A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis

Rheumatology (United Kingdom)

Volumn 58, Issue 10, 2019, Pages 1755-1766

  Bechman, Katie ^a   Subesinghe, Sujith ^a   Norton, Sam ^a   Atzeni, Fabiola ^b   Galli, Massimo ^c   Cope, Andrew P ^a   Winthrop, Kevin L ^d   Galloway, James B ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF MESSINA   (Italy)

^c UNIVERSITY OF MILAN   (Italy)

^d OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

immunosuppressants; meta analysis; rheumatoid arthritis; systematic review; viruses

Indexed keywords

BARICITINIB; PLACEBO; TOFACITINIB; UPADACITINIB; ANTIRHEUMATIC AGENT; AZETIDINE DERIVATIVE; FUSED HETEROCYCLIC RINGS; JANUS KINASE INHIBITOR; PIPERIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; SULFONAMIDE;

ARTICLE; FOLLOW UP; HERPES ZOSTER; HUMAN; INCIDENCE; INFECTION RISK; META ANALYSIS; OPPORTUNISTIC INFECTION; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RHEUMATOID ARTHRITIS; SYSTEMATIC REVIEW; ADULT; FEMALE; MALE; MIDDLE AGED;

ADULT; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; AZETIDINES; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; FEMALE; HERPES ZOSTER; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; INCIDENCE; INFECTIONS; JANUS KINASE INHIBITORS; MALE; MIDDLE AGED; PIPERIDINES; PYRIMIDINES; PYRROLES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SULFONAMIDES;

EID: 85069782886     PISSN: 14620324     EISSN: 14620332     Source Type: Journal    
DOI: 10.1093/rheumatology/kez087     Document Type: Article

References (56)

