Current treatment options for enthesitis


Authors: Š. Forejtová;  M. Votavová
Authors‘ workplace: Revmatologický ústav Praha
Published in: Čes. Revmatol., 25, 2017, No. 3, p. 124-139.
Category: Review Article

Overview

Enthesitis is one of the basic clinical manifestations of spondyloarthritis. Initially, the pharmacological treatment of enthesitis was limited to local corticosteroid injections or continuous non-steroidal anti-rheumatic therapy, since efficacy of non-biologic DMARDs has never been conclusively proven. Over the past decade, several anti-TNFα agents such as infliximab, etanercept, golimumab or certolizumab have been evaluated in several studies. At the same time, it has been found that T lymphocytes in entheses (i.e. at the site of the attachment of the tendon and the bone) play an important role in the pathogenesis of spondyloarthritis. A major role in the development of spondyloarthritis is played by IL-23 and its receptor, which directly affect Th17 lymphocytes. These can be found in but are not limited to entheses, and produce cytokines such as IL-21, IL-22 and IL-17, which then contribute to the development of four pathological processes in spondyloarthropathies, such as pannus formation in the joints, development of osteitis and joint erosion, bone formation and development of psoriatic plaques. Efficacy in the treatment of enthesitis was demonstrated in ustekinumab, a monoclonal antibody against the p40 subunit of IL-12 and IL-23, as well as secukinumab, a fully human anti-IL-17A antibody. Other agents that have been shown to be effective in treating spondyloarthropathy are apremilast, an inhibitor of phosphodiesterase 4; limited data also exist for tofacitinib, a JAK-3 inhibitor. There are also studies ongoing with other IL-17 inhibitors, and partial results are known for ixekizumab. There is only limited data demonstrating the effect of physiotherapy in the treatment of enthesitis..

Key words:
Enthesitis, spondyloarthritis, anti-TNFα, anti- IL17, secukinumab, apremilast, tofacitinib


Sources

1. Lories RJ, McInnes IB. Primed for inflammation: enthesis-resident T cells. Nature Medicine 2012; 7: 1018–9.

2. Kehl AS, Corr M, Weisman MH. Entezitis. New insights into pathogenesis, diagnostic modalities and treatment. Arthritis Rheum 2016; 68: 312–322.

3. Van Duivenvoorde LM, Dorris LM, Satumtira N, van Tok MN, Redlich K, Tak PP, et al. Relationship between inflammation, bone destruction, and osteoproliferation in the HLA-B27/human β2-mikroglobulin-transgenic rat model in spondyloarthritis. Arthritis Rheum 2012; 64: 3210–9.

4. Orbai AM, Weitz J, Siegel EL, Siebert S, Savage LJ, et al. Systemic Review of Treatment Effectiveness and Outcome Measures for Enthesitis in Psoriatic Arthritis. J Rheumatol 2014; 41: 2290–4.

5. Mander M, Simpson JM, Mc Lellan A, Walker D, Goodacre JA, Dick WC. Studies with an enthesitis index as a method of clinical assessment in ankylosing spondylitis. Ann Rheum Dis 1987; 46: 197–202.

6. Antoni CE, Kavanaugh A, Kirkham B, Tunucu Z, Burmester GT, et al. Sustained benefits of infliximab therapy for dermatological and articular manifestation of psoriatic arthritis: Results from the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT). Arthritis Rheum 2005; 52: 1227–36.

7. Antoni CE, Krueger GG, de Vlam K, Birbara C, Beutler A, et al. Infliximab improves signs and symptoms of psoriatic arthritis. Results of the IMPACT 2 trial. Ann Rheum Dis 2005; 64: 1150–7.

8. Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: Results of a double–blind, randomise, placebo-controlled trial. Arthritis Rheum 2005; 52: 3279–89.

9. Genovese MC, Mease PJ, Thomson GT, Kivitz AJ, Perdok RJ, et al. Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. J Rheumatol 2007; 34: 1040–50.

10. Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, et al. Golimumab, a new human tumour necrosis factor antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis.: Twenty-four-week efficacy and safety results of a randomised, placebo–controlled study. Arthritis Rheum 2009; 60: 976–86.

11. Gottlieb A, Menter A, Mendelsohn A, Shen YK, Li S, et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody for psoriatic arthritis: Randomised, double–blind, placebo-controlled crossover trial. Lancet 2009; 373: 633–40.

