Radiographic Progression In Patients Research Articles

Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials

BackgroundFew clinical trials have investigated the prevention of radiographic progression in children with juvenile idiopathic arthritis treated with antirheumatic drugs. This study aimed to investigate radiographic progression in patients with systemic juvenile idiopathic arthritis (sJIA) and patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with the anti–interleukin-6 receptor antibody tocilizumab for 2 years in the TENDER and CHERISH randomized controlled trials, respectively.MethodsStandard radiographs of both wrists and both hands in the posteroanterior view were obtained within 4 weeks of baseline and were repeated at weeks 52 ± 4 and 104 ± 4 in both trials. All films were scored by two independent readers using the adapted Sharp–van der Heijde (aSH) and Poznanski scoring methods. Although the Poznanski score indicates bone growth limitation or cartilage growth decrease, which are not the same as joint space narrowing in rheumatoid arthritis, its change reflects damage to cartilage. Therefore, impairment in the Poznanski score as well as the aSH score was considered as a measure of structural joint damage. Radiographic progression was defined as worsening of radiographic scores beyond the smallest detectable difference.ResultsPoznanski and aSH scores were available at baseline and at one or more postbaseline time points for 33 and 47 of 112 sJIA patients and 61 and 87 of 188 pcJIA patients, respectively, providing a representative subset of the study populations. The inter-reader and intra-reader agreement intra-class correlation coefficient was > 0.8. Median baseline Poznanski and aSH scores, respectively, were − 2.4 and 24.6 for sJIA patients and − 1.5 and 8.0 for pcJIA patients. Compared with baseline, aSH scores remained stable for all sJIA patients at week 52, whereas 9.4% of sJIA patients had radiographic progression according to Poznanski scores at week 52; at 104 weeks, radiographic progression according to aSH and Poznanski scores was observed in 5.4% and 11.5%, respectively. In pcJIA patients, radiographic progression from baseline at 52 weeks and at 104 weeks was 12.5% and 2.9%, respectively, using aSH scoring and 6.5% and 4%, respectively, using Poznanski scoring.ConclusionTocilizumab may delay radiographic progression in children with sJIA and children with pcJIA.Trial registrationTrial registration numbers and dates: TENDER, NCT00642460 (March 19, 2008); CHERISH, NCT00988221 (October 1, 2009)

Biomarkers for treatment change and radiographic progression in patients with rheumatoid arthritis in remission: a 5 year follow-up study.

To identify biomarkers of treatment change and radiographic progression in patients with RA under remission. RA patients in remission (DAS28-ESR <2.6) were selected and followed up for 5 years. An MRI of the dominant hand and an US assessment of knees/hands and serum levels of inflammation/angiogenesis biomarkers were performed at baseline and at 12th month. Synovial biopsies were obtained in patients with Power Doppler signal. Conventional radiographies of hands/feet were taken at baseline and after 5 years. Radiographic progression was defined as the change in the modified Sharp van der Heijde Score at 5 years >10.47 (small detectable change). Sixty patients were included, 81.6% were ACPA+ and 45% were taking biological DMARDs. At baseline, 66.6% had Power Doppler signal. After 5 years, 73.3% of patients remained in remission. Change of therapy was performed in 20 patients (33.3%) and was associated with BMI [odds ratio (OR) 1.3, 95% CI: 1, 1.7], lack of biological DMARD therapy (OR 24.7, 95% CI: 2.3, 257.2), first-year progression of MRI erosions (OR 1.2, 95% CI: 1, 1.3) and calprotectin serum levels (OR 2.8, 95% CI: 1, 8.2). Radiographic progression occurred in six (10%) patients. These patients had higher first-year progression of MRI erosions (P = 0.03) and bone oedema (P = 0.04). Among 23 patients undergoing synovial biopsy, mast cell density was independently associated with clinical flares. One-third of RA patients lost clinical remission and changed therapy throughout the 5 years of follow-up, which was independently associated with BMI, lack of biological DMARDs therapy and first-year progression of MRI erosion score and calprotectin serum levels. Significant radiographic progression was uncommon.

