Patient's reported outcomes – a new philosophy for analyzing the effectiveness of therapy in immunoinflammatory diseases

A fundamentally important task of modern pharmacotherapy of immunoinflammatory diseases (IID) is a significant improvement in the quality of life (QOL) of patients, the fastest and most complete elimination of the most unpleasant manifestations of the disease, restoration of function and working capacity. Specialists in the therapy of various IID took part in panel dedicated to the discussion of this problem: Professor E.L. Nasonov, PhD., member of the Academy of Science; Professor A.M. Lila, PhD; V.N. Amirjanova, PhD; A.E. Karateev, PhD; T.V. Korotaeva, PhD; O.V. Knyazev, PhD; T.A. Lisitsyna, PhD; M.M Hobeish, PhD; E.S. Filatova. PhD.
One of the central issues was the discussion of the need to use the patient's reported outcomes (PROs) indicator in analyzing the results of IID therapy (rheumatoid arthritis, psoriatic arthritis, psoriasis and inflammatory bowel disease). The need for its use is due to the fact that the principal goal of treatment with modern disease modifying antirheumatic drugs (DMARDs) is not only to achieve low activity or remission of IID, but also to maximize the general condition and QOL of patients. Therefore, such manifestations of IID as pain, fatigue, dysfunction, depression and anxiety, etc., must be analyzed in the course of treatment. The development of these symptoms is determined by the main immunopathological process and is associated, among others, with systemic overproduction of a number of pro-inflammatory cytokines. Modern DMARDs: Janus kinase (JAK) inhibitors, in particular tofacitinib, are capable of directly blocking the effect of cytokines on cells (suppressing the intracellular JAK / STAT signaling pathway), quickly and effectively eliminating pain, fatigue and dysfunction. The use of JAK inhibitors seems to be especially appropriate in patients with IID with high inflammatory activity and severe clinical manifestations.

1. Nasonov EL, Lila AM. Janus kinase inhibitors in immuno-inflammatory rheumatic diseases: new opportunities and prospects. Nauchno-Prakticheskaya Revmatologiya. 2019;57(1):8-16. (In Russ.).

2. Smolen JS, Strand V, Koenig AS, et al. Discordance between patient and physician assessments of global disease activity in rheumatoid arthritis and association with work productivity. Arthritis Res Ther. 2016 May 21;18(1):114. doi: 10.1186/s13075-016-1004-3.

3. Michaud K, Pope J, van de Laar M, et al. A Systematic Literature Review of Residual Symptoms and Unmet Need in Patients with Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2020 Jul 3. doi: 10.1002/acr.24369. Online ahead of print.

4. Aletaha D, Wang X, Zhong S, et al. Differences in disease activity measures in patients with rheumatoid arthritis who achieved DAS, SDAI, or CDAI remission but not Boolean remission. Semin Arthritis Rheum. 2020 Apr;50(2):276-284. doi: 10.1016/j.semarthrit.2019.09.005.

5. Lee YC, Cui J, Lu B, et al. Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study. Arthritis Res Ther. 2011 Jun 8;13(3):R83. doi: 10.1186/ar3353.

6. Kilic G, Kilic E, Nas K, et al. Residual symptoms and disease burden among patients with psoriatic arthritis: is a new disease activity index required? Rheumatol Int. 2019 Jan;39(1):73-81. doi: 10.1007/s00296-018-4201-3. Epub 2018 Nov 13.

7. Belousova EA, Abdulganieva ВI, Alekseeva OP, et al. Experience of tofacitinib using in therapy of ulcerative colitis in real clinical practice. Koloproktologia. 2019;18(4):86-99. (In Russ.).

8. Nikiphorou Е, Santos EJF, Marques A, et al. 2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis. Ann Rheum Dis. 2021 Oct;80(10):1278-85. doi: 10.1136/annrheumdis-2021-220249. Epub 2021 May 7.

9. Kilic L, Erden A, Bingham CO, et al. The Reporting of Patient-reported Outcomes in Studies of Patients with Rheumatoid Arthritis: A Systematic Review of 250 Articles. J Rheumatol. 2016 Jul;43(7):1300-5. doi: 10.3899/jrheum.151177.

