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Objectives: To compare if the 4th and 5th metatarsophalangeal (MTP) joints evaluated by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) could classify more patients with erosive rheumatoid arthritis (RA) compared with conventional radiography (CR) of the hands, wrists, and feet. Furthermore, we characterize and quantify bone erosions in the two MTP joints by HR‐pQCT. Methods: This single‐center cross‐sectional study included patients with established RA (disease duration ≥5 years). Blinded to patient data, the number and volume of erosions in the 4th and 5th MTP joints were measured by HR‐pQCT, whereas the erosive scores by CR of 44 joints in the hands, wrists, and feet were assessed according to the Sharp/van der Heijde method. Results: Among 42 participants, 30 patients were classified with erosive RA and 12 with non‐erosive RA by CR. HR‐pQCT of two MTP joints could classify more patients with erosive RA compared with CR of 44 joints (p =.03). The optimal cut‐off value for the number and volume of erosions per patient in the 4th and 5th MTP joints by HR‐pQCT was 7.5 erosions and 11.7 mm3, respectively, for detecting erosive disease by CR. Erosions in the two MTP joints by HR‐pQCT were found most frequently and were largest at the lateral quadrant of the 5th metatarsal head. Conclusion: The superiority of HR‐pQCT of the 4th and 5th MTP joints compared with CR of 44 joints for classifying erosive RA provides a basis for larger studies evaluating if HR‐pQCT could be used for diagnosing erosive RA in the future. [ABSTRACT FROM AUTHOR]

Objective: To compare in images obtained by High-Resolution peripheral Quantitative Computed Tomography(HR-pQCT) and conventional radiography(CR) of the second and third metacarpophalangeal(MCP) joints the minimal erosive cortical break needed to differentate between pathological and physiological cortical breaks.Methods: In this single-centre cross-sectional study, patients with established RA(disease duration ≥ 5 years) had their second and third MCP joints of the dominant hand investigated by HR-pQCT and CR. Empirical estimation was used to find the optimal cutoff value for the number of erosions and total erosive volume, which were detectable between patients with and without erosions in the second and third MCP joints according to CR.Results: The total erosive volume in the second and third MCP joints by HR-pQCT for CR detected erosive disease was estimated to be 56.4(95% CI: 3.5 - 109.3) mm3. The sensitivity and specificity at this cutpoint were 78% and 83%, with an area under the receiver operating characteristic curve(AUC) of 0.81. The optimal cutoff value for the number of erosions by HR-pQCT was 8.5(95% CI:5.9 - 11.1) for CR detected erosive disease in the second and third MCP joints by CR. The sensitivity and specificity at this cutpoint were 74% and 88%, respectively, with an AUC of 0.81.Conclusion: Erosions by HR-pQCT were larger in patients with erosive damage in the second and third MCP joints by CR. We found that CR had poor sensitivity for detecting erosive disease when the erosive volume was less than 56.4 mm3 or the number of erosions less than 8.5. [ABSTRACT FROM AUTHOR]

Maria Maddalena Angioni,1 Alberto Floris,1 Ignazio Cangemi,1 Mattia Congia,1 Elisabetta Chessa,1 Sandro Orrù,2 Matteo Piga,1 Alberto Cauli1 1Rheumatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, University Clinic AOU, Cagliari, 09042, Italy; 2Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, 09042, ItalyCorrespondence: Maria Maddalena AngioniRheumatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, University Clinic AOU Cagliari, S.S. 554, Bivio per Sestu, Monserrato, Cagliari, 09042, ItalyTel +39 07051093340Email m.maddalena.angioni@gmail.comIntroduction: Psoriatic Arthritis (PsA) is a multifactorial disease, where the relative burden of genetic, epigenetic and environmental factors in clinical course and damage accrual is not yet definitively clarified. In clinical practice, there is a real need for useful candidate biomarkers in PsA diagnosis and disease progression, by exploring its underlying transcriptomic and epigenomic mechanisms. This work aims to profile the transcriptome in monozygotic (MZ) twins with psoriatic arthritis (PsA) highly concordant for clinical presentation, but discordant for the radiographic outcomes’ severity.Methods: We describe i) the clinical case of two MZ twins; ii) their comparative gene expression profiling (HTA 2.0 Affymetrix) and iii) signal pathways and pathophysiological processes in which differentially expressed genes are involved (in silico analysis by the IPA software, QIAGEN).Results: One hundred sixty-three transcripts and 36 coding genes (28 up and 8 down) were differentially expressed between twins, and in the brother with the most erosive form, the transcriptomic profiling highlights the overexpression of genes known to be involved in immunomodulatory processes and on a broad spectrum of PsA manifestations.Discussion: Twins’ clinical cases are still a gold mine in medical research: twin brothers are ideal experimental models in estimating the relative importance of genetic versus nongenetic components as determinants of complex phenotypes, non-Mendelian and multifactorial diseases as PsA.Keywords: psoriatic arthritis, gene expression profiling, diseases in twin, genetic, environment–gene interaction, joint erosions

