PsA Secukinumab XCT Structural Progression Study

Prevention of Metacarpophalangeal Joints Structure Damage in Patients With Psoriatic Arthritis Using Secukinumab

Psoriatic arthritis is related with chronic inflammation and progressive radiographic damages, and it in turn lead to disability and loss in function-ability. Recent advance in treatment pathway through anti IL-17 gives promising clinical improvement. Yet, its effect on radiographic progression remains uncertain. This study aimed to ascertain the effect of secukinumab on structural progression in PsA by evaluation through high resolution peripheral quantative computed tomography (HRpqCT).

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease associated with psoriasis. PsA is associated with distinctive clinical features including changes in skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis. Synovial inflammation in peripheral joints is the most prevalent feature of the disease ranging in severity from mild joint inflammation to disabling peripheral arthritis [1]. Within 2 years of diagnosis, radiological erosions were developed in 47% of the patients [2]. Without proper monitoring and treatment, it will lead to significant structure damage and loss of physical function, and even arthritis mutilans, which is the most severe destructive form of PsA [3]. Prevention of structural damage is one of the primary goals of treating PsA patients to maximise health-related quality of life [4]. Detection of bone erosions in PsA patients is usually achieved by conventional radiographs although the sensitivity is low [5]. High-resolution peripheral quantitative CT (HR-pQCT) is a novel technique for detailed bone microstructure analysis with high reproducibility in assessing bony erosions [6]. With its high spatial resolution of 130 μm, HR-pQCT exhibited a higher sensitivity in detecting erosion compared with radiograph and magnetic resonance imaging (MRI) [7]. Recently, Finzel et al. described an indirect method to assess volume based on measurements of the width and depth of the erosions using HR-pQCT [8]. Quantitative measurement of erosion volume can also be achieved [6]. Using this method, erosion repair under biological disease-modifying antirheumatic drugs (DMARDs) treatment has been demonstrated in patients with rheumatoid arthritis (RA) [8, 9]. Bone apposition at the margin of erosions (osteosclerosis) with the formation of a new cortical lining was associated with a decrease in erosion depth or width, which may indicate either periosteal or endosteal repair processes [8, 9]. Valid measurement of erosion volume using HR-pQCT will facilitate the testing of treatments that may help to heal erosion. Decrease in erosion volume and the presence of osteosclerosis on HR-pQCT could be promising markers for erosion healing. Interleukin 17 (IL-17) is a proinflammatory cytokine which produced by type 17 helper T cells (Th17). It is now considered to be a key cytokine in the pathogenesis of a number of autoimmune disorders in humans including PsA [10]. IL-17 was also reported to be associated with the presence of joint erosion [11]. Recently, secukinumab, an anti-interleukin-17A monoclonal antibody, was reported to be effective in reducing disease activity and decreased the rate of radiographic joint damage compared with placebo [12]. However, whether healing of erosion could occur in PsA has never been evaluated. On the other hand, osteophytes formation at the entheseal regions of the joints in PsA is distinctive feature compared with RA [13]. The formation of osteophytes is tightly regulated by anabolic pathways, which resembles the pathogenesis of new bone formation in ankylosing spondylitis (AS). Tumor necrosis factor (TNF) inhibition was unable to halt the structural progression in AS patients [14-16], it also lacked efficacy in stopping the progression of osteophytes in PsA patients [17]. Inhibition of IL-17 by secukinumab was effective in the treatment of both AS [18] and PsA [12]. Secukinumab also decreased the rate of radiographic joint damage regarding to erosion and joint space narrowing [12]. However, it is unknown if it has any effect in the progression of osteophytes. In an animal model, although over-expression of IL-17 alone failed to induce entheseal and periosteal bone formation, inhibition of IL-17 leaded to significant reduction of such bone formation in an IL-23 overexpression model [19]. Moreover, IL-17A accelerates bone formation by stimulating the proliferation and osteoblastic differentiation of mesenchymal progenitor cells after injury [20]. It is worth exploring if secukinumab could prevent the progression of osteophytes in PsA patients.

Difference in changes in the volume of erosions on metacarpophalangeal joints (MCP) 2-4 measured by HR-pQCT at 24 weeks between secukinumab and placebo group

Difference in changes in the volume of erosions on metacarpophalangeal joints (MCP) 2-4 measured by HR-pQCT at 48 weeks between secukinumab and placebo group

Erosion healing is defined as a decrease in erosion volume of ≥0.4 mm3 from baseline, and the presence of grade 2 osteosclerosis at the margin of erosion

Erosion healing is defined as a decrease in erosion volume of ≥0.4 mm3 from baseline, and the presence of grade 2 osteosclerosis at the margin of erosion

HAQ (0-3) assessing functional disability, with higher score representing higher functional disability.

HAQ (0-3) assessing functional disability, with higher score representing higher functional disability.

SF-36 is a questionnaire representing subject's physical & mental well being ranging from 0-100, with 100 representing better outcome.

SF-36 is a questionnaire representing subject's physical & mental well being ranging from 0-100, with 100 representing better outcome.

The van der Heijde-sharp score assess erosion (0-528) and joint space narrowing (0-208) in x-ray, which higher score represent higher radiographic damages

Inclusion Criteria: ≥18 years old; without severe deformity in MCP joints which would influence the longitudinal assessment of HR-pQCT; with active disease, which is defined as three or more than tender joints and three or more than swollen joints, despite previous treatment with nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs. Exclusion Criteria: limited in ability to perform usual self-care, vocational, and avocational activities; pregnancy; previous therapy with biologic; the presence of active inflammatory diseases other than PsA; active infection in 2 weeks before randomization or a history of ongoing, chronic, or recurrent infections including tuberculosis; history of hepatitis B & C; history of malignant disease within the past 5 years (excluding basal cell carcinoma or actinic keratosis, in-situ cervical cancer, or non-invasive malignant colon polyps); contraindications to secukinumab.

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