Deepak R. Jadon

Serum bone-turnover biomarkers are associated with the occurrence of peripheral and axial arthritis in psoriatic disease:a prospective cross-sectional comparative study

BackgroundA recent systematic review identified four candidate serum-soluble bone-turnover biomarkers (dickkopf-1, Dkk-1; macrophage-colony stimulating factor, M-CSF; matrix metalloproteinase-3, MMP-3; osteoprotegerin, OPG) showing possible association with psoriatic arthritis (PsA). We aimed to: (i) confirm and determine if these four biomarkers are associated with PsA; (ii) differentiate psoriasis cases with and without arthritis; and (iii) differentiate PsA cases with and without axial arthritis.MethodsA prospective cross-sectional comparative two-centre study recruited 200 patients with psoriasis without arthritis (PsC), 127 with PsA without axial arthritis (pPsA), 117 with PsA with axial arthritis (psoriatic spondyloarthritis, PsSpA), 157 with ankylosing spondylitis (AS) without psoriasis, and 50 matched healthy controls (HC). Serum biomarker concentrations were measured using ELISA. Multivariable regression and receiver operating characteristic analyses were performed.ResultsMMP-3 concentrations were significantly higher and M-CSF significantly lower in each arthritis disease group compared with HC (pu2009≤u20090.02). MMP-3 concentrations were significantly higher (adjusted odds ratio, ORadj 1.02 per ng/ml increase in concentration; pu2009=u20090.0004) and M-CSF significantly lower (ORadj 0.44 per ng/ml increase; pu2009=u20090.01) in PsA (pPsA and PsSpA combined) compared with PsC. Dkk-1 concentrations were significantly higher (ORadj 1.22 per ng/mL increase; pu2009=u20090.01), and OPG concentrations significantly lower (ORadj 0.20 per ng/mL increase; pu2009=u20090.02) in patients with axial arthritis (PsSpA and AS combined) than in those without (pPsA). Furthermore, Dkk-1 concentrations were significantly higher along a spectrum of increasing axial arthritis; Dkk-1 concentrations were higher in AS compared with PsSpA (ORadj 1.18 per ng/mL increase; pu2009=u20090.02). Receiver operating characteristic analysis showed MMP-3 to be the best single biomarker for differentiating PsA from PsC (AUC 0.70 for a cut-off of 14.51xa0ng/mL; sensitivity 0.76, specificity 0.60).ConclusionsMMP-3 and M-CSF are biomarkers for the presence of arthritis in psoriatic disease, and could therefore be used to screen for PsA in psoriasis cohorts. Dkk-1 and OPG are biomarkers of axial arthritis; they could therefore be used to screen for the presence of axial disease in PsA cases, and help differentiate PsSpA from AS. High concentrations of Dkk-1 in AS and PsSpA compared with HC, support previous reports that Dkk-1 is dysfunctional in the spondyloarthritides.

Prevalence and predictors of tumour necrosis factor inhibitor persistence in psoriatic arthritis

ObjectivesnTo evaluate TNF-α inhibitor (TNFi) persistence when used as first- or second-line biologic therapy for the management of PsA, and to determine baseline clinical and laboratory parameters associated with TNFi persistence.nnnMethodsnA retrospective single-centre cohort study was performed on all patients with PsA initiated on TNFi therapy between 2003 and 2015. Demographic, clinical and laboratory characteristics were compared with TNFi persistence, using Kaplan-Meier survival and Cox proportional hazards models.nnnResultsnOne hundred and eighty-eight patients with PsA were prescribed TNFi therapy as first-line biologic therapy over a period of 635 person-years [46% male, mean (s.d.) age 47.3 (11.4) years; median (interquartile range) disease duration 11 (7-16) years]. At 12 months of follow-up 79% of patients persisted with TNFi therapy, and 73% at 24 months. Of those discontinuing TNFi, 35% stopped due to primary inefficacy, 22% secondary inefficacy and 43% adverse events. Multivariable analysis identified female sex (hazard ratio (HR) 2.57; 95% CI: 1.26, 5.24; P = 0.01) and the presence of metabolic syndrome-related co-morbidities (HR = 2.65, 95% CI: 1.24, 5.69; P = 0.01) as predictors of lower persistence. Of 32 cases treated with a second TNFi, persistence at 12 months was 56%. TNFi persistence was 2-fold less likely in these 32 cases compared with first-line TNFi users (HR = 2.02, 95% CI: 1.20, 3.42; P = 0.01).nnnConclusionnPatients with PsA who are female and have metabolic syndrome-related co-morbidities have lower TNFi persistence. Although persistence was lower in patients who had switched to a second TNFi, a substantial proportion of these cases responded, advocating switching to a second TNFi as a valid therapeutic strategy.

