique opportunities for designing new disease treatments.
14605465 Carcinoma of the pancreas with neuroendocrine differentiation and nodular panniculitis. 2003 Oct BACKGROUND: On rare occasions tumours of the pancreas produce high amounts of pancreatic lipase. The enzyme activity in the blood and in different tissues causes a syndrome called nodular panniculitis by focal necrosis of lipids and a concomittant inflammatory reaction. CASE REPORT: A 72-year-old man was admitted to the dermatology clinic with the diagnosis of erythema nodosum. The patient had been well until 3 months earlier when painful red nodes developed on the skin of both shanks. He complained of profuse night sweating and a weight loss of 10 kg within that time but did not have fever. He also had noticed a painful swelling of his right index finger, left middle finger and the third toe on his left foot. Biopsy of the nodes revealed a focal necrosis of fatty tissue. Laboratory examinations showed a highly elevated concentration of serum pancreatic lipase. Further investigations showed a tumour in the pancreas and several osteolytic lesions. Tumour biopsy revealed a neuroendocrine carcinoma. After tumour resection serum lipase level immediately fell to almost normal values, and all skin and bone manifestations disappeared quickly. CONCLUSION: Due to its clinical appearance the panniculitis syndrome is most often mistaken for either erythema nodosum or rheumatoid arthritis. A resection of the tumour after correct diagnosis should always be considered because the widespread manifestations in the skin and bones do not represent distant metastasis and have a very good chance to dissolve completely.
12949498 Signalling pathways of the TNF superfamily: a double-edged sword. 2003 Sep Two different tumour-necrosis factors (TNFs), first isolated in 1984, were found to be cytotoxic to tumour cells and to induce tumour regression in mice. Research during the past two decades has shown the existence of a superfamily of TNF proteins consisting of 19 members that signal through 29 receptors. These ligands, while regulating normal functions such as immune responses, haematopoiesis and morphogenesis, have also been implicated in tumorigenesis, transplant rejection, septic shock, viral replication, bone resorption, rheumatoid arthritis and diabetes; so indicating their role as 'double-edged swords'. These cytokines either induce cellular proliferation, survival, differentiation or apoptosis. Blockers of TNF have been approved for human use in treating TNF-linked autoimmune diseases in the United States and other countries.
12912699 Microsurgical approach to the conjunctival flap. 2003 Aug OBJECTIVES: To describe a microsurgical approach to a selective pedunculated conjunctival flap for the treatment of chronic corneal ulceration with or without corneal perforation, and to present the results of 50 consecutive cases. DESIGN: Retrospective, noncomparative case series and case reports. Patients All patients who had microsurgical conjunctival flap procedures for the treatment of chronic corneal ulcers between 1982 and 1996 at the Connecticut Eyecare Center, New Haven. INTERVENTIONS: Partial pedunculated conjunctival flap surgery. METHODS: Review of the initial ocular diagnoses and characteristics as well as retrospective study of the postoperative course. MAIN OUTCOME MEASURES: Resolution of the corneal ulcer and postoperative stability of the conjunctival flap. RESULTS: Sixty-two percent of the corneal ulcers treated were nonperforated, and 38% were perforated. The diagnoses included herpes simplex virus (14 patients), bacterial ulcer (11 patients), rheumatoid arthritis (8 patients), aphakic bullous keratopathy (6 patients), graft rejection (4 patients), herpes zoster virus (5 patients), and other (2 patients). Postoperatively, 94% of the conjunctival flaps were stable, and 3% had failed. The procedures were definitive in 64% of cases and temporary in 36%; 61% of patients received a corneal transplant 6 to 24 months postoperatively, and in 38% the flaps were removed 6 to 12 months after the original lesion had healed. CONCLUSION: A selective pedunculated conjunctival flap is an effective and practical surgical approach to the treatment of perforated and nonperforated corneal ulcers that have not responded to other types of medical therapy.
