Vaccination status of patients using anti-TNF therapy and the physicians’ behavior shaping the phenomenon: Mixed-methods approach

Autoři: Hussain Abdulrahman Al-Omar aff001;  Hadeel Magdy Sherif aff001;  Ahmed Yaccob Mayet aff001
Působiště autorů: Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



Anti-tumor necrosis factor (Anti-TNF) therapy improves the prognosis and reduces the morbidity and mortality associated with many chronic inflammatory autoimmune diseases. However, as it is linked to an increased infection risk, appropriate vaccination is required. The study aimed at investigating the vaccination status of patients receiving Anti-TNF therapy and physicians’ perceptions of and views about vaccinating these patients.


A sequential explanatory mixed-methods approach was used. The study comprised a quantitative, retrospective drug utilization review for determining institutional consumption of Anti-TNF therapy and an assessment of vaccination status in patients prescribed Anti-TNF therapy to audit physicians’ adherence to Anti-TNF therapy-related vaccination recommendations. Patient data from electronic medical records (EMRs) obtained from tertiary care hospitals between September 2015 and September 2017 were used. Further, a qualitative study using a phenomenographic approach with semi-structured interviews of 12 physicians was carried out to explore the physicians’ perceptions, views, and recommendations of vaccinating patients who are undergoing Anti-TNF therapy and identifying factors that may cause poor adherence to vaccination recommendations.


Forty-three of 310 patients receiving Anti-TNF therapy were vaccinated. Infliximab was the most frequently prescribed agent, accounting for 96.7% of total orders. Eight of the 12 physicians stated that they were aware of vaccination guidelines and seven viewed pre–Anti-TNF therapy vaccination as essential because of the high infection risk and claimed to incorporate it in their daily practice. Barriers to adherence included ignorance of recommendations, workload, vaccine unavailability, and advanced disease state.


Although the recommendations published by professional medical societies emphasized the importance of vaccination before initiating Anti-TNF therapy, few patients were vaccinated. Medical administration in hospitals should develop policies, procedures, and guidelines for vaccination; implement education programs for physicians and patients and procure vaccines in a timely way to improve their use.

Klíčová slova:

Health education and awareness – Inflammatory bowel disease – Influenza – Patients – Physicians – Qualitative studies – Vaccination and immunization – Vaccines


1. American Academy of Dermatology Work G, Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol. 2011;65(1):137–74. doi: 10.1016/j.jaad.2010.11.055 21306785

2. Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis. 2011;70(6):896–904. doi: 10.1136/ard.2011.151027 21540199

3. Dignass A, Lindsay JO, Sturm A, Windsor A, Colombel JF, Allez M, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012;6(10):991–1030. doi: 10.1016/j.crohns.2012.09.002 23040451

4. Gomollon F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1: Diagnosis and Medical Management. J Crohns Colitis. 2017;11(1):3–25. doi: 10.1093/ecco-jcc/jjw168 27660341

5. Hatemi G, Silman A, Bang D, Bodaghi B, Chamberlain AM, Gul A, et al. EULAR recommendations for the management of Behcet disease. Ann Rheum Dis. 2008;67(12):1656–62. doi: 10.1136/ard.2007.080432 18245110

6. Silva LC, Ortigosa LC, Benard G. Anti-TNF-alpha agents in the treatment of immune-mediated inflammatory diseases: mechanisms of action and pitfalls. Immunotherapy. 2010;2(6):817–33. doi: 10.2217/imt.10.67 21091114

7. Singh JA, Saag KG, Bridges SL Jr., Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1–26. doi: 10.1002/art.39480 26545940

8. Zhou Y, Lower EE, Li H, Baughman RP. Clinical management of pulmonary sarcoidosis. Expert Review of Respiratory Medicine. 2016;10(5):577–91. doi: 10.1586/17476348.2016.1164602 26959110

9. Callhoff J, Sieper J, Weiss A, Zink A, Listing J. Efficacy of TNFalpha blockers in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis: a meta-analysis. Ann Rheum Dis. 2015;74(6):1241–8. doi: 10.1136/annrheumdis-2014-205322 24718959

10. Lemos LL, de Oliveira Costa J, Almeida AM, Junior HO, Barbosa MM, Kakehasi AM, et al. Treatment of psoriatic arthritis with anti-TNF agents: a systematic review and meta-analysis of efficacy, effectiveness and safety. Rheumatol Int. 2014;34(10):1345–60. doi: 10.1007/s00296-014-3006-2 24728068

11. Mao EJ, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalisation and surgery in Crohn's disease and ulcerative colitis. Alimentary pharmacology & therapeutics. 2017;45(1):3–13.

12. Wiens A, Venson R, Correr CJ, Otuki MF, Pontarolo R. Meta-analysis of the efficacy and safety of adalimumab, etanercept, and infliximab for the treatment of rheumatoid arthritis. Pharmacotherapy. 2010;30(4):339–53.

