Dynamics of patient reported outcomes during the use various biological disease-modifying antirheumatic drugs for rheumatoid arthritis

One of the main tasks of modern complex therapy of rheumatoid arthritis (RA) is to improve the quality of life of patients. To do this, it is necessary not only to achieve remission or low activity, but also to successfully control the main, most painful, manifestations of the disease. Therefore, when evaluating the results of RA treatment, the dynamics of not only standard indices (DAS28 (Disease Activity Score 28), CDAI (Clinical Disease Activity Index), SDAI (Simplified Disease Activity Index)), but also the so-called “patient reported outcomes” (PRO) – a patient’s global assessment of disease activity (PGA), pain, functional disorders and fatigue.

This review examines the effect of one of the main classes of anti–rheumatic drugs - biological disease-modifying antirheumatic drugs (bDMARDs) on the PROs. The results of a series of randomized controlled trials are presented, in which changes in PROs were studied using various tumor necrosis factor α (TNF-α) inhibitors, abatacept T-lymphocyte co-stimulation inhibitor, rituximab CD20 inhibitor and interleukin (IL) 6 inhibitors.

The use of bDMARDs in combination with methotrexate (MTX) provides a reduction in PGA and pain by 50-60%, functional disorders according to HAQ (Health Assessment Questionnaire) and fatigue according to FACIT-F (Functional Assessment of Chronic Illness Therapy – Fatigue) – by 15-30%. B DMARDs monotherapy (with the exception of the effect of tocilizumab on HAQ) does not exceed MTX monotherapy in its effect on PROs. Monotherapy with tocilizumab provides more favorable dynamics of PGA and pain than monotherapy with TNF-α inhibitors. An important advantage of IL-6 inhibitors is the rapid achievement of a clinical effect, which is noted already in the first 2 weeks after the first administration of the drug. 

1. Nasonov EL. Pharmacotherapy for rheumatoid arthritis: Russian and international guidelines. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2016;54(5):557-571 (In Russ.). doi: 10.14412/1995-4484-2016-557-571

2. Sparks JA. Rheumatoid arthritis. Ann Intern Med. 2019;170(1): ITC1-ITC16. doi: 10.7326/AITC201901010

3. Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-699. doi: 10.1136/annrheumdis-2019-216655

4. Scott IC, Ibrahim F, Panayi G, Cope AP, Garrood T, Vincent A, et al.; TITRATE Programme Investigators. The frequency of remission and low disease activity in patients with rheumatoid arthritis, and their ability to identify people with low disability and normal quality of life. Semin Arthritis Rheum. 2019;49(1):20- 26. doi: 10.1016/j.semarthrit.2018.12.006

5. Gamboa-Cárdenas RV, Ugarte-Gil MF, Loreto M, Sacnun MP, Saurit V, Cardiel MH, et al. Clinical predictors of remission and low disease activity in Latin American early rheumatoid arthritis: Data from the GLADAR cohort. Clin Rheumatol. 2019;38(10): 2737-2746. doi: 10.1007/s10067-019-04618-x

6. Thomas K, Lazarini A, Kaltsonoudis E, Drosos A, Papalopoulos I, Sidiropoulos P, et al. Treatment patterns and achievement of the treat-to-target goals in a real-life rheumatoid arthritis patient cohort: Data from 1317 patients. Ther Adv Musculoskelet Dis. 2020;12:1759720X20937132. doi: 10.1177/1759720X20937132

7. Zhao SS, Kearlsey-Fleet L, Bosworth A, Watson K; BSRBR-RA Contributors Group, Hyrich KL. Effectiveness of sequential biologic and targeted disease modifying anti-rheumatic drugs for rheumatoid arthritis. Rheumatology (Oxford). 2022 Mar 31: keac190. doi: 10.1093/rheumatology/keac190

8. Mucke J, Krusche M, Burmester GR. A broad look into the future of rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2022;14:1759720X221076211. doi: 10.1177/1759720X221076211

