Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial

The Lancet

Volumn 391, Issue 10139, 2018, Pages 2513-2524

  Genovese, Mark C ^a   Fleischmann, Roy ^b   Combe, Bernard ^c   Hall, Stephen ^d   Rubbert Roth, Andrea ^e   Zhang, Ying ^f   Zhou, Yijie ^f   Mohamed, Mohamed Eslam F ^f   Meerwein, Sebastian ^f   Pangan, Aileen L ^f  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c UNIV MONTPELLIER   (France)

^d CABRINI INSTITUTE   (Australia)

^e CANTONAL HOSPITAL ST GALLEN   (Switzerland)

^f ABBVIE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

C REACTIVE PROTEIN; CHLOROQUINE; DISEASE MODIFYING ANTIRHEUMATIC DRUG; HYDROXYCHLOROQUINE; LEFLUNOMIDE; METHOTREXATE; PLACEBO; SALAZOSULFAPYRIDINE; UPADACITINIB; ANTIRHEUMATIC AGENT; JANUS KINASE INHIBITOR;

ADULT; ARTICLE; CARDIOVASCULAR DISEASE; CONTROLLED STUDY; DAS28; DIGESTIVE SYSTEM PERFORATION; DISEASE EXACERBATION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; HERPES ZOSTER; HUMAN; LIVER DISEASE; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MALE; MALIGNANT NEOPLASM; OUTCOME ASSESSMENT; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; RHINOPHARYNGITIS; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; ADMINISTRATION AND DOSAGE; AGED; CLINICAL TRIAL; DELAYED RELEASE FORMULATION; DOSE RESPONSE; MIDDLE AGED; MULTICENTER STUDY; SEVERITY OF ILLNESS INDEX;

AGED; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; DELAYED-ACTION PREPARATIONS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HUMANS; JANUS KINASE INHIBITORS; METHOTREXATE; MIDDLE AGED; SEVERITY OF ILLNESS INDEX;

EID: 85048340669     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(18)31116-4     Document Type: Article

References (34)

