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Ankylosing spondylitis is a chronic, progressive disease, and its treatment is relevant to the gut microbiota. Anti‐tumor necrosis factor‐alpha (anti‐TNF‐α) therapy alters the gut microbiota in many diseases, including inflammatory bowel disease. However, little is known about the effect of TNF‐α blocker treatment on the gut microbiota in ankylosing spondylitis. Herein, the effect of a TNF‐α blocker on the gut microbiota in proteoglycan‐induced arthritis was investigated. Proteoglycan‐induced mice were treated with an rhTNFR:Fc solution of etanercept (5 µg/g) for 4 weeks. rhTNFR:Fc treatment attenuated the arthritis incidence and severity of arthritis in the proteoglycan‐induced mice and decreased inflammation in the ankle joints and ameliorated ileal tissue destruction. Moreover, high gut permeability occurred, and zonula occludens‐1 and occludin protein levels were reduced in proteoglycan‐induced mice. These levels were significantly restored by the administration of rhTNFR:Fc. The serum TNF‐α and IL‐17 levels were also decreased. In addition, flora analysis via 16S rDNA high‐throughput sequencing revealed that rhTNFR:Fc treatment restored the gut microbiota composition to a composition similar to that in control mice. In conclusion, anti‐TNF‐α therapy attenuated proteoglycan‐induced arthritis progression and modulated the gut microbiota and intestinal barrier function. These results provide new insights for anti‐TNF‐α therapy strategies via regulating the gut microbiota in ankylosing spondylitis. Anti‐TNF alpha therapy attenuated the incidence and severity of ankylosing spondylitis in mice. Anti‐TNF alpha therapy modulated gut microbiota of ankylosing spondylitis in mice. Anti‐TNF alpha therapy repaired the gut barrier function of ankylosing spondylitis in mice.

Nailfold capillaroscopy is a non-invasive investigation, which allows for the study of the microvasculature (anatomical and functional). Rheumatoid arthritis (RA) is associated with a high risk of cardiovascular atherosclerotic diseases, with endothelial dysfunction (macrovascular and microvascular) representing the first step in atherosclerosis development. The aim of this study is represented by the assessment of microvascular endothelial dysfunction in RA patients by means of nailfold capillaroscopy and to assess its evolution after a period of 12 months of anti TNF-alpha treatment. The study included 70 consecutive patients with RA and 70 healthy subjects, matched for age and gender, as the control group. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were evaluated in all patients, but in controls, only rheumatoid factor, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were measured. The RA activity was measured by DAS28. Nailfold capillaroscopy was carried out in all patients and controls, determining the baseline nailfold capillary density (Db), nailfold capillary density during reactive hyperemia (Dh), and nailfold capillary density after venous congestion (Dc). Data were presented as mean ± standard deviation. Statistical analysis was performed using ANOVA and Pearson’s correlation, with p < 0.05 being statistically significant. Db, Dh, and Dc were lower in RA patients than in controls (p < 0.0001), correlating with RA activity and TNF-α (p < 0.05). After 12 months of anti TNF-α treatment, microvascular endothelial dysfunction improved (p < 0.0001). Microvascular endothelial dysfunction can be assessed by nailfold capillaroscopy, with anti TNF-α medication contributing to its improvement.

A number of mediators are involved in the inflammatory processes that affect joints and vascular wall of patients with rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFa) is one such mediator, and it is widely regarded as an important target for anti-rheumatic treatment. Most recent studies show that anti-TNFa medication suppresses inflammation and reduces overall activity of RA. The aim of the current study was to investigate changes of mean platelet volume (MPV) in response to the 3-month anti-TNFa therapy in RA. Twenty-one RA patients without established cardiovascular disease were recruited for anti-TNFa therapy and underwent thorough clinical and laboratory evaluation at baseline, 2 weeks, and 12 weeks. Anti-TNFa therapy resulted in a significant ( p  = 0.01) increase in MPV over the duration of the study (7.7 ± 0.9, 7.8 ± 1.1, and 8.4 ± 1.1 fL at baseline, 2 weeks, and 12 weeks, respectively). The results of the study expand perspectives of the use of MPV in conditions associated with high-grade inflammation, particularly RA, for monitoring anti-inflammatory treatment. More prospective studies with large numbers of patients are warranted to ascertain associations of high and low values of MPV with diverse markers of inflammation and vascular pathology.

