Objective: To evaluate the efficacy and safety of duloxetine in the treatment of patients with osteoarthritis (OA) or chronic low back pain (CLBP). Methods: Relevant randomized controlled trials (RCTs) were searched in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Included RCTs compared the efficacy and safety of duloxetine vs placebo in the treatment of OA or CLBP. Weighted mean difference (WMD) were calculated for continuous outcomes while risk ratio (RR) were calculated for dichotomous outcomes. Results: Nine RCTs were included in our meta-analysis. Duloxetine had significant improvement over placebo in Brief Pain Inventory 24-h average pain [WMD: À0.67; 95% confidence interval (CI):-0.80, À0.53], weekly mean of the 24-h average pain

Objective: In recent years, an increasing number of drugs have been proved to be associated with the induction of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This article reviews the latest research progress on drug-induced AAV. Data sources: We conducted a comprehensive and detailed search of the PubMed database. The search terms mainly included drug-induced, ANCA, and vasculitis. Study selection: We summarized the original articles and reviews on drug-induced AAV in recent years. The extracted information included the definition, epidemiology, associated drugs, pathogenesis, clinical features, diagnosis, treatment, and prognosis of drug-induced AAV. We also focused on the differences between drug-induced AAV and primary vasculitis. Results: The offending drugs leading to drug-induced AAV are almost from pharmacologic categories and we need to be vigilant when using these drugs. The pathogenesis of drug-induced AAV might be multifactorial. The formation of neutrophil extracellular traps is an important mechanism for the development of drug-induced AAV. The clinical features of drug-induced AAV are similar to those of primary AAV. Understanding the difference between drug-induced AAV and primary AAV is helpful to identify drug-induced AAV. Stopping the offending drug at once after diagnosis may be sufficient for those patients with mild symptoms. Immunosuppressive therapy should only be used in patients with vital organs involvement. Conclusions: Patients with drug-induced AAV usually have a good prognosis if they stop using the offending drug immediately. Recent advances in research on AAV are expected to help us better understand the pathogenesis of drug-induced AAV.

Objective: To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD). Methods: PubMed, Embase, Cochrane library and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to April 2020. The active drugs included three JAK inhibitors and eight bDMARDs while the control drugs included placebo or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Outcomes include American College of Rheumatology 20% response (ACR20), Disease Activity Score in 28 joints (DAS28), Health Assessment Questionnaire–Disability Index (HAQ-DI) and discontinuations for adverse events (AEs). We estimated summary odds ratios (ORs) and weighted mean differences (WMDs) using network meta-analysis with random effects. Results: Eighty-eight RCTs with 31,566 patients were included. All JAK inhibitors and bDMARDs were more effective than placebo in ACR20 (ORs ranging between 3.05 and 5.61), DAS28 (WMDs ranging between −1.91 and −0.80) and HAQ-DI (WMDs ranging between −0.34 and −0.21). Tocilizumab, certolizumab pegol and upadacitinib showed relatively good efficacy in these three outcomes according to their relative ranking. Notably, tocilizumab was more effective than other active drugs in DAS28 (WMDs ranging between −1.11 and −0.49). Compared with the lower recommended doses, increasing the doses of JAK inhibitors (baricitinib 4 mg versus 2 mg, tofacitinib 10 mg versus 5 mg and upadacitinib 30 mg versus 15 mg) cannot provide significant additional benefits. In terms of discontinuations for AEs, all active drugs showed no significant difference compared with placebo except certolizumab pegol [OR 1.65, 95% credible interval (CrI) 1.06–2.61] and rituximab (3.17, 1.11–10.80). Conclusions: Tocilizumab, certolizumab pegol and upadacitinib may have relatively good efficacy in patients with RA after treatment failure with csDMARDs. RA patients taking a JAK inhibitor may have a preference for a lower recommended dose.

No abstract

No abstract

Background: Renal interstitial fibrosis (RIF) is one of the main poor prognostic factors of lupus nephritis (LN). Here, we tested whether iguratimod could inhibit RIF in LN. Methods: MRL/lpr mice, an animal model of lupus, were treated with iguratimod or vehicle solution. Pathological changes of kidney was evaluated blindly by the same pathologist. Renal type I collagen (COL-I), IgG, E-cadherin, fibroblast-specific protein 1 (FSP-1) were detected by immunofluorescence, immunohistochemical staining or quantitative real-time PCR. After treated with transforming growth factor β1 (TGF-β1) and iguratimod, E-cadherin, fibronectin, Smad2/3, p38 MAPK, p-Smad2/3 and p-p38 MAPK in HK2 cells were measured by western blotting, quantitative real-time PCR or immunofluorescence. Results: In MRL/lpr mice, iguratimod eased the renal interstitial deposition of collagen fibers, further confirmed by decreased expression of COL-I after iguratimod treatment. Moreover, upstream pathological processes of RIF, including IgG deposition along the tubular basement membrane, infiltration of inflammatory cells into renal interstitium and tubular injury, were also prevented effectively by iguratimod treatment. Furthermore, iguratimod suppressed the expression of FSP-1 and raised the expression of E-cadherin in renal tubular epithelial cells, suggesting that iguratimod reversed the process of tubular epithelial-to-mesenchymal transition (EMT). In HK2 cells induced by TGF-β1, co-treatment with iguratimod not only reversed cellular morphologic change, but also prevented down-regulation of E-cadherin and up-regulation of fibronectin. Finally, iguratimod blocked TGF-β1-induced phosphorylation of Smad2/3 and p38 MAPK in HK2 cells. Conclusions: Our results suggest that iguratimod shows an inhibitory effect on the progress of RIF in vivo and in vitro, so iguratimod may be a potential drug for the treatment of RIF in LN.

INTRODUCTION Objectives / Review question: The aim of this network meta-analysis is to evaluate the comparative efficacy and safety of Janus kinase inhibitors and biologics in patients with active rheumatoid arthritis who inadequately respond to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologics. P: patients with active rheumatoid arthritis who inadequately respond to csDMARDs or INPLASY 1

No abstract