Objective: To evaluate the relationship between the UltraSound Score for Erosions (USSe) and the modified Sharp/van der Heijde score for erosions (SHSe).Methods: One hundred eight patients with rheumatoid arthritis (RA) were included. On radiography, SHSe was evaluated by 2 or 3 blinded readers (in case of discordance). On ultrasonography, erosions were scored on 6 bilateral joints (metacarpophalangeal joints 2,3,5; metatarsophalangeal joints 2,3,5) with a 4-point scale to calculate the USSe.Results: The Pearson correlation was good (r = 0.68, P < 0.001) and the agreement illustrated by a Bland-Altman plot was excellent (91%) between the 2 scores, which were complementary in detecting erosions.Conclusion: The USSe seems to be a valuable tool for assessing erosive damage in RA. [ABSTRACT FROM AUTHOR]

Objective: The Tight Control of inflammation in Psoriatic arthritis (TICOPA; isrctn.com: ISRCTN30147736) trial compared standard care (StdC) and tight control (TC) in early psoriatic arthritis (PsA), demonstrating better outcomes for TC. This substudy evaluated the performance metrics of modern imaging outcomes and compared them to the clinical data.Methods: Non-contrast 0.2T magnetic resonance imaging (MRI; single hand) was assessed using the Outcomes in Rheumatology (OMERACT) PsA MRI Scoring System (PsAMRIS) with an additional global inflammation score. Ultrasound (US; same hand) was scored for greyscale, power Doppler, and erosions at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints and scores summated.Results: Seventy-eight patients had paired (baseline and 48 weeks) US data and 61 paired MRI data; 50 had matched clinical, MR, and US data. Significant within-group changes were seen for the inflammatory PsAMRIS components at MCP level: MRI global inflammation [median difference (range), standardized response mean (SRM)]: 3.25 (-5.0 to 12.0), 0.68; 1.0 (-4.5 to 17.5), 0.45 for TC and StdC, respectively. Similar within-group differences were obtained for US: 1.0 (-13.0 to 23.0), 0.45; 3.0 (-6.0 to 21.0), 0.77 for TC and StdC, respectively. No differences were seen between treatment groups. Significant correlations were found between baseline and change MRI and US scores. A significant correlation was found between baseline PsA disease activity scores and MRI global inflammation scores (Spearman ρ for MCP, PIP: 0.46, 0.63, respectively). No differences in erosion progression were observed.Conclusion: The PsAMRIS and US inflammation scores demonstrated good responsiveness. No between-group differences were demonstrated, but this substudy was likely underpowered to determine differences between the 2 treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction/objectives: To evaluate the clinical relevance of high-resolution hand and wrist ultrasound (US) findings and their possible associations with anti-citrullinated peptide antibodies in primary Sjögren's syndrome (pSS). Methods: Ninety-seven consecutive pSS patients (American-European Consensus Group, 2002) without meeting the American College of Rheumatology (ACR) criteria (1987) for rheumatoid arthritis (RA); 20 RA patients (ACR/European League Against Rheumatism (EULAR) criteria, 2010); and 80 healthy individuals with comparable age, gender, and ethnicity were enrolled in a case-control study. Disease activity was assessed by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). US was performed by one expert blinded to anti-CCP, anti-MCV, and IgM rheumatoid factor tested by ELISA. Results: Frequencies of grade 3 synovitis (9.3 vs. 0%, p = 0.004), tenosynovitis (36.1 vs. 3.8%, p < 0.001), and erosions (27.8 vs. 7.5%, p = 0.001) on US were higher in pSS patients than in healthy