9. Fujiwara T, Kondo M, Yamada H, Haraguchi A, Fujimura K, Sakuraba K, et al. Factors affecting patient satisfaction related to cost and treatment effectiveness in rheumatoid arthritis: Results from the multicenter observational cohort study, FRANK Registry. Arthritis Res Ther. 2022;24(1):53. doi: 10.1186/s13075-022-02746-5

10. Haridoss M, Bagepally BS, Natarajan M. Health-related quality of life in rheumatoid arthritis: Systematic review and meta-analysis of EuroQoL (EQ-5D) utility scores from Asia. Int J Rheum Dis. 2021;24(3):314-326. doi: 10.1111/1756-185X.14066

11. Jørgensen TS, Turesson C, Kapetanovic M, Englund M, Turkiewicz A, Christensen R, et al. EQ-5D utility, response and drug survival in rheumatoid arthritis patients on biologic monotherapy: A prospective observational study of patients registered in the south Swedish SSATG registry. PLoS One. 2017;12(2):e0169946. doi: 10.1371/journal.pone.0169946

12. Combe B, Rincheval N, Berenbaum F, Boumier P, Cantagrel A, Dieude P, et al. Current favourable 10-year outcome of patients with early rheumatoid arthritis: Data from the ESPOIR cohort. Rheumatology (Oxford). 2021;60(11):5073-5079. doi: 10.1093/rheumatology/keab398

13. Strand V. Patient-reported outcomes and realistic clinical endpoints for JAK inhibitors in rheumatoid arthritis. Expert Rev Clin Immunol. 2022;18(3):193-205. doi: 10.1080/1744666X.2022.2049242

14. Taylor PC, Woods M, Rycroft C, Patel P, Blanthorn-Hazell S, Kent T, et al. Targeted literature review of current treatments and unmet need in moderate rheumatoid arthritis in the United Kingdom. Rheumatology (Oxford). 2021;60(11):4972-4981. doi: 10.1093/rheumatology/keab464

15. Nasonov EL, Olyunin YuA, Lila AM. Rheumatoid arthritis: The problems of remission and therapy resistance. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2018;56(3):363-271 (In Russ.). doi: 10.14412/1995-4484-2018-263-271

16. Gordeev AV, Olyunin YuA, Galushko EA, Zotkin EG, Lila AM. Difficult-to-treat rheumatoid arthritis. What is it? Modern Rheumatology Journal. 2021;15(5):7-11 (In Russ.). doi: 10.14412/1996-7012-2021-5-7-11

17. Berghea F, Berghea CE, Zaharia D, Trandafir AI, Nita EC, Vlad VM. Residual pain in the context of selecting and switching biologic therapy in inflammatory rheumatic diseases. Front Med (Lausanne). 2021;8:712645. doi: 10.3389/fmed.2021.712645

18. Michaud K, Pope J, van de Laar M, Curtis JR, Kannowski C, Mitchell S, et al. Systematic literature review of residual symptoms and an unmet need in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(11):1606-1616. doi: 10.1002/acr.24369

19. Navarro-Millán I, Chen L, Greenberg JD, Pappas DA, Curtis JR. Predictors and persistence of new-onset clinical remission in rheumatoid arthritis patients. Semin Arthritis Rheum. 2013;43(2):137- 143. doi: 10.1016/j.semarthrit.2013.02.002

20. Carpenter L, Barnett R, Mahendran P, Nikiphorou E, Gwinnutt J, Verstappen S, et al. Secular changes in functional disability, pain, fatigue and mental well-being in early rheumatoid arthritis. A longitudinal meta-analysis. Semin Arthritis Rheum. 2020;50(2):209- 219. doi: 10.1016/j.semarthrit.2019.08.006

21. Jones B, Flurey CA, Proudman S, Ferreira RJO, Voshaar M, Hoogland W, et al. Considerations and priorities for incorporating the patient perspective on remission in rheumatoid arthritis: An OMERACT 2020 special interest group report. Semin Arthritis Rheum. 2021;51(5):1108-1112. doi: 10.1016/j.semarthrit.2021.07.010

