Janus kinase inhibitors vs. abatacept about safety and efficacy for patients with rheumatoid arthritis-associated interstitial lung disease: a retrospective nested case-control study

Abstract Background Interstitial lung disease (ILD) related to rheumatoid arthritis (RA) is among the leading causes of death and an essential prognostic factor. There is only limited evidence for the safety of anti-rheumatic drugs for patients with RA-ILD. The aim of this study is to investigate the safety and efficacy of Janus kinase inhibitors (JAKis) by comparing it with abatacept (ABT) in patients with RA-ILD. Methods This single centre, retrospective nested case–control study enrolled patients with RA-ILD treated with JAKi or ABT. To determine the safety of the two drugs for existing ILD, we compared their drug persistency, incidence rates of pulmonary complications, and change of chest computed tomography (CT) image. For their efficacy as RA treatment, disease activity scores and prednisolone (PSL)-sparing effect were compared. We performed propensity score matching to match the groups’ patient characteristics. Results We studied 71 patients with RA-ILD (ABT, n = 45; JAKi, n = 26). At baseline, the JAKi group had longer disease duration, longer duration of past bDMARD or JAKi use and higher usual interstitial pneumonia rate. After propensity score matching, no significant differences in patient characteristics were found between the two groups. No significant difference in the drug persistency rate for the first 2 years (ABT, 61.9%; JAKi, 42.8%; P = 0.256) was observed between the two matched groups. The incidence rate of pulmonary complications did not differ significantly between the two groups (P = 0.683). The CT score did not change after the treatment for the ABT group (Ground-glass opacities (GGO): P = 0.87; fibrosis: P = 0.78), while the GGO score significantly improved for the JAKi group (P = 0.03), although the number was limited (ABT: n = 7; JAKi: n = 8). The fibrosis score of the JAKi group did not change significantly.(P = 0.82). Regarding the efficacy for RA, a significant decrease in disease activity scores after the 1-year treatment was observed in both groups, and PSL dose was successfully tapered, although no significant differences were observed between the two drugs. Conclusions JAKi is as safe and effective as ABT for patients with RA-ILD. JAKi can be a good treatment option for such patients

Possible influence of multiple SNP markers to urological morbidity induced by radiotherapy with carbon-ions among 133 prostate cancer patients

Purpose: To develop efficient predictive method for risk of dysuria after radiotherapy (RT). Patients and Methods: A total of 197 prostate cancer patients who underwent C-ion RT at a total dose of 64.4 +/- 2.7 GyE and evaluated for urinary morbidity (dysuria) according to the Late Effects of Normal Tissue/Subjective, Objective, Management, and Analytic scoring system (LENTSOMA). Three hundred seventy-three SNPs in 109 candidate genes were genotyped by MassARRAY system. Patients were categorized into control (grade 0) and case (grade >1) groups. First, association between the genotype at each SNP site and dysuria were assessed using the Fisher exact test (P ) had 3 or more risk genotypes. Conclusions: Although more patients are required to validate the results, this study supports the assumptions that radiosensitivity is caused by multigenetic factors and that the number of high-risk genotypes on SNPs might predict radiosensitivity.The 13th International Congress of Radiation Researc

The proangiogenic factor ephrin-A1 is up-regulated in radioresistant murine tumor by irradiation.

While the pre-treatment status of cancer is generally correlated with outcome, little is known about microenvironmental change caused by anti-cancer treatment and how it may affect outcome. For example, treatment may lead to induction of gene expression that promotes resistance to therapy. In the present study, we attempted to find a gene that was both induced by irradiation and associated with radioresistance in tumors. Using single-color oligo-microarrays, we analyzed the gene expression profiles of two murine squamous cell carcinomas, NR-S1, which is highly radioresistant, and SCCVII, which is radiosensitive, after irradiation with 137-Cs gamma rays or carbon ions. Candidate genes were those differentially regulated between NR-S1 and SCCVII after any kind of irradiation. Four genes, Efna1 (Ephrin-A1), Sprr1a (small proline-rich protein 1A), Srgap3 (SLIT-ROBO Rho GTPase activating protein 3) and Xrra1 [RIKEN 2 days neonate thymus thymic cells (NOD) cDNA clone E430023D08 3\u27], were selected as candidate genes associated with radiotherapy-induced radioresistance. We focused on Efna1, which encodes a ligand for the Eph receptor tyrosine kinase known to be involved in the vascular endothelial growth factor (VEGF) pathway. We used immunohistochemical methods to detect expression of Ephrin-A1, VEGF, and the microvascular marker CD31 in radioresistant NR-S1 tumor cells. Ephrin-A1 was detected in the cytoplasm of NR-S1 tumor cells after irradiation, but not in SCCVII tumor cells. Irradiation of NR-S1 tumor cells also led to significant increases in microvascular density, and up-regulation of VEGF expression. Our results suggest that radiotherapy-induced changes in gene expression related with angiogenesis might also modulate microenvironment and influence responsiveness of tumors

Prediction of radiation morbidity from polymorphisms in candidate genes among prostate cancer patients treated with carbon ion therapy.

