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27-07-2018 | Psoriatic arthritis | Article

Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study

Journal: Arthritis Research & Therapy

Authors: Eleni Kampylafka, Isabelle d’Oliveira, Christina Linz, Veronika Lerchen, Fabian Stemmler, David Simon, Matthias Englbrecht, Michael Sticherling, Jürgen Rech, Arnd Kleyer, Georg Schett, Axel J. Hueber

Publisher: BioMed Central

Abstract

Background

Although the effects of interleukin-17A (IL-17A) inhibition on the signs and symptoms of psoriatic arthritis (PsA) are well defined, little is known about its impact of local inflammatory and structural changes in the joints. The PSARTROS study was designed to elucidate the effects of IL-17A inhibition on inflammation and bone changes in joints affected by PsA.

Methods

This was a prospective open-label study in 20 patients with active PsA receiving 24 weeks of treatment with the IL-17A inhibitor secukinumab. Magnetic resonance imaging (MRI), power Doppler ultrasound (PDUS), and high-resolution peripheral quantitative computer tomography (HR-pQCT) of the hands were performed at baseline and after 24 weeks to assess synovitis, periarticular inflammation, bone erosion, enthesiophyte formation, and bone structure. Demographic and clinical measures of joint disease (DAPSA and DAS28-ESR), skin disease (PASI and BSA), and composite measures (minimal disease activity, or MDA) were also recorded.

Results

Treatment with secukinumab led to significant improvement of signs and symptoms of PsA; 46% reached MDA and 52% DAPSA low disease activity. MRI synovitis (P = 0.034) and signal in PDUS (P = 0.030) significantly decreased after 24 weeks of treatment. Bone erosions in MRI and HR-pQCT and enthesiophytes in the HR-pQCT did not show any progression, and structural integrity and functional bone strength remained stable.

Conclusions

IL-17 inhibition by secukinumab over 24 weeks led to a significant decrease of synovial inflammation and no progression of catabolic and anabolic bone changes in the joints of patients with PsA.

