Objective The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn’s disease. Design In a double-blind, randomised, placebo-controlled proof-of-concept study, 59 patients with moderate to severe Crohn’s disease (Crohn’s Disease Activity Index (CDAI) ≥220 to ≤450) were assigned in a 2:1 ratio to 2×10 mg/kg intravenous secukinumab or placebo. The primary end point, addressed by Bayesian statistics augmented with historical placebo information, was the probability that secukinumab reduces the CDAI by ≥50 points more than placebo at week 6. Ancillary analyses explored associations of 35 candidate genetic polymorphisms and faecal calprotectin response. Results 59 patients (39 secukinumab, 20 placebo, mean baseline CDAI 307 and 301, respectively) were recruited. 18/59 (31%) patients discontinued prematurely (12/39 (31%) secukinumab, 6/20 (30%) placebo), 10/59 (17%) due to insufficient therapeutic effect (8/39 (21%) secukinumab, 2/20 (10%) placebo). Fourteen serious adverse events occurred in 10 patients (seven secukinumab, three placebo); 20 infections, including four local fungal infections, were seen on secukinumab versus none on placebo. Primary end point analysis estimated <0.1% probability (ΔCDAI (SD) =33.9 (19.7), 95% credible interval −4.9 to 72.9) that secukinumab reduces CDAI by ≥50 points more than placebo. Secondary area under the curve analysis (weeks 4–10) showed a significant difference (mean ΔCDAI=49; 95% CI (2 to 96), p=0.043) in favour of placebo. Post hoc subgroup analysis showed that unfavourable responses on secukinumab were driven by patients with elevated inflammatory markers (CRP≥10 mg/l and/or faecal calprotectin≥200 ng/ml; mean ΔCDAI=62; 95% CI (−1 to 125), p=0.054 in favour of placebo). Absence of the minor allele of tumour necrosis factor-like ligand 1A was strongly associated with lack of response measured by baseline-adjusted changes in calprotectin at week 6 (p=0.00035 Bonferroni-corrected). Conclusions Blockade of IL-17A was ineffective and higher rates of adverse events were noted compared with placebo. Clinical trial registration This trial was registered at ClinicalTrial.gov with the number NCT01009281.

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Psoriasis is a chronic, relapsing, autoimmune disorder of the skin affecting 2-3% of general population. Approximately 30% of psoriasis patients are also affected with the psoriatic arthritis, a chronic inflammatory spondyloarthritis. The review aims to present the current knowledge on immunopathogenesis of both diseases to emphasize the involvement of various T helper cell subsets. An extensive literature search in electronic databases was performed on the topic of different Th cell subsets' involvement in the pathogenesis of psoriasis and psoriatic arthritis. Studies were assessed and selected to present the recent progress in the area. Current data strongly suggest that both PsO and PsA are T cell-mediated diseases, with a key role of various proinflammatory cytokines in their development. The involvement of T cells is highlighted by the superior efficacy of biologic therapies targeting T cell-derived proinflammatory cytokines in both diseases. Initially, PsO and PsA were thought to be Th1-mediated diseases; however, in the last years, several studies have shown the important role of other T cell subsets, including Th17, Th22, Th9 and Treg cells, in the pathogenesis of both diseases, which has led to the development of new therapies.

Age-related macular degeneration (AMD) is an eye disease typically associated with the aging and can be classified into two types—namely, the exudative and the nonexudative AMD. Currently available treatments for exudative AMD use intravitreal injections, which are associated with high risk of infection that can lead to endophthalmitis, while no successful treatments yet exist for the nonexudative form of AMD. In addition to the pharmacologic therapies administered by intravitreal injection already approved by the Food and Drug Administration (FDA) in exudative AMD, there are some laser treatments approved that can be used in combination with the pharmacological therapies. In this review, we discuss the latest developments of treatment options for AMD. Relevant literature available from 1993 was used, which included original articles and reviews available in PubMed database and also information collected from Clinical Trials Gov website using “age-related macular degeneration” and “antiangiogenic therapies” as keywords. The clinical trials search was limited to ongoing trials from 2015 to date.

The human gastrointestinal track harbors hundreds of species of commensal organisms, collectively known as microbiota. The composition of the intestinal microbiota is changeable by various factors, such as host genotype, diet, antibiotics, pathogen infections, among others. Changes in these factors can cause microbiome disruption known as dysbiosis, leading to the outgrowth of potential pathogenic bacteria or decrease in the number of beneficial bacteria. Dysbiosis has been implicated in numerous inflammatory and autoimmune diseases. This review is focused on host-microbiota interactions, specifically on influence of bacterial-derived signals on immune cell function and the mechanisms by which these signals modulate the development and progression of inflammatory and autoimmune diseases.

Objectives: The aim of the study was to examine the cytokine status in bipolar patients during immediate remission after acute episodes of mania or depression and in patients with sustained (≥6 months) remission, compared with healthy controls. Methods: The study was performed on 121 bipolar patients, of whom 35 were in immediate remission after mania, 41 were in immediate remission after depression, and 45 were in >6-month remission on lithium monotherapy or lithium combined with other drugs. The control group consisted of 78 healthy individuals without any history of psychiatric or immunological illnesses. Serum concentrations of IL-1β, IL-2, IL-6, IL-10, TNF-α and IFN-γ were determined using the Human Th1/Th2 Cytometric Bead Array method. Results: The concentration of IL-10 was higher in patients in remission after mania and the concentration of IFN-γ was higher in those in remission after depression than in healthy controls. On the other hand, cytokine concentrations in patients with sustained remission were not different from those of healthy subjects. Conclusions: The results obtained in this study show that sustained remission in bipolar patients achieved mostly by lithium maintenance brings the cytokine status to a level similar to healthy control subjects.

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Psoriasis is a chronic, immune-mediated inflammatory skin disease, affecting approximately 2-4% of the population in western countries. Patients with a more severe form of the disease are typically considered for systemic therapy, including biologics. In spite of the overall superiority of biologic agents, the treatment response may differ substantially among individual patients. As with other medical conditions, a range of factors contribute to response heterogeneity observed in psoriasis. Proper identification of these factors can significantly improve the therapeutic decisions. This review focuses on potential genetic and nongenetic factors that may affect the treatment response and outcomes in patients with psoriasis.