controls. ESSDAI presented a moderate correlation with the synovitis number (p = 0.001) and tenosynovitis (p < 0.001). Most pSS patients with erosions on US (81.5%) had negative anti-CCP. Nevertheless, anti-CCP ≥ 3× cut-off value was associated with the presence of erosions in pSS (p = 0.026). Erosions in pSS were mainly small size contrasting with moderate/large size in RA (p < 0.001), and positive power Doppler synovitis predominated in RA (p < 0.001). Conclusions: US identified significant frequencies of grade 3 synovitis, tenosynovitis, and erosions in pSS. Synovitis and tenosynovitis numbers were correlated with ESSDAI. Association between erosions on US and anti-CCP (high titers) in pSS possibly identifies a subgroup with severe arthritis. These findings suggest that US is a useful method for assessing joint involvement in pSS. Key Points • US identified significant frequencies of grade 3 synovitis, tenosynovitis, and erosions in pSS patients in comparison with age- and race-healthy individuals. • Numbers of synovitis and tenosynovitis on US were correlated with ESSDAI values. • Most pSS patients with erosions on US were negative for anti-CCP, but anti-CCP ≥ 3× cut-off value was associated with the presence of erosions in this disease. • Erosions in pSS were mainly small size contrasting with moderate/large size in RA, and positive power Doppler synovitis predominated in RA. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint structural deterioration. Driven by recent expectations that patients in clinical trials randomized to placebo should be 'rescued' with active therapy within 6 months of starting treatment, the relative benefit of arresting joint damage with biologic agents beyond this period is unclear. With longer-term evidence of the rate of joint deterioration with minimal treatment, the efficacy of biologic agents and novel treatments might be projected beyond the placebo-controlled phase observed in clinical trials. The aim of this study was to estimate radiographic structural deterioration over time in patients with moderate-to-severe RA minimally treated with DMARDs.Methods: A literature review identified evidence of joint structural deterioration in patients with (DMARD-IR population) and without (non-DMARD-IR population) a history of inadequate response to DMARDs. Patients were minimally treated with one non-biologic DMARD or palliative care (non-DMARD-IR population only). Outcomes of interest were the (modified) Total Sharp Score (TSS) and subscales (Erosion Subscore [ES] and Joint Space Narrowing [JSN] Subscore), and Larsen score. Pooled joint-deterioration curves over time were obtained with meta-analysis models.Results: Mean change from baseline in TSS increased in the DMARD-IR population from 1.14 (95 % credible interval [CrI] 0.66, 1.67) to 9.84 (5.68, 14.46) at Weeks 12 and 104, respectively, and a non-linear increase of 1.56 (0.79, 2.34) and 5.13 (-1.35, 11.67) in the non-DMARD-IR population. At the same time points, mean changes (95 % CrI) were 0.51 (0.27, 0.83) and 4.43 (2.38, 7.21) for ES and 0.36 (0.09, 0.67) and 3.14 (0.80, 5.78) for JSN in the DMARD-IR population, whereas corresponding changes in the non-DMARD-IR population were 0.69 (0.31, 1.12) and 2.93 (0.92, 5.02), and 0.29 (0.17, 0.44) and 2.55 (1.45, 3.80), respectively. Larsen scores were only available for the non-DMARD-IR population, with mean changes (95 % CrI) of 0.08 (0.04, 0.11) and 0.65 (0.36, 0.96) at Weeks 12 and 104, respectively.Conclusion: Minimal treatment of RA with one non-biologic DMARD results in deterioration of joint structure in patients with or without a history of inadequate response to non-biologic DMARDs. [ABSTRACT FROM AUTHOR]