Blood platelet volume predicts treatment-specific outcomes of metastatic castration-resistant prostate cancer

In the present guidelines for the management of metastatic castration-resistant prostate cancer (mCRPC), it is unclear who benefits most from androgen receptor axis-targeted agents (ARATs) or docetaxel as the first-line treatment. We conducted a retrospective study to explore new treatment-specific biomarkers in mCRPC. A total of 211 patients with mCRPC who received either ARAT or docetaxel as first-line treatment were included. Patients were compared for radiographic progression and prostate-specific antigen (PSA) progression. Multivariable Cox regression models were used to assess the association between pretreatment biomarkers and risk of events. The statistical interaction between biomarkers and clinical outcomes was also evaluated. Of all analyzed biomarkers, multivariable Cox regression models identified MPV [≤ median (9.7fL)] as an independent prognostic factor of radiographic progression [hazard ratio (HR), 2.35; 95% confidence interval (CI), 1.15-4.80; P = 0.019] and PSA progression (HR, 1.96; 95% CI, 1.01-3.95; P = 0.048) in patients treated with ARAT, whereas such associations were not observed in those treated with docetaxel. Interaction analyses showed that those initially treated with docetaxel have lower risk of radiographic progression (HR, 0.33; 95% CI, 0.13-0.79; P = 0.014) and PSA progression (HR, 0.48; 95% CI, 0.23-0.98; P = 0.044) than ARAT when MPV was small. The present study identified pretreatment MPV as a significant treatment-specific prognostic factor of PSA and radiographic progression in patients with mCRPC who received first-line treatment. Furthermore, our results suggested that those with small MPV may better be treated initially with docetaxel than ARAT.

FRI0107 EFFECTIVENESS OF ABATACEPT ON CLINICAL DISEASE ACTIVITY AND RADIOGRAPHIC PROGRESSION IN RHEUMATOID ARTHRITIS PATIENTS IN DAILY CLINICAL PRACTICE IN JAPAN: COMPARISONS ACCORDING TO ACPA STATUS

Background:The clinical effectiveness of abatacept (ABA) in rheumatoid arthritis (RA) patients has been reported to be higher when the patients’ anti-cyclic citrullinated peptide antibody (ACPA) status is positive. The report from the ORA registry demonstrated that the ACPA positivity was associated with a better response to ABA [1]. In a sub-analysis of the AMPLE trial, patients with very high ACPA titers who were treated with ABA had a statistically significant response compared to patients with lower titers [2]. However, these studies did not demonstrate the data regarding the structural progression.Objectives:This study aimed to evaluate the effectiveness of ABA on the clinical disease activity as well as the radiographic progression in patients with RA in the clinical settings.Methods:All eligible patients were registered in the TBCR, a Japanese multicenter registry system for RA patients treated with biologics [3]. The present study included 553 consecutive patients whose ACPA data were obtained, treated with ABA and observed for longer than 52 weeks. We primarily compared the status of disease activity (SDAI) and radiographic progression (van der Heijde modified total Sharp score: mTSS) between ACPA-positive [ACPA (+)] and ACPA-negative [ACPA (-)] RA patients. The ACPA positive was defined as ≥13.5 U/ml of anti-CCP antibody.Results:Number of cases was 446/ 107 [ACPA (+)/ ACPA (-)], respectively. Baseline characteristics between groups were quite similar; mean age was 68.0/ 67.3 years, rate of methotrexate (MTX) use rate was 41.2/ 50.0%, rate of bio-naive was 28.0/ 31.8%, and mean SDAI score was 22.2/ 20.8. Significant difference was observed in mean change in SDAI score from baseline to 52 weeks between the ACPA (+) and ACPA (-) group (-13.4 vs -9.9, p = 0.027) (Figure 1A). Proportion of patents that achieved low disease activity (LDA; SDAI ≤11) at 52 weeks was significantly higher in the ACPA (+) group compared to the ACPA (-) group (72.1 vs 56.0%, p &lt; 0.01) (Figure 1B). In univariate and multivariate logistic regression analysis, ACPA positivity was an independent predictor for achievement of LDA at 52 weeks (Table). There observed no significant difference between ACPA (+) and ACPA (-) group in the proportion of patients that achieved structural remission (ΔmTSS ≤0.5) at 52 weeks (66.2 vs 62.1%) (Figure 2A) as well as mean change in mTSS (1.66 vs 1.17), erosion score (0.60 vs 0.53), and joint narrowing (JSN) score (1.06 vs 0.64) (Figure 2B).Table.UnivariateMultivariateVariablesOR (95%CI)p-valueadjusted OR (95%CI)p-valueAge0.99 (0.98-1.01)0.4391.00 (0.97-1.02)0.749male (vs female)1.12 (0.70-1.80)0.6340.79 (0.40-1.58)0.511disease duration0.99 (0.97-1.00)0.0530.99 (0.97-1.01)0.468Biologics-naïve1.23 (0.81-1.85)0.3351.18 (0.67-2.08)0.575Concomitant MTX use1.12 (0.75-1.69)0.5851.14 (0.66-1.95)0.649Concomitant PSL use0.82 (0.55-1.23)0.3290.97 (0.58-1.64)0.923SDAI @baseline0.96 (0.94-0.97)&lt;0.0010.96 (0.94-0.98)&lt;0.001mHAQ @baseline0.50 (0.36-0.69)&lt;0.0010.57 (0.38-0.86)0.008ACPA positive2.03 (1.29-3.17)0.0022.61 (1.36-5.00)0.004Bold italic, p&lt;0.05Conclusion:Consistent with previous reports, the ACPA-positive group demonstrated significantly higher LDA achievement rate at 52 weeks and indeed the ACPA positivity was significantly associated with LDA achievement in multivariate analysis. However, the ACPA-negative group demonstrated quite similar transition of SDAI score and LDA achievement rate except at 52 weeks compared with the ACPA-positive group. Additionally, there was no significant difference in the structural progression at 52 weeks between the groups. ABA treatment may be considered not only in the ACPA-positive RA patients but also in the ACPA-negative patients in the clinical practice.