Trajectory of radiographic change over a decade: the effect of transition from conventional synthetic disease-modifying antirheumatic drugs to anti-tumour necrosis factor in patients with psoriatic arthritis

ObjectivesnTo describe the trajectory of radiographic progression among patients with PsA who transitioned from conventional synthetic DMARDs to anti-TNF-α inhibitors in routine care.nnnMethodsnA retrospective sample of patients with PsA (ClASsification criteria for Psoriatic ARthritis) was taken from the Bath longitudinal cohort. All patients had radiographs of the hands and feet taken: 5 years before (T0), at the time of (T1) and 5 years after (T2) commencing anti-TNF treatment. Radiographs were scored blinded using the PsA-modified Sharp-van der Heijde score (mSvdHS) and for osteoproliferation (Psoriatic Arthritis Ratingen Score) by A.Allard, A.Antony and W.T. This sample size was calculated to ensure 90% power to determine the smallest detectable difference of the mSvdHS to a 5% significance level. Cumulative probability plots were used to determine the probability of radiographic progression pre- (T0-T1) and post- (T1-T2) anti-TNF treatment.nnnResultsnEighty-four radiographs from 28 patients were selected for inclusion. The median [interquartile range (IQR)] disease duration at baseline (T0) was 8.5 (0-19.5) years. The interval between T0-T1 and T1-T2 was 4.2 years (3.34-6.65) and 4.9 years (4.25-5.87), respectively. The median mSvdHS at baseline (T0) was 8.5 (IQR 1.75-27.5). The median (IQR) rate of change in mSvdHS per year reduced after commencing anti-TNF, from 2.1 (0.88-3.92) between T0-T1 to 1.0 (IQR 0.05-2.35) between T1-T2 (P = 0.012).nnnConclusionnThe trajectory of damage accumulation over a 10-year period in this observational clinical cohort is low overall. The rate of radiographic damage as measured by the mSvdHS slows following commencement of anti-TNF.

AB0908 Ability of the reductive x-ray score for psoriatic arthritis (REXSPA) to detect change in an observational cohort of patients with psa

Background The measurement of radiographic joint damage is important in characterising disease severity, progression, and prognosis in psoriatic arthritis (PsA). Existing radiographic measures are time-consuming to perform, leading to limited data collection from existing longitudinal observational studies. Objectives We have previously proposed a Reductive X-ray Score for Psoriatic Arthritis (ReXSPA)1 as more feasible method, and in this study set out to examine the sensitivity of ReXSPA in a new cohort of patients. Methods A retrospective sample of 28 patients who had hand and feet radiographs at 3 time points (5 years before [T0], at the time of [T1], and 5 years post [T2] commencement of anti-TNF treatment) were taken from the Bath longitudinal PsA cohort. Radiographs were scored for erosion, joint space narrowing and proliferation to calculate the Sharp-van der Heijde modified method (VDH) and ReXSPA scores. A sample of 9 radiographs were scored by all assessors (WT, AA and AA) to determine inter- and intra-rater reliability using intra-class correlation coefficients (ICC). Sensitivity to change was determined from timepoint T0 to T2 using the Standardised Response Mean (SRM) and Smallest Detectable Change (SDC). Results The patients’ mean age (SD) at T0 was 61 years (13.4), the mean disease duration was 11.2 years (11.14). Patients were followed up for a mean (SD) of 10.2 years (2.76). Overall inter- and intra-rater reliability for ReXSPA and VDH were 0.80 and >0.92u2009and 0.91 and >0.90u2009respectively. The median (IQR) of ReXSPA score was 8.5 (1–14), 12.5 (5–20) and 14.5 (8–36) at T0, T1, and T2 respectively. The percentage SDC was 0.91 for the ReXSPA method and 0.77 for the VDH method, and the SRMs were 0.92 and 0.87 respectively (table 1), demonstrating the sensitivity of both methods in detecting change. There was a trend towards slowing in radiographic progression following the initiation of TNF-inhibitors, but ReXSPA was less sensitive compared to the VDH and was not able to detect a significant change in the rate of progression post-TNF inhibition (p 0.08) (Graphic 1).Abstract AB0908 – Table 1 Sensitivity to change of each scoring method Method Mean Change SD of change SEM SRM SDC SDC as% of total score VDHErosionJSN 22.117.2916.96 19.1410.6215.17 3.622.012.87 0.871.460.89 4.092.273.24 0.770.711.56 ReXPSAErosionJSNProliferation 10.93.216.360.96 10.05.315.112.32 1.891.000.970.44 0.921.650.802.40 2.141.131.090.50 0.911.031.241.39 Sharp-van der Heijde modified method (VDH), Standard deviation (SD), Standard error of mean (SEM), Standardised response mean (SRM), Smallest detectable change (SDC).Abstract AB0908 – Figure 1 Cumulative probability plot demonstrating ReXSPA progression pre- and post- TNF inhibition Conclusions The RexSPA is a reliable and sensitive alternate scoring method for the detection of radiographic progression in an observational cohort of patients with PsA, but not as sensitive to change as the VDH method. Reference [1] Tillett W, et al. (2016) Novel Composite Radiographic Score for Longitudinal Observational Studies of Psoriatic Arthritis: A Proof-of-concept Study. J Rheum; 43(2):367–370 Disclosure of Interest None declared