Objective. RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach. Methods. A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase. In the validation phase, the most significant SNPs in the genome-wide association study representing new candidate loci for RA were tested in an independent cohort of 863 ACPA-positive patients with joint damage and 1152 healthy controls. All individuals from the discovery and validation cohorts were Caucasian and of Southern European ancestry. Results. In the discovery phase, 60 loci not previously associated with RA risk showed evidence for association at P<5x1CT-4 and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level (P < 0.05, same direction of effect as in the discovery phase). When combining the discovery and validation cohorts, an intronic SNP in the Solute Carrier family 8 gene (SLC8A3) was found to be associated with ACPA-positive RA at a genome-wide level of significance RA [odds ratio (95% CI): 1.42 (1.25, 1.6), Pcombined = 3.19x10-8]. Conclusions. SLC8A3 was identified as a new risk locus for ACPA-positive RA. This study demonstrates the advantage of analysing relevant subsets of RA patients to identify new genetic risk variants. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate the effects of benzo[a]pyrene (B[a]P), a major toxic component of cigarette smoke, on the expression of Slug and to determine the effect of B[a]P/Slug on the invasive properties of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Method: The expression of Slug was measured by real-time PCR following the stimulation of FLS with different concentrations of B[a]P or EGF. The phosphorylation of the key enzymes in the signaling pathway was analyzed by western blots. Inhibitors of PI3K/Akt/mTOR pathway were used to confirm the critical pathway for Slug expression. An in vitro cell invasion assay was performed using RA FLS treated with Slug cDNA, Slug small interference RNA, or control. Results: Slug expression increased significantly following treatment with B[a]P or EGF in a dose-dependent manner. The stimulation of FLS with B[a]P or EGF induced the phosphorylation of Akt kinase, but not in ERK, JNK and p38. The Slug mRNA expression induced by B[a]P and EGF decreased significantly following the treatment with PI3K/Akt/mTOR inhibitors. Slug overexpression using Slug cDNA upregulated the invasive function of FLS, and Slug depletion using siRNA showed the opposite effect compared with the control. In addition, the stimulation with B[a]P increased the invasive function of the control siRNA-treated FLS but not in the Slug siRNA-treated FLS. Conclusion: Our data showed that B[a]P regulates the invasive properties of RA FLS through Slug expression. This mechanism may provide a novel molecular link underlying the association between smoking and increased radiographic progression in RA. [Copyright &y& Elsevier]

Abstract: We managed three patients who had both palmar fasciitis and polyarthritis coexisting with gynecological malignancies. The first patient was followed up for 3years, during which she experienced mutilating osteolysis of the fingers and very severe inflammation as assessed by osteoarticular ultrasonography. The second patient had active synovitis by ultrasonography without structural joint damage. Finally, in the last patient, magnetic resonance imaging showed synovitis and extensor tenosynovitis of the fingers. The many differential diagnoses of this paraneoplastic syndrome are discussed. [Copyright &y& Elsevier]

The aim of this study was to evaluate magnetic resonance images (MRI) of the wrist of rheumatoid arthritis (RA) patients. MRI and plain X-ray of the wrists were performed in 15 patients with RA, 7 patients with another chronic inflammatory joint disease (CIJD), and 10 control subjects. Patients had only minor changes on plain X-ray. Coronal T1 weighted spin echo sequences were performed before and after an intravenous pulse of gadolinium (GD). Contiguous 3 mm thick slices were obtained. Synovitis was frequently objectivized in the two groups of patients. MRI detected far more erosions and central bone geodes than plain X-ray. Geodes were frequent among controls while cortical bone erosions were frequent in patients. Most of the erosions were enhanced after GD injection in the RA patients but not in the 2 other groups. Thus MRI is not only useful in diagnosing inflammatory changes of the wrist but also in distinguishing early stage RA from other CIJD. [ABSTRACT FROM AUTHOR]

Chikungunya virus arthritis is an acute severe polyarthritis following upon the bite of infected mosquitoes in endemic areas. With rapid air transport an increasing number of tourists are being exposed to potential infection. Whether tourists returning home in the incubation viremic stage can infect local mosquito populations in their home countries is unknown. Most cases recover from the severe joint pains within several weeks but up to 12% retain some residual joint symptoms for years. A case report is given of probable Chikungunya arthritis progressing to joint destruction before ultimately subsiding after 15 years leaving a sequela of destroyed metatarsal heads and late osteoarthritic changes in the ankles. [ABSTRACT FROM AUTHOR]