P255 Secukinumab provides sustained improvement in nail psoriasis and inhibition of radiographic progression in PsA patients with nail phenotype: 52-week results from a Phase 3 study

Abstract Background Nail psoriasis (PsO) affects up to 80% of patients with psoriatic arthritis (PsA) and is associated with significant pain, psychosocial disability and decreased physical function and quality of life (QoL). Secukinumab demonstrated efficacy for patients with nail PsO in TRANSFIGURE, and improvements in the signs and symptoms and low radiographic progression in patients with PsA in FUTURE 5 (NCT02404350). We report the efficacy of secukinumab on nail PsO and other disease facets, including radiographic progression, in the nail subset from FUTURE 5 through 52 weeks. Methods Patients (N = 996) with active PsA were randomised to subcutaneous secukinumab 300 mg loading dosage (LD), 150 mg LD, 150 mg no LD or placebo. All groups received secukinumab or placebo at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter. Efficacy assessments through Week 52 included mNAPSI, radiographic progression (mTSS), ACR, PASI, HAQ-DI, SF-36 physical component summary, PsAQoL, and dactylitis and enthesitis resolution. Analyses through Week 16 used non-responder imputation for binary and mixed-effect model repeated measures for continuous variables. Data beyond Week 16 are presented as observed. Results 663/996 (66.6%) of PsA patients had concomitant nail PsO at baseline. Baseline characteristics were balanced between groups. The total mean mNAPSI score at baseline was 16.4. Secukinumab 300 and 150 mg LD, improved nail PsO vs placebo at Weeks 8, 12 and 16 (all P &amp;lt; 0.0001, except secukinumab 150 mg LD vs placebo at Week 8 [p = 0.0002]), with further improvements through Week 52. Mean change from baseline in mTSS score at Weeks 24 and 52 are shown in the Table. Proportions of patients with no radiographic progression (change from baseline in mTSS≤0.5) with secukinumab at 52 weeks were 94.0% (300 mg LD), 83.5% (150 mg LD) and 88.4% (150 mg no LD). ACR20/50 and PASI 90 responses, dactylitis and enthesitis resolution, physical function and QoL also improved with secukinumab vs placebo at Week 16, with sustained improvements through 52 weeks. Conclusion Secukinumab provided sustained improvements in nail disease, signs and symptoms of PsA, physical function and QoL, along with low radiographic progression, through 52 weeks in PsA patients with moderate-to-severe nail PsO. Disclosures B. Kirkham: Consultancies; Gilead, AbbVie, Janssen, Lilly, Novartis, Roche. Honoraria; Gilead, AbbVie, Janssen, Lilly, Novartis, Roche. Grants/research support; Gilead, AbbVie, Janssen, Lilly, Novartis, Roche. P. Nash: Honoraria; Novartis, AbbVie, Roche, Pfizer, Bristol-Myers Squibb, Janssen, Celgene. Grants/research support; Novartis, AbbVie, Roche, Pfizer, Bristol-Myers Squibb, Janssen, Celgene. P.J. Mease: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, Galapagos, Gilead, Genentech, GlaxoSmithKline, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, INC pharma, UCB. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Sun Pharmaceutical Industries, INC pharma, UCB. A.C. Balsa: Consultancies; Pfizer, AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion, UCB. Honoraria; Pfizer, AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion, UCB. Grants/research support; Pfizer, AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion, UCB. A. Singhal: Member of speakers’ bureau; AbbVie. Grants/research support; AbbVie, Gilead, Sanofi, Regeneron, Amgen, Roche, Bristol-Myers Squibb, Janssen, Lilly, Novartis, Pfizer, UCB, AstraZeneca, MedImmune, FujiFilm, Nichi-Iko, Mallinckrodt. E. Quebe-Fehling: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. L. Pricop: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. C. Gaillez: Shareholder/stock ownership; Novartis, Bristol-Myers Squibb. Other; Employee of: Novartis.

Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta-Analysis.

To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study-specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random-effects models. Twenty-four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors (TNFi), 8 involved nonsteroidal antiinflammatory drugs (NSAIDs), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), was not significantly different between TNFi-treated and biologics-naive patients at 2 years (mSASSS difference -0.73 [95% confidence interval (95% CI) -1.52, 0.12], I2 = 28%) and ≥4 years (mSASSS difference -2.03 [95% CI -4.63, 0.72], I2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNFi-treated and biologics-naive patients at ≥4 years (mSASSS difference -2.17 [95% CI -4.19, -0.15]). No significant difference in spinal radiographic progression was observed between NSAID-treated and control patients (mSASSS difference -0.30 [95% CI -2.62, 1.31], I2 = 71%) or between secukinumab-treated and biologics-naive patients (mSASSS difference -0.34 [95% CI -0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis. Although no significant protective effect of TNFi treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNFi after ≥4 years. Therefore, long-term TNFi exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long-term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

Radiographic Progression in Patients With Ankylosing Spondylitis According to Uveitis Based on the Observation Study of Korean Spondyloarthropathy Registry.

This study aims to investigate radiographic progression according to the presence or absence of uveitis in patients with ankylosing spondylitis (AS). A total of 598 patients (529 males, 69 females, mean age 38.1±9.2 years; range, 18 to 73 years) from the Observation Study of Korean Spondyloarthropathy Registry who met the modified New York criteria for AS were included in this study. At baseline, all data were stratified into two groups according to the presence or absence of uveitis. Baseline and radiographic progression were assessed for five years in this registry. Modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was read by two radiologists. Reliability was assessed using inter- and intra- class correlation coefficient for each radiograph. Comparison of mSASSS changes was analyzed by analysis of covariance model after adjusting for confounding factors. The evaluation of mSASSS showed good agreement between the two readers. A total of 193 patients (32.27%) had a history of uveitis that presented at a mean age of 39.6 years, including 30 females (15.54%). There were statistically significant differences in age (p=0.01), sex (p=0.04), hip joint involvement (p<0.01), and human leukocyte antigen B27 carrier state (p=0.02) between the two groups according to uveitis. A simple comparison revealed no significant difference in mSASSS change for five years between the two groups (mean: 3.05±0.62 vs. 3.78±0.78, p=0.47). After adjusting for confounding factors in multiple comparisons by Bonferroni correction, patients with uveitis had no significant association with mSASSS change for five years (mean: 6.29±1.32 vs. 5.49±1.39, p=0.68). Our study confirms that there is no significant association between uveitis and radiographic progression in patients with AS after adjusting for confounding factors.

Blood platelet volume to predict treatment-specific outcomes of metastatic castration-resistant prostate cancer.

242 Background: In the present guidelines for the management of metastatic castration-resistant prostate cancer (CRPC), it is unclear who benefits from androgen receptor axis-targeted agents (ARATs) or docetaxel as a first-line treatment. Methods: We conducted a single-institutional retrospective study to explore treatment-specific biomarkers for treatment response of metastatic CRPC. A cohort of 211 patients with metastatic CRPC treated with either ARAT (abiraterone acetate or enzalutamide) or docetaxel as a first-line treatment was evaluated. In addition to well-established biomarkers such as hemoglobin, neutrophil-to-lymphocyte ratio, alkaline phosphatase, and lactate dehydrogenase, we also assessed red cell distribution width, platelet count, and mean platelet volume (MPV). Laboratory measures were assessed within 1 month before starting treatment. Prostate-specific antigen progression-free survival (PSA-PFS) and radiographic progression-free survival (RPFS) were evaluated. Multivariable Cox regression models were used to assess the association between biomarkers and the risk of events. We also studied the statistical interaction between biomarkers and clinical outcomes. Results: Of all blood-based biomarkers, multivariable Cox regression models identified pre-treatment MPV (≤9.0 fL) as an independent prognostic factor of both PSA progression (hazard ratio [HR]: 2.62, 95% confidence interval [CI]: 1.25-5.48, P = 0.011) and radiographic progression (HR: 4.46, 95% CI: 1.79-11.1, P = 0.001). In addition, these models showed a lower risk of PSA progression (HR: 0.38, 95% CI: 0.15-0.96, P = 0.041) and radiographic progression (HR: 0.16, 95% CI: 0.05-0.50, P = 0.002) with docetaxel compared with ARAT when pre-treatment MPV was small. Conclusions: The present study identified MPV as a significant treatment-specific prognostic factor of PSA progression and radiographic progression in patients with metastatic CRPC treated with a first-line treatment. Furthermore, our results suggested that small MPV was associated with superior survival benefit on docetaxel over ARAT.