12906317 Anti-angiogenic therapy: rationale, challenges and clinical studies. 2002 Physiological angiogenesis occurs during embryogenesis, wound healing and reproductive functions in adults. Abnormal angiogenesis takes place in certain chronic diseases (diabetes, psoriasis, rheumatoid arthritis, etc.) and tumours. Genetic changes and local stresses including hypoxia, glucose deprivation and oxidative stress play a pivotal role in angiogenesis switch, which is necessary for tumour development and is rate-limiting for tumour progression. Angiogenesis is tightly regulated by pro- and anti-angiogenic growth factors with a series of complex and interrelated steps. Activated endothelial cells (ECs) migrate as a solid cord and, subsequently, form lumina; the sprout tips then anastomose to form vessel loops or networks. One of the final events is the laying down of a basement membrane and the structural support of pericytes. The molecular alterations that sustain angiogenesis represent novel targets for rationally designed anti-cancer treatment strategies. Inhibition of angiogenesis presents certain advantages on conventional therapies, such as the direct accessibility from the circulation, and the potential low rate of drug resistance related to the genetic stability of ECs. Certain anti-angiogenic compounds were found to have potent anticancer property in in vivo experimental studies. Nevertheless, in contrast to preclinical studies, the first generation of anti-angiogenic drugs tested in clinical trials have shown a moderate activity in advanced disease partly due to suboptimal schedules of therapy or biases in study design.
12850650 Treatment of chronic mechanical spinal pain with intravenous pamidronate: a review of medi 2003 Jul We explored the effect of intravenous infusions of a bisphosphonate, pamidronate, in the management of chronic mechanical spinal pain, a worldwide public health problem in terms of lost workdays, medical treatment costs, and suffering. Bisphosphonates have an anti-nociceptive effect in animals. In humans, intravenous pamidronate relieves numerous painful conditions, including metastatic bone pain, ankylosing spondylitis, rheumatoid arthritis, and complex regional pain syndrome. We reviewed the charts of 25 patients who had experienced disabling spinal pain for several years, and whom we treated with intravenous pamidronate. None had a history of osteoporotic vertebral fractures or metastatic disease. Pain rating scores decreased in 91% of patients: on a 0-10 numeric rating scale, the mean pain change was -3.6 points and mean percentage change was -41% (P<0.0001). There was no increase in opioid or nonopioid analgesic medications associated with pain relief. The apparent analgesic effect of pamidronate for chronic mechanical spinal pain needs to be confirmed with placebo-controlled trials.
12827397 [Treatment of ankylosing spondylitis and undifferentiated spondyloarthritis with TNF alpha 2003 Jun The spondyloarthritides (SpA) are common inflammatory rheumatic diseases with an overall prevalence of 0.6-1.9%. Ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA) are the most common subsets of SpA. Women are almost as frequently affected as men, but the total burden of disease may be similar. At least one third of AS patients are severely affected with impaired function and a poor quality of life similar to patients with rheumatoid arthritis. However, AS starts 20-30 years earlier in life. Thus, AS has a relevant socioeconomic impact on society. After decades of no progress concerning treatment options in SpA, there is now accumulating evidence that the new anti-TNF alpha agents do not only reduce signs and symptoms of AS caused by inflammation but they may also diminish structural damage. Very recent magnetic resonance imaging (MRI) data of a follow-up study support this assumption. The following paper reviews the currently available literature on anti-TNF alpha therapy in AS and uSpA. Efficacy, side effects and experiences with different doses are discussed. In expectation of the approval of infliximab and etanercept for the treatment of active AS international guidelines for initiation, monitoring and discontinuation of these agents have been recently proposed.
12744047 [Complete atrioventricular block (with Adams-Stokes syndrome) in systemic connective tissu 2002 Dec The association of high grade atrioventricular heart block with systemic connective tissue diseases is very rare. To date, only sporadic case reports or reviews appeared in the literature. Three cases of such association observed by the author are described here. The patients were a 51 years old man with systemic sclerosis and two women, a 64 years old patient with visceral nodous seropositive rheumatoid arthritis, and second was a 74 years old patient with systemic lupus erythematosus, the oldest of the group of patients with this disease. In two of the three patients, Adams-Stokes attack was a cause of death. The author did not observe this high grade atrioventricular block in patients with systemic connective tissue diseases the last 32 years. First and second grade heart blocks were, however, o chi asionally seen and responded well to the treatment of the systemic disease. Thus, in patients with systemic connective tissue diseases and emergency symptoms, it is recommended to consider also this rare association. While, two decades ago, patients frequently died after the Adams-Stokes attack, the treatment of the high grade block is now successful due the permanent cardiostimulator. In the last years, there are almost no reports about the association of systemic connective tissue diseases with high grade heart block, presumably because of the efficient new treatment approached to systemic diseases including modern immunomodulation drugs.
