Инновационная терапия ревматических заболеваний и инфекции: современные аспекты. Часть 1. Ингибиторы фактора некроза опухоли-альфа

В современной ревматологии несомненного внимания заслуживает проблема коморбидных инфекций (КИ), актуальность которой обусловлена как нарушениями иммунитета в рамках фонового иммуновоспалительного ревматического заболевания (ИВРЗ), так и необходимостью применения препаратов с иммуносупрессивным действием. Применение инновационных генно-инженерных биологических препаратов и таргетных базисных противовоспалительных препаратов позволило достичь больших успехов в лечении ИВРЗ. Однако с накоплением мирового клинического опыта стало понятно, что применение данных лекарственных средств сопровождается увеличением риска развития инфекционных осложнений (включая тяжёлые) различной этиологии и локализации. Представление современных данных о частоте и локализации основных КИ у больных ИВРЗ при лечении указанными препаратами является целью настоящего нарративного (описательного) обзора, первая часть которого посвящена вопросам инфекционных осложнений терапии ингибиторами фактора некроза опухоли-альфа.

1. Krabbe S, Grøn KL, Glintborg B, Nørgaard M, Mehnert F, Jarbøl DE, et al. Risk of serious infections in arthritis patients treated with biological drugs: a matched cohort study and development of prediction model. Rheumatology (Oxford). 2021; 60 (8): 3834–3844. doi: 10.1093/rheumatology/keaa876

2. Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P, et al; Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset Study Group. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum. 2004; 50 (11): 3432–3443. doi: 10.1002/art.20568.

3. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, et al; Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. 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. 2000; 343 (22): 1594–1602. doi: 10.1056/NEJM200011303432202.

4. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, et al; Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum. 2004; 50 (4): 1051–1065. doi: 10.1002/art.20159.

5. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 2003; 48 (1): 35–45. doi: 10.1002/art.10697.

6. Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, et al. Adalimumab, a fully human anti tumor necrosis factoralpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol. 2003; 30 (12): 2563–2571.

7. van de Putte LB, Atkins C, Malaise M, Sany J, Russell AS, van Riel PL, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004; 63 (5): 508–516. doi: 10.1136/ard.2003.013052.

8. Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, 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. 2004; 50 (5): 1400–1411. doi: 10.1002/art.20217.

9. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006; 54 (1): 26–37. doi: 10.1002/art.21519.

10. van Riel PL, Taggart AJ, Sany J, Gaubitz M, Nab HW, Pedersen R, et al; Add Enbrel or Replace Methotrexate Study Investigators. Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with an inadequate response to methotrexate: the ADORE study Ann Rheum Dis. 2006; 65 (11): 1478–1483. doi: 10.1136/ard.2005.043299.

11. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004; 363 (9410): 675–681. doi: 10.1016/S0140-6736(04)15640-7.

12. Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002; 46 (6): 1443–1450. doi: 10.1002/art.10308.

13. Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, et al. Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FОРWARD Study. Ann Rheum Dis. 2009 Jun; 68 (6): 789–96. doi: 10.1136/ard.2008.099010.

14. Kay J, Matteson EL, Dasgupta B, Nash P, Durez P, Hall S, et al. Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, doseranging study. Arthritis Rheum. 2008; 58 (4): 964–75. doi: 10.1002/art.23383.

15. Emery P, Fleischmann RM, MОРeland LW, Hsia EC, Strusberg I, Durez P, et al. Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexatenaive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebocontrolled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum. 2009 Aug; 60 (8): 2272–83. doi: 10.1002/art.24638.

16. Emery P, Fleischmann RM, Doyle MK, Strusberg I, Durez P, Nash P, et al. Golimumab, a human anti–tumor necrosis factor monoclonal antibody, injected subcutaneously every 4 weeks in patients with active rheumatoid arthritis who had never taken methotrexate: 1-year and 2-year clinical, radiologic, and physical function findings of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Care Res (Hoboken). 2013; 65 (11): 1732–42. doi: 10.1002/acr.22072.