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review.

We aimed to perform a structured literature review of spinal radiographic progression, as assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), in patients with ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) treated with biologic therapy. Searches were limited to English language manuscripts published in the 11 years prior to 9 July 2019. Randomized controlled trials, open-label extensions (OLEs) and observational studies reporting mSASSS progression in patients with AS or nr-axSpA treated with biologics were eligible for inclusion. Bias was assessed using the methodological index for nonrandomized studies (MINORS) tool. Among the 322 studies identified in the literature search, 23 (11 OLEs and 12 cohort studies) met the eligibility criteria and were selected for inclusion. Most studies reported mSASSS progression in patients with AS receiving tumor necrosis factor inhibitor (TNFi) treatment. One study reported mSASSS progression in patients with AS treated with secukinumab, an interleukin-17A inhibitor. The mean (range) MINORS score was 11.3 (7–15) for the 15 noncomparative studies and 15 (12–22) for the 8 comparative studies. Although results of the individual studies were variable, mSASSS progression in patients with AS was generally minimal and slow with long-term TNFi therapy. Moreover, odds ratios for the likelihood of mSASSS progression with/without TNFi favoured TNFi therapy in several of the cohort studies. The rate of mSASSS progression following continuous secukinumab treatment was low and remained stable over 4 years. Of two studies reporting progression in patients with nr-axSpA treated with TNFis, one showed no mSASSS progression; however, the lack of control limited comparative conclusions.

The role of smoking in the development and progression of structural damage in axial SpA patients: A systematic review and meta-analysis

The objective of this study was to determine whether smoking was associated with the cumulative radiographic spinal damage and radiographic progression in patients with ankylosing spondylitis (AS). Thus, we conducted a systematic review and meta-analysis of the available studies to date. An electronic search was conducted from inception to June 21, 2016, in EMBASE, the MEDLINE/PubMed Cochrane Central Register of Controlled Trials databases. Cross-sectional and longitudinal cohort studies investigating the association between smoking and cumulative spinal structural damage or radiographic progression were included. The outcome of interest was the presence of syndesmophytes in cross-sectional studies and radiographic progression in longitudinal studies. The quality assessment was done using the Agency for Healthcare Research and Quality checklist. The authors of potentially relevant studies were contacted regarding the unpublished data. Data from eligible cross-sectional studies were extracted and arranged in a 2x2 table. The odds ratios (ORs) and 95% confidence intervals (CIs) for the dichotomous outcome of interest were computed. The combined data of eight eligible cross-sectional studies for the assessment of association between smoking and cumulative spinal structural damage suggested a significant association (OR, 2.02; 95% CI, 1.51-2.70). No significant heterogeneity was detected between studies (I2=23.0%, p=0.25). The heterogeneity of the longitudinal study data did not permit us to undertake a meta-analysis. Hence, a qualitative review was performed. The results of our meta-analysis show that smoking is associated with increased cumulative spinal structural damage in patients with AS. Therefore, rheumatologists should encourage patients with AS to quit smoking.

Machine learning-based prediction of radiographic progression in patients with axial spondyloarthritis.

Machine learning is applied to characterize the risk and predict outcomes in multi-dimensional data. The prediction of radiographic progression in axial spondyloarthritis (axSpA) remains limited. Hence, we tested the feasibility of supervised machine learning algorithms to predict radiographic progression in axSpA. This is a retrospective and hospital-based study. Clinical and laboratory data obtained from two independent axSpA groups were used as training and testing datasets. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and mSASSS worsening by ≥ two units was defined as progression. Seven machine learning models with different algorithms were fitted, and their performance for the testing dataset was assessed using receiver-operating characteristic (ROC) and precision-recall (PR) curve. The training and testing groups had equivalent characteristics, and radiographic progression was identified in 25.3% and 23.7%, respectively. The generalized linear model (GLM) and support vector machine (SVM) were the top two best-performing models with an average area-under-curve (AUC) of ROC of over 0.78. SVM had the higher AUC of PR compared with GLM (0.56 versus 0.51). Balanced accuracy was over 65% in all models. mSASSS was the most informative variable, followed by the presence of syndesmophyte(s) at the baseline and sacroiliac joint grades. Clinical and radiographic data-driven predictive models showed reasonable performance in the prediction of radiographic progression in axSpA. Further modelling with larger and more detailed data could provide an excellent opportunity for the clinical translation of the predictive models to the management of high-risk patients.Key Points• Clinical and radiographic data-driven predictive models showed reasonable performance in the prediction of radiographic progression in axSpA.• Further modelling with larger and more detailed data could provide an excellent opportunity for the clinical translation of the predictive models to the management of high-risk patients.

