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.
Upadacitinib for the Treatment of Active Non-radiographic Axial Spondyloarthritis (SELECT-AXIS 2): A Randomised, Double-blind, Placebo-controlled, Phase 3 Trial
Lancet 2022 doi: 10.1016/S0140-6736(22)01212-0
Upadacitinib significantly improved the signs and symptoms of nr-axSpA compared with placebo at Week 14 in this investigation. Prior to this, upadacitinib had been shown to be effective in patients with AS. This study aimed to assess the efficacy and safety of upadacitinib in non-radiographic axial spondyloarthritis.
Efficacy and Safety of Upadacitinib for Active Ankylosing Spondylitis Refractory to Biological Therapy: A Double-blind, Randomised, Placebo-controlled Phase 3 Trial
Ann Rheum Dis 2022 doi:10.1136/annrheumdis-2022-222608
Van der Heijde et al., carried out a study to show whether upadacitinib offers an effective treatment option for bDMARD-naïve and bDMARD-IR patients with active AS. Their results indicated that upadacitinib 15 mg significantly improved the signs and symptoms of active AS. The treatment was well tolerated for 14 weeks in bDMARD-IR patients, consistent with results observed in the upadacitinib AS bDMARD-naïve study.
Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT-COMPARE study
RMD Open. 2022;8(1):e002012 doi: 10.1136/rmdopen-2021-002012Upadacitinib continues to show consistently better clinical responses, compared with adalimumab, through 3 years, including rates of remission and low disease activity, physical function and pain severity.Following the favourable upadacitinib efficacy data seen in the SELECT-COMPARE study at 72 weeks, Fleischmann, et al. assessed the long-term safety and efficacy of upadacitinib versus adalimumab over 3 years in the long-term extension of this study, with promising results. ...
A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition
Rheumatology (Oxford). 2021. Epub ahead of print. doi: 10.1093/rheumatology/keab740.JAK inhibitors are likely to become an important part of the overall treatment paradigm for spondyloarthritis (SpA).Although not fully understood, the pathogenesis of SpA is complex and thought to involve both environmental and genetic factors that together elicit a chronic inflammatory response involving the innate and adaptive immune systems. Several different cytokines, TNF, IL-17A, IL-12/23 and IL-23, which are directly/indirectly affected by JAK molecules, are involved in the pathogenesis o...
Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis
Ann Rheum Dis 2020; doi:10.1136/annrheumdis-2020-21841220Both ACR and EULAR recommend adding a biologic or targeted synthetic DMARD in patients who do not achieve treatment goals at follow-up. Findings indicated that an immediate switch in mechanism of action (from JAKi to TNFi and vice versa) following treat-to-target principles is feasible with minimal risk of flare regardless of whether patients are switched due to non-response or incomplete-response.SELECT-COMPARE followed treat-to-target principles to examine the efficacy of switching in two pati...
Upadacitinib versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase 3, Double-Blind, Randomized Controlled Trial
Arthritis Rheumatol 2019 DOI: 10.1002/art.41032UPA demonstrated superiority to ADA in terms of clinical, functional and patient-reported outcomes with comparable radiographic inhibition. As many RA patients fail to achieve LDA and remission with TNF inhibitors and MTX there is a requirement for additional treatment options. In this SELECT-COMPARE study the clinical and functional outcomes of UPA were compared to ADA in MTX-IR patients. 1629 MTX-IR were randomly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W or PBO, with background MTX. Key end...
Safety and Effectiveness of Upadacitinib or Adalimumab Plus Methotrexate in Patients with Rheumatoid Arthritis Over 48 Weeks with Switch to Alternate Therapy in Patients with Insufficient Response
Ann Rheum Dis 2019 DOI: 10.1136/annrheumdis-2019-215764Consistent with Wk26 data, significantly more UPA patients achieved LDA and remission versus ADA and PBO over 48 weeks. RA patients often change therapy due to inadequate response and intolerance. The SELECT COMPARE study was designed to explore switching to JAK inhibitors from TNF inhibitors without a wash-out period (and vice versa). The long-term safety and efficacy of UPA was compared to ADA and PBO in MTX-IR.1629 patients were blindly assigned 2:2:1 to; UPA 15mg QD, ADA 40mg Q2W and PBO, wi...
Pharmacokinetics of Upadacitinib with Clinical Regimens of the Extended-Release Formulation Utilized in Rheumatoid Arthritis Phase 3 Trials
Clin Pharmacol Drug Dev. 2019 Feb;8(2):208-216. doi: 10.1002/cpdd.462Upadacitinib (UPA) extended release (ER) formulation dosing achieved the target profile that enables single dosing in patients with RA. In early clinical studies, UPA was given as an immediate release (IR) formulation, however patients were noted to experience fluctuations in blood plasma concentrations. To enhance patient compliance in UPA Phase 3 trials, ER tablets have been developed. Here, authors aimed at characterising the pharmacokinetics of UPA single and multiple doses of ER compared wi...