12662151 Keystone symposia: antibody-based therapeutics for cancer. 2003 Apr This important conference focused on the latest developments in therapeutic antibodies, particularly for their design, production and formulation for cancer therapy. Engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials, highlighted by the recent FDA approvals of Zevalin (ibritumomab tiuxetan, IDEC Pharmaceuticals) for cancer radioimmunotherapy and Humira (adalimumab, Abbott Laboratories) for rheumatoid arthritis [1,2]. An impressive array of international speakers was assembled in Banff by the organisers L Weiner (Fox Chase Cancer Center, USA) and P Carter (Amgen and Seattle Genetics). The meeting highlighted emerging new technologies, both for the discovery of novel cancer biomarkers and for innovative immunotherapeutic designs. The latest successes were also presented for antibodies directed to the conventional cancer targets, including CD20, carcinoembryonic antigen (CEA), erbB-family proteins and vascular endothelial growth factor (VEGF). Importantly, recent structural details emerged that will direct future designs of these cancer-targeting molecules, ranging from antibody-dependent cellular-cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) enhancement to improved cytotoxic payloads using radionuclides, toxins, enzymes, drugs and viral delivery. The conference also highlighted the latest in vitro antibody libraries for the selection of high-affinity reagents against refractory cancer targets, and included the design of small domain modules for highly-efficient in vivo targeting to large, high avidity complexes for enhanced cytotoxicity. The major challenges in this rapidly growing area include the need to initiate and sustain innate and adaptive immune responses for the generation of efficient, long-term tumour therapy. This conference was sponsored by Amgen and accredited by the Accreditation Council for Continuing Medical Education (ACCME).
12492905 Quantitative assessment of apoptotic and proliferative gingival keratinocytes in oral and 2002 Dec BACKGROUND: Periodontal disease is caused by a chronic infection inducing an inflammatory reaction that leads to a breakdown of tooth-supporting tissue. The maintenance of an equilibrium between the host defence and microorganisms in the sulcus is essential to preserve health. All multicellular organisms have mechanisms for killing their own cells, and use physiological cell death for defence, development, homeostasis and ageing. Apoptosis and proliferation are very important phenomena in regulating this and a disturbance is often associated with disease e.g. cancer, AIDS, Alzheimer's disease, rheumatoid arthritis. OBJECTIVE: The aim of this study was to determine whether the number of apoptotic and proliferative gingival keratinocytes differed between patients with gingivitis and those with periodontitis. MATERIAL AND METHODS: The distribution of neutrophil elastase, PCNA/cyclin, DNA fragmentation (apoptosis) and p53 was determined with immunocytochemical techniques. We used paraffin-embedded sections from gingival biopsies and did quantitative analyses. RESULTS AND CONCLUSION: These showed that 5-12% of the keratinocytes in the basal layers of the epithelium proliferated in the two groups. Fewer apoptotic cells were seen in the oral epithelium than in the sulcus in all subjects in both groups. Only in the most apical part of the sulcus, close to the junctional epithelium, did the number of apoptotic keratinocytes exceed the proliferative ones in patients with periodontitis.
12463458 Infliximab in the treatment of active and severe ankylosing spondylitis. 2002 Nov For treatment of the spondylarthropathies (SpA), of which ankylosing spondylitis (AS) is the prototype, there is no effective disease modifying treatment available. In contrast to rheumatoid arthritis (RA), few studies have been performed on the treatment of patients with AS with disease modifying antirheumatic drugs, none of which have proved clearly effective in axial disease. Many patients with AS carry a heavy burden of disease and AS itself is responsible for direct and indirect socioeconomic costs. To find an effective treatment for severe ankylosing spondylitis is therefore thought to be an unmet medical need. In the last four years several pilot studies and recently a few randomised controlled trials have raised good evidence that TNFalpha blockade is very effective in AS and other SpA. Disease activity, function and quality of life improved upon treatment with TNFalpha blockers. Thus, biologicals seem to represent a major breakthrough in the treatment of AS and other SpA. Side effects similar to those observed in RA treatment occur. But there is furthermore a need for safety data for long-term treatment with biologicals over several years. In the light of the high costs and the unknown long-term side effects, a definition for patients who might be candidates for such a treatment is needed. This article gives detailed information about current experience with the new treatment options in active and severe AS with anti-TNFalpha therapy.