Anti-gm-csf Otilimab versus Sarilumab or Placebo in Patients with Rheumatoid Arthritis and Inadequate Response to Targeted Therapies: A Phase III Randomised Trial (contRAst 3)
Ann Rheum Dis. 2023 doi 10.1136/ard-2023-224449 Epub ahead of print
The ContRAst 3 study investigated otilimab, in RA patients with inadequate responses to multiple treatments. Otilimab did not significantly improve ACR20 versus placebo at Weeks 12 or 24. In addition, there we no significant improvements in secondary endpoints, including disease activity, disability, and pain.
Anti-GM-CSF Otilimab Versus Tofacitinib or Placebo in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Conventional or Biologic DMARDs: Two Phase 3 Randomised Trials (contRAst 1 and contRAst 2)
Ann Rheum Dis 2023;0:1–11 doi 10.1136/ard-2023-224482
Fleischmann, et al investigated the safety and efficacy of otilimab versus tofacitinib and placebo in RA patients treated with MTX (contRAst 1) or csDMARDs (contRAst 2). They found that while otilimab achieved the primary endpoint of ACR20 versus placebo in Week 12, it did not demonstrate non-inferiority to tofacitinib.
Incidence, Prevalence, and Co-occurrence of Autoimmune Disorders Over Time and by Age, Sex, and Socioeconomic Status: A Population-based Cohort Study of 22 Million Individuals in the UK
Lancet. 2023; 401(10391):1878–1890 doi 10.1016/S0140-6736(23)00457-9
Incidence rates for autoimmune diseases increased between 2000 and 2019 in the UK, notably in coeliac disease, Sjogren's syndrome, and Graves' disease. Pernicious anaemia and Hashimoto's thyroiditis had the greatest decrease in incidence. These disorders affected about 10% of the population, with socioeconomic, seasonal, and regional variations observed.
Differential Properties of Janus Kinase Inhibitors in the Treatment of Immune-mediated Inflammatory Diseases
Rheumatology (Oxford) 2023 doi 10.1093/rheumatology/kead448 Epub ahead of print
JAKis differ in structure, which affects their inhibitory concentration for different JAKs.
This review by Taylor, et al. compares the pharmacological profiles of JAKis, including abrocitinib, baricitinib, filgotinib, peficitinib, tofacitinib, and upadacitinib.
Filgotinib Modulates Inflammation-Associated Peripheral Blood Protein Biomarkers in Adults with Active Rheumatoid Arthritis and Prior Inadequate Response to Methotrexate
Rheumatol Ther. 2023 doi 10.1007/s40744-023-00583-9 Epub ahead of print
This study by Tanaka, et al. shows that filgotinib reduces peripheral protein biomarkers associated with JAK/STAT signalling, inflammatory signalling, immune cell migration, and bone resorption in RA patients. Notably, filgotinib 200 mg significantly reduced IL-6, TNF, CXCL13 levels as early as Week 4.
J. Clin. Med. 2023;12(13):4527 doi 10.3390/jcm12134527
This review by Taylor, et al. reviews the long-term safety and efficacy data for baricitinib. Results from several studies showed that baricitinib has greater efficacy and survival compared to TNF inhibitors, and that the rate of CDAI <10 for baricitinib-treated RA patients increased over the course of seven years. Data also showed that remission rates were higher in real-world evidence than in RCTs.
Pain and Inflammation as Mediators of Tofacitinib Treatment Effect on Fatigue in Patients with Ankylosing Spondylitis: A Mediation Analysis
Rheumatol Ther. 2023 doi 10.1007/s40744-023-00570-0 Epub ahead of print
Kristensen, et al. used mediation modelling to show that tofacitinib indirectly improved fatigue symptoms via back pain and morning stiffness. This study was carried out using FACIT-F- and BASDAI Q1-based models to determine the relationship between these variables.
Baricitinib Safety for Events of Special Interest in Populations at Risk: Analysis from Randomised Trial Data Across Rheumatologic and Dermatologic Indications
Adv Ther. 2023:1–17 doi: 10.1007/s12325-023-02445-w Epub ahead of print
Analysis of pooled data from the baricitinib clinical development programmes finds a low incidence rate of MACE, myocardial infarction, lung cancer, VTE, and overall mortality in patients <65 years without risk factors.
Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: post hoc analysis of SELECT-COMPARE
Rheumatology (Oxford). 2022. Epub ahead of print doi: 10.1093/rheumatology/keac477
Post hoc analysis findings provide the first data evaluating the importance of treatment order with JAKinib vs TNFi as initial therapy, suggesting that a JAKinib first strategy leads to more rapid improvements in treatment outcomes following csDMARD failure.
Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy
RMD Open. 2022;8(1):e001994 doi: 10.1136/rmdopen-2021-001994Post hoc analysis of the RA-BEGIN trial finds that, over a one-year period, patients treated with baricitinib (monotherapy or in combination with methotrexate [MTX]) report greater pain relief and a more rapid attainment of clinically meaningful thresholds of pain improvement, than patients who receive MTX monotherapy.Often overlooked, when treating RA solely to a disease activity target, patient-reported pain is common in RA, even in those reaching inflammatory remission. The fact that pain per...