A simplified radiographic score effectively predicts radiographic progression of early arthritis in a large nationwide French cohort.

Evaluating radiographic progression is a key component of the follow-up of patients with RA. Existing scores are ill-suited to everyday clinical practice. The objective here was to validate a new simplified radiographic score (SRS) for evaluating radiographic progression in patients with early arthritis. Patients with arthritis of <6 months' duration were included in the large, prospective, nationwide, French ESPOIR cohort. Radiographs of the hands and feet were obtained at inclusion then 1 and 5 years later. The modified Sharp scores and SRS were determined by blinded readers. Interobserver reliability and intraobserver repeatability of each score, as well as agreement between the two scores, were assessed by computing the intraclass correlation coefficients. The rates of progression over the first year and the next 4 years were determined. The 506 patients with complete data for the first 5 years were included. At inclusion, the intraclass correlation coefficient between the two scores was good for erosions (0.715, P < 0.001), joint space narrowing (0.892, P < 0.001) and the total score (0.896, P < 0.001). Agreement between the two scores was also good for radiographic progression after 1 year (0.781, P < 0.001). The SRS had good positive and negative predictive values for slow and for rapid progression. SRS determination was less time consuming. The SRS is effective for monitoring radiographic progression in early arthritis and is easier to use and less time-consuming than the Sharp score. The usefulness of the SRS in clinical practice deserves further evaluation.

The effect of tumour necrosis factor inhibitors on radiographic progression in axial spondyloarthritis: a systematic literature review.

The effect of TNF-α inhibitors (TNFi), with or without concomitant NSAIDs, on radiographic progression in axial SpA remains unclear. Therefore, we performed a systematic literature review up to January 2019 to determine whether longer use of standard dose TNFi is superior vs lower duration or lower dose TNFi therapy, conventional synthetic DMARDs alone, or no therapy in inhibiting radiographic progression in patients with axial SpA. Our search yielded 373 titles of which 14 full text articles and five abstracts were eligible for quantitative analysis. Studies had an overall moderate to critical risk of bias. Data could not be pooled due to clinical and methodological heterogeneity. Individual studies showed conflicting results with mainly no significant difference in radiographic progression when comparing effect of TNFi therapy to no TNFi therapy or when comparing to less TNFi therapy until 2 years of follow-up. Results that are more significant are shown after 2 years' follow-up, mainly in subgroups with baseline syndesmophytes. Data on the additional or synergistic effect of concomitant NSAID use were inconclusive.

No radiographic wrist damage after treatment to target in recent-onset juvenile idiopathic arthritis

BackgroundTo evaluate radiographic progression of patients with new-onset juvenile idiopathic arthritis (JIA) in response to an early, tightly-controlled, treatment-to-target.MethodsPatients with JIA participating in the BeSt-for-Kids-study, randomized to 3 treatment strategy arms, were eligible if at least 1 conventional wrist-radiograph was available. Bone damage as reflected by carpal length was assessed using the Poznanski-score. The BoneXpert-method was used to determine the Bone Age (BA, > 5 years) and bone mineral density (BMD) of the wrist. These scores were evaluated over time and compared between the treatment arms and mean JADAS10-score using linear mixed models corrected for age and symptom duration.ResultsIn 60 patients, 252 radiographs were analysed. Baseline age and symptom duration were different between the arms. No difference in comparison to the healthy reference population was found at baseline for the Poznanski-score (IQR varying from − 0,82; 0.68), nor for BA (varying from − 0.88 to 0.74). Baseline BMD was statistically significantly lower in arm 3 (initial treatment with etanercept and methotrexate) (− 1.48; − 0.68) compared to arm 1 (− 0.84; − 0.04) and arm 2 (− 0.93; 0.15). After treatment to target inactive disease, the Poznanski-scores and the BA remained clinically unchanged, while the BMD in arm 3 improved (p < 0.05 vs arm 1).ConclusionsRecent-onset JIA patients, treated-to-target aimed at inactive disease, showed no signs of radiographic wrist damage (Poznanski-score, BA or BMD) either at baseline or at follow-up, irrespective of treatment arm. A lower BMD at baseline in arm 3, initially treated with methotrexate and etanercept, improved significantly after treatment.Trial registrationNTR, NL1504 (NTR1574). Registered 01-06-2009.