Videocapillaroscopy is a simple, non-invasive investigation that allows the “in vivo” study of the nailfold capillaries. This method is inexpensive, easily accepted by patients and the results can be easily interpreted. It is mainly used in patients with Raynaud’s phenomenon and systemic sclerosis, but this examination can also be performed on patients who are suspected of having microcirculation alterations, such as rheumatoid arthritis and psoriatic arthritis. It may aid in the diagnosis, evaluation and prognosis of other rheumatic diseases, besides systemic sclerosis. The aim of this study is to identify the nailfold videocapillaroscopic abnormalities in rheumatoid arthritis and psoriatic arthritis patients and analyze the correlation between their evolution and 12 months of anti-TNF-α therapy. The abnormal capillaroscopic findings comprised widened, dilated or giant capillaries and the distortion of the normal nailfold architecture, avascular areas, hemorrhages and neoangiogenesis. Overall, capillary density, dilated capillaries, giant capillaries, elongated capillaries and angiogenesis significantly improved after 12 months. Moreover, no avascular areas were found after 12 months of anti-TNF treatment.

Since their introduction in 1999, anti-tumour necrosis factor-α (anti-TNF-α) therapies have been suspected repeatedly to be associated with the occurrence of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS). However, recent publications were restricted to descriptions of monophasic demyelinating events or cases of relapsing–remitting MS (RRMS). We here provide the first case report of primary progressive MS (PPMS) onset upon anti-TNF-α therapy as well as a literature review of previously published cases of anti-TNF-α therapy-associated MS onset. The 51-year old male patient was treated with adalimumab due to psoriasis arthritis. About 18 months after treatment initiation, he developed slowly progressing neurological deficits including gait impairment, paraesthesia of the lower limbs, strangury and visual impairment, which led to the discontinuation of adalimumab therapy. Magnetic resonance imaging of the brain and the spinal cord revealed multiple inflammatory lesions and cerebrospinal fluid examination showed slight pleocytosis and positive oligoclonal bands. Thus, PPMS was diagnosed according to the 2017 revision of the McDonald criteria. As PPMS often causes only subtle symptoms in the beginning and early treatment discontinuation of anti-TNF-α therapy seems essential to improve the patient’s outcome, we think that it is important to increase the awareness of slowly progressing neurological deficits as a potential adverse event of anti-TNF-α therapy among all clinicians involved in the initiation and monitoring of these drugs. In addition, the occurrence of both RRMS and progressive MS upon anti-TNF-α therapy might suggest a shared TNF-α-mediated pathophysiological mechanism in the evolution of all MS subtypes.

Backgrounds Behçet’s disease (BD) is a rare vasculitic disorder affecting all sizes of vessels. Among BD patients, 4 to 25% of patients with diagnosed age younger than 16 years old are defined as juvenile BD (JBD). This study aimed to evaluate the clinical manifestations and treatments of patients with JBD, with a particular focus on the effectiveness and safety of anti-tumor necrosis factor (TNF)-alpha therapy. Methods We retrospectively reviewed data of all patients diagnosed with JBD at age of 16 years or younger in a tertiary hospital in Taiwan. The clinical manifestations, laboratory data, treatments, disease courses, and clinical outcomes were evaluated. The effectiveness of anti-TNF-alpha therapy was measured based on changes in Behçet’s Disease Current Activity Form (BDCAF) scores, prednisolone dosages and the immunosuppression load scores. Results Fifty-five patients were included in the study. The median age at disease onset was 11 years. The most common clinical presentation was recurrent oral aphthous ulcers (100%), followed by genital ulceration (69.1%), skin lesions (36.4%), gastrointestinal symptoms (29.1%), ocular involvement (27.3%), and arthralgia (27.3%). Ninety-one percent of the patients fulfilled the International Criteria for Behçet’s Disease, and 36.4% met the Paediatric Behçet’s Disease criteria. The most frequently used medications were prednisolone (74.5%) and colchicine (54.5%). Six patients with refractory or severe JBD received anti-TNF-alpha therapy. These patients were diagnosed at a younger age compared with those who did not receive anti-TNF-alpha therapy (7.5 vs 13 years; P  = 0.012), the BDCAF scores reduced significantly at the 1st month, the 6th month and 1 year after the treatment. They did not use steroids after the first year of treatment, and, after treatment for 6 months, their immunosuppression load scores reduced significantly. Due to the limited case numbers, literature reviews of anti-TNF-alpha therapy for refractory JBD were conducted, which had a total 18 JBD patients receiving anti-TNF-alpha therapy, of which fifteen patients had favorable outcomes after treatment with minimal side effects. Conclusions Anti-TNF-alpha therapy may be necessary for JBD patients with refractory disease courses. Anti-TNF-alpha therapy was effective and safe in these patients, especially regarding its corticosteroid- and immunosuppressive drug-sparing effects.