12. Sterry W, Ortonne JP, Kirkham B, Brocq O, Robertson D, et al. Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double blind multicentre trial. BMJ 2010; 340: c147.

13. Heuft–Dorenbosch L, Spoorenberg A, van Tubergen A, Landewe E, van ver Tempel H, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 2003; 62: 127–32.

14. Ritchlin C, Rahman P, Kavanugh A, McInnes IB, Puig L, et al.Efficacy and safety of the anti–IL12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double–blind, placebo–controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis 2014; 73: 990–9.

15. Healy PJ, Heliwell PS. Measuring clinical enthesitis in psoriatic arthritis.: Assessment of existing measures and development of an instrument specific to psoriatic arthritis. Arthritis Rheum 2008; 59: 686–91.

16. Mease PJ, Fleischmann R, Deodhar AA, Wollenhaupt J, Khraishi M, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase-3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis 2014; 73: 48–55.

17. Sakkas LI, Alexiou I, Simopoulou T, Vlychou M. Enthesitis in psoriatic arthritis. Semin Arthritis Rheum 2013; 43: 325–34.

18. Clegg DO, Reda DJ, Mejias E, Cannon GW, Taylor T, et al. Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Comparative Study. Arthritis Rheum 1996: 39: 2013–20.

19. Kumar N, Kay IJ, Walker DJ. The treatment of enthesitis in psoriatic arthritis. J Rheumatol 2004; 31: 2311–2.

20. Kingsley GH, Kowalczyk A, Taylor H, Ibrahim F, Packham JC, et al. A randomized placebo controlled trial of methotrexate in psoriatic arthritis. Rheumatology 2012; 51: 1368–77.

21. Baranauskaite A, Raffayová H, Kungurov NV, Kubanova A, Venalis A, et al. Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis: the RESPOND study. Ann Rheum Dis 2012; 71: 541–8.

22. Kaltwasser JP, Nash P, Gladman D, Rosen CF, Behrens F, et al. Efficacy and Safety od Leflunomide in the Treatment of Psoriatic Arthritis and Psoriasis. Arthritis Rheum 2004; 50: 1939–50.

23. Behrens F, Finkenwirth C, Pavelka K, Stolfa J, Sipek– Dolnicar T, et al. Leflunomid in psoriatic arthritis: results from a large European prospective observational study. Arthritis Care Res (Hoboken) 2012; 65: 464–70.

24. Fraser AD, van Kuijk AW, Westhovens R, Karim Z, Wakefield R, et al. A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus ciclosporin in patients with active psoriatic arthritis. Ann Rheum Dis 2005; 64: 859–64.

25. Braun J, Brandt J, Listing J, Zink A, Alten RG, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002; 359: 1187–93.

26. Van der Heijde D, Schiff MH, Sieper J, Kivitz AJ, Wong RL, et al. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann Rheum Dis 2009; 68: 922–9.

27. Rudwaleit M, Van Den Bosch F, Kron M, Kary S, Kupper H. Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy. Arthritis Research&Therapy 2010; 12: R117.

28. Rudwaleit M, Claudepierre P, Kron M, Kary S, Wong R, Kupper H. Effectiveness of adalimumab in patients with ankylosing spondylitis associated with enthesitis and peripheral arthritis. Arthritis Research &Therapy 2010; 12: R43.

29. Mease P, Sieper J, Van den Bosch F, Rahman P, Karunaratne PM, et al. Randomized Controlled Trial of Adalimumab in Patients with Nonpsoriatic Peripheral Spondyloarthritis. Arthritis Rheum 2015; 67: 914–23.

30. Van der Heijde D, Braun J, Deodhar A, Inman RD, Xu S, et al.Comparison of three enthesitis indices in a multicentre, randomized, placebo-controlled trial of golimumab in ankylosing spondylitis (GO–RAISE). Rheumatology 2013; 52: 321–5.

31. Braun J, Baraliakos X, Heldmann F, Kiltz U. Tumour necrosis factor alpha antagonist in the treatment of axial spondyloarthritis. Expert Opi Investig Drugs 2014; 23: 647–59.

32. Kavanaugh A, Mease IP. Treatment of psoriatic arthritis with tumour necrosis factor inhibitors: Long-term outcomes including enthesitis and dactylitis with golimumab treatment in the long-term extension of a randomised, placebo-controlled study (GO-REVEAL). J Rheumatol (Suppl) 2012; 89: 90–3.

