Investigational IRAK-4 inhibitors for the treatment of rheumatoid arthritis.

Investigational IRAK-4 inhibitors for the treatment of rheumatoid arthritis. Expert Opin Investig Drugs. 2020 Apr 07;: Authors: Wiese MD, Manning-Bennett AT, Abuhelwa AY Abstract Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that can lead to permanent disability and deformity. Despite current treatment modalities, many patients are still unable to reach remission. Interleukin-1 receptor-associated kinase 4 (IRAK-4) inhibitors are novel agents designed to suppress immune signalling pathways involved in inflammation and joint destruction in RA. Four IRAK-4 inhibitors have entered clinical trials.Areas covered: This review summarizes the current stage of development of IRAK-4 inhibitors in clinical trials, detailing their chemistry, pharmacokinetics and therapeutic potential in the treatment of RA. PubMed, Embase and restricted Google searches were conducted using the term 'IRAK-4', and publicly accessible clinical trial databases were reviewed.Expert opinion: IRAK-4 inhibitors are an exciting therapeutic option in RA management because unlike other targeted disease modifying agents, they target the innate immune system. The role of IRAK-4 as a key component of Toll/Interleukin-1 receptor signalling and its potential for a low rate of infectious complications is particularly exciting and this may facilitate their use in combination treatment. A key aspect of upcoming clinical trials will be the identification of biomar...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research

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Authors: Rivellese F, Pontarini E, Pitzalis C Abstract Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. RA mainly affects the joints, with inflammation of the synovial membrane, characterized by hyperplasia, neo-angiogenesis, and immune cell infiltration that drives local inflammation and, if untreated, can lead to joint destruction and disability. In parallel to the well-known clinical heterogeneity, the underlying synovitis can also be significantly heterogeneous. In particular, in about 40% of patients with RA, synovitis is characterized by a dense lymphocytic infiltrate that can acquire the f...
Source: Current Topics in Microbiology and Immunology - Category: Microbiology Tags: Curr Top Microbiol Immunol Source Type: research
ConclusionsTofacitinib efficacy/safety were similar in both populations, except TB IR, which was higher in Indian patients but in line with those in bDMARD ‐treated RA patients from high‐risk countries (IR = 0.00‐2.56; TB IR>0.05 [World Health Organization]). Limitations included the small Indian population and baseline differences between populations.
Source: International Journal of Rheumatic Diseases - Category: Rheumatology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsHere we show that the 2C ‐DAS28 modified disease activity score defines important biological and clinical phenotypes associated with treatment outcome in RA and characterizes important underlying response mechanisms to biologic drugs.
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: FULL LENGTH Source Type: research
This study evaluated the efficacy and safety of baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) therapy. METHODS: In this phase 3, double-blind, 52-week, placebo-controlled study, 290 patients with moderately to severely active RA and inadequate response to MTX were randomly assigned 1:1 to placebo or baricitinib 4-mg once daily, stratified by country (China, Brazil, Argentina) and presence of joint erosions. Primary endpoint measures included American College of Rheumatology 20% response (ACR...
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
Rheumatoid arthritis (RA), a chronic systemic inflammatory disease, is a primary cause of disability worldwide. The involvement of fibroblast-like synoviocytes (FLSs) in the regulation of the pathogenesis of RA has been highlighted. Mesenchymal stem cells (MSCs) are important candidates for cell-based treatment in many inflammatory autoimmune diseases. Herein, we identify whether MSC-derived exosomes loaded with microRNA-320a (miR-320a) regulate RA-FLSs. Synovial tissues from 22 patients with RA and 9 patients with osteoarthritis were collected. RA-FLSs were obtained from patients with RA, and their functions were evaluate...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Abstract Background/Aims: To explore the associations between body composition and pain, disease activity, and disability in rheumatoid arthritis (RA). Methods: The study enrolled 335 patients with RA and underwent body composition measurement with an InBody analyzer. The associations of body mass index (BMI), body fat mass, and skeletal muscle mass with disease activity score in 28 joints (DAS28), an index derived to measure the subjective component of DAS28 (DAS28-P), a pain visual analogue scale (VAS), and disability measured with the health assessment questionnaire (HAQ) were explored. Obesity was defined...
Source: The Korean Journal of Internal Medicine - Category: Internal Medicine Authors: Tags: Korean J Intern Med Source Type: research
Abstract Osteoarthritis (OA) is the most common chronic degenerative joint disease, and it remains the main cause of chronic disability in elderly individuals. Sema4D (semaphorin 4D) is involved in the immune system and related to bone injury, osteoporosis, osteoblast differentiation, and rheumatoid arthritis. However, the role of Sema4D in OA remains unclear. Hence, the LPS-stimulated chondrocyte cell injury model was constructed in this study to investigate the role of Sema4D in OA development. The results showed that Sema4D was increased in LPS-treated ATDC5 cells, and the knockdown of Sema4D suppressed the dec...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
EMPOWR Acetabular System, Non-Sterile, Model Numbers 803-15-023 803-15-026 803-15-027 803-15-028 803-15-029 803-15-030 Product Usage: The EMPOWR Acetabular Impactor Balls is intended for use in joint replacement in patients suffering from disability due to noninflammatory degenerative joint disease including osteoarthritis and avascular necrosis of the natural femoral head; rheumatoid arthritis, correction of functional deformity, femoral fracture, and in the salvage of previously failed surgical attempts.
Source: Medical Device Recalls - Category: Medical Devices Source Type: alerts
Conclusions: The results suggest an association between VAV1 gene rs2617822 polymorphism and RA.
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
Rheumatoid arthritis (RA) is a disease with a high disability rate, resulting in severe family and social burden. The aim of treatment is to improve the health-related quality of life (QoL) of patients. The pu...
Source: Health and Quality of Life Outcomes - Category: International Medicine & Public Health Authors: Tags: Research Source Type: research
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