View and download slide summaries of the latest original articles focusing on cytokine signalling therapies within rheumatoid arthritis. All materials produced by the CSF team are subsequently reviewed and approved by individual Steering Committee members.
Safety Profile of Upadacitinib over 15 000 Patient-years Across Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis and Atopic Dermatitis
RMD Open. 2023;9(1):e002735 doi: 10.1136/rmdopen-2022-002735
Integrated analysis of the safety profile of upadacitinib demonstrates that it was generally well-tolerated in RA, PsA, AS and AD, with no new safety risks identified, compared with previous reports.
Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs
Rheumatol Ther. 2022. Epub ahead of print doi: 10.1007/s40744-022-00507-z
This post-hoc analysis of 31 clinical trials in ulcerative colitis, rheumatoid arthritis and psoriatic arthritis concludes that combined influenza adverse event incidence rates were highest in ulcerative colitis, while in each indication they were generally similar across tofacitinib, placebo, and comparator groups.
Oral surveillance and JAK inhibitor safety: the theory of relativity
Nat Rev Rheumatol. 2022. Epub ahead of print doi: 10.1038/s41584-022-00767-7Putting the data into context, Winthrop, et al. conclude that the ORAL Surveillance data are not dissimilar to those from the original developmental programme, which suggested additional safety concerns at the 10 mg dosage and that resulted in the 5 mg twice daily dosage as the approved dose for RA.Following the recent results of the ORAL Surveillance (ORALSURV) study, and the consequent changes to the utilisation of JAKinibs, made by the regulatory authorities, Winthrop, et al. aim to put the O...
Effect of dose adjustments on the efficacy and safety of tofacitinib in patients with rheumatoid arthritis: a post hoc analysis of an open-label, long-term extension study (ORAL Sequel)
Clin Rheumatol. 2022 Jan 1. Epub ahead of print doi: 10.1007/s10067-021-05908-zPost-hoc analysis shows that dosing up from tofacitinib 5 to 10 mg BID is associated with improved efficacy for up to 12 months, versus staying on 5 mg BID, and dosing down from 10 to 5 mg BID is not generally associated with a significant loss of efficacy.Although clinical trials have generally shown no significant differences, in terms of efficacy and safety, when switching tofacitinib dose up or down, these per-protocol switches are not directly informative for clinical decision-making in dai...
Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies
Rheumatology (Oxford). 2021;60(4):1708-1716.Long-term evaluation of tofacitinib has found limited progression of structural damage in patients with RA treated with tofacitinib for up to 5 years. Similar results were also observed for patients receiving tofacitinib monotherapy or combination therapy for up to 3 years.It is well known that inflammation in RA leads to structural damage over time, and therapies such as DMARDS have the ability to reduce inflammation whilst inhibiting the progression of structural damage. In this study, van der...
Upadacitinib in Rheumatoid Arthritis: A Benefit–Risk Assessment Across a Phase III Program
Drug Saf. 2021 Feb 2. DOI: 10.1007/s40264-020-01036-wUpadacitinib 15 mg has a favourable benefit–risk profile according to an assessment of data from the phase III SELECT clinical trial programme.In this review of data for the once-daily, oral JAK inhibitor, Conaghan PG, et al. provided insights into the benefit–risk profile of upadacitinib in approximately 4400 patients with RA. Based on pooled data from five pivotal studies, benefits and risks were assessed up to the time of regulatory submission, and additional long-term integrated safety revie...
Safety Profile of Upadacitinib in Rheumatoid Arthritis: Integrated Analysis from the SELECT Phase III Clinical Programme
Ann Rheum Dis 2020 DOI:10.1136/annrheumdis-2020-218510This integrated Phase III safety analysis of UPA showed that UPA had a similar profile to ADA and MTX for serious infections, malignancies, and thromboembolic events. Patients receiving UPA had increased risk of HZ and creatine phosphokinase elevation versus ADA.This integrated Phase III safety analysis of UPA examined >3500 RA patients and 4000 patient-years of exposure. Data were pooled from 3834 patients in SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY studie...
Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data
Annals of the Rheumatic Diseases 05 August 2020 2020 Nov;79(11):1400-1413. doi: 10.1136/annrheumdis-2019-216761. Epub 2020 Aug 5.Concerns surrounding increased rates of PE and cardiovascular associated deaths has led to black box warnings when prescribing JAK inhibitors. As such, ongoing investigations regarding cardiovascular and VTE event risks in JAK inhibitor therapies, both clinical and real-world, are vital. Mease and colleagues consider data from clinical tofacitinib development programmes, and the ongoing real-data study A3921133. Conclusions from data analysis state that those with pre-existing cardiovascular and...
Fenebrutinib Versus Placebo or Adalimumab in Rheumatoid Arthritis: A Randomized, Double-Blind, Phase II Trial (ANDES Study)
Arthritis Rheumatol. 2020 Sep; 72(9): 1435–1446.In this randomised phase II trial with MTX treatment-refractory RA patients, greater efficacy was observed with fenebrutinib 150 mg once daily or 200 mg twice daily compared to placebo, while response rates were numerically similar to those observed with adalimumab. BTK inhibitors have demonstrated clinical efficacy in B cell malignancies and multiple sclerosis, although there is limited clinical evidence of its efficacy in RA. Fenebrutinib (FEN) an orally active and selective non-covalent inhib...
Tofacitinib in Combination with Methotrexate in Patients with Rheumatoid Arthritis: Patient-reported Outcomes from the 24-month Phase 3 ORAL Scan study
Clin Exp Rheumatol . Sep-Oct 2020;38(5):848-857. Epub 2019 Dec 19.In the ORAL SCAN study, patients receiving TOF 5 mg or 10 mg BID reported significant improvements in patient-reported outcomes at month 3 compared with placebo, which were maintained through 24 months of treatment.RA causes a significant health and socioeconomic burden and affects all aspects of health related quality of life. ORAL Scan included patients with active RA and inadequate response to MTX who were randomised to receive TOF 5 mg or 10 mg BID plus MTX or PBO. This study evaluated the i...