OA17 Efficacy and safety of upadacitinib in giant cell arteritis: 2-year results from the re-randomized, double-blind SELECT-giant cell arteritis phase 3 trial

Abstract Background/Aims In the SELECT-GCA phase 3 trial, treatment of patients with giant cell arteritis (GCA) with upadacitinib 15 mg (UPA15) demonstrated superior rates of disease remission, fewer disease flares, and reduced glucocorticoid use compared with placebo. The current study analyzed the 2-year outcomes. Methods SELECT-GCA included a 52-week randomized, placebo-controlled period 1 and a 52-week randomized, blinded extension period 2. Patients aged ≥50 years with a diagnosis of active GCA were randomized (2:1:1) to UPA15 or upadacitinib 7.5 mg (UPA7.5) once daily with a 26-week glucocorticoid taper or placebo with a 52-week glucocorticoid taper. Period 2 involved patients in remission for ≥24 consecutive weeks before the week 52 visit. Patients originally randomized to UPA7.5 or UPA15 were re-randomized (2:1) to continue the same dose of UPA or to switch to placebo in period 2. Patients originally randomized to placebo continued placebo. Efficacy outcomes were evaluated through week 104 and included remission, disease flare-related endpoints, and cumulative glucocorticoid exposure. The safety analysis included all patients who received ≥1 dose of study drug in period 1 and continued the same treatment in period 2. Exposure-adjusted treatment-emergent adverse events (TEAEs) are reported through 2 years in this population. Results 181/428 patients (42%) achieved ≥24 consecutive weeks of sustained remission in period 1 and entered period 2 (placebo continuous, n = 34; UPA7.5 continuous, n = 30; UPA7.5 to placebo, n = 14; UPA15 continuous, n = 68; UPA15 to placebo, n = 35). Most (91%) of these patients completed the study, with 82% remaining on study drug. From week 52 through week 104, 67.3% of patients on continuous UPA15 maintained remission vs 28.6% who switched from UPA15 to placebo. Patients on continuous UPA15 showed a 90% reduction in risk of disease flare from week 52 through week 104 compared with those who switched from UPA15 to placebo. Safety was generally similar for UPA and placebo groups among patients who continued the same treatment in period 2. Rates of serious TEAEs were lower for both UPA doses than placebo. Compared to placebo, UPA15 showed lower rates of serious infections but higher rates of herpes zoster and elevated creatine kinase. One venous thromboembolism event occurred with UPA15 in a patient with multiple risk factors and none in the other treatment groups. No major adverse cardiovascular events or deaths occurred in period 2 in any treatment group. Conclusion For patients with GCA receiving UPA15, continued use of UPA in those who were in remission for ≥24 weeks during period 1, rather than switching to placebo, was associated with maintenance of remission and an approximately 1-gram reduction in the cumulative use of glucocorticoids in period 2. In this population, no new clinically significant safety risks were identified with use of UPA for 2 years. Disclosure W. Schmidt: Honoraria; Has received speaker fees/honoraria (includes speakers bureau, symposia, and expert witness) from Abbvie, Alfasigma, Amgen, Chugai, Eli Lilly, GlaxoSmithKline, Medac, Novartis, Pfizer, and UCB. Grants/research support; Has received grants/research support from AbbVie and Novartis. Other; Has been an advisor or review panel member for Abbvie, Boehringer Ingelheim, Fresenius Kabi, GlaxoSmithKline, and Novartis. A.R. Setty: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. C. Dejaco: Consultancies; Has received consultancy fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow, and Sanofi. Honoraria; Has received speaker fees/honoraria (includes speakers bureau, symposia, and expert witness) from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow, and Sanofi. A. Rubbert-Roth: Consultancies; Has received consultancy fees from AbbVie, Amgen, BMS, Boehringer, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, and Sanofi. Honoraria; Has received speaker fees/honoraria (includes speakers bureau, symposia, and expert witness) from AbbVie, Amgen, BMS, Boehringer, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, and Sanofi. M.C. Cid: Consultancies; Has received consultancy fees from GSK, AbbVie, CSL-Vifor, and AstraZeneca. Honoraria; Has received speaker fees/honoraria (includes speakers bureau, symposia, and expert witness) from GSK, CSL-Vifor, AbbVie, and AstraZeneca. Grants/research support; Has received a research grant from Kiniksa Pharmaceuticals and funding from Mininsterio de Ciencia e Innovación. T. Ishii: Consultancies; Has received consultancy fees from AbbVie, Asahi Kasei Pharma, Astellas, Ayumi Pharmaceutical, BMS, Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Ono Pharmaceutical, Pfizer, and Sanofi. A.D. Joshi: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. N. Zerad: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. A. Kadakia: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. S. Zhao: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. W. Zhao: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. I. Lagunes: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. C. Phillips: Corporate appointments; Is an employee of AbbVie. Shareholder/stock ownership; May hold AbbVie stock or stock options. D. Blockmans: Consultancies; Has received consultant fees from GSK, Roche, AbbVie, and AstraZeneca. P.A. Merkel: Consultancies; Has received consultancy fees from AbbVie, Alpine, Amgen, ArGenx, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, CSL Behring, GlaxoSmithKline, iCell, Interius, Kinevant, Kyverna, Metagenomia, Neutrolis, Novartis, NS Pharma, Otsuka, Q32, Quell, Regeneron, Sanofi, Sparrow, Takeda, and Vistera. Shareholder/stock ownership; Has stock options or bond holdings for Kyverna, Q32, Lifordi, Neutrolis, and Sparrow. Grants/research support; Has received grant/research support from AbbVie, Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eicos, Electra, GlaxoSmithKline, Neutrolis, and Takeda.