Usability of Prefilled Syringe and Autoinjector for SB4 (An Etanercept Biosimilar) in Patients with Rheumatoid Arthritis.

INTRODUCTION: This study aimed to compare the usability of subcutaneous administration of SB4 (an etanercept biosimilar) via prefilled syringe (PFS) and autoinjector (AI) based on injection site pain, patient preference, and safety in patients with rheumatoid arthritis (RA). METHODS: This was an open-label, single-arm, multicenter study to evaluate the usability and safety of the AI and PFS of SB4. Adult patients with RA received two injections of SB4 via the PFS, followed by six injections by the AI every week, up to 8 weeks. The primary endpoint was the change in injection site pain score immediately post-injection from week 1 (PFS) to week 3 (AI). Injection site pain after 15-30 min post-injection, overall impression, and preference for PFS and AI were also assessed. Safety was assessed up to 11 weeks after the first injection. RESULTS: A total of 54 patients were enrolled and 52 patients (96.3%) completed the 8-week treatment period. The mean difference in pain scores between PFS and AI was - 0.057 and the 95% CI of the difference was [- 0.63, 0.51], which was within the equivalence margin of ± 5. Overall impression of the device slightly favored the AI. Overall preference for the AI was more favorable when compared to the PFS in all categories. Adverse events were mild to moderate and found to be generally consistent with those expected for reference etanercept. There were no deaths or serious adverse events reported. CONCLUSIONS: This study demonstrated comparable usability and safety between the PFS and AI when self-administrated by patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03193957. FUNDING: Samsung Bioepis.

Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: The Janus kinase 1 (JAK1) pathway has been implicated in the pathogenesis of psoriatic arthritis. We aimed to investigate the efficacy and safety of filgotinib, a selective JAK1 inhibitor, for the treatment of psoriatic arthritis. METHODS: The EQUATOR trial was a randomised, double-blind, placebo-controlled phase 2 trial that enrolled adults from 25 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Patients (aged ≥18 years) had active moderate-to-severe psoriatic arthritis (defined as at least five swollen joints and at least five tender joints) fulfilling Classification for psoriatic arthritis (CASPAR) criteria, active or a documented history of plaque psoriasis, and an insufficient response or intolerance to at least one conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Patients continued to take csDMARDs during the study if they had received this treatment for at least 12 weeks before screening and were on a stable dose for at least 4 weeks before baseline. Using an interactive web-based system, we randomly allocated patients (1:1) to filgotinib 200 mg or placebo orally once daily for 16 weeks (stratified by current use of csDMARDs and previous use of anti-tumour necrosis factor). Patients, study team, and sponsor were masked to treatment assignment. The primary endpoint was proportion of patients achieving 20% improvement in American College of Rheumatology response criteria (ACR20) at week 16 in the full analysis set (patients who received at least one dose of study drug), which was compared between groups with the Cochran-Mantel-Haenszel test and non-responder imputation method. This trial is registered with ClincalTrials.gov, number NCT03101670. FINDINGS: Between March 9, and Sept 27, 2017, 191 patients were screened and 131 were randomly allocated to treatment (65 to filgotinib and 66 to placebo). 60 (92%) patients in the filgotinib group and 64 (97%) patients in the placebo group completed the study; five patients (8%) in the filgotinib group and two patients (3%) in the placebo group discontinued treatment. 52 (80%) of 65 patients in the filgotinib group and 22 (33%) of 66 in the placebo group achieved ACR20 at week 16 (treatment difference 47% [95% CI 30·2-59·6], p<0·0001). 37 (57%) patients who received filgotinib and 39 (59%) patients who received placebo had at least one treatment-emergent adverse event. Six participants had an event that was grade 3 or worse. The most common events were nasopharyngitis and headache, occurring at similar proportions in each group. One serious treatment-emergent adverse event was reported in each group (pneumonia and hip fracture after a fall), one of which (pneumonia) was fatal in the filgotinib group. INTERPRETATION: Filgotinib is efficacious for the treatment of active psoriatic arthritis, and no new safety signals were identified. FUNDING: Galapagos and Gilead Sciences.

New insights into the role of T cells in pathogenesis of psoriasis and psoriatic arthritis.

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.

The effect of cigarette smoking on the clinical course of inflammatory bowel disease.

INTRODUCTION: Cigarette smoking is considered an important risk factor for developing Crohn's disease (CD), contributing to a more severe course of the disease. Conversely, smoking is believed to have a beneficial effect on the course of ulcerative colitis (UC), a second major condition of inflammatory bowel disease (IBD). AIM: To investigate the effect of tobacco use on the clinical course of IBD. MATERIAL AND METHODS: A group of 95 adults with IBD were enrolled to the study. Demographic and clinical data of patients as well as their smoking status were analysed based on their medical history. Values were considered significant when p ≤ 0.05. RESULTS: Current smokers constituted the majority of CD patients. They tended to develop a more severe course of the disease, compared to former smokers and non-smokers. Current smokers suffered a moderate-to-severe form of the disease and required immunosuppressive therapy more frequently. They were also hospitalised and underwent surgeries more frequently than patients from other investigated subgroups. The study failed, however, to fully confirm the beneficial effect of smoking on the clinical outcome of UC. The investigated non-smokers and former smokers suffered a more severe disease, but the analysis did not find any statistical differences in the frequencies of hospitalisations nor immunosuppressant usage among the investigated subgroups. CONCLUSIONS: The study confirmed a detrimental effect of smoking on the outcome of CD, but failed to fully confirm its beneficial effect on UC.

[Role of Th17 lymphocytes in pathogenesis of colorectal cancer]. / Rola limfocytów Th17 w patogenezie raka jelita grubego.

Colorectal cancer (CRC) is estimated to be the first leading cause of death from cancer among men and women in the EU. Every year in Poland, 15,254 cases of CRC are diagnosed, and 10,501 patients die of the disease, making it the second leading cause of death from cancer. In more than 90% of cases, the disease begins as adenomatous polyps with epithelial dysplasia as a common feature. Inflammatory bowel diseases (IBD), a group of chronic inflammatory diseases of the gastrointestinal tract characterized by remissions and relapses, constitute an independent risk factor of CRC development. CRC developing in IBD patients, however, has features distinct from sporadic cancer, suggesting the influence of unique factors. The high risk of CRC in IBD patients probably results from chronic inflammation. In most cases, neoplastic lesions arise within the inflamed gastrointestinal mucosa during the process of re-epithelization, which is a healing response to ulceration. The recently discovered Th17 lymphocytes, which demonstrate strong pro-inflammatory capabilities, might link the two diseases. Th17 lymphocytes produce a number of pro-inflammatory cytokines, such as interleukin (IL)-17A, IL-17F, IL-21, IL-22 and tumor necrosis factor (TNF)-a, and play a key role in mucosal defense against various pathogens. Numerous observations suggest that Th17 lymphocytes are involved in pathogenesis of different autoimmune diseases and pathologic inflammatory states. Mounting evidence suggests that Th17 cells contribute to the pathogenesis of IBD and CRC. However, their precise role in both diseases is unknown.