Radiographic Progression In Psoriatic Arthritis Research Articles

Biologic Disease-Modifying Antirheumatic Drugs for Preventing Radiographic Progression in Psoriatic Arthritis: A Systematic Review and Network Meta-Analysis.

The prevention of joint deformity is among the most important treatment goals of psoriatic arthritis. Some biologics disease-modifying antirheumatic drugs (bDMARDs) have been demonstrated to be effective for both the skin and joints, as well as for slowing radiographic progression. However, there has been a lack of direct comparisons of bDMARDs. To evaluate the comparative effects of bDMARDs in preventing radiographic progression in psoriatic arthritis, we conducted a systematic review and network meta-analysis. On March 7 2022, a search for relevant randomized trials was conducted on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Our outcomes included radiographic non-progression, a mean change in the total radiographic score, and adverse events leading to discontinuation (DAE) at week 24. We included 11 trials on 10 bDMARDs, involving 4010 participants. Most bDMARDs were more effective than placebos in achieving radiographic non-progression, including adalimumab (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.66–8.29), etanercept (OR 4.19, 95% CI 1.65–10.61), certolizumab pegol (OR 2.83, 95% CI 1.55–5.2), secukinumab 300 mg (OR 2.63, CI 1.62–4.27), infliximab (OR 2.54, CI 1.13–5.69), ixekizumab (OR 2.22, 95% CI 1.06–4.65), golimumab (OR 2.21, 95% CI 1.24–3.93), and abatacept (OR 1.54, 95% CI 1.03–2.28). A significant reduction in the total radiographic score was found in infliximab (standardized mean difference (SMD) −0.59, 95% CI −0.87, −0.3), etanercept (SMD −0.51, 95% CI −0.78, −0.23), adalimumab (SMD −0.45, 95% CI −0.64, −0.26), ixekizumab (SMD −0.37, 95% CI −0.62, −0.12), secukinumab 300 mg (SMD −0.33, 95% CI −0.50, −0.15), golimumab (SMD −0.33, 95% CI −0.58, −0.09), secukinumab 150 mg (SMD −0.25, 95% CI −0.43, −0.07), certolizumab pegol (SMD −0.23, 95% CI −0.44, −0.03), and ustekinumab (SMD −0.19, 95% CI −0.35, −0.33). No significant differences in DAE were detected between bDMARDs. In conclusion, anti-tumor necrosis factor agents (adalimumab, infliximab, and etanercept) may be preferred for treating psoriatic arthritis for their superiority in preventing radiographic progression.

Radiographic Progression Inhibition with Intravenous Golimumab in Psoriatic Arthritis: Week 24 Results of a Phase III, Randomized, Double-blind, Placebo-controlled Trial

Evaluate effects of intravenous (IV) golimumab (GOL) on radiographic progression in psoriatic arthritis (PsA). This phase III, randomized, double-blind, placebo-controlled trial (GO-VIBRANT) randomized patients with active PsA to receive IV placebo (n = 239) or IV GOL 2 mg/kg (n = 241) at weeks 0, 4, 12, and 20. Radiographic progression (controlled secondary endpoint) was evaluated as change from baseline at Week 24 in PsA-modified total Sharp/van der Heijde scores (SvdH). The proportions of patients with a change from baseline at Week 24 in the total PsA-modified SvdH exceeding the smallest detectable change (SDC) or > 0 or 0.5 also were determined. Overall, 474 patients (237/arm) contributed radiographic data. Results obtained from the 2 blinded, independent radiographic readers demonstrated good agreement (total score intraclass correlation coefficients: baseline = 0.93, Week 24 = 0.92, Week 24 change score = 0.73). GOL demonstrated significant inhibition of radiographic progression relative to placebo from baseline to Week 24 (mean changes in PsA-modified total SvdH: -0.36 vs 1.95; treatment difference: -2.32; p < 0.001). At Week 24, smaller proportions of GOL- versus placebo-treated patients demonstrated an increase in the total PsA-modified SvdH score exceeding the SDC (8.0% vs 27.0%, respectively; difference: -19.0%; p < 0.001), > 0 (28.3% vs 57.0%, respectively; difference: -28.7%; p < 0.001), or > 0.5 (18.6% vs 41.8%, respectively; difference: -23.2%; p < 0.001). Results were consistent for erosion and joint space narrowing scores, in hands and feet, and in patients with/without baseline concomitant methotrexate use. Prevention of radiographic progression by GOL was independent of clinical response. IV GOL is significantly better than placebo in inhibiting radiographic progression of structural damage in active PsA. [Clinical trial registration number (www.ClinicalTrials.gov): NCT02181673].

Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity.

