The effect of tofacitinib on function and quality of life indicators in patients with rheumatoid arthritis resistant to synthetic and biological disease-modifying antirheumatic drugs in real clinical practice: Results of a multicenter observational study

Tofacitinib (TOFA), a representative of a new class of targeted synthetic disease-modifying antirheumatic drugs (s-DMARD), is a promising drug for treating rheumatoid arthritis (RA) and other immune inflammatory diseases.

Objective: to evaluate the efficiency and safety of therapy with TOFA in combination with methotrexate (MTX) and other s-DMARDs in real clinical practice in patients with active RA and previous ineffective therapy.

Patients and methods. A 6-month Russian multicenter study of function and quality of life enrolled 101 patients with resistant RA: 18 men and 83 women; mean age, 51.03±11.28 years; mean disease duration, 105.4±81.43 months; rheumatoid factor-positive individuals (89.1%); and anticyclic citrullinated peptide antibody-positive ones (74.7%). 93 (92,1%) of these patients completed a 24-week study. TOFA was used as both second-line drug (after failure of therapy with s-DMARD) (n=74) and as a third-line drug (after failure of therapy with s-DMARDs and biological agents (BAs) (n=74). The tools RAPID3, HAQ, and EQ-5D were used to determine disease outcomes from a patient's assessment.

Results. All the three tools demonstrated significant positive changes at 3–6 months following therapy initiation. RAPID3 scores for the status of a patient achieving a low disease activity or remission coincided with the mean DAS28-ESR and SDAI scores in 60% and 68% of cases, respectively. The achievement rates of the minimally clinically significant improvement (ΔHAQ≥0.22) and functional remission (HAQ≤0.5) at 6 months of TOFA therapy were 79.6 and 30.1%, respectively. The mean change value in EQ-5D scores over 6 months was -0.162±0.21. There were no significant between the groups of patients who used TOFA as a second- or third-line agent in the majority of indicators, except EQ-5D scores at 6 months.

Conclusions. The results of our multicenter study using considerable Russian material confirmed the pronounced positive effect of TOFA used as a second-line agent (after s-DMARD failure) and a third-line agent (after s-DMARD and BA failure) on patients' assessment of disease activity, functional ability in daily life, and quality of life.

1. Амирджанова ВН, Койлубаева ГМ. Методология оценки качества жизни в практике ревматолога. Научно-практическая ревматология. 2003;41(2):72-6. [Amirdzhanova VN, Koilubaeva GM. Quality of life assessment methodology in practice of rheumatologist. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2003;41(2):72-6. (In Russ.)]. doi: 10.14412/1995-4484-2003-773.

2. Marra CA, Rashidi AA, Guh D, et al. Are indirect utility measures reliable and responsive in rheumatoid arthritis patients? Qual Life Res. 2005 Jun;14(5):1333-44.

3. Harrison MJ, Davies LM, Bansback NJ, et al. The validity and responsiveness of generic utility measures in rheumatoid arthritis: a review. J Rheumatol. 2008 Apr;35(4):592-602. Epub 2008 Feb 15.

4. Каратеев ДЕ. Новое направление в патогенетической терапии ревматоидного артрита: первый ингибитор Янус-киназ тофацитиниб. Современная ревматология. 2014;8(1):39-44. [Karateev DE. A new trend in pathogenetic treatment of rheumatoid arthritis: tofacitinib, the first inhibitor of Janus kinase. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2014;8(1):39-44. (In Russ.)]. doi: 10.14412/1996-7012-2014-1-39-44.

5. Мясоутова ЛИ. Клинический случай применения тофацитиниба. Современная ревматология. 2015;9(1M):8. [Myasoutova LI. Clinical case of the use of tofacitinib. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2015;9(1M):8.] doi: 10.14412/1996-7012-2015-1-8.

6. Бабаева АР, Калинина ЕВ, Каратеев ДЕ. Опыт применения тофацитиниба в лечении резистентного ревматоидного артрита. Современная ревматология. 2015;9(2):28-32. [Babaeva AR, Kalinina EV, Karateev DE. Experience with tofacitinib in the treatment of resistant rheumatoid arthritis. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2015;9(2):28-32. (In Russ.)]. doi: 10.14412/1996-7012-2015-2-28-32.

7. Демидова НВ, Лучихина ЕЛ, Каратеев ДЕ. Выраженный и быстрый терапевтический эффект тофацитиниба в комбинации с подкожным метотрексатом у пациентки с ревматоидным артритом, имеющей факторы неблагоприятного прогноза, резистентной к стандартным базисным средствам и генно-инженерным биологическим препаратам (клинический случай). Современная ревматология. 2016;10(1):37-40. [Demidova NV, Luchikhina EL, Karateev DE. The marked and rapid therapeutic effect of tofacitinib in combination with subcutaneous methotrexate in a rheumatoid arthritis patient with poor prognostic factors who is resistant to standard disease-modifying antirheumatic drugs and biologicals: A clinical case. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2016;10(1):37-40. (In Russ.)]. doi: 10.14412/1996-7012-2016-1-37-40.

