BackgroundTocilizumab (TCZ) is a humanised monoclonal antibody inhibitor of interleukin-6 receptor, indicated in combination with methotrexate in the treatment of rheumatoid arthritis (RA) in patients with inadequate response or intolerance to prior therapy.PurposeThe aim of our study was to explore the potential role of KCNMB1 genetic polymorphisms as a predictor of tocilizumab efficacy in RA patients.Material and methodsThe KCNMB1 (A >G) (rs703505) genetic variant was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 24 weeks with the use of the 28 joint disease activity score criteria (DAS28). Clinical response was evaluated at 14 weeks using DAS28 and good response and remission were classified according to EULAR criteria. EULAR good response was defined as a change in DAS28 >1.2 and DAS28 ≤3.2. EULAR remission was defined as DAS28 ≤2.6 at 14 weeks. Statistical analysis was performed using SPSS v.20.ResultsClinical data for 140 tocilizumab treated patients were obtained. Patients were aged (mean±SD) 53.25 ± 12.42 years; 79% were female. Mean DAS28 at baseline was 5.71 ± 1.13. KCNMB1-GG genetic polymorphism was associated with EULAR good response (GG vs no GG p = 0.26, OR=0.37, 95% CI 0.14 to 0.93) and with EULAR remission (p = 0.01, OR=0.29, 95% CI 0.09 to 0.87).ConclusionOur results confirm that KCNMB1 (A >G) rs703505 polymorphisms could be useful as a genetic marker of tocilizumab efficacy in RA patients. More studies are necessary to confirm these results.No conflict of interest.

BackgroundCD69 receptor is a C lectin transmembrane protein expressed by T cells, natural killer (NK) cells and active B cells. This receptor is involved in the production and regulation of T cells, B cells and NK cells, and these are involved in interleukin 6 (IL-6) production. IL-6 is a multifunctional glycoprotein involved in the immune response, inflammation and bone metabolism; IL-6 makes significant contributions to autoimmune and inflammatory diseases such as rheumatoid arthritis (RA). Tocilizumab is a humanised monoclonal antibody inhibitor of IL-6 receptor, indicated in combination with methotrexate in the treatment of RA in patients with inadequate response or intolerance to prior therapies.PurposeThe aim of this study was evaluate the role of the CD69 A>G (rs11052877) genetic polymorphism on the response to tocilizumab in RA patients.Material and methodsThe CD69 A>G (rs11052877) genetic polymorphism was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 3, 6, 9 and 12 months after the first infusion of the drug, using the 28 joint disease activity score criteria (DAS28), and good responders were classified according to EULAR criteria. EULAR good response was defined as a change in DAS28 >1.2 and DAS28 ≤3.2. Statistical analysis was performed using SPSS V.20.ResultsClinical data from 140 tocilizumab treated patients were obtained. The patients were aged (mean±SD) 53.25±12.42 years and 79% were women. Even though we found a greater proportion of good responders among CD69 GG carriers than among A/G or A/A carriers at 3 months (60% vs 43.27%), 6 months (72.73% vs 59.17%), 9 months (76.19% vs 65.66%) and 12 months (90% vs 73.95%), these results were not statistically significant (p=0.17, p=0.22, p=0.34 and p=0.09)ConclusionThese results show that the CD69 A>G (rs11052877) genetic polymorphism by itself is not useful as a predictor of tocilizumab response in RA patients but its influence should be studied further.No conflict of interest

BackgroundInterleukin (IL)-6 is involved in the pathogenesis of rheumatoid arthritis (RA) via its broad effects on immune and inflammatory responses. Sustained IL-6 activity can cause tissue damage in different tissues. Previous studies have shown that G allele at the -174G >C (rs1800795) polymorphism is related to high producing IL-6.PurposeThe aim of our study was to explore the potential role of IL-6 genetic polymorphisms as a predictor of tocilizumab efficacy in RA patients and to compare the results with a previous GWAS.Material and methodsThe IL-6 (G >C) (rs1800795) genetic variant was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 24 weeks with the use of the 28 joint disease activity score criteria (DAS28) and good response and remission were classified according to EULAR criteria. EULAR good response was defined as a change in DAS28 >1.2 and DAS28 ≤3.2. EULAR remission was defined as DAS28 ≤2.6 at 14 weeks. Statistical analysis was performed using SPSS v.20ResultsClinical data for 140 tocilizumab treated patients were obtained. The patients were aged (mean±SD) 53.25 ± 12.42 years; 79% were female. Mean DAS28 at baseline was 5.71 ± 1.13. The IL-6 G >C genetic polymorphisms were not significantly associated with a good EULAR response (CC vs no CC p = 0.35, OR=1.07, 95% CI 0.05 to 19.7; GC vs no GC p = 0.97, OR=1.03, 95% CI 0.22 to 4.70; GG vs no GG p = 0.50, OR=0.58, 95% CI 0.12 to 2.67), or remission (CC vs no CC p = 0.85, OR=1.11, 95% CI 0.41 to 2.98; GC vs no GC p = 0.98, OR=1.01, 95% CI 0.52 to 1.94; GG vs no GG p = 0.88, OR=0.96, 95% CI 0.48 to 1.89).ConclusionOur results confirm that IL-6 G >C rs 1800795 polymorphisms are not useful as a genetic marker of tocilizumab efficacy in RA patients. More studies are necessary to confirm these results.No conflict of interest.

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LDL), high density lipoprotein (HDL), triglycerides (TG), alanine-aminotransferase (ALT) and aspartate aminotransferase (AST), liver size and fibrosis before and during treatment with sebelipase alfa, and adverse events. From the outpatient programme were obtained dose, administrations and weeks of treatment. The efficacy was evaluated by normalising the analytical values of the lipidic and liver profiles in three patients who participated in the clinical trial until April 2018. Results Three male brothers 12, 15 and 17 years' old diagnosed with LALD before 5 years, heterozygous for mutation in the LIPA gene c.894G>A, c.256C>T. Before the trial, patients presented abnormal analytical values (except TG), hepatomegaly and fibrosis. Patients received continuous treatment with sebelipase-alfa at a dose of 1 mg/kg/2 weeks intravenously. Preparation of the medication was carried out by the hospital pharmacy service. In April 2018, after 225, 183 and 114 weeks of treatment respectively, all three patients maintained the values analysed in the range of normality (except HDL in two and TG in one patient). Hepatomegaly reversed in all patients. The means of the values and of the percentages of variation to the basal were: cholesterol 150.66 ±22.89 mg/dL (À34.19%), LDL 89.33±12.20 mg/dL (À46.90%), HDL 35.66±6.35 mg/dL (+1.55%), AST 30.66 ±4.04 IU/L (À64.88%), ALT 21.33±4.93 mg/dL (À65.99%) and TG 130±85.91 mg/dL (+2.12%). Concerning safety, two patients who suffered diarrhoea, and adverse effects related to the infusion were not reported. Conclusion LALD is a rare disease, and sebelipase-alfa is the first drug authorised for its treatment. The response to treatment with sebelipase-alfa has been favourable from the beginning, with an improvement in the studied variables and a good safety profile in the reported cases.