ObjectivesTo evaluate the relationship between radiographic progression and disease activity in subjects with PsA treated with adalimumab (ADA) or placebo (PBO) and the impact of concomitant MTX.MethodsThis was a post hoc analysis of the randomized, double-blind, PBO-controlled ADEPT trial. Subjects were categorized according to time-averaged (TA) disease activity (remission, low, moderate or high) based on Disease Activity Score of 28 joints with CRP [DAS28(CRP)], Disease Activity Index for Psoriatic Arthritis (DAPSA) or Psoriatic Arthritis Disease Activity Score (PASDAS), and achievement of minimal disease activity (MDA) at week 24. Radiographic progression was assessed as change in modified total Sharp score (ΔmTSS) from baseline to week 24. The analyses included interaction terms between disease activity and treatment on radiographic progression, comparison of radiographic progression in subjects categorized by disease activity and treatment, and correlation between disease activity and radiographic progression by treatment.ResultsThe interaction terms for TA disease activity and treatment on ΔmTSS were significant (P = 0.002–0.008). Irrespective of concomitant MTX, ΔmTSS was lower with ADA vs PBO in all disease activity categories. Importantly, even in subjects having moderate or high disease activity or not achieving MDA, ΔmTSS was significantly lower on ADA than PBO (P = 0.05–0.001 for TA-DAPSA, TA-PASDAS and MDA). Correlations between TA disease activity scores and ΔmTSS were moderately positive and significant (P < 0.001) with PBO but non-significant with ADA.ConclusionAmong subjects with PsA treated with ADA, there was evidence of a ‘disconnect’ between disease activity and radiographic progression: inhibition of radiographic progression was greater than expected based on control of clinical disease activity alone. MTX had no added effect.Trial registrationClinicalTrials.gov, http://clinicaltrials.gov, NCT00646386.

Psoriatic arthritis is associated with bone loss of the metacarpals.

BackgroundBoneXpert (BX) is a newly developed medical device based on digital X-ray radiogrammetry to measure human cortical bone thickness. The aim of this study was to quantify cortical bone loss of the metacarpals in patients with psoriatic arthritis (PsA) and compare these findings with other radiological scoring methods.MethodsThe study includes 104 patients with verified PsA. The BX method was used to measure the Metacarpal Index (MCI) at the metacarpal bones (II–IV). Additionally, the T-score of the MCI (T-scoreMCI) was calculated. Radiographic severity was determined by the Psoriatic Arthritis Ratingen Score (Proliferation Score and Destruction Score) as published by Wassenberg et al. and the Psoriatic Arthritis modified van der Heijde Sharp Score (Joint Space Narrowing Score and Erosion Score).ResultsFor the total PsA study cohort, the T-scoreMCI was significantly reduced by −1.289 ± 1.313 SD. The MCI negatively correlated with the Proliferation Score (r = −0.732; p < 0.001) and the Destruction Score (r = −0.771; p < 0.001) of the Psoriatic Arthritis Ratingen Score. Lower coefficients of correlations were observed for the Psoriatic Arthritis modified van der Heijde Sharp Score. In this context, a severity-dependent and PsA-related periarticular demineralisation as measured by the MCI was quantified. The strongest reduction of −30.8 % (p < 0.01) was observed for the MCI in the Destruction Score.ConclusionsThe BX MCI score showed periarticular demineralisation and severity-dependent bone loss in patients with PsA. The measurements of the BX technique were able to sensitively differentiate between the different stages of disease manifestation affecting bone integrity and thereby seem to achieve the potential to be a surrogate marker of radiographic progression in PsA.

Biological agents in psoriatic arthritis.

Anti-tumor necrosis factors (TNFs) are effective drugs for the treatment of psoriatic arthritis (PsA) regarding reduction of pain and inflammation, enthesitis, dactylitis, as well as psoriatic skin and nail disease. Moreover, radiographic progression in PsA is decelerated. The efficacy of anti-TNFs seems to be independent of synthetic disease-modifying anti-rheumatic drugs, suggesting only a minor role of combination therapy in PsA. Anti-TNFs are generally well tolerated in patients with PsA. Adverse events are similar to those reported in patients with rheumatoid arthritis. Ustekinumab, a recently approved IL-12/IL-23-antibody is another promising biological agent in the treatment of PsA.

Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials

ObjectiveEvaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA).MethodsWe conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3,...

SAT0290 Effect of tnf antagonists on radiographic progression in psoriatic arthritis: Systematic review and meta-analysis of randomized controlled trials

BackgroundPsoriatic arthritis (PsA) can cause important structural damages which can lead to disability. TNF antagonists have shown their clinical efficacy in PsA, but only a few data are available regarding...

Biomarkers of Radiographic Progression in Psoriatic Arthritis: A Report from the GRAPPA 2011 Annual Meeting

Clinical markers of radiographic progression have been studied in patients with psoriatic arthritis (PsA), and results have clearly confirmed the progression of radiographic damage over a 2-year period. Biomarkers of radiographic progression damage (erosion and new bone formation) have also been identified as a critical research issue in these patients. At the 2011 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members discussed development of a pivotal observational study (PsA Biodam study) to determine the validity of several soluble biomarkers in predicting structural damage in patients with PsA receiving standard therapies. Specific protocol issues discussed were the inclusion criteria, selection of candidate biomarkers, timing of sample collection, the primary radiographic outcome measure, radiographic scoring methods, possible substudies, and funding strategies.

