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Perspective on this Article from An Expanded Risk Prediction Model for Lung Cancer

Demographic and Clinical Characteristics of Glioma Patients in the Parent Epidemiological Study (N=1247).

Supplemental Figures 1-2 including: (1) Supplementary Figure 1. Genome-wide genetic association and lung cancer risk in discovery stage; (2) Supplementary Figure 2. Genome-wide gene-asbestos exposure interactions and lung cancer risk in discovery stage.

Background: Occupational asbestos exposure has been found to increase lung cancer risk in epidemiologic studies.Methods: We conducted an asbestos exposure–gene interaction analyses among several Caucasian populations who were current or ex-smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian controls, and used a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNP) with gene–asbestos interaction effects. The top ranked SNPs from the discovery phase were replicated within the International Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in those groups that had GWAS and asbestos exposure data, including 1,548 cases and 1,527 controls. This step was followed by de novo genotyping to replicate the results from the in silico replication, and included 1,539 cases and 1,761 controls. Multiple logistic regression was used to assess the SNP–asbestos exposure interaction effects on lung cancer risk.Results: We observed significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325 heterozygous and homozygous variant allele(s) carriers (P < 5 × 10−7 by likelihood ratio test; df = 1). Among the heterozygous and homozygous variant allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and rs12170325, each unit increase in the natural log-transformed asbestos exposure score was associated with age-, sex-, smoking status, and center-adjusted ORs of 1.34 [95% confidence interval (CI), 1.18–1.51], 1.24 (95% CI, 1.14–1.35), 1.28 (95% CI, 1.17–1.40), and 1.26 (95% CI, 1.15–1.38), respectively, for lung cancer risk.Conclusion: Our findings suggest that MIRLET7BHG polymorphisms may be important predictive markers for asbestos exposure–related lung cancer.Impact: To our knowledge, our study is the first report using a systematic genome-wide analysis in combination with detailed asbestos exposure data and replication to evaluate asbestos-associated lung cancer risk. Cancer Epidemiol Biomarkers Prev; 24(10); 1564–73. ©2015 AACR.

Background: Tobacco-induced lung cancer is characterized by a deregulated inflammatory microenvironment. Variants in multiple genes in inflammation pathways may contribute to risk of lung cancer.Methods: We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication, and meta-analysis) of inflammation gene variants in ever-smoking lung cancer cases and controls. A discovery set (1,096 cases and 727 controls) and an independent and nonoverlapping internal replication set (1,154 cases and 1,137 controls) were derived from an ongoing case–control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11,737 inflammation pathway single-nucleotide polymorphisms (SNP) and selected nominally significant (P < 0.05) SNPs for internal replication.Results: There were six SNPs that achieved statistical significance (P < 0.05) in the internal replication data set with concordant risk estimates for former smokers and five concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published genome-wide association studies (GWAS) and a case–control study. Two of these variants (a BCL2L14 SNP in former smokers and an SNP in IL2RB in current smokers) were further validated. In risk score analyses, there was a 26% increase in risk with each additional adverse allele when we combined the genotyped SNP and the most significant imputed SNP in IL2RB in current smokers and a 36% similar increase in risk for former smokers associated with genotyped and imputed BCL2L14 SNPs.Conclusions/Impact: Before they can be applied for risk prediction efforts, these SNPs should be subject to further external replication and more extensive fine mapping studies. Cancer Epidemiol Biomarkers Prev; 21(7); 1213–21. ©2012 AACR.

PDF file - 54K, Summary of Inflammation subpathways, genes and SNP's in Illumina chip

Background: Established psychosocial risk factors increase the risk for experimentation among Mexican origin youth. Now, we comprehensively investigate the added contribution of select polymorphisms in candidate genetic pathways associated with sensation seeking, risk taking, and smoking phenotypes to predict experimentation.Methods: Participants (N = 1,118 Mexican origin youth) recruited from a large population-based cohort study in Houston, TX, provided prospective data on cigarette experimentation over 3 years. Psychosocial data were elicited twice—baseline and final follow-up. Participants were genotyped for 672 functional and tagging variants in the dopamine, serotonin, and opioid pathways.Results: After adjusting for gender and age, with a Bayesian False Discovery Probability set at 0.8 and prior probability of 0.05, six gene variants were significantly associated with risk of experimentation. After controlling for established risk factors, multivariable analyses revealed that participants with six or more risk alleles were 2.25 [95% confidence interval (CI), 1.62–3.13] times more likely to have experimented since baseline than participants with five or fewer. Among committed never-smokers (N = 872), three genes (OPRM1, SNAP25, HTR1B) were associated with experimentation as were all psychosocial factors. Among susceptible youth (N = 246), older age at baseline, living with a smoker, and three different genes (HTR2A, DRD2, SLC6A3) predicted experimentation.Conclusions: Our findings, which have implications for development of culturally specific interventions, need to be validated in other ethnic groups.Impact: These results suggest that variations in select genes interact with a cognitive predisposition toward smoking. In susceptible adolescents, the impact of the genetic variants appears to be larger than committed never-smokers. Cancer Epidemiol Biomarkers Prev; 21(1); 228–38. ©2011 AACR.

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PDF file, 63KB, Minor allele frequencies (MAF), genotype counts, and results in the 13-cRA treatment arm.

Purpose: Accumulating evidence supports the contention that genetic variation is associated with neurocognitive function in healthy individuals and increased risk for neurocognitive decline in a variety of patient populations, including cancer patients. However, this has rarely been studied in glioma patients.Experimental Design: To identify the effect of genetic variants on neurocognitive function, we examined the relationship between the genotype frequencies of 10,967 single-nucleotide polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase) and neurocognitive function in 233 newly diagnosed glioma patients before surgical resection. Four neuropsychologic tests that measured memory (Hopkins Verbal Learning Test—Revised), processing speed (Trail Making Test A), and executive function (Trail Making Test B, Controlled Oral Word Association) were examined.Results: Eighteen polymorphisms were associated with processing speed and 12 polymorphisms with executive function. For processing speed, the strongest signals were in IRS1 rs6725330 in the inflammation pathway (P = 2.5 × 10−10), ERCC4 rs1573638 in the DNA repair pathway (P = 3.4 × 10−7), and ABCC1 rs8187858 in metabolism pathway (P = 6.6 × 10−7). For executive function, the strongest associations were in NOS1 rs11611788 (P = 1.8 × 10−8) and IL16 rs1912124 (P = 6.0 × 10−7) in the inflammation pathway, and POLE rs5744761 (P = 6.0 × 10−7) in the DNA repair pathway. Joint effect analysis found significant gene polymorphism-dosage effects for processing speed (Ptrend = 9.4 × 10−16) and executive function (Ptrend = 6.6 × 10−15).Conclusions: Polymorphisms in inflammation, DNA repair, and metabolism pathways are associated with neurocognitive function in glioma patients and may affect clinical outcomes. Clin Cancer Res; 21(14); 3340–6. ©2015 AACR.

Purpose: We performed a study to determine if a fluorescence in situ hybridization (FISH)–based assay using isolated peripheral blood mononuclear cells (PBMCs) with DNA probes targeting specific sites on chromosomes known to have abnormalities in non–small cell lung cancer (NSCLC) cases could detect circulating genetically abnormal cells (CACs).Experimental Design: We evaluated 59 NSCLC cases with stage I through IV disease and 24 controls. PBMCs and matched tumors were hybridized with 2 two-color [3p22.1/CEP3 and 10q22.3 (SP-A)/CEP10) and 2 four-color [CEP3, CEP7, CEP17, and 9p21.3 (URO); and EGFR, c-MYC, 6p11-q11, and 5p15.2 (LAV)] FISH probes. Percentages of cytogenetically abnormal cells (CACs) in peripheral blood and in matched tumor specimens were quantified by using an automated fluorescent scanner. Numbers of CACs were calculated based on the percentage of CACs (defined as PBMCs with genetic abnormalities) per milliliter of blood and expressed per microliter of blood.Results: Patients with NSCLC had significantly higher numbers of CACs than controls. Mean number of CACs ranged from 7.23 ± 1.32/μL for deletions of 10q22.3/CEP10 to 45.52 ± 7.49/μL for deletions of 3p22.1/CEP3. Numbers of CACs with deletions of 3p22.1, 10q22.3, and 9p21.3, and gains of URO, increased significantly from early to advanced stage of disease.Conclusions: We have developed a sensitive and quantitative antigen-independent FISH-based test for detecting CACs in peripheral blood of patients with NSCLC, which showed a significant correlation with the presence of cancer. If this pilot study can be validated in a larger study, CACs may have a role in the management of patients with NSCLC. Clin Cancer Res; 16(15); 3976–87. ©2010 AACR.