1. Singh, JA, Saag, KG, Bridges, SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 68 (2016), 1–26.
2. Smolen, JS, Landewé R, Bijlsma, J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 76 (2017), 960–977.
3. Lipsky, PE, van der Heijde, DM, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 343 (2000), 1594–1602.
4. Keystone, EC, Kavanaugh, AF, Sharp, JT, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 50 (2004), 1400–1411.
5. Smolen, JS, Kay, J, Doyle, MK, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 374 (2009), 210–221.
6. Kalden, JR, Schulze-Koops, H, Immunogenicity and loss of response to TNF inhibitors: implications for rheumatoid arthritis treatment. Nat Rev Rheumatol 13 (2017), 707–718.
7. Listing, J, Strangfeld, A, Rau, R, et al. Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low—results from RABBIT, the German biologics register. Arthritis Res Ther, 8, 2006, R66.
8. Rendas-Baum, R, Wallenstein, GV, Koncz, T, et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-alpha inhibitors. Arthritis Res Ther, 13, 2011, R25.
9. Rubbert-Roth, A, Finckh, A, Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res Ther, 11(suppl 1), 2009, S1.
10. Favalli, EG, Raimondo, MG, Becciolini, A, Crotti, C, Biggioggero, M, Caporali, R, The management of first-line biologic therapy failures in rheumatoid arthritis: current practice and future perspectives. Autoimmun Rev 16 (2017), 1185–1195.
11. Burmester, GR, Blanco, R, Charles-Schoeman, C, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet 381 (2013), 451–460.
12. Emery, P, Keystone, E, Tony, HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67 (2008), 1516–1523.
13. Fleischmann, R, van Adelsberg, J, Lin, Y, et al. Sarilumab and nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol 69 (2017), 277–290.
14. Genovese, MC, Kremer, J, Zamani, O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med 374 (2016), 1243–1252.
15. Westhovens, R, Taylor, PC, Alten, R, et al. Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). Ann Rheum Dis 76 (2016), 998–1008.
16. O'Shea, JJ, Schwartz, DM, Villarino, AV, Gadina, M, McInnes, IB, Laurence, A, The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med 66 (2015), 311–328.
17. Genovese, MC, Smolen, JS, Weinblatt, ME, et al. Efficacy and safety of ABT-494, a selective JAK-1 inhibitor, in a phase IIb study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Rheumatol 68 (2016), 2857–2866.
18. Kremer, JM, Emery, P, Camp, HS, et al. A phase IIb study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to anti-tumor necrosis factor therapy. Arthritis Rheumatol 68 (2016), 2867–2877.
19. Aletaha, D, Neogi, T, Silman, AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 62 (2010), 2569–2581.
20. Mohamed, ME, Zeng, J, Marroum, P, Song, IH, Othman, AA, Pharmacokinetics of upadacitinib with the clinical regimens of the extended-release formulation utilized in rheumatoid arthritis phase 3 trials. Clin Pharmacol Drug Dev, 2018 published online April 24. DOI:10.1002/cpdd.462.
21. Woodworth, T, Furst, DE, Alten, R, et al. Standardizing assessment and reporting of adverse effects in rheumatology clinical trials II: the Rheumatology Common Toxicity Criteria v.2.0. J Rheumatol 34 (2007), 1401–1414.
22. National Cancer Institute. Common terminology criteria for adverse events (CTCAE) version 4.0. May 28, 2009, National Institutes of Health, Bethesda https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. (Accessed 1 March 2018)
23. National Cholesterol Education Program. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). May, 2001, National Institutes of Health, Bethesda https://www.nhlbi.nih.gov/files/docs/guidelines/atp3xsum.pdf. (Accessed 15 March 2018)
24. Bretz, F, Maurer, W, Brannath, W, Posch, M, A graphical approach to sequentially rejective multiple test procedures. Stat Med 28 (2009), 586–604.
25. Dossing, A, Tarp, S, Furst, DE, et al. Interpreting trial results following use of different intention-to-treat approaches for preventing attrition bias: a meta-epidemiological study protocol. BMJ Open, 4, 2014, e005297.
26. Fleischmann, RM, van der Heijde, D, Gardiner, PV, Szumski, A, Marshall, L, Bananis, E, DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable. RMD Open, 3, 2017, e000382.
27. Burmester, GR, Kremer, JM, Van den Bosch, F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet, 2018 published online June 13. http://dx.doi.org/10.1016/S0140-6736(18)31115-2.
28. Kim, SC, Schneeweiss, S, Liu, J, Solomon, DH, Risk of venous thromboembolism in patients with rheumatoid arthritis. Arthritis Care Res 65 (2013), 1600–1607.
29. Genovese, MC, Smolen, JS, Takeuchi, T, et al. Safety profile of baricitinib for the treatment of rheuamtoid arthritis up to 5.5 years: an updated integrated safety analysis. Arthritis Rheumatol, 69(suppl 10), 2017, 511 (abstr).
30. Mease, P, Kremer, J, Cohen, S, Curtis, JR, Charles-Schoeman, C, Loftus, EV, Incidence of thromboembolic events in the tofacitinib rheumatoid arthritis, psoriasis, sporiatic arthritis and ulcerative colitis development programs. Arthritis Rheumatol, 69(suppl 10), 2017, 16L (abstr).
31. del Rincon, ID, Williams, K, Stern, MP, Freeman, GL, Escalante, A, High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 44 (2001), 2737–2745.
32. Taylor, PC, Kremer, JM, Emery, P, et al. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis, 2018 published online Feb 20. DOI:10.1136/annrheumdis-2017-212461.
33. Charles-Schoeman, C, Gonzalez-Gay, MA, Kaplan, I, et al. Effects of tofacitinib and other DMARDs on lipid profiles in rheumatoid arthritis: implications for the rheumatologist. Semin Arthritis Rheum 46 (2016), 71–80.
34. Genovese, MC, Becker, JC, Schiff, M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 353 (2005), 1114–1123.