The Path Forward to Biomarker Discovery in Psoriatic Disease: A Report from the GRAPPA 2010 Annual Meeting

At the 2010 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), wide-ranging discussions were held regarding biomarker research in psoriatic disease. Consensus was reached on 2 areas of priority: (1) the study of soluble biomarkers of radiographic progression in psoriatic arthritis (PsA); and (2) the analysis of comorbidity biomarkers, specifically cardiovascular and articular, in a psoriasis inception cohort. For each of these areas, rigorous definition of the clinical phenotype of PsA will be essential. To date, 2 instruments have been identified to define the phenotype: the ClASsification of Psoriatic ARthritis criteria and various screening questionnaires. In this overview, we discuss the challenges of the clinical phenotype of PsA and review GRAPPA plans for developing a research program for biomarker discovery.

Clinical efficacy of TNF-α inhibitors: an update

Over the last decade, TNF-α antagonists became the most powerful tools for controlling patient suffering from a number of rheumatic diseases. Infliximab, etanercept and adalimumab can induce remission and prevent both clinical and radiological disease progression in rheumatoid arthritis with significant improvement in patients’ symptoms, function and quality of life. They improve joint symptoms and significantly retard radiographic progression in psoriatic arthritis. TNF-α antagonists have been demonstrated to reduce disease activity, retard radiologic progression and increase quality of life in ankylosing spondylitis patients. Long-term follow-up studies demonstrated sustained efficacy and acceptable safety profiles that were comparable in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. Etanercept is the only US FDA-approved TNF antagonist for juvenile rheumatoid arthritis. TNF-α antagonists may improve some clinical manifastations of Behcet’s disases, including uveitis. Tuberculosi...

Risk factors for radiographic progression in psoriatic arthritis: subanalysis of the randomized controlled trial ADEPT

IntroductionTo identify independent predictors of radiographic progression in psoriatic arthritis (PsA) for patients treated with adalimumab or placebo in the Adalimumab Effectiveness in PsA Trial (ADEPT).MethodsUnivariate analyses and multivariate linear regression analyses assessed risk for radiographic progression (change in modified total Sharp score, ΔmTSS > 0.5) from baseline to week 24 for C-reactive protein (CRP) and other baseline variables, and for 24-week time-averaged CRP (univariate analysis only). Subanalyses determined mean ΔmTSS for CRP subgroups. Analyses were post hoc, with observed data.ResultsOne hundred and forty-four adalimumab-treated patients and 152 placebo-treated patients were assessed. Mean CRP was 64% lower by week 2 with adalimumab and essentially unchanged with placebo. Univariate analyses indicated that elevated CRP at baseline and time-averaged CRP were strongly associated with radiographic progression for placebo-treated patients but not for adalimumab-treated patients. Multivariate analysis confirmed that elevated baseline CRP was the only strong independent risk factor for radiographic progression (for CRP ≥1.0 mg/dl: odds ratio = 3.28, 95% confidence interval = 1.66 to 6.51, P < 0.001). Adalimumab treatment reduced risk of progression approximately fivefold. The difference between mean ΔmTSS for adalimumab versus placebo was greatest for patients with baseline CRP ≥2.0 mg/dl (-0.5 vs. 2.6).ConclusionsSystemic inflammation in PsA, as indicated by elevated baseline CRP, was the only strong independent predictor of radiographic progression. This association was observed predominantly for placebo-treated patients. Adalimumab treatment substantially reduced the overall risk of radiographic progression, and provided greatest radiographic benefit for patients with the greatest CRP concentrations at baseline.Trial RegistrationTrial registration: NCT00195689.

Effectiveness of psoriatic arthritis therapies

Objective: To review the effectiveness of systemic therapies for psoriatic arthritis (PsA). Methods: Data on the efficacy of PsA therapies from selected literature, including American and international medical journals and recent abstracts from key rheumatology meetings, were reviewed. Results: Most therapeutic agents used to treat PsA are used on the basis of data from patients with rheumatoid arthritis (RA), and have not been adequately assessed in patients with PsA. However, the progressively destructive nature of the disease demands aggressive treatment with agents tested specifically in PsA. Conventional agents used to treat RA, such as methotrexate and sulfasalazine, have adverse effects that often lead to drug discontinuation and may not always be effective in reducing symptoms or radiographic progression in PsA. Newer medications, such as etanercept and infliximab, specifically inhibit the actions of tumor necrosis factor, which plays a major role in joint destruction. The Food and Drug Administration has recently approved etanercept for treatment of PsA. Current data with infliximab are limited to small open-label trials; however, randomized controlled trials are underway. Conclusions: PsA and RA are distinct diseases, and the efficacy and safety of an agent in RA cannot necessarily be equated with efficacy and safety in PsA. For most conventional agents, data from controlled clinical trials in PsA are scant. Etanercept is currently the only therapeutic agent with sufficient data from placebo-controlled, randomized trials to receive a Food and Drug Administration indication for the treatment of PsA. Semin Arthritis Rheum 33:29-37.