Purpose: The development of second primary tumors (SPT) or recurrence alters prognosis for curatively treated head and neck squamous cell carcinoma (HNSCC) patients. The 13-cis-Retinoic acid (13-cRA) has been tested as a chemoprevention agent in clinical trials with mixed results. Therefore, we investigated whether genetic variants in the PI3K/PTEN/AKT/mTOR pathway could serve as biomarkers to identify which patients are at high risk of an SPT/recurrence, while also predicting response to 13-cRA chemoprevention.Experimental Design: A total of 137 pathway single-nucleotide polymorphisms were genotyped in 440 patients from the Retinoid Head and Neck Second Primary Trial and assessed for SPT/recurrence risk and response to 13-cRA. Risk models were created based on epidemiology, clinical, and genetic data.Results: Twenty-two genetic loci were associated with increased SPT/recurrence risk, with six also being associated with a significant benefit following chemoprevention. Combined analysis of these high-risk/high-benefit loci identified a significant (P = 1.54 × 10−4) dose–response relationship for SPT/recurrence risk, with patients carrying four to five high-risk genotypes having a 3.76-fold [95% Confidence Interval (CI), 1.87–7.57] increase in risk in the placebo group (n = 215). Patients carrying four to five high-risk loci showed the most benefit from 13-cRA chemoprevention, with a 73% reduction in SPT/recurrence (95% CI, 0.13–0.58) compared with those with the same number of high-risk genotypes who were randomized to receive placebo. Incorporation of these loci into a risk model significantly improved the discriminatory ability over models with epidemiology, clinical, and previously identified genetic variables.Conclusions: These results show that loci within this important pathway could identify individuals with a high-risk/high-benefit profile and are a step toward personalized chemoprevention for HNSCC patients. Clin Cancer Res; 18(13); 3705–13. ©2012 AACR.

PURPOSE Impaired neurocognitive function (NCF) is extremely common in patients with higher grade primary brain tumor. We previously reported evidence of genetic variants associated with NCF in glioma patients prior to treatment. However, little is known about the effect of genetic variants on NCF decline after adjuvant therapy. METHODS Patients (N = 102) completed longitudinal NCF assessments that included measures of verbal memory, processing speed, and executive function. Testing was conducted in the postoperative period with an average follow up interval of 1.3 years. We examined polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase). RESULTS Five polymorphisms were associated with longitudinal changes in processing speed and 14 polymorphisms with executive function. Change in processing speed was strongly associated with MCPH1 rs17631450 (P = 2.2 × 10-7) and CCDC26 rs7005206 (P = 9.3 × 10-7) in the telomerase pathway; while change in executive function was more strongly associated with FANCF rs1514084 (P = 2.9 × 10-6) in the DNA repair pathway and DAOA rs12428572 (P = 2.4 × 10-5) in the cognitive pathway. Joint effect analysis found significant genetic-dosage effects for longitudinal changes in processing speed (Ptrend = 1.5 × 10-10) and executive function (Ptrend = 2.1 × 10-11). In multivariable analyses, predictors of NCF decline included progressive disease, lower baseline NCF performance, and more at-risk genetic variants, after adjusting for age, sex, education, tumor location, histology, and disease progression. CONCLUSION Our longitudinal analyses revealed that polymorphisms in telomerase, DNA repair, and cognitive pathways are independent predictors of decline in NCF in glioma patients.

ObjectivesThis study evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) versus a non-TNFi (biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)) as the first-line treatment following conventional synthetic DMARDs, as well as potential modifiers of response, observed in US clinical practice.MethodsData were from a large US healthcare registry (Consortium of Rheumatology Researchers of North America Rheumatoid Arthritis Registry). The analysis included patients (aged ≥18 years) with a documented diagnosis of rheumatoid arthritis (RA), a valid baseline Clinical Disease Activity Index (CDAI) score of >2.8 and no prior bDMARD or tsDMARD use. Outcomes were captured at 1-year postinitiation of a TNFi (adalimumab, etanercept, certolizumab pegol, golimumab or infliximab) or a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) and included CDAI, 28-Joint Modified Disease Activity Score, patient-reported outcomes (including the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, sleep, anxiety, morning stiffness and fatigue) and rates of anaemia. Groups were propensity score-matched at baseline to account for potential confounding.ResultsThere were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for outcomes assessed, except the incidence rate ratio for anaemia, which slightly favoured the TNFi group (19.04 per 100 person-years) versus the non-TNFi group (24.01 per 100 person-years, p=0.03). No potential effect modifiers were found to be statistically significant.ConclusionsThe findings of no significant differences in outcomes between first-line TNF versus first-line non-TNF groups support RA guidelines, which recommend individualised care based on clinical judgement and consideration of patient preferences.

To better inform clinicians about the use of etanercept biosimilar (SB4) in patients with rheumatoid arthritis (RA), COMPANION-B, a prospective real-world observational study, evaluated the effectiveness of the voluntary switch from originator (etanercept, ETN) to SB4 in patients with stable RA (low-disease activity/remission).The study recruited adult patients (18 years or older) with RA (2010 American College of Rheumatology criteria) prescribed ETN as their first or second biologic for at least 6 months across 14 sites in Canada and five in Australia. Patients had stable disease (Disease Activity Score-28 using erythrocyte sedimentation rate [DAS28-ESR] less than 3.2) at enrollment with no evidence of flare within the previous 3 months. Concomitant disease-modifying antirheumatic drugs (DMARDs) were permitted. Patients could elect to continue ETN or voluntarily switch to SB4 in consultation with their doctors. The primary effectiveness measure was the proportion of patients with disease worsening (defined as a DAS28-ESR increase of at least 1.2 from baseline and minimum score of at least 3.2 or a defined modification in RA treatment) during 12 months of follow-up. The secondary effectiveness measure was the proportion of patients with disease worsening at month 6. Serious adverse events (SAEs) and non-serious adverse reactions (NSARs) were recorded.Of 163 patients enrolled, 109 elected to continue on ETN and 54 switched to SB4; 65.8% of patients received non-biologic DMARD(s), 52.6% methotrexate, and 10.5% oral corticosteroid(s). At month 12, the proportion of patients with disease worsening was comparable in the ETN group (22.8% [95% CI 15.0-32.2]) and SB4 group (17.6% [95% CI 8.4-30.9]). Similarly, the proportions of patients with disease worsening were also comparable at month 6 (ETN: 7.9% [95% CI 3.5-15.0]; SB4: 7.8% [95% CI 2.2-18.9]). SAEs were low and similar across both groups (ETN: 8.7%; SB4: 5.7%). NSARs were slightly higher in the SB4 vs. ETN group (13.2% vs. 2.9%).SB4 demonstrated comparable effectiveness to ETN over 12 months in patients with stable RA who voluntarily switched to the biosimilar in a real-world setting.

Background The goal of this study is to use comprehensive molecular profiling to characterize clinical response to anti-TNF therapy in a real-world setting and identify reproducible markers differentiating good responders and non-responders in rheumatoid arthritis (RA). Methods Whole-blood mRNA, plasma proteins, and glycopeptides were measured in two cohorts of biologic-naïve RA patients (n = 40 and n = 36) from the Corrona CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory coNditions) registry at baseline and after 3 months of anti-TNF treatment. Response to treatment was categorized by EULAR criteria. A cell type-specific data analysis was conducted to evaluate the involvement of the most common immune cell sub-populations. Findings concordant between the two cohorts were further assessed for reproducibility using selected NCBI-GEO datasets and clinical laboratory measurements available in the CERTAIN database. Results A treatment-related signature suggesting a reduction in neutrophils, independent of the status of response, was indicated by a high level of correlation (ρ = 0.62; p n = 1962) from the CERTAIN database confirmed the observation (odds ratio of good/moderate response = 1.20 [95% CI = 1.03–1.41, p = 0.02]). Conclusion Differences in innate/adaptive immune cell type composition at baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy.