33. Kavanaugh A, Mc Innes IB, Mease P, Krueger GG, Glademan D,et al. Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: result from a long–term extension of randomised, placebo controlled trial (GO–REVEAL study). Ann Rheum Dis 2014; 73: 1689–94.

34. Dougados M, Combe B, Braun J, Landewé R, Sibilia J, et al. A randomised, multicentre, double–blind, placebo-controlled trial of etanercept in adults with refractory heel enthesitis in spondyloarthritis: the HEEL trial. Ann Rheum Dis 2010; 69: 1430–5.

35. Mease PJ, Goffe BS, Metz J, van der Stoep A, Finck B, et al. Etanercept in the treatment of psoriatic arthritis and psoriasis. A randomised trial. Lancet 2000; 356: 385–90.

36. Landewe R, Braun J, Deodhar S, Dougados M, Maksymowych WP, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis 2014; 73: 39–47.

37. Sieper J, Landewe R, Rudwaleit M, van der Heijde D, Dougados M, et al. Effect of certolizumab pegol over ninety-six weeks in patients with axial spondyloarthritis. Arthritis Rheum 2015; 67: 668–77.

38. McInnes IP, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, et al. Efficacy and safety of ustekinumabin patients with active psoriatic arthritis: I year results of phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 2013; 382: 780–9.

39. Ritchlin C, Rahman P, Kavanaugh A, McInnes IB, Puig L, et al. Efficacy and safety of the anti–IL 22/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis therapy: 6-month a 1-year results of the phase 3, multicentre, double–blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis 2014; 73: 990–9.

40. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med 2015. 373: 2534–48.

41. Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P et al. Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med 2015. 373: 1329–39.

42. McInnes I, Mease PJ, Kirkham B,Kavanaugh A, Ritchlin CT, et al. Secukinumab, a human anti–interleukin–17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double–blind, placebo-controlled, phase 3 trial. Lancet 2015; 386: 1137–46.

43. McInnes IB, Mease PJ, Ritchlin CT, Rahman P, Gottlieb AB, et al. Secukinumab provides sustained improvements in the signs and symptoms of active psoriatic arthritis: 104 weeks results from a phase 3 trial. Arthritis Rheum 2016; 68 (suppl 10), abstract 2757.

44. Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic–naive patients with active psoriatic arthritis: results from the 24-–week randomised, double-blind, placebo-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis 2017; 76: 79–87.

45. Kavanaugh K, Mease PJ, Gomez–Reino JJ, Adebajo AO, Wollenhaupt J, et al. Treatment of psoriatic arthritis in phase 3 randomised, place-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis 2014; 73: 1020–6.

46. Gladman D, Kavanaugh A, Gomez–Reino J, Wollenhaupt J, Cutolo M, et al. Apremilast treatment and long-term(156-week) improvements in enthesitis and dactylitis in patients with psoriatic arthritis: pooled analysis of a large database of 3 phase III, randomized, controlled trials. Arthritis Rheum 2016; 68 (suppl 10), abstract 1711.

47. Wells AF; Edwards CJ, Kivitz AJ, Bird P, Nguyen D, et al.Apremilast monotherapy as the first systemic treatment in DMARD-naive patients with psoriatic arthritis: 3-year treatment results. Arthritis Rheum 2016; 68 (suppl 10), abstract 1680.

48. van der Heijde D, Deodhar A, Wei JC, Drescher E, Fleishaker D, et al. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16–week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis 2017; 0: 1–8.

49. Dean BJ, Lostis E, Oakley T, Rombach I, Morrey ME, Carr AJ The risks and benefits of glucocorticoid treatment for tendinopathy: a systematic review of the effects of local glucocorticoid on tendon. Semin Arthritis Rheum. 2014; 43: 570–6.

50. Coombes BK, Bisset L, Vincenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systemic review of randomized controlled trials. Lancet 2010; 376: 151–67.

51. Metcalfe D, Achten J, Costa ML. Glucocorticoid injections in lesions of the Achilles tendon. Foot Ankle Int 2009; 30: 661–5.