Heavy ion beams possess high linear energy transfer components and a prominent Bragg peak in the human body. These properties promote higher relative biological effectiveness and a favorable dose distribution. Some patients, however, develop adverse effects in the rectum and /or bladder/urethra. Using DNA samples collected from 95 Japanese prostate cancer patients who underwent radiotherapy with the Heavy Ion Medical Accelerator in Chiba, 905 SNPs were genotyped from 127 candidate genes for radiation susceptibility. These genes were selected from our previous gene expression analyses of cultured human cell lines and mouse strains that had exhibited variable radiosensitivities. The SNPs in the candidate genes were selected from jSNP and dbSNP databases and their allele frequencies were examined using 133 healthy controls. The acute and late radiation morbidities were scored using Late Effects of Normal Tissues-subjective, objective, management, and analytic criteria. Significant differences were observed of genotype frequencies for SNPs in candidate gene loci. Area under the curve of the Receiver Operating Characteristic Curve (ROC) was estimated for each SNP marker for radiation morbidity to construct a predictive score. The top 7 markers were used in constructing predictive scores for dysuria within 3 months, and the top 5 markers at 6 months after starting radiotherapy. The top 10 markers were used in constructing predictive scores for polyuria within 3 months, and the top 11 markers at 6 months after starting radiotherapy. The distribution of ten predictive scores according to response values showed the potential discriminating power of these analyses.ASHG 55th Annual Meetin

EFNA1, a radioresistant marker, detected in a murine tumor model by gamma and carbon ion irradiation

Using single-color oligo-microarrays, we analyzed the gene expression profiles of two murine squamous cell carcinomas: NR-S1 (radioresistant) and SCCVII (radiosensitive), after irradiation with 137-Cs gamma rays at doses of 30, 50 and 70 Gy or 290 MeV/u carbon ions at a dose of 30 Gy. Potential genes related to radiosensitivity were selected by comparing the expression values before and after irradiation (with both gamma rays and carbon ions) using a filter for at least 1.5-fold changes. Furthermore, candidate genes which had significantly different ratio values between the two tumors (P < 0.05) were detected by unpaired Student\u27s t-tests. Subsequent analysis by quantitative reverse-transcription polymerase chain reaction (RT-PCR) confirmed our microarray data. Protein expression and function were examined by immunohistochemical studies.Results: Four genes, Efna1, Sprr1a, Srgap3 and Xrra1, were selected as potential genes related to radioresistance after gamma and carbon ion irradiation. RT-PCR confirmed that Efna1 was induced in radioresistant NR-S1. Efna1, a proangiogenic factor, was expressed in the cytoplasm of tumor cells and significant increases in microvascular density were observed in the radioresistant NR-S1.Conclusions: We found that Efna1 may be a potential molecule related to radioresistance in murine tumors.The 14th European Cancer Conference, ESTRO26 meeting, European Society for therapeutic radiology and oncolog

Additional file 1 of Janus kinase inhibitors vs. abatacept about safety and efficacy for patients with rheumatoid arthritis-associated interstitial lung disease: a retrospective nested case-control study

Supplementary Material

Influence of Multiple Genetic Polymorphisms on Genitourinary Morbidity After Carbon Ion Radiotherapy for Prostate Cancer

Purpose: To investigate the genetic risk of late urinary morbidity after carbon ion radiotherapy in prostate cancer patients.Methods and Materials: A total of 197 prostate cancer patients who had undergone carbon ion radiotherapy were evaluated for urinary morbidity. The distribution of patients with dysuria was as follows: Grade 0, 165; Grade 1, 28; and Grade 2, 4 patients. The patients were divided (2:1) consecutively into the training and test sets and then categorized into control (Grade 0) and case (Grade 1 or greater) groups. First, 450 single nucleotide polymorphisms (SNPs) in 118 candidate genes were genotyped in the training set. The associations between the SNP genotypes and urinary morbidity were assessed using Fisher\u27s exact test. Then, various combinations of the markers were tested for their ability to maximize the area under the receiver operating characteristics (AUC-ROC) curve analysis results. Finally, the test set was validated for the selected markers.Results: When the SNP markers in the SART1, ID3, EPDR1, PAH, and XRCC6 genes in the training set were subjected to AUC-ROC curve analysis, the AUC-ROC curve reached a maximum of 0.86. The AUC-ROC curve of these markers in the test set was 0.77. The SNPs in these five genes were defined as "risk genotypes." Approximately 90% of patients in the case group (Grade 1 or greater) had three or more risk genotypes.Conclusions: Our results have shown that patients with late urinary morbidity after carbon ion radiotherapy can be stratified according to the total number of risk genotypes they harbor