This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as “existing use” starting before registry entry or “initiated use” starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with

Introduction Prednisone is frequently administered in combination with other therapies for the treatment of rheumatoid arthritis (RA); however, its chronic use is associated with an increased risk of comorbidities and mortality. The objective of this analysis was to evaluate changes in prednisone use among patients with RA treated with tocilizumab (TCZ) in routine US clinical practice. Methods TCZ-naïve patients in the Corrona RA registry who initiated TCZ were included. The primary outcome was the proportion of patients with changes in prednisone use over 12 months (primary analysis) and 6 months (secondary analysis). Changes in disease activity over 6 and 12 months (± 3 months) were assessed using the Clinical Disease Activity Index (CDAI). Outcomes were assessed in the overall population and separately for patients receiving TCZ monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs. Results Of patients receiving prednisone at baseline (mean [SD] dose: 7.7 [5.2] mg/day), 30.6% discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased their dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at baseline had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased their dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement from baseline in CDAI score over 6 and 12 months were comparable between patients who initiated TCZ monotherapy vs. TCZ combination therapy. Conclusions In this real-world analysis, many patients initiating TCZ monotherapy or combination therapy were able to discontinue or decrease their prednisone dose over 12 months. Similar changes in prednisone dose were observed over 6 months. Trial Registration ClinicalTrials.gov identifier, NCT01402661. Funding Corrona, LLC and Genentech, Inc. Plain Language Summary Plain language summary available for this article., Plain Language Summary Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint damage and disability. The steroid prednisone is a fast-acting and effective treatment for RA and is often prescribed alongside disease-modifying antirheumatic drugs (DMARDs). The health risks associated with the long-term use of prednisone have led to recommendations to minimize prednisone dose and duration of treatment. Few studies have examined the extent to which biologic DMARDs allow rheumatologists to reduce or discontinue the use of prednisone. The objective of this study was to evaluate changes in prednisone dose while receiving tocilizumab (TCZ) in patients with RA seen in routine US clinical practice. Patients who were enrolled in the Corrona RA registry and were beginning treatment with TCZ were included. Changes in prednisone use were evaluated 12 months after starting treatment. Of patients receiving prednisone at study initiation, 30.6% had discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased the dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at study initiation had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased the dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement in disease activity over 6 and 12 months were comparable between patients who initiated TCZ monotherapy or combination therapy with other DMARDs.

We thank Zheng et al 1 for their interest in our study2 and for providing constructive comments. They mention that even though the baseline mean Clinical Disease Activity Index (CDAI) was not statistically different, the proportion of patients with moderate or high disease at baseline was different and this could have been a key effect modifier.1 We used standardised differences to evaluate variables at baseline. Calculation of the standardised difference not only accounts for the means of the two cohorts, but also the SD. We noticed that continuous CDAI was balanced across the two therapy classes (as listed in the manuscript table 1, SD=−0.015)2 and similarly observed for categorical CDAI (low/moderate/high; SD=0.0515; results not shown …

Objective.To characterize skin severity and joint activity outcomes and associated treatment changes in patients with psoriatic arthritis (PsA) through 12 months of follow-up after enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry.Methods.Patients ≥ 18 years of age with a diagnosis of PsA and a history of psoriasis between March 21, 2013, and September 30, 2016, were enrolled (n = 647). Demographics, clinical features, and treatment characteristics were collected and stratified by skin severity and joint activity. Change in joint and skin from enrollment to the 12-month visit was classified by change in category of Clinical Disease Activity Index (CDAI) or body surface area (BSA). Tests of association evaluated the relationship between changes in therapy and changes in skin severity and joint activity.Results.Patients with improvement in both joint activity and skin severity saw the largest median reduction in both CDAI and BSA, while those who worsened in both had the greatest median increase in both CDAI and BSA. The majority of PsA patients (> 50%) had no change in skin severity regardless if they had reduced therapy (50%), no therapy changes (54%), or increased therapy (56%; P = 0.5875). However, there was a significant association between changes in therapy and changes in joint activity (P < 0.001). Patients who increased therapy were more likely to have improvement in joint activity (32%) compared to patients who reduced therapy (22%) or had no therapy changes (11%).Conclusion.The clinical implication for our findings suggests the assessment and incorporation of both skin and joint components may be advisable.

Objective To develop and evaluate an adjusted score for the multi-biomarker disease activity (MBDA) test to account for the effects of age, sex and adiposity in patients with RA. Methods Two models were developed to adjust MBDA score for age, sex and adiposity, using either serum leptin concentration or BMI as proxies for adiposity. Two cohorts were studied. A cohort of 325 781 RA patients who had undergone commercial MBDA testing and had data for age, sex and serum leptin concentration was used for both models. A cohort of 1411 patients from five studies/registries with BMI data was used only for the BMI-adjusted MBDA score. Univariate and multivariate linear regression analyses evaluated the adjusted MBDA scores and conventional clinical measures as predictors of radiographic progression, assessed in terms of modified total Sharp score (ΔmTSS). Results Two models were developed, based on findings that MBDA score was higher in females than males and increased with age, leptin concentration and BMI. In pairwise regression analyses, the leptin-adjusted (P = 0.00066) and BMI-adjusted (P = 0.0027) MBDA scores were significant independent predictors of ΔmTSS after adjusting for DAS28-CRP, whereas DAS28-CRP was not, after adjusting for leptin-adjusted (P = 0.74) or BMI-adjusted (P = 0.87) MBDA score. Moreover, the leptin-adjusted MBDA score was a significant predictor of ΔmTSS after adjusting for the BMI-adjusted MBDA score (P = 0.025) or the original MBDA score (0.027), whereas the opposite was not true. Conclusion Leptin-adjusted MBDA score significantly adds information to DAS28-CRP and the original MBDA score in predicting radiographic progression. It may offer improved clinical utility for personalized management of RA.

Background: Melanoma and renal-cell carcinoma (RCC) are known to be immunological neoplasms. Previous studies have shown increased risks in patients with melanoma of developing RCC and in those with RCC of developing melanoma. However, data regarding immunocompromised status in these patients are lacking. Methods: We conducted a retrospective review of patients who had a diagnosis of melanoma and/or RCC. Using summary statistics, we calculated total person-years at risk for developing melanoma among patients with RCC and for developing RCC among patients with melanoma, and compared the results with the SEER data. We also assessed medical history related to immune status and the use of immunosuppressive drugs. Results: Among 13,879 patients with melanoma and 7597 patients with RCC, 89 had diagnoses of both melanoma and RCC (0.6% and 1.2% of melanoma and RCC patients, respectively): eight were diagnosed with both cancers concurrently, 54 were diagnosed with melanoma first, and 27 were diagnosed with RCC first. Standardized incidence ratios (SIRs) were 2.87 (95%CI 2.16–3.74) for developing RCC among the melanoma patients and 2.31 (95%CI 1.52–3.37) for developing melanoma among the RCC patients, compared to age-, sex-, race-, and calendar-specific adjusted incidence rates of each cancer in the SEER registry. None of the 81 patients with sequential diagnoses had a history of immunocompromised disease, nor did they receive chronic immunosuppressive drugs. Only two received chemotherapy and/or radiotherapy. Conclusion: We demonstrated a strong association between the diagnoses of melanoma and RCC. These increased risks could not be attributed to either immune status or previous antineoplastic treatment.

To compare disease burden and biologic use among psoriatic arthritis (PsA) or rheumatoid arthritis (RA) patients recruited to the Corrona registry. Retrospective study of patients with PsA or RA enrolled in Corrona between January 2002 and March 2013 and grouped in 2-year intervals. Clinical outcomes and biologic use were assessed. Biologic use increased over time in both cohorts, with 62 and 52% of patients with PsA and RA, respectively, receiving biologics by 2012-2013. However, 25 and 35% of patients with PsA and RA, respectively, continued to experience moderate/high disease activity. Overall, the progressive increase in biologic use accompanied progressive decreases in Clinical Disease Activity Index (from 14.2 to 10.4 for RA, and 12.4 to 8.1 for PsA) and mean Health Assessment Questionnaire score (from 0.36 to 0.34, and 0.3 to 0.24). Mean patient pain, the proportion of patients reporting morning stiffness, and the mean duration of morning stiffness remained similar for both cohorts. PsA and RA treated in the rheumatology setting had a comparable impact on patient quality of life and functional ability. Disease burden improved with increased biologic utilization in both groups; however, moderate/severe disease remains in a significant proportion of PsA and RA patients.