Low bone mineral density of vertebral lateral projections can predict spinal radiographic damage in patients with ankylosing spondylitis.

To investigate the association between bone mineral status and spinal radiographic damage in patients with ankylosing spondylitis (AS) and determine whether bone mineral status can predict further spinal radiographic damage after 2years. Bone mineral density (BMD) of the lumbar spine (anteroposterior and lateral projections), femoral neck, and total hip and trabecular bone score (TBS) of the lumbar spine were measured in AS patients (n = 54) who fulfilled the modified New York criteria. Spinal radiographic damage was scored on cervical and lumbar spine radiographs using modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) at baseline and after 2years. Simple and multiple linear regression analyses were performed to examine predictors of spinal radiographic damage. Patients with advanced AS exhibited low BMD on lumbar spine lateral projections, femoral neck, and total hip and low TBS. Low vertebral bone mass at baseline, assessed by BMD of the lateral projections or TBS, was independently associated with baseline mSASSS. After 2years, mSASSS change from baseline was significantly associated with high baseline mSASSS, high baseline erythrocyte sedimentation rate and C-reactive protein (CRP) levels, and low baseline BMD of the lumbar spine lateral projections. The best predictive model for spinal radiographic progression consisted of baseline mSASSS, baseline CRP, and low BMD of lateral lumbar spine (area under curve = 0.826). BMD at vertebral lateral projections and TBS were inversely associated with baseline mSASSS in AS patients. Low BMD at vertebral lateral projections, as well as baseline mSASSS and inflammatory markers, might predict spinal radiographic damage in AS.Key Points• Vertebral bone mineral density of lateral projections and trabecular bone score are inversely associated with baseline mSASSS in patients with ankylosing spondylitis.• Baseline mSASSS, inflammatory markers, and low vertebral bone mineral density might predict spinal radiographic progression in patients with ankylosing spondylitis.

Impact of flare on radiographic progression after etanercept continuation, tapering or withdrawal in patients with rheumatoid arthritis.

The structural consequences of flare after dose reduction/discontinuation of biologic DMARDs in patients with RA who achieve remission are unclear. We compared the incidence of radiographic progression in patients with RA who did and did not experience flare after etanercept (ETN) reduction/withdrawal. Eligible adults with moderately active RA despite MTX received ETN 50 mg plus MTX weekly in a 36-week, open-label induction period; patients achieving sustained low disease activity by week 36 were randomized to ETN 50 mg plus MTX, ETN 25 mg plus MTX, or placebo plus MTX in a 52-week, double-blind maintenance period. In post hoc analyses, radiographic progression (Δ modified total Sharp score ⩾0.5 units/year) was compared in patients with and without flare [based on DAS28 relapse (main analysis), and clinical disease activity index and simplified disease activity index relapse (sensitivity analyses)]. Findings from patients receiving full- and reduced-dose combination therapy were pooled for comparison with those from patients receiving MTX only. Significantly more patients receiving MTX monotherapy experienced flare, defined as DAS28 relapse (62% vs 21%; P < 0.0001) and radiographic progression (17% vs 9%; P < 0.001), than patients receiving full-/reduced-dose combination therapy in the double-blind period. Patients with flare defined as clinical disease activity index and simplified disease activity index relapse had higher rates of radiographic progression than those without flare in the full-/reduced-dose combination therapy group (P < 0.01). Radiographic progression may be a consequence of flare after biologic DMARD dose reduction/withdrawal in patients with RA. If these approaches are taken, careful monitoring for signs/symptoms of relapse is needed. ClinicalTrials.gov, https://clinicaltrials.gov, NCT00565409.

Spinal radiographic progression over 2\xa0years in ankylosing spondylitis patients treated with secukinumab: a historical cohort comparison

ObjectiveThe aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2 years with secukinumab (MEASURE 1) with a historical cohort of biologic-naïve patients treated with NSAIDs (ENRADAS).MethodsBaseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change ≤ 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (≤ day 30) and post-baseline day 31–743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (≤ day 30) and year 2 (days 640–819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (> day 30) radiographs.ResultsA total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2 years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p = 0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of ≤ 0, ≤ 0.5, ≤ 1, and ≤ 2), but the differences were not statistically significant.ConclusionSecukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2 years versus a cohort of biologic-naïve patients treated with NSAIDs.