THU0391 Axial Disease in Psoriatic Arthritis () Study: Serum-Soluble Bone-Turnover Biomarkers of Psoriatic Arthritis Phenotypes

Background Psoriatic spondyloarthritis (PsSpA), peripheral-only psoriatic arthritis (pPsA) and ankylosing spondylitis (AS) are characterised by differing patterns of osteoproliferation and bone resorption, which may be reflected by levels of serum-soluble bone-turnover biomarkers. Objectives To investigate four such potential biomarkers (Dkk-1, M-CSF, MMP-3 and OPG) as predictors of: (i) PsSpA occurrence; (ii) axial radiographic severity; (iii) psoriatic arthritis mutilans (PAM) occurrence. Methods A prospective single-centre cross-sectional study (ADIPSA) recruited pPsA (n=127; fulfilling CASPAR criteria), PsSpA (n=118; psoriasis with radiographic sacroiliitis and/or spondylitis) and AS (n=157; fulfilling modified New York criteria) cases, and assessed them clinically, radiographically, and in terms of serum biomarkers. Serum was obtained from two other centres of clinically characterised psoriasis-only (PsC; n=200) cases, and sex/age-matched healthy controls (HC; n=50). ELISA was used to measure serum Dkk-1, M-CSF, MMP-3 and OPG concentrations. Multivariable regression analyses compared serum concentrations across disease groups. Results OPG is a biomarker of axial disease in spondyloarthritis (SpA) cases; concentrations were significantly lower in SpA cases with axial disease (RAD) than in those without (non-RAD) (adjusted odds ratio, ORadj 0.20 per ng/ml increase in concentration; 95%CI 0.05, 0.80; p=0.02), independently of having psoriasis. Dkk-1 is a biomarker of axial disease in SpA cases, with a pattern for increasing concentration along a spectrum of increasing axial involvement. Dkk-1 concentrations were significantly higher in SpA cases with axial disease than in those without (ORadj 1.22; 95%CI 1.05, 1.42; p=0.01), independently of having psoriasis, and significantly lower in PsSpA than AS cases (ORadj 0.85; 95%CI 0.74, 0.98; p=0.02). M-CSF is a biomarker of arthritis. Compared with HC, M-CSF concentrations were significantly lower in pPsA (ORadj 0.14; 95%CI 0.06, 0.32; p<1x10–5), PsSpA (ORadj 0.07; 95%CI 0.03, 0.17; p<1x10–8), and AS (ORadj 0.37; 95%CI 0.16, 0.85; p<1x10–7). Similarly, M-CSF concentrations were significantly lower in PsA than PsC cases (ORadj 0.44; 95%CI 0.24, 0.82; p=0.01). MMP-3 is a biomarker of arthritis. Compared with HC, MMP-3 concentrations were significantly higher in pPsA (ORadj 1.06; 95%CI 1.01, 1.10; p=0.02), PsSpA (ORadj 1.06; 95%CI 1.01, 1.11; p=0.02), and AS (ORadj 1.06; 95%CI 1.01, 1.11; p=0.01). Similarly, MMP-3 concentrations were significantly higher in PsA than PsC cases (ORadj 1.02; 95%CI 1.01, 1.03; p=0.0004). There were no significant associations between biomarkers and either morphology or radiographic severity (mSASSS or PASRI). Biomarker levels were no different in PsA cases with/without PAM. Conclusions OPG and Dkk-1 appear to be biomarkers of axial disease in SpA patients (pPsA, PsSpA, AS), independently of cutaneous psoriasis status. M-CSF and MMP-3 appear to be biomarkers of arthritis, but dont differentiate SpA phenotypes. No biomarkers for PAM occurrence in PsA were found. The high concentration of Dkk-1 in AS and PsSpA, supports previous evidence that Dkk-1 is dysfunctional in axial SpA. Disclosure of Interest None declared