10. Ogdie A, de Wit M, Duffin K, et al. Defining Outcome Measures for Psoriatic Arthritis: A Report from the GRAPPAOMERACT Working Group. J Rheumatol. 2017 May;44(5):697-700. doi: 10.3899/jrheum.170150.

11. Tveit K, Duvetorp A, ∅stergaard M, et al. Treatment use and satisfaction among patients with psoriasis and psoriatic arthritis: results from the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP). J Eur Acad Dermatol Venereol. 2019 Feb;33(2):340-354. doi: 10.1111/jdv.15252.Epub 2018 Nov 28.

12. Svoboda SA, Ghamrawi RI, Owusu DA, et al. Treatment Goals in Psoriasis: Which Outcomes Matter Most? Am J Clin Dermatol. 2020 Aug;21(4):505-11. doi: 10.1007/s40257-020-00521-3.

13. Fairbrass KM, Costantino SJ, Gracie DJ, Ford AC. Prevalence of irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease in remission: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2020 Dec;5(12):1053-62. doi: 10.1016/S2468-1253(20)30300-9. Epub 2020 Oct 2.

14. Narula N, Alshahrani AA, Yuan Y, et al. Patient-Reported Outcomes and Endoscopic Appearance of Ulcerative Colitis: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2019 Feb;17(3): 411-8.e3. doi: 10.1016/j.cgh.2018.06.015.Epub 2018 Jun 18.

15. Ma C, Panaccione R, Fedorak RN, et al. Heterogeneity in definitions of endpoints for clinical trials of ulcerative colitis: a systematic review for development of a core outcome set. Clin Gastroenterol Hepatol. 2018 May;16(5):637-47.e13. doi: 10.1016/j.cgh.2017.08.025. Epub 2017 Aug 24.

16. Salaffi F, Giacobazzi G, Carlo M. Chronic Pain in Inflammatory Arthritis: Mechanisms, Metrology, and Emerging Targets-A Focus on the JAK-STAT Pathway. Pain Res Manag. 2018 Feb 7;2018:8564215. doi: 10.1155/2018/8564215. eCollection 2018.

17. Choy EHS, Calabrese LH. Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid arthritis. Rheumatology (Oxford). 2018 Nov 1;57(11):1885-95. doi: 10.1093/rheumatology/kex391.

18. Sebba A. Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis. Open Access Rheumatol. 2021 Mar 5;13:31-43. doi: 10.2147/OARRR.S291388.eCollection 2021.

19. Maqbool S, Ihtesham A, Langove MN, et al. Neuro-dermatological association between psoriasis and depression: an immune-mediated inflammatory process validating skin-brain axis theory. AIMS Neurosci. 2021 Mar 10;8(3):340-354. doi: 10.3934/Neuroscience.2021018. eCollection 2021.

20. Matcham F, Rayner L, Steer S, Hotopf M. The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2013 Dec; 52(12):2136-48. doi: 10.1093/rheumatology/ket169. Epub 2013 Sep 3.

21. Kamalaraj N, El-Haddad C, Hay P, Pile K. Systematic review of depression and anxiety in psoriatic arthritis. Int J Rheum Dis. 2019 Jun;22(6):967-73. doi: 10.1111/1756-185X.13553. Epub 2019 Apr 26.

22. Barberio B, Zamani M, Black CJ, et al. Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and metaanalysis. Lancet Gastroenterol Hepatol. 2021 May;6(5):359-70. doi: 10.1016/S2468-1253(21)00014-5. Epub 2021 Mar 12.

23. Osimo EF, Pillinger T, Rodriguez IM, et al. Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls. Brain Behav Immun. 2020 Jul;87:901-9. doi: 10.1016/j.bbi.2020.02.010. Epub 2020 Feb 27.

24. Wittenberg GM, Stylianou A, Zhang Y, et al. Effects of immunomodulatory drugs on depressive symptoms: A mega-analysis of randomized, placebo-controlled clinical trials in inflammatory disorders. Mol Psychiatry. 2020 Jun;25(6):1275-85. doi: 10.1038/s41380-019-0471-8. Epub 2019 Aug 19.

