BACKGROUND: Upadacitinib, a selective JAK1 inhibitor, has demonstrated promising results in the treatment of axial Spondyloarthritis (AxSpA). AxSpA management remains challenging since there is a gap in knowledge regarding the potential effect of upadacitinib in axSpA patients. Exploring novel therapeutic options is crucial. Therefore, we performed this systematic review and meta-analysis to summarize and synthesize results collected from available randomized-- controlled trials (RCTs) about the efficacy and safety of upadacitinib for patients with axSpA.
METHODS: A systematic literature search of Medline via PubMed, Web of Science, Scopus, EBSCO, and Cochrane Central was conducted in October 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan 5.4 software. The main outcomes were assessment in Spondylarthritis International Society (ASAS) 20, ASAS40, SPARCC MRI sacroiliac joint, and Bath Ankylosing Spondylitis disease activity index (BASDAI) 50.
RESULTS: Three RCTs with a total of 920 participants were included in this study. Upadacitinib showed significant improvement in the ASAS40 response, ASAS20 response, BASDAI50 response, and SPARCC MRI Sacroiliac Joint change from baseline compared to placebo at 14-week duration (RR 2.19, 95% CI (1.79 to 2.68), P < 0.00001), (RR 1.62, 95% CI [1.42 to 1.84), P < 0.00001), (RR 2.16, 95% CI (1.75 to 2.67), P < 0.00001), and (MD -3.32 points, 95% CI (-3.96 to -2.68), P < 0.00001) respectively. However, this efficacy decreased after the 52-week duration in terms of ASAS40 RR 2.19 vs. 1.02, ASAS20 RR 1.62 vs. 0.98, BASDAI 50 RR 2.16 vs. 1.05, and ASAS Partial Remission RR 3.82 vs. 1.07.
CONCLUSIONS: Upadacitinib 15 mg showed satisfactory and promising efficacy in the treatment of AxSpA, with no difference in safety profile compared to the placebo.

Upadacitinib, classified as a highly soluble drug, is commercially marketed as RINVOQ®, a modified-release formulation incorporating hydroxypropyl methylcellulose as a matrix system to target extended release throughout the gastrointestinal (GI) tract. Our study aimed to explore how drug release will occur throughout the GI tract using a plethora of in vitro and in silico tools. We built a Physiologically-Based Pharmacokinetic (PBPK) model in GastroPlus™ to predict the systemic concentrations of the drug when administered using in vitro dissolution profiles as input to drive luminal dissolution. A series of in vitro dissolution experiments were gathered using the USP Apparatus I, III and IV in presence of biorelevant media, simulating both fasted and fed state conditions. A key outcome from the current study was to establish an in vitro-in vivo correlation (IVIVC) between (i) the dissolution profiles obtained from the USP I, III and IV methods and (ii) the fraction absorbed of drug as deconvoluted from the plasma concentration-time profile of the drug. When linking the fraction dissolved as measured in the USP IV model, a Level A IVIVC was established. Moreover, when using the different dissolution profiles as input for PBPK modeling, it was also observed that predictions for plasma Cmax and AUC were most accurate for USP IV compared to the other models (based on predicted versus observed ratios). Furthermore, the PBPK model has the utility to extract the predicted concentrations at the level of the colon which can be of utmost interest when working with specific in vitro assays.

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To review the characteristics, efficacy, safety, pharmacoeconomics, and place in therapy of upadacitinib, a Janus kinase (JAK) inhibitor, in the treatment of rheumatoid arthritis (RA).
PubMed (January 2003-May 2022) was searched using upadacitinib and ABT-494.
Human studies published in peer-reviewed publications in English were the primary sources for efficacy and safety data.
In randomized, double-blind, controlled clinical studies, upadacitinib demonstrated statistically significant improvement in RA symptoms as monotherapy and in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) when compared with csDMARD monotherapy or to adalimumab or abatacept in combination with csDMARD therapy in patients with RA. American College of Rheumatology 20% response rates were 68% to 79% for upadacitinib monotherapy and 64% to 84% for upadacitinib plus csDMARD therapy, compared with 28% to 59% for csDMARD-only therapy and 63% to 74% for biologic DMARD (bDMARD) plus csDMARD therapy. Long-term extension studies demonstrated similar findings. Upadacitinib had similar rates of serious infections, herpes zoster, major cardiovascular events, and venous thromboembolic events as other JAK inhibitors. Upadacitinib was similar in cost to tofacitinib and twice as high as baricitinib based on current estimated costs to patients, but actual costs may vary.
Upadacitinib is an alternative therapy to other JAK inhibitors and bDMARDs in patients with moderate to severe RA who have had an inadequate response to a tumor necrosis factor inhibitor alone or in combination with a csDMARD.
Upadacitinib is an effective JAK inhibitor for use in RA.