Application of the European Society of Cardiology, Adult Treatment Panel III and American College of Cardiology/American Heart Association guidelines for cardiovascular risk management in a French cohort of rheumatoid arthritis

AbstractBackgroundPatients with rheumatoid arthritis (RA) have greater rates of cardiovascular mortality and RA is an independent cardiovascular risk factor. For the management of cholesterol, the American College of Cardiology/American Heart Association (ACC/AHA) developed new guidelines for the general population. None of the European or American guidelines are specific to RA. The European League Against Rheumatism (EULAR) recommends applying a coefficient to cardiovascular risk equations based on the characteristics of RA. Our objective was to compare the three different sets of guidelines for the eligibility of statin therapy in RA-specific population with very high risk of cardiovascular disease.Methods and resultsWe calculated the proportion of patients eligible for statins according to the guidelines of the European Society of Cardiology (ESC), the Adult Treatment Panel III (ATP-III) and the ACC/AHA in a French cohort of statin-naïve RA patients at least 40years age. Of the 547 women and 130 men analyzed, statins would be recommended for 9.1% of the women and 26.4% of the men, 15.6% of the women and 53.1% of the men, 38.8% of the women and 78.5% of the men, according to the ESC, ATP-III and ACC/AHA guidelines respectively.ConclusionsIn RA patients, as has been observed in the general population, discordance in risk assessment and cholesterol treatment was observed between the three sets of guidelines. The use of the new ACC/AHA guidelines would expand the eligibility for statins and may be applied to RA population a condition at very high risk of cardiovascular disease

Calprotectin is not independent from baseline erosion in predicting radiological progression in early rheumatoid arthritis. Comment on ‘Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis’ by Jonsson et al

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Calprotectin is not independent from baseline erosion in predicting radiological progression in early rheumatoid arthritis. Comment on ‘Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis’ by Jonsson et al

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Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies

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Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies

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Overall survival (OS) and efficacy results of second-line treatment in patients (pts) with metastatic clear cell renal cell carcinoma (mRCC) treated in the randomized phase II BIONIKK trial.

607 Background: To date, no biomarker of efficacy of nivolumab+/-ipilimumab (N+/-I) or anti-VEGFR TKI has been prospectively validated in mRCC. The BIONIKK trial showed promising objective response rate (ORR) and progression-free survival (PFS) with these treatments in first line (L1) after selection by tumour molecular group. We report OS and efficacy results of the second-line (L2) treatment. Methods: BIONIKK is a French multicentre non-comparative phase II trial, randomising 199 mRCC pts to receive N (58), NI (101) or TKI (40) in L1 according to four molecular groups (ccrcc1-4). ORR and PFS were already reported. With an additional follow-up of ≥20 months, we report OS from randomization and from the start of L2, as well as ORR and PFS with a TKI in L2 by molecular group. Results: With a median follow-up of 42.1 months (40.5-45.2), 86 (43%) patients died: 27/58 (46.5%), 39/101 (39%) and 20/40 (50%) in the N, NI, and TKI arm, respectively. Median OS were 43.4 months (95%CI=31.4-NR) with N, 52.7 months (95%CI=46-NR) with NI and 38.1 months (95%CI=33.2-NR) with TKI (table). 175 (88%) patients discontinued first-line treatment, including 20 deaths, and 129 (74%) received a L2, 38/58 (65.5%), 64/101 (63%), and 27/40 (67.5%) after N, NI and TKI, respectively. The most frequent L2 received after N+/-I was a TKI in 96/102 (94%) pts, including cabozantinib in 49, sunitinib/pazopanib in 32, axitinib in 13, and lenvatinib in 2. N was the most frequent L2 after TKI, 20/27 (74%). ORR with TKI in L2 was 28.5% (10/35) after N, 39% (24/61) after NI and 80% (4/5) after TKI, with marked benefit in ccrcc2 pts (table). The mPFS with TKI in L2 was 8.2 (95%CI=6.9-19.3) after N, 11.4 (95%CI= 8.9-16.8) after NI, and 12.1 (95%CI =11.4-NR) months after TKI, with a higher benefit in ccrcc2 pts (vs. ccrcc1+4, p=0.04). Conversely, ORR and mPFS with N after TKI in ccrcc2-pts were 12.5% (2/16) and 5.4 (2.6-NR) months, respectively. Median OS L2 was reported in the table. The updated ORR and PFS in L1 will presented at the Meeting, as well as PFS2 and efficacy by TKI type in L2. Conclusions: We report for the first-time OS and L2 efficacy results by molecular group in a randomized trial. Molecular selection also has an impact on treatment efficacy in L2. These results, together with those reported in L1, can inform clinicians on the best treatment sequence in L1-2. Clinical trial information: NCT02960906 . [Table: see text] </jats:p

Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma

International audienceBackground: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets.Methods: We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort.Results: Unsupervised clustering identified two \&quot;TME subtypes\&quot;, in each of the cohorts: the \&quot;immune-enriched\&quot; and the \&quot;immune-low\&quot;. Within AXIPAP trial cohort, the \&quot;immune-enriched\&quot; cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95% CI, 6 to 29) versus 37 months (95% CI, 20 to NA, p=0.001). The two immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in clear cell RCC, were significantly higher in the \&quot;immune-enriched\&quot; group (adjusted p&lt;0.05). Finally, five differentially overexpressed genes were identified, corresponding mainly to B lymphocyte populations.Conclusion: For the first time, using RNA-seq and immunohistochemistry, we have highlighted a specific immune TME subtype of metastatic pRCC, significantly more infiltrated with T and B immune population. This \&quot;immune-enriched\&quot; group appears to have a worse prognosis and could have a potential predictive value for response to immunotherapy, justifying the confirmation of these results in a cohort of metastatic pRCC treated with CPI and in combination with targeted therapies.Trial registration number: NCT02489695

Nephrectomy improves overall survival in patients with metastatic renal cell carcinoma in cases of favorable MSKCC or ECOG prognostic features

International audienceObjectives : The role of cytoreductive nephrectomy (CN) in the treatment of patients harboring metastatic renal cell carcinoma (mRCC) has become controversial since the emergence of effective targeted therapies. The aim of our study was to compare the overall survival (OS) between CN and non-CN groups of patients presenting with mRCC in the era of targeted drugs and to assess these outcomes among the different Memorial Sloan-Kettering Cancer Center (MSKCC) and The Eastern Cooperative Oncology Group (ECOG) performance status subgroups. Methods and materials A total of 351 patients with mRCC at diagnosis recruited from 18 tertiary care centers who had been treated with systemic treatment were included in this retrospective study. OS was assessed by the Kaplan-Meier method according to the completion of a CN. The population was subsequently stratified according to MSKCC and ECOG prognostic groups. Results Median OS in the entire cohort was 37.1 months. Median OS was significantly improved for patients who underwent CN (16.4 vs. 38.1 months, P&lt;0.001). However, subgroup analysis demonstrated that OS improvement after CN was only significant among the patients with an ECOG score of 0 to 1 (16.7 vs. 43.3 months, P = 0.03) and the group of patients with good and intermediate MSKCC score (16.8 vs. 42.4 months, P = 0.02). On the contrary, this benefit was not significant for the patients with an ECOG score of 2 to 3 (8.0 vs. 12.6 months, P = 0.8) or the group with poor MSKCC score (5.2 vs. 5.2, P = 0.9). Conclusions CN improves OS in patients with mRCC. However, this effect does not seem to be significant for the patients in ECOG performance status groups of 2 to 3 or poor MSKCC prognostic grou