Despite the promising results of the National Lung Screening Trial in reducing lung cancer mortality among high risk smokers, several challenges remain to be addressed. These include the high false positive rates and the large number of smokers screened in order to prevent one lung cancer death. In addition, host genetic susceptibility has not been integrated into selection of who should be screened. These challenges highlight the need to develop robust ways to identify susceptible smokers for appropriate screening.We used the cytokinesis block micronucleus (CBMN) assay to assess smoking induced genetic instability among NLST participants. Blood cultures were prepared at time of entry into the screening study and DNA damage was recorded as the frequency of binucleated nucleoplasmic bridges and micronuclei. Low dose CT (LDCT) and chest X-ray (CXR) image findings were available upon unblinding of the NLST study and imaging data were merged with blood marker data for statistical analysis.A total of 641 participants were included in this study. The frequency of the CBMN endpoints at time of entry into the study was significantly higher among study participants who had a positive finding during the 3-year screening or reported lung cancer at the end of the follow-up period as compared to participants who were negative. Growth curve models were used to compare trajectories of change in CBMN endpoints between entry into the study and end-of-screening period. A statistically significant increase was predicted for CBMN endpoints among the study participants who were positive versus those who remained negative at the end-of-screening period (P

Background The prevalence of chronic obstructive pulmonary disease (COPD) in smokers enrolled as "healthy" controls in studies is 10–50%. The COPD status of ideal smoker populations for lung cancer case-control studies should be checked via spirometry; however, this is often not feasible, because no medical indications exist for asymptomatic smokers to undergo spirometry prior to study enrollment. Therefore, there is an unmet need for robust, cost effective assays for identifying undiagnosed lung disease among asymptomatic smokers. Such assays would help excluding unhealthy smokers from lung cancer case-control studies. Methods We used the cytokinesis-blocked micronucleus (CBMN) assay (a measure of genetic instability) to identify undiagnosed lung disease among asymptomatic smokers. We used a convenience population from an on-going lung cancer case-control study including smokers with lung cancer ( n = 454), smoker controls ( n = 797), and a self-reported COPD ( n = 200) contingent within the smoker controls. Results Significant differences for all CBMN endpoints were observed when comparing lung cancer to All controls (which included COPD) and Healthy controls (with no COPD). The risk ratio (RR) was increased in the COPD group vs. Healthy controls for nuclear buds (RR 1.28, 95% confidence interval 1.01–1.62), and marginally increased for micronuclei (RR 1.06, 0.98–1.89) and nucleoplasmic bridges (RR 1.07, 0.97–1.15). Conclusion These findings highlight the importance of using truly healthy controls in studies geared toward assessment of lung cancer risk. Using genetic instability biomarkers would facilitate the identification of smokers susceptible to tobacco smoke carcinogens and therefore predisposed to either disease.

Objective To characterize psoriatic arthritis (PsA) patients with dactylitis or enthesitis and evaluate the associations of these manifestations with disease activity and patient-reported outcomes. Methods Using the Corrona PsA/Spondyloarthritis Registry, patient characteristics, disease activity, and patient-reported outcomes at registry enrollment were assessed for PsA patients ages ≥18 years with or without dactylitis or enthesitis. Regression models were used to evaluate associations of dactylitis and enthesitis with outcomes, including minimal disease activity, Health Assessment Questionnaire scores, patient-reported pain and fatigue, and work productivity (Work Productivity and Activity Impairment questionnaire). Adjustments were made for age, sex, race, body mass index, disease duration, and history of biologic agent, disease-modifying antirheumatic drug, and prednisone use. Results This analysis included 1,567 PsA patients (420 with enthesitis; 228 with dactylitis). Patients with versus without dactylitis or enthesitis had greater disease activity and were less likely to be in minimal disease activity (P < 0.05). Patients with versus without enthesitis had poorer functional status as assessed by the Health Assessment Questionnaire (adjusted P = 4.15 x 10−5), greater patient-reported pain and fatigue (adjusted P < 0.0001), and greater likelihood of any impairment while working (adjusted odds ratio [OR] 1.57, P = 0.027), overall work impairment (OR 1.85, P = 0.006), and activity impairment (OR 1.77, P = 0.008). Dactylitis was associated with similar numerical trends, but differences versus patients without dactylitis did not reach statistical significance. Conclusion Enthesitis and dactylitis are associated with greater overall disease burden of PsA, underscoring the importance of identifying, assessing, and effectively managing these periarticular manifestations.

Purpose The Imaging and Radiation Oncology Core Houston (IROC-H) (formerly the Radiological Physics Center) has reported varying levels of agreement in their anthropomorphic phantom audits. There is reason to believe one source of error in this observed disagreement is the accuracy of the dose calculation algorithms and heterogeneity corrections used. To audit this component of the radiotherapy treatment process an independent dose calculation tool is needed. Methods Monte Carlo multiple source models for Elekta 6MV and 10MV therapeutic x-ray beams were commissioned based on measurement of central axis depth dose data for a 10 x 10 cm2 field size and dose profiles for a 40 x 40 cm2 field size. The models were validated against open field measurements consisting of depth dose data and dose profiles for field sizes ranging from 3 x 3 cm2 to 30 x 30 cm2. The models were then benchmarked against measurements in IROC-H's anthropomorphic head and neck and lung phantoms. Results Validation results showed 97.9% and 96.8% of depth dose data passed a ±2% Van Dyk criterion for 6MV and 10MV models, respectively. Dose profile comparisons showed an average agreement using a ±2%/2mm criterion of 98.0% and 99.0% for 6MV and 10MV models, respectively. Phantom plan comparisons were evaluated using ±3%/2mm gamma criterion, and averaged passing rates between Monte Carlo and measurements were 87.4% and 89.9% for 6MV and 10MV models, respectively. Conclusions Accurate multiple source models for Elekta 6MV and 10MV x-ray beams have been developed for inclusion in an independent dose calculation tool for use in clinical trial audits. This article is protected by copyright. All rights reserved.

Purpose The Imaging and Radiation Oncology Core – Houston (IROC-H) Quality Assurance Center (formerly the Radiological Physics Center) has reported varying levels of compliance from their anthropomorphic phantom auditing program. IROC-H studies have suggested that one source of disagreement between institution submitted calculated doses and measurement is the accuracy of the institution's treatment planning system dose calculations and heterogeneity corrections used. In order to audit this step of the radiation therapy treatment process, an independent dose calculation tool is needed. Methods Monte Carlo multiple source models for Varian Flattening Filter Free (FFF) 6MV and FFF 10MV therapeutic x-ray beams were commissioned based on central axis depth dose data from a 10 x 10 cm2 field size and dose profiles for a 40 x 40 cm2 field size. The models were validated against open field measurements in a water tank for field sizes ranging from 3 x 3 cm2 to 40 x 40 cm2. The models were then benchmarked against IROC-H's anthropomorphic head and neck phantom and lung phantom measurements. Results Validation results, assessed with a ±2%/2mm gamma criterion, showed average agreement of 99.9% and 99.0% for central axis depth dose data for FFF 6MV and FFF 10MV models, respectively. Dose profile agreement using the same evaluation technique averaged 97.8% and 97.9% for the respective models. Phantom benchmarking comparisons were evaluated with a ±3%/2mm gamma criterion, and agreement averaged 90.1% and 90.8% for the respective models. Conclusions Multiple source models for Varian FFF 6MV and FFF 10MV beams have been developed, validated, and benchmarked for inclusion in an independent dose calculation quality assurance tool for use in clinical trial audits. This article is protected by copyright. All rights reserved.

Objective.Psoriatic arthritis (PsA) is commonly comorbid with psoriasis; the extent of skin lesions is a major contributor to psoriatic disease severity/burden. We evaluated whether extent of skin involvement with psoriasis [body surface area (BSA) > 3% vs ≤ 3%] affects overall clinical and patient-reported outcomes (PRO) in patients with PsA.Methods.Using the Corrona PsA/Spondyloarthritis Registry, patient characteristics, disease activity, and PRO at registry enrollment were assessed for patients with PsA aged ≥ 18 years with BSA > 3% versus ≤ 3%. Regression models were used to evaluate associations of BSA level with outcome [modified minimal disease activity (MDA), Health Assessment Questionnaire (HAQ) score, patient-reported pain and fatigue, and the Work Productivity and Activity Impairment questionnaire score]. Adjustments were made for age, sex, race, body mass index, disease duration, and history of biologics, disease-modifying antirheumatic drug, and prednisone use.Results.This analysis included 1240 patients with PsA with known BSA level (n = 451, BSA > 3%; n = 789, BSA ≤ 3%). After adjusting for potential confounding variables, patients with BSA > 3% versus ≤ 3% had greater patient-reported pain and fatigue and higher HAQ scores (p = 2.33 × 10−8, p = 0.002, and p = 1.21 × 10−7, respectively), were 1.7× more likely not to be in modified MDA (95% CI 1.21–2.41, p = 0.002), and were 2.1× more likely to have overall work impairment (1.37–3.21, p = 0.0001).Conclusion.These Corrona Registry data show that substantial skin involvement (BSA > 3%) is associated with greater PsA disease burden, underscoring the importance of assessing and effectively managing psoriasis in patients with PsA because this may be a contributing factor in PsA severity.