Association of Changes in Anticitrullinated Protein Antibody Levels With Resource Use and Disease Activity Measures in Rheumatoid Arthritis Patients a US Observational Cohort

PurposeAnticitrullinated protein antibody (ACPA) concentration, beyond ACPA positivity, is indicative of more aggressive radiographic progression in patients with rheumatoid arthritis (RA). However, there is limited information on the association of changes in ACPA with resource use measures and/or disease activity measures. We evaluate associations between changes in levels of ACPA and outcomes, including durable medical equipment (DME) use, hospitalizations, and disease activity, in patients with established RA. MethodsPatients from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study who had ACPA measurements at baseline and month 12 were included. Changes in ACPA levels from baseline to month 12 were categorized as a decrease (<−10%), no change (−10% to +10%), or increase (>+10%). DME use and hospitalizations were assessed twice yearly using patient questionnaires; disease activity was assessed annually. Binary multivariate logistic regression was used to analyze the association between changes in ACPA levels and DME use and hospitalizations; linear regression was used to assess the association with disease activity. FindingsOf 840 patients included in the analysis, 291 (34.6%), 266 (31.7%), and 283 (33.7%) had a decrease, no change, or increase in ACPA levels, respectively. A decrease in ACPA levels was associated with a reduction in DME use (adjusted odds ratio [aOR] = 0.64; 95% CI, 0.44–0.93; P = 0.02) and hospitalizations (aOR = 0.62; 95% CI, 0.41–0.95; P = 0.03) versus no change or increase. Adjusted mean changes in disease activity score in 28 joints (C-reactive protein), total and swollen joint counts, and pain scores were significantly greater in patients with decreased ACPA levels versus those with no change or increase (P < 0.05). ImplicationsAmong patients with RA, reductions in ACPA levels of >10% were associated with reductions in DME use, hospitalizations, and disease activity. ClinicalTrials.gov identifier: NCT01793103.

Structural progression in axial spondyloarthritis.

Functional disability in axial spondyloarthritis is related to the structural progression caused by the disease, thus largely contributing to its global burden and still representing a major challenge in management. Diagnosis at an early inflammatory stage of the disease is the hallmark for a better disease control and management. The natural history of axial spondyloarthritis is now better understood with imaging studies and long-term follow-up data, with some predictive factors for structural progression being identified. Non-steroidal anti-inflammatory drugs are still considered as the first line treatment for axial spondyloarthritis, however, their impact on structural progression is conflicting. Recent data on biologic disease-modifying anti-rheumatic drugs, such as tumor necrosis factor inhibitors have shown significant retardation of radiographic damage after several years of treatment, while first data with interleukin-17 inhibitors were also positive. Novel emerging drugs are being evaluated with promising results on halting disease progression. This review summarizes the predictors of radiographic progression in patients with axial spondyloarthritis as well as the current evidence on the effect of available treatments on structural progression.

Association of cumulative anti-cyclic citrullinated protein antibodies with radiographic progression in patients with rheumatoid arthritis.

Antibody against cyclic citrullinated protein (ACPA) is counted as one of the most important biomarkers in diagnosis, classification, and prognosis of rheumatoid arthritis (RA). We examined the evolution of ACPA during disease course and assess predictive value of time-weighted cumulative ACPA titer on radiographic progression in RA patients. A group of 734 patients with RA was followed longitudinally over 2years, with annual measurements of ACPA. The cumulative titers of ACPA were calculated using the trapezoidal rule and were divided into three categories: negative, low-to-moderate, and high. Radiographs of the hands were scored with the modified Sharp score (SHS). Multivariable logistic regression models were performed to identify independent predictors over follow-up for individual patients with different combinations of risk factors. The effect size was computed by Cohen's d method. The patients with radiographic progression had a higher SHS at baseline; and smoking status, diabetes, RF positivity, and use of biologic DMARDs were independently associated with radiographic progression (all P < 0.05). As for ACPA, reversion happened more commonly in men and was associated with younger onset age and lower titer at baseline, but it had no direct relevance to radiographic outcome. In multivariable regression analysis, only high cumulative or baseline titer of ACPA had a predictive power for rapid radiographic progression (all P < 0.05), and cumulative ACPA titer was superior in terms of statistical significance (Cohen's d, 0.637 versus 0.583). High cumulative ACPA titer was independently associated with accelerated radiographic progression, especially with initiation of joint damage.