Radiographic progression in patients with rheumatoid arthritis treated with JAK inhibitors
Authors:
M. Filková
Authors‘ workplace:
Revmatologický ústav Praha
Published in:
Čes. Revmatol., 30, 2022, No. 4, p. 158-165.
Category:
Review Article
Overview
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition leading to irreversible joint destruction and deformities. In addition to the assessment of therapeutic response using composite disease activity scores, radiographic progression remains an important parameter of effective treatment. Inhibitors of Janus kinases (JAK) target intracellular signaling pathways of many mediators with an essential role in the pathogenesis of RA. Clinical efficacy, safety, and inhibition of radiographic progression of four JAK inhibitors of different selectivity used in our daily practice tofacitinib, baricitinib, upadacitinib, and filgotinib were demonstrated in clinical trials in RA. Data from baricitinib and tofacitinib clinical trials show their effect on inhibition of radiographic progression irrespective of disease activity or concomitant therapy with glucocorticoids supporting an important disease-modifying effect of JAK inhibitors.
Keywords:
rheumatoid arthritis – JAK inhibitors – radiographic progression
Sources
1. Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018; 4: 18001.
2. Karouzakis E, Neidhart M, Gay RE, Gay S. Molecular and cellular basis of rheumatoid joint destruction. Immunol Lett 2006; 106(1): 8–13.
3. Firestein GS, McInnes IB. Immunopathogenesis of Rheumatoid Arthritis. Immunity 2017; 46(2): 183–196.
4. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O‘Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nature reviews Drug discovery 2017; 16(12): 843–862.
5. Landewe RB, Connell CA, Bradley JD, Wilkinson B, Gruben D, Strengholt S, et al. Is radiographic progression in modern rheumatoid arthritis trials still a robust outcome? Experience from tofacitinib clinical trials. Arthritis Res Ther 2016; 18(1): 212.
6. van der Heijde D, Simon L, Smolen J, Strand V, Sharp J, Boers M, et al. How to report radiographic data in randomized clinical trials in rheumatoid arthritis: guidelines from a roundtable discussion. Arthritis Rheum 2002; 47(2): 215–218.
7. Lee EB, Fleischmann R, Hall S, Wilkinson B, Bradley JD, Gruben D, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med 2014; 370(25): 2377–2386.
8. van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, Garcia Meijide JA, Wagner S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 2012; 367(6): 508–519.
9. van der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum 2013; 65(3): 559–570.
10. Fleischmann R, Mysler E, Hall S, Kivitz AJ, Moots RJ, Luo Z, et al. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet 2017; 390(10093): 457–468.
11. Kremer J, Li ZG, Hall S, Fleischmann R, Genovese M, Martin- Mola E, et al. Tofacitinib in combination with nonbiologic disease– modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med 2013; 159(4): 253–261.
12. Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet 2013; 381(9865): 451–460.
13. Fleischmann R, Kremer J, Cush J, Schulze–Koops H, Connell CA, Bradley JD, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 2012; 367(6): 495–507.
14. Smolen JS, Landewe 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.
15. Charles-Schoeman C, van der Heijde D, Burmester GR, Nash P, Zerbini CAF, Connell CA, et al. Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies. J Rheumatol 2018; 45(2): 177–187.
16. van der Heijde D, Landewe RBM, Wollenhaupt J, Strengholt S, Terry K, Kwok K, et al. Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies. Rheumatology (Oxford) 2021; 60(4): 1708– 1716.
17. Fleischmann R, Schiff M, van der Heijde D, Ramos-Remus C, Spindler A, Stanislav M, et al. Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease–Modifying Antirheumatic Drug Treatment. Arthritis & Rheumatology 2017; 69(3): 506–517.
18. Taylor PC, Keystone EC, van der Heijde D, Weinblatt ME, Del Carmen Morales L, Reyes Gonzaga J, et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 2017; 376(7): 652–662.
19. Dougados M, van der Heijde D, Chen YC, Greenwald M, Drescher E, Liu J, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis 2017; 76(1): 88–95.
20. Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med 2016; 374(13): 1243–1252.
21. van der Heijde D, Kartman CE, Xie L, Beattie S, Schlichting D, Mo D, et al. Radiographic Progression of Structural Joint Damage Over 5 Years of Baricitinib Treatment in Patients With Rheumatoid Arthritis: Results From RA-BEYOND. J Rheumatol 2022; 49(2): 133–141.
22. Lopez-Romero P, de la Torre I, Haladyj E, Aletaha D, Smolen JS. Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis. Ann Rheum Dis 2022; 81(5): 622–631.
23. Smolen JS. Treat to Target in Rheumatology: A Historical Account on Occasion of the 10th Anniversary. Rheumatic diseases clinics of North America 2019; 45(4): 477–485.