8. Лучихина ЕЛ, Каратеев ДЕ, Демидова НВ и др. Эффективность и безопасность терапии тофацитинибом у больных активным ревматоидным артритом с резистентностью к стандартной терапии: предварительные результаты открытого клинического исследования. Современная ревматология. 2016;10(2): 17-23. [Luchikhina EL, Karateev DE, Demidova NV, et al. Efficacy and safety of Tofacitinib in patients with activ rheumatoid arthritis resistant to conventional therapy: Preliminary results of an open-label clinical trial. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2016;10(2): 17- 23. (In Russ.)]. doi: 10.14412/1996-7012-2016-2-17-23.

9. Каратеев ДЕ, Абдулганиева ДИ, Бабаева АР и др. Применение тофацитиниба для лечения больных ревматоидным артритом, резистентных к синтетическим и биологическим базисным противовоспалительным препаратам, в реальной клинической практике (результаты многоцентрового наблюдательного исследования). Современная ревматология. 2016;10(3):52-61. [Karateev DE, Abdulganieva DI, Babaeva AR, et al. Use of tofacitinib in real clinical practice to treat patients with rheumatoid arthritis resistant to synthetic and biological disease-modifying antirheumatic drugs: Results of a multicenter observational study. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2016;10(3):52-61. (In Russ.)]. doi: 10.14412/1996-7012-2016-3-52-61.

10. Felson DT, Smolen JS, Wells G, et al. American College of Rheumatology/ European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis. 2011 Mar;70(3):404-13. doi: 10.1136/ard.2011.149765.

11. Pincus T, Swearingen CJ, Bergman M, Yazici Y. RAPID3 (Routine Assessment of Patient Index Data 3), a rheumatoid arthritis index without formal joint counts for routine care: proposed severity categories compared to DAS and CDAI categories. J Rheumatol. 2008 Nov;35(11):2136-47. Epub 2008 Sep 15.

12. Pincus T, Furer V, Keystone E, et al. RAPID3 (Routine Assessment of Patient Index Data 3) severity categories and response criteria: Similar results to DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) in the RAPID 1 (Rheumatoid Arthritis Prevention of Structural Damage) clinical trial of certolizumab pegol. Arthritis Care Res (Hoboken). 2011 Aug;63(8):1142-9. doi: 10.1002/acr.20481.

13. Fries JF, Spitz PW, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980 Feb;23(2):137-45.

14. Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol. 1982 Sep-Oct;9(5):789-93.

15. Амирджанова ВН. Шкалы боли и HAQ в оценке пациента с ревматоидным артритом. Научно-практическая ревматология. 2006;44(2):60-5. [Amirdzhanova VN. The HAQ and pain scale in the evaluation of a patient with rheumatoid arthritis. Nauchnoprakticheskaya revmatologiya = Rheumatology Science and Practice. 2006;44(2):60-5. (In Russ.)].

16. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003 Jun 9;1:20.

17. The EuroQol group. EuroQol – a new facility for the measurement of health related quality of life. Health Policy. 1990 Dec;16(3): 199-208.

18. Brooks R. with the EuroQol Group. EuroQol: thecurrent state of play. Health Policy. 1996 Jul;37(1):53-72.

19. Амирджанова ВН, Эрдес ШФ. Валидация русской версии общего опросника EuroQol-5D (EQ-5D). Научно-практическая ревматология. 2007;45(3):69-76. [Amirdzhanova VN, Erdes ShF. Validation of general questionnaire EuroQol-5D (EQ-5D) Russian version. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2007;45(3):69-76. (In Russ.)]. doi: 10.14412/1995-4484-2007-691.

20. Van der Heijde D, Klareskog L, Boers M, et al. Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results. Ann Rheum Dis. 2005 Nov;64(11):1582-7. Epub 2005 Apr 28.

21. Sokka T, Hetland ML, Mä kinen H, et al. Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries. Arthritis Rheum. 2008 Sep;58(9):2642-51. doi: 10.1002/art.23794.

22. 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. 2016 May-Jun; 34(3):430-42.

23. Strand V, Lee EB, Fleischmann R, et al. Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from the randomised phase III ORAL Start trial. RMD Open. 2016 Sep 28;2(2):e000308.eCollection 2016.

24. Strand V, Kremer J, Wallenstein G, et al. Effects of tofacitinib monotherapy on patient- reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs. Arthritis Res Ther. 2015 Nov 4; 17:307. doi: 10.1186/s13075-015-0825-9.

25. Strand V, Burmester GR, Zerbini CA, et al. Tofacitinib with methotrexate in thirdline treatment of patients with active rheumatoid arthritis: patient-reported outcomes from a phase III trial. Arthritis Care Res (Hoboken). 2015 Apr;67(4):475-83. doi: 10.1002/acr.22453.

26. Strand V, van Vollenhoven RF, Lee EB, et al. Tofacitinib or adalimumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis. Rheumatology (Oxford). 2016 Jun;55(6): 1031-41. doi: 10.1093/rheumatology/kev442.