17. Keystone E, Heijde Dv, Mason D Jr, Landewé R, Vollenhoven RV, Combe B, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2008; 58 (11): 3319–29. doi: 10.1002/art.23964.

18. Smolen J, Landewé RB, Mease P, Brzezicki J, Mason D, Luijtens K, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis. 2009; 68 (6): 797–804. doi: 10.1136/ard.2008.101659.

19. Fleischmann R, Vencovsky J, van Vollenhoven RF, Borenstein D, Box J, Coteur G, et al. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis. 2009; 68 (6): 805–11. doi: 10.1136/ard.2008.099291.

20. Weinblatt ME, Fleischmann R, Huizinga TW, Emery P, Pope J, Massarotti EM, et al. Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study. Rheumatology (Oxford). 2012; 51 (12): 2204–14. doi: 10.1093/rheumatology/kes150.

21. Choy E, McKenna F, Vencovsky J, Valente R, Goel N, Vanlunen B, et al. Certolizumab pegol plus MTX administered every 4 weeks is effective in patients with RA who are partial responders to MTX. Rheumatology (Oxford). 2012 Jul; 51 (7): 1226–34. doi: 10.1093/rheumatology/ker519.

22. Yamamoto K, Takeuchi T, Yamanaka H, Ishiguro N, Tanaka Y, Eguchi K, et al. Efficacy and safety of certolizumab pegol without methotrexate co-administration in Japanese patients with active rheumatoid arthritis: the HIKARI randomized, placebo-controlled trial. Mod Rheumatol. 2014 Jul; 24 (4): 552–60. doi: 10.3109/14397595.2013.843764.

23. Smolen JS, Emery P, Ferraccioli GF, Samborski W, Berenbaum F, Davies ОР, et al. Certolizumab pegol in rheumatoid arthritis patients with low to moderate activity: the CERTAIN double-blind, randomised, placebo-controlled trial. Ann Rheum Dis. 2015; 74 (5): 843–50. doi: 10.1136/annrheumdis-2013-204632.

24. Salliot C, Gossec L, Ruyssen-Witrand A, Luc M, Duclos M, Guignard S, Dougados M. Infections during tumour necrosis factor-alpha blocker therapy for rheumatic diseases in daily practice: a systematic retrospective study of 709 patients. Rheumatology. 2007; 46 (2): 327–334. doi: 10.1093/rheumatology/kel236.

25. Kroesen S, Widmer AF, Tyndall A, Hasler P. Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy. Rheumatology (Oxford). 2003; 42 (5): 617–621. doi: 10.1093/rheumatology/keg263.

26. Curtis JR, Patkar N, Xie A, Martin C, Allison JJ, Saag M, et al. Risk of serious bacterial infections among rheumatoid arthritis patients exposed to tumor necrosis factor alpha antagonists. Arthritis Rheum. 2007; 56 (4): 1125–1133. doi: 10.1002/art.22504.

27. Dixon WG, Symmons DP, Lunt M, Watson KD, Hyrich KL, Silman AJ; British Society for Rheumatology Biologics Register Control Centre Consortium; British Society for Rheumatology Biologics Register. Serious infection following anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis: Lessons from interpreting data from observational studies. Arthritis Rheum. 2007; 56 (9): 2896–2904. doi: 10.1002/art.22808.

28. Galloway JB, Hyrich KL, Mercer LK, Dixon WG, Fu B, Ustianowski AP, et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology. 2011; 50 (1): 124–131. doi: 10.1093/rheumatology/keq242.

29. Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, StoyanovaScholz M, et al. Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum. 2005; 52 (11): 3403–3412. doi: 10.1002/art.21386.

30. Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology. 2013; 52 (1): 53–61. doi: 10.1093/rheumatology/kes305.

31. RABBIT — Rheumatoide Arthritis: Beobachtung der Biologika-Therapie: Risk of Infections. URL https://biologika-register.de/en/rabbit/results/risk-of-infections. Accessed 11th March 2026.

