POS0196 UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS REFRACTORY TO BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS: 56-WEEK DATA FROM THE PHASE 3 SELECT-PSA 2 STUDY
Authors: P. J. Mease, A. Lertratanakul, K. Papp, F. Van den Bosch, S. Tsuji, E. Dokoupilova, M. Keiserman, X. Bu, L. Chen, R. Mccaskill, P. Zueger, E. Mcdearmon-Blondell, A. Pangan, W. Tillett
Journal: Annals of the Rheumatic Diseases (2021)

Background: Upadacitinib (UPA) is an oral Janus kinase inhibitor currently under evaluation for the treatment of psoriatic arthritis (PsA). Previous 24-week results from the SELECT-PsA 2 study in patients with PsA and prior inadequate response to ≥1 biologic disease-modifying antirheumatic drug (bDMARD) demonstrated UPA efficacy with a safety profile consistent with that observed in rheumatoid arthritis. 1 Objectives: To evaluate the 56-week efficacy and safety of UPA in the SELECT-PsA 2 study. Methods: Patients were randomized to 56 weeks of blinded treatment with UPA 15 or 30 mg once daily (QD), or placebo (PBO) switched to UPA 15 or 30 mg QD at Week 24. Efficacy endpoints included proportions of patients achieving 20/50/70% improvement in American College of Rheumatology (ACR) criteria (ACR20/50/70), 75/90/100% improvement in the Psoriasis Area and Severity Index (PASI75/90/100), resolution of dactylitis and enthesitis, and minimal disease activity (MDA). Non-responder imputation was used for missing data. Treatment-emergent adverse events (TEAEs) were summarized for events occurring while on UPA and ≤30 days after last dose (for those who discontinued). Results: Of 641 patients who received ≥1 dose of study drug, 74.7% completed 56 weeks of treatment. Clinical improvements based on the proportion of patients achieving ACR20/50/70 and MDA (Figure 1), PASI75/90/100, and resolution of dactylitis and enthesitis were generally maintained through 56 weeks of UPA treatment. Week 56 results for patients who switched from PBO to UPA at Week 24 had a similar trajectory to those for patients originally randomized to UPA. Overall, improvements observed with UPA 15 mg were similar to or approached those with UPA 30 mg over 56 weeks. Dose-dependent increases were observed for exposure-adjusted event rates (EAERs) of serious infections, herpes zoster (HZ), hepatic disorders, hematologic lab-related adverse events, and creatine phosphokinase (CPK) elevations, but not for exposure-adjusted incidence rates (EAIRs) of major adverse cardiovascular events (MACE), venous thromboembolic events (VTEs), or malignancies (Table 1). Generally, rates of TEAEs were lower with UPA 15 mg versus 30 mg. Conclusion: In patients with PsA and prior inadequate response to ≥1 bDMARD, UPA efficacy was maintained over 56 weeks with no new safety signals. References: [1]Mease PJ, et al. Ann Rheum Dis 2020. Epub ahead of print. Table 1. Safety through Week 56 Event UPA 15 mg QD (n=290; PY=419.4 ) UPA 30 mg QD (n=308; PY=423.5 ) EAER, events/100 PY (95% CI ) Infection 89.7 (81.0–99.2) 113.6 (103.9–124.2) Serious infection 2.6 (1.5–4.7) 6.1 (4.2–9.0) Opportunistic infection a 0.7 (0.2–2.2) 0.9 (0.4–2.5) HZ 3.8 (2.3–6.2) 8.5 (6.1–11.8) Active TB 0 0 Gastrointestinal perforation (adjudicated) 0 0 Hepatic disorder 4.8 (3.1–7.4) 17.7 (14.1–22.2) Anemia 2.1 (1.1–4.1) 5.4 (3.6–8.2) Neutropenia 1.0 (0.4–2.5) 3.1 (1.8–5.3) Lymphopenia 0.7 (0.2–2.2) 2.4 (1.3–4.4) CPK elevation 5.2 (3.5–8.0) 8.7 (6.3–12.1) Renal dysfunction 0.5 (0.1–1.9) 0.2 (0.0–1.7) EAIR, n/100 PY (95% CI ) NMSC b 1.2 (0.5–2.9) 1.0 (0.4–2.5) Malignancy other than NMSC c 1.2 (0.5–2.9) 1.2 (0.5–2.9) Lymphoma d 0.5 (0.1–1.9) 0 MACE (adjudicated) 0.2 (0–1.7) 0.2 (0–1.7) VTE (adjudicated) 0.2 (0–1.7) 0.2 (0–1.7) a Excludes TB and HZ. b UPA 15 mg: 4 cases of BCC and 1 case of SCC of the skin; UPA 30 mg: 3 cases of BCC and 3 cases of SCC of the skin. c UPA 15 mg: 2 cases of prostate cancer, and single cases of malignant melanoma, ovarian cancer, and rectal cancer; UPA 30 mg: single cases of basosquamous carcinoma (considered NMSC after medical review), malignant melanoma, oropharyngeal SCC, and rectal adenocarcinoma, as well as endometrial cancer and ovarian cancer (in the same patient). d UPA 15 mg: 2 events of treatment-emergent abnormal lymphocyte morphology; abnormal lymphocytes were not reported in subsequent laboratory testing BCC, basal cell carcinoma; CI, confidence interval; NMSC, non-melanoma skin cancer; PY, patient-years; SCC, squamous cell carcinoma; TB, tuberculosis Acknowledgements: AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Russell Craddock, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie. Disclosure of Interests: Philip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squib, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, GSK, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Apinya Lertratanakul Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Kim Papp Speakers bureau: AbbVie, Akros, Allergan, Almirall, Amgen, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Consultant of: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GSK, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Grant/research support from: AbbVie, Akros, Allergan, Almirall, Amgen, Arcutis, Avillion, Bausch Health, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, Genentech/Roche, GSK, Janssen, Kyowa Kirin, LEO, Meiji, MSD, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, Takeda, UCB, and Valeant, Filip van den Bosch Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Shigeyoshi Tsuji Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, and UCB., Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, and UCB., Grant/research support from: AbbVie, Eli Lilly, Janssen, Novartis, and UCB., Eva Dokoupilova Grant/research support from: AbbVie, Affibody AB, Eli Lilly, Galapagos, Gilead, GSK, Hexal AG, MSD, Novartis, Pfizer, R-Pharm, Sanofi-Aventis, and UCB, MAURO KEISERMAN Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Xianwei Bu Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Liang Chen Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Reva McCaskill Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Patrick Zueger Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Erin McDearmon-Blondell Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, Aileen Pangan Shareholder of: May own stock/shares in AbbVie, Employee of: Currently employed by AbbVie, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, and Janssen