Background Anti-Tumor Necrosis Factor (TNF) therapies are able to control rheumatoid arthritis (RA) disease activity and limit structural damage. Yet no predictive factor of response to anti-TNF has been identified. Metabolomic profile is known to vary in response to different inflammatory rheumatisms so determining it could substantially improve diagnosis and, consequently, prognosis. The aim of this study was to use mass spectrometry to determine whether there is variation in the metabolome in patients treated with anti-TNF and whether any particular metabolomic profile can serve as a predictor of therapeutic response. Methods Blood samples were analyzed in 140 patients with active RA before initiation of anti-TNF treatment and after 6 months of Anti-TNF treatment (100 good responders and 40 non-responders). Plasma was deproteinized, extracted and analyzed by reverse-phase chromatography–QToF mass spectrometry. Extracted and normalized ions were tested by univariate and ANOVA analysis followed by partial least-squares regression-discriminant analysis (PLS-DA). Orthogonal Signal Correction (OSC) was also used to filter data from unwanted non-related effects. Disease activity scores (DAS 28) obtained at 6 months were correlated with metabolome variation findings to identify a metabolite that is predictive of therapeutic response to anti-TNF. Results After 6 months of anti-TNF therapy, 100 patients rated as good responders and 40 patients as non-responders according to EULAR criteria. Metabolomic investigations suggested two different metabolic fingerprints splitting the good-responders group and the non-responders group, without differences in anti-TNF therapies. Univariate analysis revealed 24 significant ions in positive mode ( p  < 0.05) and 31 significant ions in negative mode ( p  < 0.05). Once intersected with PLS results, only 35 ions remained. Carbohydrate derivates emerged as strong candidate determinants of therapeutic response. Conclusions This is the first study describing metabolic profiling in response to anti-TNF treatments using plasma samples. The study highlighted two different metabolic profiles splitting good responders from non-responders.

Background Anti-tumor necrosis factor-alpha (TNF-α) agents have considerable advances in treating inflammatory bowel disease (IBD). These drugs carry possible risk of adverse symptoms, and no meta-analysis has examined this issue and the potential duration-response relationship. Purpose The purpose of this study was to assess duration-response relationship between anti-TNF-α agents and risk of adverse symptoms from all available randomized control trials (RCTs) with placebo arms in IBD. Methods PubMed, OVID, and Cochrane Library were searched to January 2015. The RCTs comparing anti-TNF-α therapy with placebo in adults with IBD were eligible. We estimated pooled relative risks (RRs) of adverse symptoms for anti-TNF-α therapy and examined both non-linear and linear duration-response relations between therapy duration and significant related adverse symptoms. Results Twenty-three RCTs with 7325 patients were included. Adverse symptoms of headache, nausea/vomit, abdominal pain, fever, and arthralgia showed no significant relationship with anti-TNF-α therapy, respectively. Fatigue was significantly associated with anti-TNF-α therapy (RR 1.35, 95 % confidence interval (CI) 1.01–1.81), and subgroup analysis indicated that long therapy duration (>30 weeks) and combination without azathioprine (AZA) were two risk factors for the occurrence of fatigue (RR 1.74, 95 % CI 1.03–2.93; RR 1.65, 95 % CI 1.13–2.40). In the trials without AZA combination, there was a linear duration-response relationship between therapy duration and risk of fatigue ( P  = 0.0217), and duration of 35 weeks increased the risk of fatigue by 50 %. Conclusion This meta-analysis suggested a promotive effect of anti-TNF-α therapy to the occurrence of fatigue, and for the anti-TNF-α therapy without AZA combination, a linear duration-response relationship existed between therapy duration and risk of fatigue.

We discuss two cases receiving different anti-tumornecrosis-factor alpha antagonists (anti-TNF-α); one for psoriatic arthritis (PA) and the other for ankylosing spondylitis (AS). Due to neurological symptoms cerebral magnetic resonance imaging (MRI) was performed and cerebral lesions were detected. Our interpretations of these cerebral lesions and the resulting diagnostic and therapeutic consequences are presented in regard of data published in the medical literature.

Heart failure is a systemic disorder characterised by tissue hypoxia and secondary organ dysfunction which occurs in response to various myocardial insults that include ischaemia, viral infections, and toxins. In addition to maladaptive neurohumoral activation, heart failure is associated with an inflammatory state that appears to have a detrimental effect on cardiac function and prognosis. This has led to the suggestion that anti-inflammatory interventions may have therapeutic potential in the symptomatic and prognostic treatment of patients with heart failure. This review considers the role of inhibition of the cytokine tumour necrosis factor α in the treatment of heart failure.