32. Askling J, Fored CM, Brandt L, Baecklund E, Bertilsson L, Feltelius N, et al. Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists. Ann Rheum Dis. 2007; 66 (10): 1339–1344. doi:10.1136/ard.2006.062760.

33. Atzeni F, Sarzi-Puttini P, Botsios C, Carletto A, Cipriani P, Favalli EG. et al. Long-term anti-TNF therapy and the risk of serious infections in a cohort of patients with rheumatoid arthritis: comparison of adalimumab, etanercept and infliximab in the GISEA registry. Autoimmun Rev. 2012; 12 (2): 225–9. doi: 10.1016/j.autrev.2012.06.008.

34. van Dartel SA, Fransen J, Kievit W, Dutmer EA, Brus HL, Houtman NM, et al. Predictors for the 5-year risk of serious infections in patients with rheumatoid arthritis treated with anti-tumour necrosis factor therapy: a cohort study in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. Rheumatology (Oxford). 2013; 52 (6): 1052–1057. doi: 10.1093/rheumatology/kes413.

35. Kay J, Fleischmann R, Keystone E, Hsia EC, Hsu B, Mack M, et al. Golimumab 3-year safety update: an analysis of pooled data from the long-term extensions of randomised, double-blind, placebo-controlled trials conducted in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. Ann Rheum Dis. 2015; 74 (3): 538–46. doi: 10.1136/annrheumdis-2013-204195.

36. Keystone E, Genovese MC, Hall S, Miranda PC, Bae SC, Han C, et al. Five-year safety and efficacy of golimumab in patients with active rheumatoid arthritis despite prior treatment with methotrexate: final study results of the phase 3, randomized placebo-controlled goforward trial. Ann Rheum Dis. 2013; 72 (Suppl 3): 867–868. doi: 10.1136/annrheumdis-2013-eular.2589.

37. Bykerk VP,Cush J,Winthrop K,Calabrese L, Lortholary O, de LonguevilleM, et al. Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an integrated analysis from clinical trials. Ann Rheum Dis. 2015; 74 (1): 96–103. doi: 10.1136/annrheumdis-2013-203660.

38. Frisell T, Bower H, Morin M, Baecklund E, Di Giuseppe D, Delcoigne B, et al. Safety of biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis as used in clinical practice: results from the ARTIS programme. Ann Rheum Dis. 2023 May; 82 (5): 601–610. doi: 10.1136/ard-2022-223762.

39. Liu X, Wei C, Wang J, Li M. Effect of tumour necrosis factor-a inhibitors exposure on surgical site infections in rheumatoid arthritis patients undergoing elective orthopaedic surgery: a meta-analysis. Int Wound J. 2024; 21 (1): e14538. doi: 10.1111/iwj.14538.

40. Xiao R, Tang P, Zhou J, Zheng W, Cao Y, Zhu Y, et al. Safety of TNF-α inhibitОРs therapy in patients with rheumatoid arthritis: an umbrella review. EClinicalMedicine. 2025 Sep 10; 88: 103488. doi: 10.1016/j.eclinm.2025.103488.

41. Wallis D, Thavaneswaran A, Haroon N, Ayearst R, Inman RD. Tumour necrosis factor inhibitor therapy and infection risk in axial spondyloarthritis: results from a longitudinal observational cohort. Rheumatology (Oxford). 2015; 54 (1): 152–6. doi: 10.1093/rheumatology/keu255.

42. Atzeni F, Sebastiani M, Panetta V, Salaffi F, Marchesoni A, Ramonda R, et al. Anti-TNF therapy is associated with an increase in serious infections in patients with spondyloarthritis (SpA),especially during the first 12 months of treatment: results from the GISEA registry. Arthritis Rheum. 2015; 67 (Suppl 10): 3432–3. http://acrabstracts.org/abstract/anti-tnf-therapy-is-associated-with-an-increase-in-serious-infections-in-patients-with-spondyloarthritis-spa-especially-during-thefirst-12-monts-of-treatment-results-from-the-gisea-registry

43. Glintborg B, Østergaard M, Dreyer L, Krogh NS, Tarp U, Hansen MS, et al. Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor � therapy: results from the nationwide Danish DANBIO registry. Arthritis Rheum. 2011; 63 (2): 382–90. doi: 10.1002/art.30117.