52. Srivastava P, Aggarwal A. Ultrasound-guided retro-calcaneal bursa corticosteroid injection for refractory Achilles tendinitis in patients with seronegative spondyloartropathy: efficacy and follow-up study. Rheumatol Int 2016; 36: 875–80.

53. Regel A, Sepriano A, Baraliakos X, van der Heijde D, Braun J, et al. Efficacy and safety of non–pharmacological and non-biological pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open 2017, publikováno on-line.

54. Krukowska J, Wrona J, Sienkiewicz M, Czernicki J. A comparative analysis of analgesic efficacy of ultrasound and shock wave therapy in the treatment of patients with inflammation of the attachment of the plantar fascia in the course of calcaneal spurs. Arch Orthop Trauma Surg. 2016; 136: 1289–96.

55. Murtezani A, Ibraimi Z, Vllasolli TO, Sllamniku S, Krasniqi S, Vokrri L. Exercise and Therapeutic Ultrasound Compared with Corticosteroid Injection for Chronic Lateral Epicondylitis: A Randomized Controlled Trial. Ortop Traumatol Rehabil 2015; 17: 351–7.

56. Bisset L, Paungmali A, Vicenzino B, Beller E. A systemic review for lateral epicondylagia. Br J Sports Med 2005; 39: 411–22.

57. Bjordal JM, Lopes–Martins R, Joensen J, Couppe Ch, Ljunggren AE, et al. A systemic review with procedural assessments and meta-analysis of Low Level Laser Therapy in lateral elbow tendinopathy (tennis elbow). BMS Musculoskeletal Disorders 2008; 9: 1–15.

58. Tumilty S, Munn J, McDonough S, Hurley DA, Basford JR, Baxter GD. Low laser treatment of tendinopathy: a systemic review with misanalysis. Photomed Laser Surg 2010; 28: 3–16.

59. Buchbinder R, Ptasznik R, Gordon J, Buchanan J, Prabaharan V, Forbes A. Ultrasound – Guided Extracorporeal Shock Wave Therapy for Plantar fasciitis. JAMA 2002; 288: 1364–72.

60. Maley DS, Pressman MM, Assili A, Kline JT. York Shane Extracorporeal shockwave therapy versus placebo for the treatment of chronic proximal plantar fasciitis: results of a randomized, placebo-controlled, double blinded, multicenter intervention trial. Foot; &Ankle Surgery 2006; 45: 196–210.

61. Gossec L, Coates LC, de Wit M, Kavanaugh A, Ramiro S, et al. Management of psoriatic arthritis in 2016: a comparison of EULAR and GRAPPA recommendations. Nat Rev Rheumatol. 2016; 12: 743–50.

62. Coates LC, Kavanaugh A, Mease PJ, Soriano ER, Acosta-Felquer ML, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations for Psoriatic Arthritis. Arthritis Rheum 2016; 68: 1060–71.

63. Gossec L, Smolen JS, Ramiro S, de Vit M, Cutolo M, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis 2016; 75: 499–510.

64. Ramiro S, Smolen JS, Landewé R, van der Heijde D, Dougados M, et al. Pharmacological treatment of psoriatic arthritis: a systemic literature review for the 2015 update of the EULAR recommendations for the management of psoriatic arthritis. Ann Rheum Dis 2016; 75: 490–8.

65. Ward MW, Deodhar A, Akl EA, Lui A, Ermann J, et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendation for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheum 2016; 68: 282–98.

66. Taylor WJ, St. Clair EW. Shifting the goal post: treatment recommendations for ankylosing spondylitis and the newly defined condition of nonradiographic axial spondyloarthritis. Arthritis Rheum 2016; 68: 265–9.

67. van der Heijde D, Ramiro S, Landewé R, Baraliakos X, Van den Bosch F, et al. 2016 update of the ASAS–EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 2017, publikováno on-line.

68. Sepriano A, Regel A, van der Heijde D, Braun J, Baraliakos X, et al. Efficacy and safety of biological and targeted–synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis. RMD Open 2017, publikováno on-line.

69. Osman MS, Maksymowych WP. An update of the use of tumour necrosis factor alpha inhibitors in the treatment of ankylosing spondylitis. Expert Rev Clin Immunol. 2017; 13: 125–31.

70. Orbai AM, de Wit M, Mease PJ, Callis Duffin K, Elmamoun M, et al. Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016. J Rheumatol. 2017, publikováno on-line.

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