Background: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Real-world data (RWD) complement clinical trial data in assessing long-term safety. To our knowledge, this is the first long-term comparative RWD analysis of tofacitinib. Objectives: To compare 5-year adverse event (AE) incidence rates (IRs) in patients (pts) starting tofacitinib vs biological (b)DMARDs using cohorts from the US Corrona RA registry. Methods: This prospective, observational 5-year study embedded in the ongoing US Corrona RA registry routinely collected 9 categories of predefined AEs from participating physicians. Real-world safety event rates of major adverse cardiovascular events (MACE), serious infectious events (SIEs) and herpes zoster (HZ; serious and non-serious) were compared in pts with RA who started tofacitinib or a bDMARD regardless of dose/schedule between 6 Nov 2012 (US FDA approval) and 30 Jun 2017 (follow-up through 31 Dec 2017). Endpoints were selected a priori as having sufficient power to detect a 2-fold difference between cohorts at this datacut; there was insufficient power to assess malignancy. Baseline variables with a standardised difference >│0.10│ between tofacitinib and bDMARD initiators, and a priori selected covariates (gender, age, line of therapy, history of AE of interest) were used to construct propensity scores (PS) to derive a PS-trimmed (primary) population and a PS–matched population for sensitivity analysis (ratio: max. 4 bDMARD:1 tofacitinib; calliper=0.05). Pts were followed from initiation until an AE of interest, discontinuation and/or start of a new therapy +90 days, death or end of follow-up, whichever came first. Crude IRs (events/100 pt–years [PY]) were estimated; multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) comparing rates of first events between cohorts. Results: In total, 1544 tofacitinib (2138.2 PY) and 7083 bDMARD (9904.9 PY) initiators were included. PS–trimming resulted in 1117 tofacitinib and 5542 bDMARD initiators. Rates of MACE and SIEs were similar in both cohorts (Fig 1A); adjusted HRs (95% confidence intervals [CIs]) were: MACE 0.60 (0.30, 1.18); SIEs 0.99 (0.72, 1.36; Fig 1B). HZ IR was higher for tofacitinib vs bDMARDs (Fig 1A); HRs for HZ were significantly increased with tofacitinib vs bDMARDs (adjusted HR 2.12 [1.22, 3.66]; Fig 1B); all HZ events were non-serious with tofacitinib. Similar results were observed in PS-matched populations. Conclusion: This is the first comparative analysis of RWD for tofacitinib and bDMARDs to use PS-trimmed and PS-matched analyses to adjust for channelling/prescribing patterns for newly approved therapies. Pts starting tofacitinib or bDMARDs for RA had similar rates of MACE and SIEs. Tofacitinib initiators had higher HZ IRs vs bDMARD initiators. These results are consistent with long-term clinical trial findings. Acknowledgement: Sponsors: Corrona, LLC. Corrona is supported by contracted subscriptions with multiple companies. This was a Corrona/Pfizer collaboration with Pfizer financial support. Medical writing support provided by Anthony G McCluskey of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Joel Kremer Grant/research support from: AbbVie, Genentech, Lilly, Novartis, Pfizer, Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Regeneron, Sanofi, Pfizer, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Laura Cappelli Grant/research support from: Bristol-Myers Squibb, Consultant for: Regeneron/Sanofi Genzyme, Carol Etzel Shareholder of: Corrona, LLC, Consultant for: Merck, Employee of: Corrona, LLC, Jeffrey Greenberg Shareholder of: Corrona, LLC, Consultant for: Eli Lilly, Genentech, Janssen, Novartis, and Pfizer Inc, Employee of: Corrona, LLC, Jamie Geier Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ann Madsen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Connie Chen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alina Onofrei Employee of: Corrona, LLC, Christine Barr Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, Dimitrios A Pappas Grant/research support from: AbbVie, Consultant for: AbbVie, Employee of: Corrona, Heather J. Litman: None declared, Kimberly J Dandreo Employee of: Corrona, LLC, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Carol A. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arthur Kavanaugh Grant/research support from: UCB Pharma

Objective.To analyze prophylaxis using the CORRONA (COnsortium of Rheumatology Researchers Of North America) Gout Registry according to the American College of Rheumatology (ACR) guidelines, and to evaluate whether differences in disease characteristics influenced prophylaxis.Methods.All patients with gout in the CORRONA Gout Registry between November 1, 2012, and November 26, 2013, were included. They were divided into 2 groups: “receiving prophylaxis” versus “not receiving prophylaxis” at the time of enrollment. Patients having a flare at time of visit were excluded. Descriptive statistics and multivariable logistic regression models were performed to evaluate the factors associated with prophylaxis.Results.There were 1049 patients with gout available for analysis. There were 441 patients (42%) receiving prophylaxis and 608 (58%) not receiving prophylaxis. The most common drugs used for prophylaxis were colchicine (78%) and nonsteroidal antiinflammatory drugs (32%). Prophylaxis drug combination was used by 45 patients (10.2%). Patients in the “receiving prophylaxis” group were more likely to have a gout duration of ≤ 1 year (n = 68, p < 0.001), ≥ 1 flare in the year previous to enrollment (p < 0.001), ≥ 1 healthcare uses in the last year [Emergency Department (p = 0.029); outpatient visit to primary care, rheumatologist, or urgent care clinic (p < 0.001)], have tophi (p < 0.001), report pain > 3 (p = 0.001), and have disease activity > 10 (p < 0.001) compared with patients in the “not receiving prophylaxis” group.Conclusion.Forty-two percent of patients with gout in the CORRONA Gout Registry were receiving prophylaxis. Prophylaxis was significantly more common in patients with a higher disease burden and activity, which is in agreement with the ACR guidelines. Our study highlights disease characteristics influencing prophylaxis and furthers our knowledge on current use of flare prophylaxis.

ObjectiveTo compare the characteristics of patients with psoriatic arthritis among patient groups stratified by degree of skin and joint involvement, and to evaluate the relationship between skin severity and joint activity.MethodsBody surface area (BSA) and Clinical Disease Activity Index (CDAI) at enrolment were analysed. Patient characteristics were stratified by skin severity and joint activity. Baseline patient characteristics, clinical and disease characteristics and patient-reported outcomes were compared. The strength of the relationship of skin severity and joint activity was evaluated using methods for categorical variables (χ2 test, Cramer’s V) and continuous variables (linear regression).Results1542 adult patients in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry enrolled between 21 May 2013 and 20 September 2016 were analysed. Most patients in the BSA >3%/CDAI moderate/high subgroup had worse clinical and patient-reported outcomes. A significant (pConclusionSkin severity is modestly correlated with joint activity, and patients with higher skin severity are two times more likely to have increased joint involvement. Clinicians need to address both skin severity and joint activity in treatment decisions.

Background The MBDA score, based on 12 serum proteins, is a validated tool for assessing disease activity in RA patients. MBDA biomarkers may be influenced by age, sex and adiposity. Objectives To develop and validate an adjusted MBDA score that accounted for these three factors, using BMI or serum leptin as proxies for adiposity. Methods The MBDA score as a continuous variable was adjusted to account for age, sex and a proxy for adiposity (serum leptin) using data from 325,781 RA patients for whom MBDA tests had been ordered as part of routine care. Leptin values came from the MBDA test. As an alternative to using leptin to adjust for adiposity, a cohort of 1411 patients from 5 studies/registries (BRASS, Corrona-CERTAIN, InFoRM, OPERA, RACER) was used to adjust for BMI, which was not available in the larger cohort, adding this BMI adjustment to that for age/sex from the larger cohort. Both types of adjusted MBDA score use the low, moderate, and high disease activity cutpoints of the original MBDA score. The two adjusted MBDA scores and other variables were evaluated for the prediction of radiographic progression (RP) in the 2 cohorts with available data (OPERA, BRASS) using univariate and multivariate linear regression analyses. Rate of RP was assessed as the change in modified total Sharp score (ΔmTSS) per year after MBDA testing. Results The MBDA score increased with age, BMI and leptin concentration. In univariate analysis of the combined OPERA and BRASS cohorts (n=555), the significant variables predicting ΔmTSS were leptin-adjusted MBDA score, seropositivity for RF or anti-CCP, BMI-adjusted MBDA score, MBDA score, BMI, CRP, baseline mTSS, disease duration, DAS28-CRP, SDAI, CDAI and DAS28* (table 1). The leptin- and BMI-adjusted MBDA scores were the first and third most significant univariate predictors of ΔmTSS. To compare them directly, DAS28-CRP, MBDA score, BMI-adjusted MBDA score and leptin-adjusted MBDA score were combined in pairs in regression analyses of ΔmTSS; the BMI-adjusted (p=0.0027) and leptin-adjusted MBDA score were significant (p=0.00063) after adjusting for DAS28-CRP (p=0.87 and 0.74, respectively) and the leptin-adjusted MBDA score was significant (p=0.024 and 0.020, respectively) after adjusting for either the MBDA (p=0.32) or BMI-adjusted MBDA scores (p=0.094). Conclusions We developed two adjusted MBDA scores that combine molecular and biometric variables to account for age, sex, and adiposity. The leptin-adjusted MBDA score, significantly outperformed DAS28-CRP and the original MBDA score in predicting radiographic progression in RA patients. These results suggest that the leptin-adjusted MBDA score may offer improved clinical utility for the personalised management of patients with RA. Disclosure of Interest J. Curtis Grant/research support from: Crescendo Bioscience Inc., Consultant for: Crescendo Bioscience Inc., D. Flake II Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience Inc., UCB, and Genzyme, Consultant for: Amgen, Bristol-Myers Squibb, Crescendo Bioscience Inc., UCP, and Genzyme, N. Shadick Grant/research support from: Bristol-Myers Squibb, Consultant for: Mallinckrodt, Amgen, Bristol-Myers Squibb, UCB, DxTerity, Sanofi, Crescendo Bioscience Inc., Janssen, and Merck, M. Ostergaard Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche, Takeda, and UCB, Consultant for: AbbVie, BMS, Celgene, Crescendo Bioscience Inc., Janssen, and Merck, M. Hetland Consultant for: AbbVie, Biogen, BMS, CelltrionRoche, Crescendo Bioscience Inc., Eli Lilly, MSD, Pfizer, and UCB, Speakers bureau: Orion, C. Heegaard Brahe: None declared, Y. Hwang Consultant for: Pfizer Inc., D. Furst: None declared, V. Strand Grant/research support from: Abbvie, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo Bioscience Inc., EMDSerono, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Protagen, Regeneron, Samsung, Sandoz, Sanofi, and UCB, C. Etzel Shareholder of: CORRONA, LLC, Grant/research support from: Merck, Employee of: CORRONA, LLC, D. Pappas Shareholder of: CORRONA, LLC, Employee of: CORRONA, LLC, Paid instructor for: Novartis Pharmaceutical, X. Wang Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., C. Hwang Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., E. Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., A. Gutin Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., E. Hitraya Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., J. Lanchbury Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc.