22. Espinoza G, Maldonado G, Narvaez J, Guerrero R, Citera G, Rios C. Beyond rheumatoid arthritis evaluation: What are we missing? Open Access Rheumatol. 2021;13:45-55. doi: 10.2147/OARRR.S298393

23. Kilic L, Erden A, Bingham CO 3rd, Gossec L, Kalyoncu U. The reporting of patient-reported outcomes in studies of patients with rheumatoid arthritis: A systematic review of 250 articles. J Rheumatol. 2016;43(7):1300-1305. doi: 10.3899/jrheum.151177

24. Strand V, Kaine J, Alten R, Wallenstein G, Diehl A, Shi H, et al. Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: A post hoc analysis of data from phase 3 trials of tofacitinib. Arthritis Res Ther. 2020;22(1):243. doi: 10.1186/s13075-020-02324-7

25. Amirdzhanova VN, Kaigorodtseva EYu, Goryachev DV, Lukina GV, Pozdnyakova ES, Sigidin YA, et al. Russian registry of Infliximab. Impact of therapy on the functional status of patients with rheumatoid arthritis. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2010;48(6):23-30 (In Russ.). doi: 10.14412/1995-4484-2010-819

26. 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

27. Strand V, Singh JA. Improved health-related quality of life with effective disease-modifying antirheumatic drugs: Evidence from randomized controlled trials. Am J Manag Care. 2008;14(4): 234-254.

28. Karateev DE. Etanercept (review of international studies). Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2009;47(5):52-57 (In Russ.) doi: 10.14412/1995-4484-2009-589

29. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999;340(4):253-259. doi: 10.1056/NEJM199901283400401

30. Moreland LW, Schiff MH, Baumgartner SW, Tindall EA, Fleischmann RM, Bulpitt KJ, et al. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med. 1999; 130(6):478-486. doi: 10.7326/0003-4819-130-6-199903160-00004

31. Kekow J, Moots RJ, Emery P, Durez P, Koenig A, Singh A, et al. Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission: The COMET trial. Ann Rheum Dis. 2010;69(1):222-225. doi: 10.1136/ard.2008.102509

32. Van der Heijde D, Klareskog L, Rodriguez-Valverde V, Codreanu C, Bolosiu H, Melo-Gomes J, et al.; TEMPO Study Investigators. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum. 2006;54(4):1063-1074. doi: 10.1002/art.21655

33. Bae SC, Gun SC, Mok CC, Khandker R, Nab HW, Koenig AS, et al. Improved health outcomes with etanercept versus usual DMARD therapy in an Asian population with established rheumatoid arthritis. BMC Musculoskelet Disord. 2013;14:13. doi: 10.1186/1471-2474-14-13

34. Strand V, Rentz AM, Cifaldi MA, Chen N, Roy S, Revicki D. Health-related quality of life outcomes of adalimumab for patients with early rheumatoid arthritis: Results from a randomized multicenter study. J Rheumatol. 2012;39(1):63-72. doi: 10.3899/jrheum.101161

35. 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

36. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human antitumor 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

37. Yount S, Sorensen MV, Cella D, Sengupta N, Grober J, Chartash EK. Adalimumab plus methotrexate or standard therapy is more effective than methotrexate or standard therapies alone in the treatment of fatigue in patients with active, inadequately treated rheumatoid arthritis. Clin Exp Rheumatol. 2007;25(6):838-846.