44. Saad AA, Ashcroft DM, Watson KD, Symmons DP, Noyce PR, Hyrich KL. BSRBR. Efficacy and safety of anti-TNF therapies in psoriatic arthritis: an observational study from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2010; 49 (4): 697–705. doi: 10.1093/rheumatology/kep423.

45. Mease P, Deodhar A, Fleischmann R, Wollenhaupt J, Gladman D, Leszczyński P, et al. Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure. RMD Open. 2015; 1 (1): e000119. doi: 10.1136/rmdopen-2015-000119.

46. Kavanaugh A, McInnes IB, Mease P, Krueger GG, Gladman D, van der Heijde D, et al. Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of a randomised, placebo-controlled trial (the GO-REVEAL study). Ann Rheum Dis. 2014; 73 (9): 1689–94. doi: 10.1136/annrheumdis-2013-204902.

47. Minozzi S, Bonovas S, Lytras T, Pecoraro V, González-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 Opin Drug Saf. 2016; 15 (Suppl 1): 11–34. doi: 10.1080/14740338.2016.1240783.

48. Yu X, Zhong J, Zhuang X, Lin Z, Fu H, Zhang Y. Drug-associated infections and infestations in older adults with tumor necrosis factoralpha inhibitors: a real-world retrospective and pharmacovigilance study. Front. Pharmacol. 2025; 16: 1533902. doi: 10.3389/fphar.2025.1533902.

49. Макарова Н.В. Туберкулёзная инфекция у ревматологических больных, получающих ингибиторы фактора некроза опухоли — альфа. Туберкулёз и социально значимые заболевания. 2025; 13 (1): 59–73. doi: https://doi.org/10.54921/2413-0346-2025-13-1-59-73.

50. Keane J, Gershon S, Wise RP, Mirabile–Levens E, Kasznica J, Schwieterman WD, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha–neutralizing agent. N Engl J Med. 2001; 345 (15): 1098–1104. doi: 10.1056/NEJMoa011110.

51. Gomez–Reino JJ, Carmona L, Valverde VR, Mola EM, Montero MD; BIOBADASER Group. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active–surveillance report. Arthritis Rheum. 2003;48 (8): 2122–2127. doi: 10.1002/art.11137.

52. Askling J, Fored CM, Brandt L, Baecklund E, Bertilsson L, Coster L, et al. Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden. Arthritis Rheum. 2005; 52 (7): 1986–1992. doi: 10.1002/art.21137.

53. Tubach F, Salmon D, Ravaud P, Allanore Y, Goupille P, Bréban M, et al. Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry. Arthritis Rheum. 2009; 60 (7): 1884–94. doi: 10.1002/art.24632.

54. Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A, et al. Drug specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis. 2010; 69 (3): 522–8. doi: 10.1136/ard.2009.118935.

55. Лукина Г.В., Борисов С.Е. Скрининг и мониторинг туберкулёзной инфекции у больных ревматическими заболеваниями, получающих генно-инженерные биологические препараты. В кн.: Российские клинические рекомендации. Ревматология. Под ред. Е. Л. Насонова. М.: ГЭОТАР-Медиа, 2020; 396–412.

56. Скрининг и мониторинг туберкулёзной инфекции у больных, получающих иммуносупрессивные генно-инженерные биологические препараты: методические рекомендации: Московский научно-практический центр борьбы с туберкулёзом: составители: С. Е. Борисов и др. М.: 2019; 33.

57. Lane MA, McDonald JR, Zeringue AL, Caplan L, Curtis JR, Ranganathan P, Eisen SA. TNF-α antagonist use and risk of hospitalization for infection in a national cohort of veterans with rheumatoid arthritis. Medicine (Baltimore). 2011; 90 (2): 139–145. doi: 10.1097/MD.0b013e318211106a.