Juxta-articular inflammatory masses, sternomanubrial or sternoclavicular, were noted in two women who were subsequently found to have ankylosing spondylitis. The differential diagnosis of juxta-articular masses should include systemic rheumatic disorders as well as tumor or infection. [ABSTRACT FROM AUTHOR]

Abstract: TNF receptor-associated periodic syndrome (TRAPS) is a highly polymorphic autoinflammatory syndrome related to mutations in the TNFRSF1A gene encoding the type 1 TNF receptor. Arthralgia and nonerosive synovitis are among the most common manifestations. We report the case of a 73-year-old woman who presented with chronic erosive joint disease that progressed by flare-ups. Moderate nonspecific abdominal and cutaneous abnormalities were noted, suggesting TRAPS. This diagnosis was confirmed when genetic tests identified the R92Q mutation in the TNFRSF1A gene. Although glucocorticoid therapy was effective in alleviating the symptoms, combination therapy with methotrexate and etanercept neither decreased the frequency of the flare-ups nor slowed the pace of joint destruction. Treatment with anakinra is being considered. To our knowledge, this is the first reported case of joint destruction related to TRAPS. In patients with refractory inflammatory joint disease, the presence of extraarticular manifestations, however mundane, should suggest TRAPS. [Copyright &y& Elsevier]

Musculoskeletal ultrasound (US) now thrives as an established imaging modality for the investigation and management of chronic inflammatory arthritis. We summarize here results of the Outcome Measures in Rheumatology (OMERACT) US working group (WG) projects of the last 2 years. These results were reported at the OMERACT 12 meeting at the plenary session and discussed during breakout sessions. Topics included standardization of US use in rheumatic disease over the last decade and its contribution to understanding musculoskeletal diseases. This is the first update report of WG activities in validating US as an outcome measure in musculoskeletal inflammatory and degenerative diseases, including pediatric arthritis, since the OMERACT 11 meeting.

Objective: To describe early radiographic findings in patients from the Swedish psoriatic arthritis (SwePsA) registry, progression of destruction, correlations with clinical disease variables, and predictors of destruction., Methods: Hand and foot radiographs were available for 72 of 197 SwePsA patients followed for 5 years. Clinical data were collected according to the SwePsA protocol., Results: Disease characteristics and clinical improvement were similar in men and women. Radiographic abnormalities were more pronounced in men. Total Wassenberg radiographic score at baseline was 0 in 45% of men and 51% of women. One man and one woman had a score > 10. At 5 years, total score was 0 in 14% of men and 40% of women (p = 0.018); 17% of men and 7% of women had scores > 10. Mean total scores for men and women had increased. Baseline erythrocyte sedimentation rate was associated with baseline total radiographic score. In men, swollen joint count was positively, and in women tender joint count negatively, correlated to total radiographic score. After 5 years, only male scores, mainly hand scores, significantly correlated with 28-joint Disease Activity Score and Disease Activity Index for Psoriatic Arthritis scores, swollen joint count, and dactylitis. Achieving remission or minimal disease activity after 5 years protected against structural damage, mainly in men., Conclusion: Radiographic progression in early PsA was generally slow but substantial. Male sex appears to be a risk factor for early radiographic damage while the presence of baseline radiographic damage and dactylitis developing during followup seem to predict further destruction. Hand and foot radiograph scoring cannot be substituted with clinical signs.

Objective: Assess the reliability of early erosions in rheumatoid arthritis (EERA) software for quantifying erosive damage to the metacarpophalangeal joints of patients with rheumatoid arthritis (RA)., Methods: One hundred magnetic resonance image sets from 68 patients with early referral RA were evaluated. Reliability was assessed using 95% limits of agreement and intraclass correlation coefficient (ICC) with 95% CI., Results: Limits of agreement linearly depended on erosion volume: 0.44× between readers and 0.19× within readers. Interrater ICC was 0.976 (95% CI 0.965-0.984) and intrarater ICC was 0.996 (95% CI 0.994-0.997)., Conclusion: EERA is highly reproducible for quantifying erosions in patients with early RA.