13. Zhou Z, Dai C, Liu WX. Anti-TNF-A therapy about infliximab and adalimamab for the effectiveness in ulcerative colitis compared with conventional therapy: a meta-analysis. Hepato-gastroenterology. 2015;62(138):309–18. 25916055

14. Kantso B, Halkjaer SI, Thomsen OO, Belard E, Gottschalck IB, Jorgensen CS, et al. Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease. Vaccine. 2015;33(41):5464–9. doi: 10.1016/j.vaccine.2015.08.011 26275480

15. Minozzi S, Bonovas S, Lytras T, Pecoraro V, Gonzalez-Lorenzo M, Bastiampillai AJ, et al. Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis. Expert opinion on drug safety. 2016;15(sup1):11–34. doi: 10.1080/14740338.2016.1240783 27924643

16. Nguyen DL, Nguyen ET, Bechtold ML. Effect of Immunosuppressive Therapies for the Treatment of Inflammatory Bowel Disease on Response to Routine Vaccinations: A Meta-Analysis. Dig Dis Sci. 2015;60(8):2446–53. doi: 10.1007/s10620-015-3631-y 25796579

17. Shah ED, Farida JP, Siegel CA, Chong K, Melmed GY. Risk for Overall Infection with Anti-TNF and Anti-integrin Agents Used in IBD: A Systematic Review and Meta-analysis. Inflammatory bowel diseases. 2017;23(4):570–7. doi: 10.1097/MIB.0000000000001049 28230558

18. Germano V, Cattaruzza MS, Osborn J, Tarantino A, Rosa RD, Salemi S, et al. Infection risk in Rheumatoid Arthritis and Spondyloarthropathy patients under treatment with DMARDs, Corticosteroids and TNF-α antagonists. Journal of Translational Medicine. 2014;12(77):1–10.

19. Esteve M, Saro C, Gonzalez-Huix F, Suarez F, Forne M, Viver JM. Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis. Gut. 2004;53(9):1363–5. doi: 10.1136/gut.2004.040675 15306601

20. Martinez Montiel P, Antonio Solis J, Antonio Chirinos J, A Casis B, Sánchez F, Rodríguez S. Hepatitis B virus reactivation during therapy with etanercept in an HBsAg-negative and anti-HBs-positive patient. Liver International. 2008;28(5):718–20. doi: 10.1111/j.1478-3231.2007.01665.x 18433400

21. Nguyen CM, Bounthavong M, Mendes MAS, Christopher MLD, Tran JN, Kazerooni R, et al. Cost Utility of Tumour Necrosis Factor-α Inhibitors for Rheumatoid Arthritis. PharmacoEconomics. 2012;30(7):575–93. doi: 10.2165/11594990-000000000-00000 22640174

22. Spalding JR, Hay J. Cost Effectiveness of Tumour Necrosis Factor-α Inhibitors as First-Line Agents in Rheumatoid Arthritis. PharmacoEconomics. 2006;24(12):1221–32. doi: 10.2165/00019053-200624120-00006 17129076

23. Chaudrey K, Salvaggio M, Ahmed A, Mahmood S, Ali T. Updates in vaccination: Recommendations for adult inflammatory bowel disease patients. World J Gastroenterol. 2015;21(11):3184–96. doi: 10.3748/wjg.v21.i11.3184 25805924

24. Ferreira I, Isenberg D. Vaccines and biologics. Ann Rheum Dis. 2014;73(8):1446–54. doi: 10.1136/annrheumdis-2014-205246 24845388

25. Goyal A, Goyal K, Merola JF. Screening and vaccinations in patients requiring systemic immunosuppression: an update for dermatologists. Am J Clin Dermatol. 2015;16(3):179–95. doi: 10.1007/s40257-015-0124-x 25854805

26. Papadopoulou D, Sipsas NV. Comparison of national clinical practice guidelines and recommendations on vaccination of adult patients with autoimmune rheumatic diseases. Rheumatol Int. 2014;34(2):151–63. doi: 10.1007/s00296-013-2907-9 24322451

27. Rahier JF, Moutschen M, Van Gompel A, Van Ranst M, Louis E, Segaert S, et al. Vaccinations in patients with immune-mediated inflammatory diseases. Rheumatology (Oxford). 2010;49(10):1815–27. doi: 10.1093/rheumatology/keq183 20591834

28. van Assen S, Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2011;70(3):414–22. doi: 10.1136/ard.2010.137216 21131643

29. Wasan SK, Baker SE, Skolnik PR, Farraye FA. A practical guide to vaccinating the inflammatory bowel disease patient. Am J Gastroenterol. 2010;105(6):1231–8. doi: 10.1038/ajg.2009.733 20104218

30. Bonhomme A, Freling E, Reigneau M, Poreaux C, Valois A, Truchetet F, et al. [Vaccination status in psoriasis patients on immunosuppressant therapy (including biologics)]. Annales de dermatologie et de venereologie. 2017;144(2):92–9. doi: 10.1016/j.annder.2016.09.035 27771122