58. Watanabe K, Sakai R, Koike R, Sakai F, Sugiyama H, Tanaka M, et al. Clinical characteristics and risk factors for Pneumocystis jirovecii pneumonia in patients with rheumatoid arthritis receiving adalimumab: a retrospective review and case-control study of 17 patients. Mod Rheumatol. 2013; 23 (6): 1085–93. doi: 10.1007/s10165-012-0796-5.

59. Koike T, Harigai M, Ishiguro N, Inokuma S, Takei S, Takeuchi T, et al. Safety and effectiveness of adalimumab in Japanese rheumatoid arthritis patients: postmarketing surveillance report of 7740 patients. Mod Rheumatol. 2014; 24 (3): 390–8. doi: 10.3109/14397595.2013.843760.

60. Wissmann G, Morilla R, Martín-Garrido I, Friaza V, Respaldiza N, Povedano J, et al. Pneumocystis jirovecii colonization in patients treated with infliximab. Eur J Clin Invest. 2011 Mar; 41 (3): 343–8. doi: 10.1111/j.1365-2362.2010.02415.x.

61. Ha R, Keynan Y, Rueda ZV. Increased susceptibility to pneumonia due to tumour necrosis factor inhibition and prospective immune system rescue via immunotherapy. Front Cell Infect Microbiol. 2022 Sep 7; 12: 980868. doi: 10.3389/fcimb.2022.980868.

62. Stamp LK, Hurst M. Is there a role for consensus guidelines for P. jiroveci pneumonia prophylaxis in immunosuppressed patients with rheumatic diseases? J Rheumatol. 2010; 37 (4): 686–688. doi: 10.3899/jrheum.091426.

63. Ridola L, Zullo A, Laganà B, Lorenzetti R, Migliore A, Pica R, et al. Hepatitis B (HBV) reactivation in patients receiving biologic therapy for chronic inflammatory diseases in clinical practice. Ann Ist Super Sanita. 2021; 57 (3): 244–248. doi: 10.4415/ANN_21_03_08.

64. Salajegheh P, Yazdi F, Salajegheh A. Hepatitis B reactivation linked to tumor necrosis factor-α inhibitors in rheumatoid arthritis: a systematic review and meta-analysis. Cell Mol Biol (Noisy-le-grand). 2025; 71 (11): 74–85. doi: 10.14715/cmb/2025.71.11.10.

65. Iannone F, La Montagna G, Bagnato G, Gremese E, Giardina A, Lapadula G. Safety of etanercept and methotrexate in patients with rheumatoid arthritis and hepatitis C virus infection: a multicenter randomized clinical trial. J Rheumatol. 2014; 41 (2): 286–92. doi: 10.3899/jrheum.130658.

66. Sebastiani M, Milazzo L, Atzeni F, Vacchi C, Manfredi A, Quartuccio L, et al. Italian consensus recommendations for the management of hepatitis C infection in patients with rheumatoid arthritis. Mod Rheumatol. 2019 Nov; 29 (6): 895–902. doi: 10.1080/14397595.2018.1558918.

67. Inanc N., Direskeneli H. Serious infections under treatment with TNF-alpha antagonists compared to traditional DMARDs in patients with rheumatoid arthritis. Rheumatol Int. 2006; 27 (1): 67–71. doi: 10.1007/s00296-006-0165-9.

68. McDonald JR, Zeringue AL, Caplan L, Ranganathan P, Xian H, Burroughs TE, et al. Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis Clin Infect Dis. 2009; 48 (10): 1364–1371. doi: 10.1086/598331.69.

69. Strangfeld A, Listing J, Herzer P, Liebhaber A, Rockwitz K, Richter C, Zink A. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents. JAMA. 2009; 301 (7): 737–744. doi: 10.1001/jama.2009.146.