Objective: Rheumatoid arthritis (RA) that is negative for anticitrullinated protein antibodies (ACPA) is a subentity of RA, characterized by less severe disease. At the individual level, however, considerable differences in the severity of joint destruction occur. We performed a study on genetic factors underlying the differences in joint destruction in ACPA-negative patients., Methods: A genome-wide association study was done with 262 ACPA-negative patients with early RA included in the Leiden Early Arthritis Clinic and related to radiographic joint destruction over 7 years. Significant single-nucleotide polymorphisms (SNP) were evaluated for association with progression of radiographic joint destruction in 253 ACPA-negative patients with early RA included in the Better Anti-Rheumatic Farmaco Therapy (BARFOT) study. According to the Bonferroni correction of the number of tested SNP, the threshold for significance was p < 2 × 10(-7) in phase 1 and 0.0045 in phase 2. In both cohorts, joint destruction was measured by Sharp/van der Heijde method with good reproducibility., Results: Thirty-three SNP associated with severity of joint destruction (p < 2 × 10(-7)) in phase 1. In phase 2, rs2833522 (p = 0.0049) showed borderline significance. A combined analysis of both the Leiden and BARFOT datasets of rs2833522 confirmed this association with joint destruction (p = 3.57 × 10(-9)); the minor allele (A) associated with more severe damage (for instance, after 7 yrs followup, patients carrying AA had 1.22 times more joint damage compared to patients carrying AG and 1.50 times more joint damage than patients carrying GG). In silico analysis using the ENCODE and Ensembl databases showed presence of H3K4me3 histone mark, transcription factors, and long noncoding RNA in the region of rs2833522, an intergenic SNP located between HUNK and SCAF4., Conclusion: Rs2833522 might be associated with the severity of joint destruction in ACPA-negative RA.

Objective: To characterize cumulative joint damage (CJD) patterns in rheumatoid arthritis (RA) and determine their associations with demographic/clinical features and HLA-DRB1 gene polymorphism., Methods: Hand and foot radiographs were obtained from 404 patients with RA. CJD patterns were determined by 3 derivations from Sharp/van der Heijde scores, obtained by the mathematical division of scores for hands/feet (Sharp-h/f score), fingers/wrists (Sharp-f/w score), and erosion/space narrowing (Sharp-e/sn score), respectively. DNA and serum were obtained for determination of HLA-DRB1 polymorphism, rheumatoid factor (RF), and anticitrullinated protein antibodies (ACPA)., Results: Patients with wrist-dominant CJD pattern were more likely to have severe RA than those with finger-dominant pattern (68.4% vs 46.0%; p = 0.036) as were those with foot-dominant vs hand-dominant CJD pattern (76.5% vs 56.4%; p = 0.044). HLA-DRB1 shared epitope (SE) alleles were associated with erosion-dominant CJD pattern (p = 0.021). Patients with erosion-dominant CJD pattern had higher levels of RF and ACPA than those with space-narrowing-dominant CJD pattern (median RF 71.35 U/ml vs 22.05 U/ml, respectively; p = 0.003; median ACPA 187.9 U/ml vs 143.2 U/ml, respectively; p < 0.001). The majority of triple-positive patients (SE+, RF+, ACPA+) had erosion-dominant CJD pattern (62.3%) while the majority of triple-negative patients (SE-, FR-, ACPA-) had space narrowing-dominant CJD pattern (75%; p = 0.017). ACPA was associated with HLA-DRB1 SE alleles (p < 0.05). Patients with foot-dominant CJD pattern were taller than those with hand-dominant CJD pattern (p = 0.002); those with erosion-dominant CJD pattern had higher weight and body mass index than those with space narrowing-dominant CJD pattern (p = 0.014, p = 0.001)., Conclusion: CJD patterns were associated with disease severity, HLA-DRB1 SE status, presence and titer of ACPA and RF, and morphometric features.