Background Until recently, treatment for moderate to severe psoriatic arthritis (PsA) mainly focused on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumour necrosis factor inhibitors (TNFis). However, the persistence of TNFis alone or in combination with csDMARDs is not well understood. Objectives To assess real-word treatment patterns among patients with PsA receiving TNFi monotherapy, csDMARD monotherapy, or TNFi and csDMARD combination therapy. Methods This retrospective study utilised data from patients with PsA aged ≥18 years, enrolled in the Corrona PsA registry between March 21, 2013, and July 31, 2017, treated with a TNFi and/or csDMARD (index therapy), and with ≥6 months of follow-up time. Patients were stratified by prevalent (initiation before enrollment) or incident (initiation after enrollment) therapy use; cohorts were based on index therapy: TNFi monotherapy, csDMARD monotherapy, or combination therapy. Outcomes of interest were the percentage of patients who were persistent on their index therapy or had a therapy change (discontinued, switched, or restarted) 12 months after the index visit. Results There were 1266 patients in this study: 1144 prevalent and 122 incident (table 1). Patient characteristics at the index date were similar among patients; however, csDMARD monotherapy patients had higher disease activity than either TNFi group. Among prevalent patients, TNFi monotherapy patients were likely to be female (59%) and younger (51.9 years), nearly all patients had psoriasis, and BSA was similar and ≤5. At month 12, among patients with a follow-up visit within the 9–15–month window, the vast majority of prevalent patients and half of incident patients were persistent on their index therapy, and one quarter to one third of incident patients discontinued or switched therapy (table 1). Conclusions Most patients who were prevalent on therapy at the time of enrollment in Corrona remained persistent on their therapy for 12 months in this study, while roughly half of patients initiating therapy after enrollment remained persistent over the same period. Young, female patients were more likely to receive TNFi monotherapy; the TNFi monotherapy cohort was associated with the least disease activity. The incident group was not different from the prevalent group. Although the prevalent group is more likely to have patients who responded to treatment, the data suggest that most therapy changes occur within the first year of PsA treatment. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, and UCB, Consultant for: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, and UCB, Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, and UCB, N. Accortt Shareholder of: Amgen Inc., Employee of: Amgen Inc., S. Rebello Employee of: Corrona LLC, C. Etzel Consultant for: Merck, Employee of: Corrona LLC, R. Harrison Employee of: Corrona LLC, G. Aras Shareholder of: Amgen Inc., Employee of: Amgen Inc., M. Gharaibeh Shareholder of: Amgen Inc., Employee of: Amgen Inc., J. Greenberg Shareholder of: Corrona LLC, Consultant for: Genentech, Janssen, Novartis, Pfizer, and Eli Lilly, Employee of: Corrona LLC, D. Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc.

Background Few real-world studies have evaluated the impact of comorbidity burden or obesity on the effectiveness of tocilizumab (TCZ) for the improvement of rheumatoid arthritis (RA) disease activity. Objectives To compare the effectiveness of TCZ in treating RA in patients with high vs low comorbidity burden and in obese vs nonobese patients in US clinical practice. Methods Patients in the Corrona RA registry who initiated TCZ and had follow-up visits at 6 and 12 months after initiation were included. To assess the impact of comorbidity burden on TCZ effectiveness, outcomes were stratified by patients with low Charlson Comorbidity Index (CCI=1) vs high (CCI ≥2). To assess the impact of obesity, outcomes were stratified by patients with BMI 0.1 were identified as covariates for inclusion in adjusted comparisons. Outcomes were compared between cohorts using two-sample t-tests or χ2 tests in unadjusted analyses and linear or logistic regression models to adjust for covariates. Results Of 770 patients who initiated TCZ and had CCI data available at baseline (93.8% treated with intravenous [IV] TCZ and 6.2% with subcutaneous [SC] TCZ), 575 (74.7%) had a low CCI and 195 (25.3%) a high CCI. Patients with a high CCI were older (mean [SD] age, 61.5 [12.3] vs 56.9 [13.1] years), were more likely to be obese (52.8% vs 41.7%), had a longer disease duration (mean [SD], 12.8 [9.9] vs 11.6 [8.9] years) and had higher mean (SD) baseline CDAI (25.7 [13.4] vs 23.9 [13.9]) and HAQ (0.71 [0.57] vs 0.57 [0.51]) scores than those with a low CCI. Of the 805 TCZ initiators with BMI data available at baseline (93.9% treated with IV TCZ and 6.1% with SC TCZ), 449 (55.8%) were not obese and 356 (44.2%) were obese. Obese patients were younger (56.7 [12.0] vs 59.0 [13.7] years), had shorter disease duration (11.4 [8.6] vs 12.6 [9.7] years) and had higher baseline CDAI (25.4 [14.3] vs 23.6 [13.4]) and HAQ (0.65 [0.53] vs 0.57 [0.53]) scores than nonobese patients. Patients in all cohorts had improvement from baseline in CDAI at 6 and 12 months, with no significant differences between those with a low vs high CCI or between obese vs nonobese patients (table 1). Secondary outcomes yielded similar results (table 1). Conclusions In this real-world analysis, the effectiveness of TCZ for the improvement of RA disease activity was comparable among patients regardless of comorbidity burden or obesity. Acknowledgements This study is sponsored by Corrona, LLC. Corrona has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, Boehringer Ingelheim, BMS, Celgene, Crescendo, Eli Lilly, Genentech, Gilead, GSK, Horizon Pharma USA, Janssen, Merck, Momenta Pharmaceuticals, Novartis, Pfizer Inc., Roche, UCB and Valeant. Disclosure of Interest D. Pappas Grant/research support from: Abbvie, Consultant for: Abbvie, Employee of: Corrona, LLC, C. Etzel Shareholder of: Corrona, LLC, Consultant for: Merck, Employee of: Corrona, LLC, M. Crabtree Employee of: Corrona, LLC, J. Best Shareholder of: Genentech, Inc., Employee of: Genentech, Inc, S. Zlotnick Shareholder of: Genentech, Inc., Employee of: Genentech, Inc, J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, Pfizer, Regeneron, Sanofi