70. Che H, Lukas C, Morel J, Combe B. Risk of herpes/herpes zoster during anti-tumor necrosis factor therapy in patients with rheumatoid arthritis. Systematic review and meta-analysis. Joint Bone Spine. 2014; 81 (3): 215–221. doi: 10.1016/j.jbspin.2013.07.009.

71. Yun H., Xie F., Delzell E.S., Chen L., Levitan E., Lewis J, et al. Comparative risk of Herpes zoster among RA patients switching biologics in the U.S. care medical program. Arthritis Rheum 2013; 65 (10 Suppl): 1179. https://acrabstracts.org/abstract/comparative-risks-of-herpes-zosteramong-ra-patients-switching-biologics-in-the-u-s-medicare-program/

72. Davis M.R., Thompson G.R., Patterson T.F. Fungal infections potentiated by biologics. Infect Dis Clin North Am. 2020; 34 (2): 389–411. doi: 10.1016/j.idc.2020.02.010.

73. Hsu CY, Ko CH, Wang JL, Hsu TC, Lin CY. Comparing the burdens of opportunistic infections among patients with systemic rheumatic diseases: a nationally representative cohort study. Arthritis Res Ther. 2019; 21 (1): 211. doi: 10.1186/s13075-019-1997-5.

74. Atzeni F., Sarzi-Puttini P., Sebastiani M., Panetta V, Salaffi F, Iannone F, et al. Rate of serious infections in spondyloarthropathy patients treated with antitumour necrosis factor drugs: a survey from the Italian registry GISEA. Clin Exp Rheumatol. 2019; 37 (4): 649–55.

75. Hennessee I, Benedict K, Bahr NC, Lipner SR, Gold JAW. Incidence and risk factors for invasive fungal infections in patients initiating tumor necrosis factor–alpha inhibitors for inflammatory bowel disease and rheumatoid arthritis. Clin Infect Dis. 2025; 80 (2): 364–366. doi: 10.1093/cid/ciae444.

76. Crum NF, Lederman ER, Wallace MR. Infections associated with tumor necrosis factor-alpha antagonists. Medicine (Baltimore). 2005; 84 (5): 291–302. doi: 10.1097/01.md.0000180044.19285.9a.

77. Barbosa LSP, Ely MM, Salomé TM, de Almeida de Souza GH, Santos DA, Bastos RW, Rossato L. Fungal infections associated with TNF-Inhibitors: a 20-year of a systematic review fungal infections and TNF-inhibitors. Mycoses. 2025; 68 (3): e70040. doi: 10.1111/myc.70040.

78. Leding C, Meddis A, Holler JG, Burisch J, Kragstrup TW, Skov L, Benfield T. Tumour necrosis factor-� inhibitors, immune-mediated inflammatory diseases, and bloodstream infections: results from a nationwide casecontrol study. Clin Microbiol Infect. 2026: 32 (6); 951–958. doi: 10.1016/j.cmi.2026.02.005.

79. Goodman SM, Springer BD, Chen AF, Davis M, Fernandez DR, Figgie M, et al. 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty. Arthritis Rheum. 2022; 74 (9): 1464–1473. doi: 10.1002/art.42140.

80. Furer V, Rondaan C, Heijstek MW, Agmon-Levin N, van Assen S, Bijl M, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020; 79 (1): 39–52. doi: 10.1136/annrheumdis-2019-215882.

81. Bass AR, Chakravarty E, Akl EA, Bingham CO, Calabrese L, Cappelli LC, et al. 2022 American College of Rheumatology Guideline for vaccinations in patients with rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2023; 75 (3): 333–348. doi: 10.1002/art.42386.

82. Минздрав Российской Федерации. Иммунизация иммунокомпрометированных пациентов. Методические рекомендации. 2025; 220. Дата обращения: 12 марта 2026 г. URL: https://edu.nasci.ru/libs/files/mr_immunizaciya_immunokomprometirovannyh_pacientov.pdf. Accessed: 12th March 2026.