1. Strand V, Balsa A, Al-Saleh J et al. Immunogenicity of biologics in chronic inflammatory diseases: A systematic review. BioDrugs 2017;31:299-31.
2. Villarino AV, Kanno Y, O'Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol 2017;18:374-84.
3. O'Shea JJ, Laurence A, McInnes IB. Back to the future: oral targeted therapy for RA and other autoimmune diseases. Nat Rev Rheumatol 2013;9:173-82.
4. European Medicines Agency (EMA). Refusal of the marketing authorisation for Xeljanz: summary of opinion Initial authorisation. EMA/248755/2013. London: EMA, 2013. https://www. ema. europa. eu/en/medicines/human/ EPAR/xeljanz-0 (12 March 2019, date last accessed).
5. US Food and Drug Administration Arthritis Advisory Committee. Summary of Resubmission and Recommendations for Baricitinib. Center for drug eveluation and research summary review. 207924Orig1s000SumR, 2018. https://www. accessdata. fda. gov/drugsatfda-docs/ nda/2018/207924Orig1s000SumR. pdf (12 March 2019, date last accessed).
6. Singh JA, Saag KG, Bridges SL Jr et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res 2016;68:1-25.
7. Smolen JS, Landewe 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 2017;76:960-77.
8. Winthrop KL, Yamanaka H, Valdez H et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol 2014;66:2675-84.
9. Ghoreschi K, Laurence A, O'Shea JJ. Janus kinases in immune cell signaling. Immunol Rev 2009;228:273-87.
10. Abendroth A, Arvin AM. Immune evasion as a pathogenic mechanism of varicella zoster virus. Semin Immunol 2001;13:27-39.
11. Moher D, Shamseer L, Clarke M et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4:1.
12. Higgins JPT, Altman DG, Gøtzsche PC et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.
13. Winthrop KL, Novosad SA, Baddley JW et al. Opportunistic infections and biologic therapies in immunemediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis 2015;74:2107-16.
14. Rutherford AI, Patarata E, Subesinghe S, Hyrich KL, Galloway JB. Opportunistic infections in rheumatoid arthritis patients exposed to biologic therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Rheumatology 2018;57:997-1001.
15. Morel J, Constantin A, Baron G et al. Risk factors of serious infections in patients with rheumatoid arthritis treated with tocilizumab in the French Registry REGATE. Rheumatology 2017;56:1746-54.
16. Kremer JM, Bloom BJ, Breedveld FC et al. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690, 550 versus placebo. Arthritis Rheum 2009;60:1895-905.
17. Tanaka Y, Suzuki M, Nakamura H, Toyoizumi S, Zwillich SH. Phase II study of tofacitinib (CP-690, 550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Care Res 2011;63:1150-58.
18. Kremer JM, Cohen S, Wilkinson BE et al. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690, 550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum 2012;64:970-81.
19. Fleischmann R, Cutolo M, Genovese MC et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690, 550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum 2012;64:617-29.
20. Fleischmann R, Kremer J, Cush J et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. New Engl J Med 2012;367:495-507.
21. van Vollenhoven RF, Fleischmann R, Cohen S et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. New Engl J Med 2012;367:508-19.
22. 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 2013;381:451-60.
23. Kremer J, Li ZG, Hall S et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: A randomized trial. Ann Intern Med 2013;159:253-61.
24. van der Heijde D, Tanaka Y, Fleischmann R et al. Tofacitinib (CP-690, 550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum 2013;65:559-70.
25. Lee EB, Fleischmann R, Hall S et al. Tofacitinib versus methotrexate in rheumatoid arthritis. New Engl J Med 2014;370:2377-86.
26. Tanaka Y, Hirata S, Kubo S et al. Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study. Ann Rheum Dis 2015;74:389-95.
27. Keystone EC, Taylor PC, Drescher E et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis 2015;74:333-40.
28. Tanaka Y, Emoto K, Cai Z et al. Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis receiving background methotrexate therapy: A 12-week, double-blind, randomized placebo-controlled study. J Rheumatol 2016;43:504-11.
29. Genovese MC, Kremer J, Zamani O et al. Baricitinib in patients with refractory rheumatoid arthritis. New Engl J Med 2016;374:1243-52.
30. Taylor PC, Keystone EC, van der Heijde D et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. New Engl J Med 2017;376:652-62.
31. Fleischmann R, Schiff M, van der Heijde D et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol 2017;69:506-17.
32. Dougados M, van der Heijde D. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis 2017;76:88-95.
33. 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 2016;68:2857-66.
34. 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 2016;68:2867-77.
35. Genovese MC, Fleischmann R, Combe B et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs (SELECT-BEYOND): A double-blind, randomised controlled phase 3 trial. Lancet 2018;391:2513-24.
36. 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 (SELECTNEXT): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018;391:2503-12.
37. Cohen S, Radominski SC, Gomez-Reino JJ et al. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol 2014;66:2924-37.
38. Strand V, Ahadieh S, French J et al. Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials. Arthritis Res Ther 2015;17:362.
39. Smolen JS, Genovese MC. Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment. J Rheumatol 2019;46:7-18.
40. Galloway JB, Mercer LK, Moseley A et al. Risk of skin and soft tissue infections (including shingles) in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis 2013;72:229-34.
41. Forbes HJ, Bhaskaran K, Thomas SL et al. Quantification of risk factors for herpes zoster: population based casecontrol study. BMJ 2014;348:g2911.
42. Ku CC, Zerboni L, Ito H et al. Varicella-zoster virus transfer to skin by T Cells and modulation of viral replication by epidermal cell interferon-alpha. J Exp Med 2004;200:917-25.
43. Arvin AM. Humoral and cellular immunity to Varicella-Zoster virus: An overview. J Infect Dis 2008;197(Suppl 2):S58-60.
44. O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis 2013;72(Suppl 2):ii111-5.
45. Weinberg A, Levin MJ. VZV T cell-mediated immunity. Current Top Microbiol Immunol 2010;342:341-57.
46. van Vollenhoven RF, Tanaka Y, Lamba M et al. THU0178 relationship between NK cell count and important safety events in rheumatoid arthritis patients treated with tofacitinib. Ann Rheum Dis 2015;74(Suppl 2):258-9.
47. Emery P, McInnes I, Genovese M et al. A7. 16 Characterisation of changes in lymphocyte subsets in baricitinib-treated patients with rheumatoid arthritis in two phase 3 studies. Ann Rheum Dis 2016;75(Suppl 1):A62.
48. Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol 2017;13:234-43.
49. Clark JD, Flanagan ME, Telliez JB. Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J Med Chem 2014;57:5023-38.
50. European Medicines Agency. EPAR Product Information. Olumiant EMEA/H/C/004085 -II/0001. http://www. ema. europa. eu/docs/en-GB/document-library/EPAR--- Product-Information/human/004085/WC500223723. pdf (12 March 2019, date last accessed).
51. European Medicines Agency. Xeljanz: EPAR Product Information. Xeljanz -EMEA/H/C/004214-IB/0001. http:// www. ema. europa. eu/docs/en-GB/document-library/ EPAR---Product-Information/human/004214/ WC500224911. pdf (12 March 2019, date last accessed).
52. Smitten AL, Choi HK, Hochberg MC et al. The risk of herpes zoster in patients with rheumatoid arthritis in the United States and the United Kingdom. Arthritis Rheum 2007;57:1431-38.
53. Winthrop KL, Park SH, Gul A, Cardiel MH. Tuberculosis and other opportunistic infections in tofacitinib-treated patients with rheumatoid arthritis. Ann Rheum Dis2016;75:1133-8.
54. Hodge JA, Kawabata TT, Krishnaswami S et al. The mechanism of action of tofacitinib an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol 2016;34:318-28.
55. Singh JA, Cameron C, Noorbaloochi S et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: A systematic review and meta-analysis. Lancet 2015;386:258-65.
56. Strangfeld A, Listing J, Herzer P et al. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents. JAMA 2009;301:737-44. 1766