25. Dey M, Parodis I, Nikiphorou E. Fatigue in Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Comparison of Mechanisms, Measures and Management. J Clin Med. 2021 Aug 13;10(16):3566. doi: 10.3390/jcm10163566.

26. Husni ME, Merola JF, Davin S. The psychosocial burden of psoriatic arthritis. Semin Arthritis Rheum. 2017 Dec;47(3):351-60. doi: 10.1016/j.semarthrit.2017.05.010.

27. Ogdie A, de Vlam K, McInnes IB, et al. Efficacy of tofacitinib in reducing pain in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis. RMD Open.2020 Feb;6(1):e001042. doi: 10.1136/rmdopen-2019-001042.

28. Boyce EG, Vyas D, Rogan EL, et al. Impact of tofacitinib on patient outcomes in rheumatoid arthritis - review of clinical studies. Patient Relat Outcome Meas. 2016 Jan 14; 7:1-12. doi: 10.2147/PROM.S62879. eCollection 2016.

29. Strand V, Kaine J, Alten R, 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 Oct 15; 22(1):243. doi: 10.1186/s13075-020-02324-7.

30. Strand V, de Vlam K, Covarrubias- Cobos JA, et al. Effect of tofacitinib on patient-reported outcomes in patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors in the phase III, randomised controlled trial: OPAL Beyond. RMD Open. 2019 Jan 11; 5(1):e000808. doi: 10.1136/rmdopen-2018-000808. eCollection 2019.

31. Wallenstein GV, Kanik KS, Wilkinson B, et al. Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials. Clin Exp Rheumatol. May-Jun 2016; 34(3):430-42. Epub 2016 Apr 28.

32. De Vlam K, Ogdie A, Bushmakin AG, et al. Median time to pain improvement and the impact of baseline pain severity on pain response in patients with psoriatic arthritis treated with tofacitinib. RMD Open. 2021 Jul; 7(2):e001609. doi: 10.1136/rmdopen-2021-001609.

33. Strober B, Gottlieb A, van de Kerkhof P, et al. Benefit-risk profile of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: pooled analysis across six clinical trials. Br J Dermatol. 2019 Jan;180(1): 67-75. doi: 10.1111/bjd.17149.Epub 2018 Oct 10.

34. Taneja V, El-Dallal M, Haq Z, et al. Effectiveness and Safety of Tofacitinib for Ulcerative Colitis: Systematic Review and Meta-analysis. J Clin Gastroenterol. 2021 Sep 9. doi: 10.1097/MCG.0000000000001608.Online ahead of print.

35. Dubinsky MC, DiBonaventura M, Fan H, et al. Tofacitinib in Patients with Ulcerative Colitis: Inflammatory Bowel Disease Questionnaire Items in Phase 3 Randomized Controlled Induction Studies. Inflamm Bowel Dis. 2021 Jun 15;27(7): 983-993. doi: 10.1093/ibd/izaa193.

36. Heiberg Agerbeck A, Martiny FHJ, Jauernik CP, et al. Validity of Current Assessment Tools Aiming to Measure the Affective Component of Pain: A Systematic Review. Patient Relat Outcome Meas. 2021 Jul 6;12:213-26. doi: 10.2147/PROM.S304950.

37. Von Glischinski M, von Brachel R, Thiele C, Hirschfeld G. Not sad enough for a depression trial? A systematic review of depression measures and cut points in clinical trial registrations. J Affect Disord. 2021 Sep 1; 292:36-44. doi: 10.1016/j.jad.2021.05.041.

38. Machado MO, Kang NC, Tai F, et al. Measuring fatigue: a meta-review. Int J Dermatol. 2021 Sep;60(9):1053-69. doi: 10.1111/ijd.15341. Epub 2020 Dec 10.

39. Mease P, Strand V, Gladman D. Functional impairment measurement in psoriatic arthritis: Importance and challenges. Semin Arthritis Rheum. 2018 Dec;48(3): 436-48. doi: 10.1016/j.semarthrit.2018.05.010.

40. Smolen JS, Landewe RB, Bijlsma JW, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685-99. doi: 10.1136/annrheumdis-2019-216655. Epub 2020 Jan 22. Поступила/отрецензирована/принята к печати Received/Reviewed/Accepted 20.08.2021/27.09.2021/29.09.2021