Trial registration

ClinicalTrials.gov Identifier: NCT02483234, June 26, 2015; retrospectively registered.
Literature
1.
Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med. 2017;376(21):2095–6.PubMed
2.
Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015;67(1):128–39.CrossRefPubMedPubMedCentral
3.
Mease P. New pathways of treatment for psoriatic arthritis. Lancet (London, England). 2017;389(10086):2268–70.CrossRef
4.
Veale DJ. Psoriatic arthritis: recent progress in pathophysiology and drug development. Arthritis Res Ther. 2013;15(6):224.CrossRefPubMedPubMedCentral
5.
Schett G, Elewaut D, McInnes IB, Dayer JM, Neurath MF. How cytokine networks fuel inflammation: toward a cytokine-based disease taxonomy. Nat Med. 2013;19(7):822–4.CrossRefPubMed
6.
McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, 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 (London, England). 2015;386(9999):1137–46.CrossRef
7.
Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler CL, 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 and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79–87.CrossRefPubMed
8.
Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329–39.CrossRefPubMed
9.
van der Heijde D, Landewe RB, Mease PJ, McInnes IB, Conaghan PG, Pricop L, et al. Brief report: Secukinumab provides significant and sustained inhibition of joint structural damage in a phase III study of active psoriatic arthritis. Arthritis Rheumatol. 2016;68(8):1914–21.CrossRefPubMedPubMedCentral
10.
Schett G, Lories RJ, D’Agostino MA, Elewaut D, Kirkham B, Soriano ER, et al. Enthesitis: from pathophysiology to treatment. Nat Rev Rheumatol. 2017;13(12):731–41.CrossRefPubMed
11.
Koenders MI, Lubberts E, Oppers-Walgreen B, van den Bersselaar L, Helsen MM, Di Padova FE, et al. Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1. Am J Pathol. 2005;167(1):141–9.CrossRefPubMedPubMedCentral
12.
Adamopoulos IE, Chao CC, Geissler R, Laface D, Blumenschein W, Iwakura Y, et al. Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors. Arthritis Res Ther. 2010;12(1):R29.CrossRefPubMedPubMedCentral
13.
Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med. 2006;203(12):2673–82.CrossRefPubMedPubMedCentral
14.
Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103(9):1345–52.CrossRefPubMedPubMedCentral
15.
Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012;18(7):1069–76.CrossRefPubMed
16.
Lories RJ, McInnes IB. Primed for inflammation: enthesis-resident T cells. Nat Med. 2012;18(7):1018–9.CrossRefPubMed
17.
Reinhardt A, Yevsa T, Worbs T, Lienenklaus S, Sandrock I, Oberdorfer L, et al. Interleukin-23-dependent gamma/delta T cells produce Interleukin-17 and accumulate in the Enthesis, aortic valve, and Ciliary body in mice. Arthritis Rheumatol. 2016;68(10):2476–86.CrossRefPubMed
18.
Cuthbert RJ, Fragkakis EM, Dunsmuir R, Li Z, Coles M, Marzo-Ortega H, et al. Brief report: group 3 innate lymphoid cells in human Enthesis. Arthritis Rheumatol. 2017;69(9):1816–22.CrossRefPubMed
19.
Uluckan O, Jimenez M, Karbach S, Jeschke A, Grana O, Keller J, et al. Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. Sci Transl Med. 2016;8(330):330ra337.CrossRef
20.
Kocijan R, Englbrecht M, Haschka J, Simon D, Kleyer A, Finzel S, et al. Quantitative and qualitative changes of bone in psoriasis and psoriatic arthritis patients. J Bone Miner Res. 2015;30(10):1775–83.CrossRefPubMed
21.
Faustini F, Simon D, Oliveira I, Kleyer A, Haschka J, Englbrecht M, et al. Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis. Ann Rheum Dis. 2016;75(12):2068–74.CrossRefPubMed
22.
Ostergaard M, McQueen F, Wiell C, Bird P, Boyesen P, Ejbjerg B, et al. The OMERACT psoriatic arthritis magnetic resonance imaging scoring system (PsAMRIS): definitions of key pathologies, suggested MRI sequences, and preliminary scoring system for PsA hands. J Rheumatol. 2009;36(8):1816–24.CrossRefPubMed
23.
Bruyn GA, Naredo E, Iagnocco A, Balint PV, Backhaus M, Gandjbakhch F, et al. The OMERACT ultrasound working group 10 years on: update at OMERACT 12. J Rheumatol. 2015;42(11):2172–6.CrossRefPubMed
24.
D’Agostino MA, Boers M, Wakefield RJ, Berner Hammer H, Vittecoq O, Filippou G, et al. Exploring a new ultrasound score as a clinical predictive tool in patients with rheumatoid arthritis starting abatacept: results from the APPRAISE study. RMD Open. 2016;2(1):e000237.CrossRefPubMedPubMedCentral
25.
Figueiredo CP, Kleyer A, Simon D, Stemmler F, d’Oliveira I, Weissenfels A, et al. Methods for segmentation of rheumatoid arthritis bone erosions in high-resolution peripheral quantitative computed tomography (HR-pQCT). Semin Arthritis Rheum. 2018;47(5):611–8.CrossRefPubMed
26.
Finzel S, Sahinbegovic E, Kocijan R, Engelke K, Englbrecht M, Schett G. Inflammatory bone spur formation in psoriatic arthritis is different from bone spur formation in hand osteoarthritis. Arthritis Rheumatol. 2014;66(11):2968–75.CrossRefPubMed
27.
Macneil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone. 2008;42(6):1203–13.CrossRefPubMed
28.
Smolen JS, Schoels M, Aletaha D. Disease activity and response assessment in psoriatic arthritis using the disease activity index for PSoriatic arthritis (DAPSA). A brief review. Clin Exp Rheumatol. 2015;33(5 Suppl 93):S48–50.PubMed
29.
Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis. 2010;69(1):48–53.CrossRefPubMed
30.
Lackner A, Duftner C, Ficjan A, Gretler J, Hermann J, Husic R, et al. The association of clinical parameters and ultrasound verified inflammation with patients’ and physicians’ global assessments in psoriatic arthritis. Semin Arthritis Rheum. 2016;46(2):183–9.CrossRefPubMed
31.
Finzel S, Englbrecht M, Engelke K, Stach C, Schett G. A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis. Ann Rheum Dis. 2011;70(1):122–7.CrossRefPubMed
32.
Finzel S, Kraus S, Schmidt S, Hueber A, Rech J, Engelke K, et al. Bone anabolic changes progress in psoriatic arthritis patients despite treatment with methotrexate or tumour necrosis factor inhibitors. Ann Rheum Dis. 2013;72(7):1176–81.CrossRefPubMed
33.
Shaw AT, Maeda Y, Gravallese EM. IL-17A deficiency promotes periosteal bone formation in a model of inflammatory arthritis. Arthritis Res Ther. 2016;18(1):104.CrossRefPubMedPubMedCentral