Objective: To develop a personalized treatment target approach in patients with rheumatoid arthritis (RA) based on baseline risk factors for joint damage progression in combination with disease activity over time., Methods: Data were used from the Nijmegen early RA cohort. Presence or absence of anticyclic citrullinated peptide antibodies (anti-CCP), high erythrocyte sedimentation rate, and erosions were translated into 4 risk profiles: 0, 1, 2, and 3. Joint damage progression was assessed with the Ratingen score, and disease activity with the original Disease Activity Score (DAS) over 3 years. The probability for joint damage progression was calculated for each risk profile and each DAS category using logistic regression models. The probabilities were translated into personalized disease activity treatment targets., Results: More risk factors at baseline as well as a higher DAS level resulted in a higher probability for joint damage progression in a dose-dependent way. Low DAS corresponded with a probability of 0.0, 0.08, 0.20, and 0.58 in patients with 0, 1, 2, and 3 risk factors, respectively. Moderate DAS corresponded with a probability of 0.06 in patients with 0 risk factors and 0.35 with 1 risk factor. High DAS resulted in a probability of 0.50 with no risk factors present at baseline., Conclusion: Presence of anti-CCP, acute-phase response, and erosions at baseline can be used to set individual treatment targets in RA. In patients without these risk factors, a moderate DAS as a target is sufficient, while for patients with all 3 risk factors, a low DAS is not strict enough to limit the risk for joint damage.

Objective: To compare the performance of an extended model and a simplified prognostic model for joint damage in rheumatoid arthritis (RA) based on 3 baseline risk factors: anticyclic citrullinated peptide antibodies (anti-CCP), erosions, and acute-phase reaction., Methods: Data were used from the Nijmegen early RA cohort. An extended model and a simplified baseline prediction model were developed to predict joint damage progression between 0 and 3 years. Joint damage progression was assessed using the Ratingen score. In the extended model, prediction factors were positivity for anti-CCP and/or rheumatoid factor, the level of erythrocyte sedimentation rate, and the quantity of erosions. The prediction score was calculated as the sum of the regression coefficients. In the simplified model, the prediction factors were dichotomized and the number of risk factors was counted. Performances of both models were compared using discrimination and calibration. The models were internally validated using bootstrapping., Results: The extended model resulted in a prediction score between 0 and 5.6 with an area under the receiver-operation characteristic (ROC) curve of 0.77 (95% CI 0.72-0.81). The simplified model resulted in a prediction score between 0 and 3. This model had an area under the ROC curve of 0.75 (95% CI 0.70-0.80). In internal validation, the 2 models showed reasonably well the agreement between observed and predicted probabilities for joint damage progression (Hosmer-Lemeshow test p > 0.05 and calibration slope near 1.0)., Conclusion: A simple prediction model for joint damage progression in early RA, by only counting the number of risk factors, has adequate performance. This facilitates the translation of the theoretical prognostic models to daily clinical practice.

Objective: Clinical remission currently is the treatment target for all patients with rheumatoid arthritis (RA). At the same level of inflammation, the prognosis regarding joint damage is believed to be different for anticitrullinated protein antibody (ACPA)-negative and ACPA-positive patients. Our objective was to show the difference in prognosis at similar disease activity levels, and to illustrate how this could be translated to differentiation of treatment targets., Methods: Data were used from the Nijmegen Early RA Cohort. The relation between the time-averaged disease activity level (by Disease Activity Score; DAS) and joint damage progression over 3 years was analyzed, separately for ACPA-negative and ACPA-positive patients. Joint damage was assessed as change in Ratingen score, and dichotomized as occurrence of erosions in joints that were unaffected at baseline. Linear and logistic multivariable regression models were used., Results: The regression coefficient of DAS on change in Ratingen score was 3.9 (p < 0.001) for ACPA-negative and 4.7 (p < 0.001) for ACPA-positive patients, showing less joint damage progression at the same disease activity level in ACPA-negative patients. This difference became greater with increasing disease activity. The probability for erosions in joints unaffected at baseline was 0.35 in ACPA-negative patients when time-averaged DAS was < 2.4 versus 0.80 in ACPA-positive patients., Conclusion: At the same level of inflammation, ACPA-negative patients have less joint damage and lower probability for damage in newly affected joints than ACPA-positive patients. Low disease activity might be a sufficiently strict treatment target for ACPA-negative patients to prevent progression of joint damage.