Role of IFN-α in Rheumatoid Arthritis.

PURPOSE OF REVIEW: Type 1 interferons (IFN-I) are of increasing interest across a wide range of autoimmune rheumatic diseases. Historically, research into their role in rheumatoid arthritis (RA) has been relatively neglected, but recent work continues to highlight a potential contribution to RA pathophysiology. RECENT FINDINGS: We emphasise the importance of disease stage when examining IFN-I in RA and provide an overview on how IFN-I may have a direct role on a variety of relevant cellular functions. We explore how clinical trajectory may be influenced by increased IFN-I signalling, and also, the limitations of scores composed of interferon response genes. Relevant environmental triggers and inheritable RA genetic risk relating to IFN-I signalling are explored with emphasis on intriguing data potentially linking IFN-I exposure, epigenetic changes, and disease relevant processes. Whilst these data cumulatively illustrate a likely role for IFN-I in RA, they also highlight the knowledge gaps, particularly in populations at risk for RA, and suggest directions for future research to both better understand IFN-I biology and inform targeted therapeutic strategies.

Precision medicine: the precision gap in rheumatic disease.

For many oncological conditions, the application of timely and patient-tailored targeted therapies, or precision medicine, is a major therapeutic development that has provided considerable clinical benefit. However, despite the application of increasingly sophisticated technologies, alongside advanced bioinformatic and machine-learning algorithms, this success is yet to be replicated for the rheumatic diseases. In rheumatoid arthritis, for example, despite an array of targeted biologic and conventional therapeutics, treatment choice remains largely based on trial and error. The concept of the 'precision gap' for rheumatic disease can help us to identify factors that underpin the slow progress towards the discovery and adoption of precision-medicine approaches for rheumatic disease. In a rheumatic disease such as rheumatoid arthritis, it is possible to identify four themes that have slowed progress, solutions to which should help to close the precision gap. These themes relate to our fundamental understanding of disease pathogenesis, how we determine treatment response, confounders of treatment outcomes and trial design.

Depression Is Not Independently Associated with a Clinically Worse Functional Improvement but Associated with a Lower Reported Satisfaction Rate after Total Knee Arthroplasty.

The aim of this study was to assess whether depression had a clinically significant influence on the functional improvement of total knee arthroplasty (TKA) according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and whether it influences patient satisfaction at 1 year. A retrospective cohort of 3,510 primary TKA was identified from an arthroplasty database. Patient demographics, comorbidities, WOMAC, and Short Form-12 (SF-12) scores were collected preoperatively and 1 year postoperatively. Patient satisfaction (overall, pain relief, return to work, and recreational activity) was assessed at 1 year. There were 444 (12.6%) patients who self-reported depression. Patients with depression were younger (p < 0.001), had a higher body mass index (BMI; p < 0.001), were more likely to be female (p < 0.001), had lung (p < 0.001), neurological (p = 0.018), kidney (p = 0.001), liver (p < 0.001), and gastric (p < 0.001) disease, report associated diabetes (p = 0.001), and back pain (p < 0.001) relative to the subgroup without depression. All preoperative WOMAC functional measures were significantly (p < 0.001) worse in patients with reported depression. When adjusting for these confounding differences, patients with depression had a clinically equal improvement in their WOMAC scores at 1 year compared to those patients without. Depression was not associated with a clinically significant difference in improvement of knee-specific outcome (WOMAC) but was independently associated with a lower rate of patient satisfaction 1 year after TKA. Patients with depression were approximately twice as likely to be dissatisfied at 1 year when compared with those without depression. This is a prognostic retrospective cohort study and reflects level of evidence III.