Background Musculoskeletal ultrasound (MSUS) imaging in patients with rheumatoid arthritis (RA) can detect synovial inflammation with higher sensitivity compared to physical examination alone. 1 Not all rheumatologists have adopted the use of MSUS in their daily practice. Objectives To compare clinical outcomes in patients whose physicians use MSUS to assess joint inflammation vs those who do not. Methods Data from patients≥18 years old with a confirmed diagnosis of RA who had an index visit in the Corrona RA Registry from 01/01/2012 to 12/31/2015 with ≥12 months of follow-up were stratified into 2 groups: patients whose physicians use MSUS frequently—ie, in >50% of their patient encounters—(MSUS group) and patients whose physicians do not use MSUS at all (No-MSUS group). Frequency of MSUS can be recorded and updated by the rheumatologist in the registry questionnaires at every Corrona visit. The index visit was the first visit in which the physician reported the frequency of MSUS use. Outcomes included mean Clinical Disease Activity Index (CDAI) and the proportion of patients in low disease activity (LDA)/remission (CDAI ≤10) at each time point and were evaluated at index and 1, 2, and 3 years post-index. Comparisons between groups were made using 2-sample t -tests for mean CDAI and Chi-square tests for achievement of LDA/remission. Results 21 physicians reported using MSUS frequently compared with 111 who did not use MSUS at all. 5446 of their patients met the criteria for analysis; 1018 (18.7%) were in the MSUS group and 4428 (81.3%) were in the No-MSUS group. At the index visit, the MSUS group was younger (mean age 57.7 years vs 59.8 years, p Conclusions A greater percentage of patients whose physicians use MSUS were in LDA/remission over time. Average disease activity of these patients was lower compared with patients whose physicians did not use MSUS. This pattern was observed at 4 different time points over a 3 year period. Reference [1] Freeston, et al. Ann Rheum Dis2010;69:417–9. Acknowledgements Corrona has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Crescendo, Eli Lilly and Company, Genentech, Gilead, GSK, Horizon Pharma USA, Janssen, Merck, Momenta Pharmaceuticals, Novartis, Pfizer Inc, Roche, UCB and Valeant. The design, study conduct, and financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. Medical writing services provided by Joann Hettasch of Fishawack Communications and funded by AbbVie. Disclosure of Interest D. Pappas Shareholder of: Corrona, Employee of: Corrona, Paid instructor for: Novartis, K. Saunders Shareholder of: Corrona, Employee of: Corrona, C. Etzel Shareholder of: Corrona, Employee of: Corrona, D. Hua: None declared, K. Deering Employee of: EPI-Q, P. Zueger Shareholder of: AbbVie, Employee of: AbbVie, V. Garg Shareholder of: AbbVie, Employee of: AbbVie

Performance of the ers-ra cardiovascular risk prediction tool : external validation in a large swedish cohort with ra

Objective Cardiovascular disease (CVD) is the leading cause of mortality in rheumatoid arthritis (RA), but CV risk prediction scores derived from the general population do not accurately predict CV risk in RA patients. The goal of these analyses was to develop and internally validate an expanded CV risk prediction score for RA. Methods Study participants were patients with RA and no known CVD from the Consortium of Rheumatology Researchers of North America registry. Two-thirds of the cohort were used to derive the CV risk prediction score, and one-third for internal validation. Traditional CV risk factors were included in the base Cox regression model, and RA-related variables were assessed in an expanded model predicting confirmed CV events. Fit and utility of the expanded model were evaluated. Results The study cohort included 23,605 RA patients with 437 CV events over a median followup of 2.2 years. The RA variables found to be significant in the regression models and included in the expanded risk model were disease activity (Clinical Disease Activity Index >10 versus ≤10), disability (modified Health Assessment Questionnaire disability index >0.5 versus ≤0.5), daily prednisone use (any versus none), and disease duration (≥10 years versus

Objective.Rebound may occur in patients with psoriatic arthritis (PsA) who discontinue TNF inhibitor (TNFi) therapy in low disease activity (LDA).Methods.Using physician and patient reports, we quantified rebound following TNFi discontinuation [defined as Clinical Disease Activity Index (CDAI) score > 10 or TNFi restart] and time to rebound in adults with PsA in LDA (CDAI score ≤ 10) at TNFi discontinuation.Results.Rebound occurred in 73% (69/94) of patients soon after discontinuation (median time to rebound 8.0 mos, 95% CI 6.0–12.0).Conclusion.Rebound occurred frequently in patients with PsA after TNFi discontinuation. TNFi discontinuation after achieving LDA should be carefully considered.

Background The multi-biomarker disease activity (MBDA) score measures 12 serum biomarkers to assess disease activity in patients with rheumatoid arthritis (RA) on a scale of 1–100. The MBDA score was validated in several different cohorts but has not been evaluated in a cohort consisting only of patients initiating TNF inhibitor therapy in clinical practice. We utilized patients enrolled in the Corrona-CERTAIN study to evaluate MBDA scores for patients initiating adalimumab (ADA) in several clinical practices in the US. Objectives Evaluate the ability of the MBDA score to assess response to treatment with ADA. Methods We studied 106 biologic-naive RA patients who had been treated with ADA for at least 12 months, had initiated ADA in CERTAIN while in moderate or high disease activity by CDAI, and for whom sera were available at baseline (BL) and Months 3 and 6. Changes (Δ) in MBDA score and DAS28-CRP were evaluated from BL to Months 3 and 6 by the one-sample paired t-test. ΔMBDA scores were evaluated for patients grouped by EULAR response categories, using the Cochran-Armitage test for trend. Receiver Operating Characteristic (ROC) analysis with bootstrap sampling (20,000 iterations) was used to evaluate MBDA score ability to discriminate ΔDAS28-CRP improvement >1.2 units at Month 3, and to determine the optimal MBDA threshold by maximizing the sum of sensitivity and specificity (Youden9s index criterion). Results At BL, median values were age 54.5 years, disease duration 2 years, BMI 28.2, DAS28-CRP 4.7, CDAI 24, SDAI 25.4; 74.5%/65.4% were RF+/ACPA+. Median MBDA score was 49 with 17 (16%) patients in low ( 44) MBDA categories. The relative magnitude and the direction of median change from BL to Months 3 and 6 were similar for MBDA score (−8, −9) and DAS28-CRP (−1.4, −1.8), with statistically significant changes from BL for each (line graphs in Figure). Similar results were observed for SDAI and CDAI. Pearson9s correlations with ΔMBDA score at Months 3 and 6 were 0.58, 0.59, respectively, for ΔDAS28-CRP; 0.48, 0.47 for ΔSDAI; and 0.42, 0.42 for ΔCDAI (all p 1.2 units (n=67) vs. ≤1.2 units (n=39) at Month 3 (15 vs. 2) and Month 6 (13 vs. 1.5) (both p 1.2 units at Month 3 was 0.82 (95% CI, 0.74–0.90). The optimal threshold for this discrimination was a reduction in MBDA score >9 units, with sensitivity/specificity=0.63/0.82 and PPV/NPV =0.86/0.56. Conclusions This study expands the previous validation of the MBDA score by demonstrating its ability to assess response to treatment with adalimumab in a US clinical practice cohort. The AUROC value of 0.82 for discriminating improvements in DAS28-CRP >1.2 units indicates a significant association between change in MBDA score and clinical improvement. Disclosure of Interest D. Pappas Grant/research support from: AbbVie, Consultant for: AbbVie, Employee of: CORRONA, LLC, E. Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., R. Bolce Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., X. Liu Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., C. Etzel Consultant for: Merck, Employee of: CORRONA, LLC

Background Prior studies have shown inconsistent relationships between skin and joint symptoms in patients with comorbid psoriasis (PsO) and psoriatic arthritis (PsA) 1–3 . Objectives To characterize the relationship between skin severity and joint activity in patients with comorbid PsA and PsO at enrollment. Methods Data from the U.S. Corrona PsA/spondyloarthritis (PsA/SpA) registry were obtained from the period 3/21/2013– 9/30/2016. Inclusion criteria included a diagnosis of PsA, a history of PsO, and age greater than 18 years. PsA patients were evaluated for skin severity as defined by Body Surface Area (BSA) and joint activity as defined by the level of clinical disease activity index (CDAI). Patient characteristics, including current and prior PsA medication use, were obtained during the enrollment visit. We evaluated the relationship of skin severity (BSA) and joint activity (CDAI) with multi-variable linear regression. Results 1,542 patients met inclusion criteria: 52.9% were women with mean (SD) age 53.7 (13.2) years, with median 9.0 years PsA disease duration, and 71 (4.6%) with fibromyalgia. 266 (18%) patients were on no DMARD therapy, 430 (29%) were on csDMARDs only, 616 (42%) were on first line biologic/targeted synthetic (ts)DMARD therapy, and 172 (12%) were on second line biologic/tsDMARD therapy. The relationship between skin severity and joint activity was statistically significant (p Conclusions The relationship between skin severity and joint activity is statistically significant and varies by age, gender, MDA, HAQ, and patient reported pain and fatigue. This suggests degree of skin involvement is important to take into account when evaluating PsA patients. References Gottlieb AB, Mease PJ, Mark Jackson J, Eisen D, Amy Xia H, Asare C, Stevens SR: Clinical characteristics of psoriatic arthritis and psoriasis in dermatologists9 offices. J Dermatolog Treat 2006;17:279–287. Jones SM, Armas JB, Cohen MG, Lovell CR, Evison G, McHugh NJ: Psoriatic arthritis: outcome of disease subsets and relationship of joint disease to nail and skin disease. Br J Rheumatol 1994;33:834–839. Cohen MR, Reda DJ, Clegg DO: Baseline relationships between psoriasis and psoriatic arthritis: analysis of 221 patients with active psoriatic arthritis. Department of Veterans Affairs Cooperative Study Group on Seronegative Spondyloarthropathies. J Rheumatol 1999;26:1752–1756. Acknowledgements Corrona, LLC has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, AstraZeneca, BMS, Crescendo, Eli Lilly and Company, Genentech, GSK, Horizon Pharma USA, Janssen, Momenta Pharmaceuticals, Novartis, Pfizer, Roche and UCB. Disclosure of Interest P. Mease Grant/research support from: Celgene, Novartis, Abbvie, Amgen, BMS, Janssen, Lilly, Pfizer, Sun, UCB, Consultant for: AbbVie, Amgen, BMS, Crescendo, Celgene, Corrona, Demira, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, Sun, Zynerba, Speakers bureau: Abbvie, Amgen, BMS, Celgene, Crescendo, Genentech, Janssen, Novartis, Pfizer, UCB, C. Etzel Consultant for: Merk, Employee of: Corrona, LLC, J. Lisse Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. Armstrong Grant/research support from: AbbVie, Janssen, Lilly; speaker9s bureau: AbbVie, Lilly, Consultant for: AbbVie, Amgen, Janssen, Merck, Lilly, Celgene, Novartis, and Pfizer, W. Huster Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Rebello Employee of: Corrona, LLC, R. Dodge Employee of: Corrona, LLC, T. Muram Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Al Sawah-Folian Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, M. Murage Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: Genentech, Janssen, Novartis and Pfizer, Eli Lilly, Employee of: Corrona, LLC, W. Malatestinic Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company