24. Aletaha D, Smolen JS. Joint damage in rheumatoid arthritis progresses in remission according to the Disease Activity Score in 28 joints and is driven by residual swollen joints. Arthritis Rheum 2011; 63(12): 3702–3711.
25. Smolen JS, Kalden JR, Scott DL, Rozman B, Kvien TK, Larsen A, et al. Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet 1999; 353(9149): 259–266.
26. Strand V, Cohen S, Schiff M, Weaver A, Fleischmann R, Cannon G, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med 1999; 159(21): 2542–2550.
27. Aletaha D, Funovits J, Breedveld FC, Sharp J, Segurado O, Smolen JS. Rheumatoid arthritis joint progression in sustained remission is determined by disease activity levels preceding the period of radiographic assessment. Arthritis Rheum 2009; 60(5): 1242–1249.
28. Smolen JS, Han C, van der Heijde DM, Emery P, Bathon JM, Keystone E, et al. Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade. Ann Rheum Dis 2009; 68(6): 823–827.
29. Aletaha D, Alasti F, Smolen JS. Rituximab dissociates the tight link between disease activity and joint damage in rheumatoid arthritis patients. Ann Rheum Dis 2013; 72(1): 7–12.
30. Smolen JS, Avila JC, Aletaha D. Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction. Ann Rheum Dis 2012; 71(5): 687–693.
31. Binder NB, Puchner A, Niederreiter B, Hayer S, Leiss H, Bluml S, et al. Tumor necrosis factor-inhibiting therapy preferentially targets bone destruction but not synovial inflammation in a tumor necrosis factor-driven model of rheumatoid arthritis. Arthritis Rheum 2013; 65(3): 608–617.
32. Redlich K, Smolen JS. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nature reviews Drug discovery 2012; 11(3): 234–250.
33. van Vollenhoven R, Takeuchi T, Pangan AL, Friedman A, Mohamed MF, Chen S, et al. Efficacy and Safety of Upadacitinib Monotherapy in Methotrexate-Naive Patients With Moderatelyto-Severely Active Rheumatoid Arthritis (SELECT-EARLY): A Multicenter, Multi-Country, Randomized, Double-Blind, Active Comparator-Controlled Trial. Arthritis & Rheumatology 2020; 72(10): 1607–1620.
34. Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECTMONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet 2019; 393(10188): 2303–2311.
35. Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, et al. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis & Rheumatology 2019; 71(11): 1788–1800.
36. Burmester GR, Kremer JM, Van den Bosch F, Kivitz A, Bessette L, Li Y, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018; 391(10139): 2503–2512.
37. Genovese MC, Fleischmann R, Combe B, Hall S, Rubbert-Roth A, Zhang Y, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet 2018; 391(10139): 2513–2524.
38. Westhovens R, Rigby WFC, van der Heijde D, Ching DWT, Stohl W, Kay J, et al. Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial. Ann Rheum Dis 2021; 80(6): 727–738.
39. Combe B, Kivitz A, Tanaka Y, van der Heijde D, Simon JA, Baraf HSB, et al. Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial. Ann Rheum Dis 2021; 80(7): 848–858.
40. Genovese MC, Kalunian K, Gottenberg JE, Mozaffarian N, Bartok B, Matzkies F, et al. Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial. JAMA 2019; 322(4): 315–325.
41. Hu L, Liu R, Zhang L. Advance in bone destruction participated by JAK/STAT in rheumatoid arthritis and therapeutic effect of JAK/ STAT inhibitors. Int Immunopharmacol 2022; 111: 109095.
42. Adam S, Simon N, Steffen U, Andes FT, Scholtysek C, Muller DIH, et al. JAK inhibition increases bone mass in steady–state conditions and ameliorates pathological bone loss by stimulating osteoblast function. Sci Transl Med 2020; 12(530).
43. Murakami K, Kobayashi Y, Uehara S, Suzuki T, Koide M, Yamashita T, et al. A Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro. PLoS One 2017; 12(7): e0181126.
Labels
Dermatology & STDs Paediatric rheumatology RheumatologyArticle was published in
Czech Rheumatology
2022 Issue 4
Most read in this issue
- Radiographic progression in patients with rheumatoid arthritis treated with JAK inhibitors
- Chronické rány jako komplikace revmatologických onemocnění
- Follicle-stimulating hormone and its effects on bone and cartilage
- Validation of the Czech version of the questionnaire evaluating the early detection of intestinal and extraintestinal manifestations in patients with axial spondyloarthritis at risk of developing idiopathic intestinal inflammation: IBD screening criteria for patients with SpA