38. Nasonov EL, Amirdzhanova VN. New aspects of the pharmacotherapy of rheumatoid arthritis: A focus on certolizumab pegol. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2011;49(1):40-49 (In Russ.). doi: 10.14412/1995-4484-2011-866

39. 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):805-811. doi: 10.1136/ard.2008.099291

40. Strand V, Mease P, Burmester GR, Nikaï E, Coteur G, van Vollenhoven R, et al. Rapid and sustained improvements in healthrelated quality of life, fatigue, and other patient-reported outcomes in rheumatoid arthritis patients treated with certolizumab pegol plus methotrexate over 1 year: Results from the RAPID 1 randomized controlled trial. Arthritis Res Ther. 2009;11(6):R170. doi: 10.1186/ar2859

41. Strand V, Smolen JS, van Vollenhoven RF, Mease P, Burmester GR, Hiepe F, et al. Certolizumab pegol plus methotrexate provides broad relief from the burden of rheumatoid arthritis: Analysis of patient-reported outcomes from the RAPID 2 trial. Ann Rheum Dis. 2011;70(6):996-1002. doi: 10.1136/ard.2010.143586

42. Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, et al.; GO-FORWARD Study. Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: The GO-FORWARD Study. Ann Rheum Dis. 2009;68(6):789-796. doi: 10.1136/ard.2008.099010

43. Smolen JS, Kay J, Doyle MK, Landewé R, Matteson EL, Wollenhaupt J, et al.; GO-AFTER study investigators. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): A multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009;374(9685):210-221. doi: 10.1016/S0140-6736(09)60506-7

44. Emery P, Fleischmann RM, Moreland 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 methotrexate-naive patients with active rheumatoid arthritis: Twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum. 2009;60(8):2272-2283. doi: 10.1002/art.24638

45. Tanaka Y, Harigai M, Takeuchi T, Yamanaka H, Ishiguro N, Yamamoto K, et al.; GO-FORTH study group. Clinical efficacy, radiographic progression, and safety through 156 weeks of therapy with subcutaneous golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis despite prior methotrexate therapy: Final results of the randomized GO-FORTH trial. Mod Rheumatol. 2016;26(4):481-490. doi: 10.3109/14397595.2015.11 09762

46. Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: A randomized trial. Ann Intern Med. 2006;144(12):865-876. doi: 10.7326/0003-4819-144-12-200606200-00003

47. Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E. Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study. Arthritis Rheum. 2006; 54(9):2807-2816. doi: 10.1002/art.22070

48. Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: A phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67(8):1096-1103. doi: 10.1136/ard.2007.080002

49. Genovese MC, Schiff M, Luggen M, Becker JC, Aranda R, Teng J, et al. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to antitumour necrosis factor therapy. Ann Rheum Dis. 2008;67(4):547- 554. doi: 10.1136/ard.2007.074773

50. Schiff M, Pritchard C, Huffstutter JE, Rodriguez-Valverde V, Durez P, Zhou X, et al. The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: The ARRIVE trial. Ann Rheum Dis. 2009;68(11):1708-1714. doi: 10.1136/ard.2008.099218

51. Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, et al.; REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54(9):2793-2806. doi: 10.1002/art.22025

52. Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, et al.; DANCER Study Group. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: Results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum. 2006;54(5):1390-1400. doi: 10.1002/art.21778

53. Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, et al. Efficacy and safety of different doses and retreatment of rituximab: A randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010;69(9):1629-1635. doi: 10.1136/ard.2009.119933

54. Behrens F, Koehm M, Rossmanith T, Alten R, Aringer M, Backhaus M, et al. Rituximab plus leflunomide in rheumatoid arthritis: A randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study). Rheumatology (Oxford). 2021;60(11):5318- 5328. doi: 10.1093/rheumatology/keab153

55. Nasonov EL. Use of tocilizumab for rheumatoid arthritis: New evidence. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2011;49(6):46-56 (In Russ.) doi: 10.14412/1995-4484-2011-521

56. Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: The tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008;58(10):2968-2980. doi: 10.1002/art.23940

57. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, et al.; OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): A double-blind, placebo-controlled, randomised trial. Lancet. 2008;371(9617):987-997. doi: 10.1016/S0140-6736(08)60453-5

58. Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, 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. 2008;67(11):1516-1523. doi: 10.1136/ard.2008.092932

59. Yazici Y, Curtis JR, Ince A, Baraf HS, Lepley DM, Devenport JN, et al. Early effects of tocilizumab in the treatment of moderate to severe active rheumatoid arthritis: A one-week sub-study of a randomised controlled trial (Rapid Onset and Systemic Ef ficacy [ROSE] Study). Clin Exp Rheumatol. 2013; 31(3):358-364.

60. Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, GomezReino JJ, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: The AMBITION study. Ann Rheum Dis. 2010;69(1):88-96. doi: 10.1136/ard.2008.105197

61. Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): Evidence of clinical and radiographic benefit from an x-ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis. 2007;66(9):1162-1167. doi: 10.1136/ard.2006.068064

62. Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J, et al. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): Significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol. 2009;19(1):12-19. doi: 10.1007/s10165-008-0125-1

63. Nasonov EL, Lila AM. The efficacy and safety of sarilumab, fully human monoclonal antibodies against interleukin 6 receptor, in rheumatoid arthritis: New evidence. Nauchno-Prakticheskaya Revmatolo - gia = Rheumatology Science and Practice. 2019;57(5):564-577 (In Russ.) doi: 10.14412/1995-4484-2019-564-57

64. Genovese MC, Fleischmann R, Kivitz AJ, Rell-Bakalarska M, Martincova R, Fiore S, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: Results of a phase III study. Arthritis Rheumatol. 2015;67(6):1424-1437. doi: 10.1002/art.39093

65. Fleischmann R, van Adelsberg J, Lin Y, Castelar-Pinheiro GD, Brzezicki J, Hrycaj P, et al. Sarilumab and nonbiologic diseasemodifying antirheumatic drugs in patients with active rheumatoid arthritis and inadequate response or intolerance to tumor necrosis factor inhibitors. Arthritis Rheumatol. 2017;69(2):277-290. doi: 10.1002/art.39944

66. Tanaka Y, Wada K, Takahashi Y, Hagino O, van Hoogstraten H, Graham NMH, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: Results of a randomized, placebo-controlled phase III trial in Japan. Arthritis Res Ther. 2019;21(1):79. doi: 10.1186/s13075-019-1856-4

67. Burmester GR, Lin Y, Patel R, van Adelsberg J, Mangan EK, Graham NM, et al. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): A randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017;76(5):840-847. doi: 10.1136/annrheumdis-2016-210310

68. Kameda H, Wada K, Takahashi Y, Hagino O, van Hoogstraten H, Graham N, et al. Sarilumab monotherapy or in combination with non-methotrexate disease-modifying antirheumatic drugs in active rheumatoid arthritis: A Japan phase 3 trial (HARUKA). Mod Rheumatol. 2020;30(2):239-248. doi: 10.1080/143975 95.2019.1639939

69. Nasonov EL, Lisitsyna TA, Zonova EV, Kuzkina SM. The effect of olokizumab on rheumatoid arthritis patient’s reported outcomes: Results of a double-blind randomized placebocontrolled multicenter phase III trial (CREDO 1). Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2021; 59(1):62-69 (In Russ.). doi: 10.47360/1995-4484-2021-62-69

70. Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, et al. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: Efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876

71. Jansen JP, Buckley F, Dejonckheere F, Ogale S. Comparative efficacy of biologics as monotherapy and in combination with methotrexate on patient reported outcomes (PROs) in rheumatoid arthritis patients with an inadequate response to conventional DMARDs – A systematic review and network meta-analysis. Health Qual Life Outcomes. 2014;12:102. doi: 10.1186/1477-7525-12-102

72. Almeida C, Choy EH, Hewlett S, Kirwan JR, Cramp F, Chalder T, et al. Biologic interventions for fatigue in rheumatoid arthritis. Cochrane Database Syst Rev. 2016;2016(6):CD008334. doi: 10.1002/14651858.CD008334.pub2

73. Barra L, Ha A, Sun L, Fonseca C, Pope J. Efficacy of biologic agents in improving the Health Assessment Questionnaire (HAQ) score in established and early rheumatoid arthritis: A meta-analysis with indirect comparisons. Clin Exp Rheumatol. 2014;32(3):333-341.