Background To characterize the differences between women and men with gout. Methods We analyzed a US national cohort of gout patients cared for by rheumatologists. Results Compared with the 1012 men with gout, women with gout (n = 262) were older (71 vs. 61 years, p

BackgroundThere is increasing interest in discontinuing biological therapies for patients with rheumatoid arthritis (RA) achieving good clinical responses, provided patients maintain clinical benefit.MethodsWe assessed patients with RA from the Corrona registry who discontinued treatment with their first tumour necrosis factor inhibitor (TNFi) while in low-disease activity (LDA) or lower levels of disease activity. Patients were followed until they lost clinical benefit, defined as increased disease activity or change in RA medications. Duration of maintenance of clinical benefit was estimated using the Kaplan–Meier method. Cox proportional hazard models were assessed to identify factors related to maintenance of benefit.ResultsWe identified 717 eligible patients with RA from 35 656 in the Corrona registry. At discontinuation, patients had a median RA duration of 8 years, mean clinical disease activity score of 4.3±0.11; 41.8% were using TNFi as monotherapy. 73.4% of patients maintained benefit for >12 months after discontinuing therapy and 42.2% did so through 24 months. Factors predictive of maintaining clinical benefit in multivariate analysis included lower disease activity, less pain and better functional status at the time of TNFi discontinuation. Among 301 patients initiating their first TNFi within the registry, faster responders (ie, those who achieved LDA in 4 months or less) did better than slower responders (HR 1.54 (95% CI 1.17 to 2.04)). RA disease duration did not affect maintenance of clinical benefit.ConclusionsDiscontinuation of a first course of TNFi may be associated with persistent clinical benefit. Half of patients maintained response through 20 months. Several patient characteristics may help predict persistent benefit.

A better understanding of how mentholated cigarette use affects the process of quitting smoking is needed to inform cessation interventions. The literature on the effects of menthol use on smoking cessation, however, is largely mixed, with some studies supporting that menthol smokers are less likely to quit successfully and others finding null effects.1 However, several studies indicate that menthol smokers are more likely to make a quit attempt2 and make more quit attempts3 than non-menthol smokers, but are less likely to quit.4–6 Moreover, some studies suggest that race is an important moderator of the associations of menthol cigarette use and quitting. For example, Black menthol smokers may have a more difficult time quitting smoking than Black non-menthol smokers1,7–10 or than White menthol smokers.7,8 Because the majority of Black smokers use mentholated cigarettes,10 it is important to understand more about why Black menthol users might be at a disadvantage when it comes to quitting. Currently, little is known about the mechanisms that might underlie relations between menthol use status and quitting behaviors, or how these factors might operate differently among Black and White smokers. Some literature suggests that menthol cigarettes, which are heavily marketed to Black smokers, may be perceived as less harmful to consumers and potentially less addictive than non-menthol cigarettes.11 These inaccurate perceptions about reduced health risks and addiction potential might affect menthol smokers’ motivation and confidence to quit smoking. For example, some research suggests that established menthol users may be less motivated than non-menthol users to quit smoking for several reasons, including the relatively greater palatability of mentholated smoking and perceptions that menthol cigarettes are more socially acceptable than non-menthol cigarettes.12,13 Moreover, because misperceptions about the harm of menthol cigarette use might be engendered by racially-targeted tobacco company marketing, relations between menthol cigarette use and motivation and confidence to quit may be particularly prominent among Black menthol smokers. Because motivation to quit smoking and confidence to quit smoking have been associated with quitting behaviors in general and are important components of theories of behavior change, more information about their associations with menthol smoking status, and potential for moderation by race, is of interest.10 We are aware of only one study examining relations between menthol cigarette use and motivation and confidence to quit smoking among a racially/ethnically diverse sample of non-treatment seeking smokers. Contrary to the suggestion that menthol smokers may have lower motivation to quit than non-menthol smokers,12 this study indicated that Black menthol smokers were more likely to report seriously considering quitting smoking within the next 6 months relative to Black non-menthol smokers.5 Likewise, Black menthol smokers in this study were more likely to report they would be somewhat or very likely to succeed at quitting if they were to make a quit attempt as compared to Black non-menthol smokers.5 However, elevated estimations of readiness and confidence appeared to confer no cessation-related benefits, as this study reported that Black menthol smokers were less likely to quit than Black non-menthol smokers.5 Authors of this study suggested that a false sense of confidence in the ability to quit smoking might undermine cessation attempts among Black menthol smokers. However, additional research is needed to replicate these findings, especially when controlling for additional covariates such as the number of years smoking (which may vary between menthol and non-menthol smokers based on menthol marketing strategies targeted toward younger smokers) and income.10,13 The purpose of the current study was to examine the associations of menthol cigarette use with motivation to quit smoking and confidence to quit smoking, respectively, and to examine whether associations were moderated by race, in analyses adjusted for age, sex, race, income, education, and tobacco dependence. A better understanding of the ways in which Black and White menthol and non-menthol smokers differ with regard to factors underlying a quit smoking attempt can help to inform interventions to improve quit rates.

Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic with high prevalence in Western countries. Genome-wide association studies had reported that a variation in the patatin-like phospholipase domain containing 3 (PNPLA3) gene is associated with high susceptibility to NAFLD. However, the relationship between this variation and hepatocellular carcinoma (HCC) has not been well established. We investigated the impact of PNPLA3 genetic variation (rs738409: C>G) on HCC risk and prognosis in the United States by conducting a case-control study that included 257 newly diagnosed and pathologically confirmed Caucasian patients with HCC (cases) and 494 healthy controls. Multivariate logistics and Cox regression models were used to control for the confounding effects of HCC risk and prognostic factors. We observed higher risk of HCC for subjects with a homozygous GG genotype than for those with CC or CG genotypes, the adjusted odds ratio (OR) was 3.21 (95% confidence interval [CI], 1.68-6.41). We observed risk modification among individuals with diabetes mellitus (OR = 19.11; 95% CI, 5.13-71.20). The PNPLA3 GG genotype was significantly associated with underlying cirrhosis in HCC patients (OR = 2.48; 95% CI, 1.05-5.87). Moreover, GG allele represents an independent risk factor for death. The adjusted hazard ratio of the GG genotype was 2.11 (95% CI, 1.26-3.52) compared with CC and CG genotypes. PNPLA3 genetic variation (rs738409: C>G) may determine individual susceptibility to HCC development and poor prognosis. Further experimental investigations are necessary for thorough assessment of the hepatocarcinogenic role of PNPLA3.

Response to primary treatment in diffuse large B-cell lymphoma (DLBCL) is highly predictive of long-term outcome. We evaluated the value of computed tomography (CT) findings relative to positron emission tomography (PET) findings, after the completion of chemotherapy. We retrospectively reviewed records from 491 patients with DLBCL at M. D. Anderson in 2001-2007; 22 patients were excluded for uncertain pathology and 169 for having received consolidative radiation, leaving 300 patients for the present analysis (median age, 61 years; 53% men, 47% women; 27% stage I-II, 73% stage III-IV; 73% completed 6-8 cycles of doxorubicin-based therapy). Factors associated with outcome on univariate analysis were response according to PET/CT and CT (p 50%, PET SUV ≥ 13 and bulky (> 5 cm) disease (p = 0.005 OS, p = 0.001 DSS, p = 0.001 PFS); and International Prognostic Index (IPI) score (p = 0.004 OS, p = 0.005 DSS, p = 0.004 PFS). On multivariate analysis, PET/CT-negative, CT residual mass (> 2 cm) significantly influenced OS, DSS and PFS (p 2 cm on CT, coupled with negative findings on PET/CT, has prognostic value in DLBCL.