31. Feuchtenberger M, Kleinert S, Schwab S, Roll P, Scharbatke EC, Ostermeier E, et al. Vaccination survey in patients with rheumatoid arthritis: a cross-sectional study. Rheumatol Int. 2012;32(6):1533–9. doi: 10.1007/s00296-011-1808-z 21327432

32. Hua C, Morel J, Ardouin E, Ricard E, Foret J, Mathieu S, et al. Reasons for non-vaccination in French rheumatoid arthritis and spondyloarthritis patients. Rheumatology (Oxford). 2015;54(4):748–50. doi: 10.1093/rheumatology/keu531 25667433

33. Krasselt M, Ivanov J-P, Baerwald C, Seifert O. Low vaccination rates among patients with rheumatoid arthritis in a German outpatient clinic. Rheumatology International. 2016:1–9. doi: 10.1007/s00296-015-3319-9

34. Luque Ramos A, Hoffmann F, Callhoff J, Zink A, Albrecht K. Influenza and pneumococcal vaccination in patients with rheumatoid arthritis in comparison with age- and sex-matched controls: results of a claims data analysis. Rheumatol Int. 2016;36(9):1255–63. doi: 10.1007/s00296-016-3516-1 27372078

35. Malhi G, Rumman A, Thanabalan R, Croitoru K, Silverberg MS, Hillary Steinhart A, et al. Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake. J Crohns Colitis. 2015;9(6):439–44. doi: 10.1093/ecco-jcc/jjv064 25908717

36. Melmed GY, Ippoliti AF, Papadakis KA, Tran TT, Birt JL, Lee SK, et al. Patients with inflammatory bowel disease are at risk for vaccine-preventable illnesses. Am J Gastroenterol. 2006;101(8):1834–40. doi: 10.1111/j.1572-0241.2006.00646.x 16817843

37. Sandler DS, Ruderman EM, Brown T, Lee JY, Mixon A, Liss DT, et al. Understanding Vaccination Rates and Attitudes Among Patients With Rheumatoid Arthritis. The American Journal of Managed Care. 2016;22(3):161–7. 27023021

38. Wasan SK, Calderwood AH, Long MD, Kappelman MD, Sandler RS, Farraye FA. Immunization rates and vaccine beliefs among patients with inflammatory bowel disease: an opportunity for improvement. Inflammatory bowel diseases. 2014;20(2):246–50. doi: 10.1097/01.MIB.0000437737.68841.87 24374881

39. Wilckens V, Kannengiesser K, Hoxhold K, Frenkel C, Kucharzik T, Maaser C. The immunization status of patients with IBD is alarmingly poor before the introduction of specific guidelines. Scandinavian Journal of Gastroenterology. 2011;46(7–8):855–61. doi: 10.3109/00365521.2011.574734 21506630

40. Dahlgren L-O, Fallsberg M. Phenomenography as a qualitative approach in social pharmacy research. Journal of social and administrative pharmacy. 1991;8(4):150–6.

41. Braun V, Clarke V. Using thematic analysis in psychology. Qualitative research in psychology. 2006;3(2):77–101.

42. Gurvits GE, Lan G, Tan A, Weissman A. Vaccination practices in patients with inflammatory bowel disease among general internal medicine physicians in the USA. Postgrad Med J. 2017;93(1100):333–7. doi: 10.1136/postgradmedj-2016-134266 27733673

43. Yeung JH, Goodman KJ, Fedorak RN. Inadequate knowledge of immunization guidelines: a missed opportunity for preventing infection in immunocompromised IBD patients. Inflammatory bowel diseases. 2012;18(1):34–40. doi: 10.1002/ibd.21668 21337671

44. McCarthy EM, Azeez MA, Fitzpatrick FM, Donnelly S. Knowledge, attitudes, and clinical practice of rheumatologists in vaccination of the at-risk rheumatology patient population. JCR: Journal of Clinical Rheumatology. 2012;18(5):237–41. doi: 10.1097/RHU.0b013e3182611547 22832287

45. Gupta A, Macrae FA, Gibson PR. Vaccination and screening for infections in patients with inflammatory bowel disease: a survey of Australian gastroenterologists. Intern Med J. 2011;41(6):462–7. doi: 10.1111/j.1445-5994.2009.02114.x 19849740

46. Corace KM, Srigley JA, Hargadon DP, Yu D, MacDonald TK, Fabrigar LR, et al. Using behavior change frameworks to improve healthcare worker influenza vaccination rates: A systematic review. Vaccine. 2016;34(28):3235–42. doi: 10.1016/j.vaccine.2016.04.071 27155491

47. Walsh AJ, Weltman M, Burger D, Vivekanandarajah S, Connor S, Howlett M, et al. Implementing guidelines on the prevention of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2013;7(10):e449–56. doi: 10.1016/j.crohns.2013.02.019 23601754

48. Otsuka SH, Tayal NH, Porter K, Embi PJ, Beatty SJ. Improving herpes zoster vaccination rates through use of a clinical pharmacist and a personal health record. Am J Med. 2013;126(9):832 e1-6.

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