Adherence, persistence and treatment switching in psoriasis.

Aim: This study aims to investigate drug utilization patterns in the treatment of psoriasis (PsO) from 1 to 5 years in a real-life setting with Adalimumab (Ada), Etanercept (Eta), Ustekinumab (Ust), Golimumab (Gol), Ixekizumab (Ixe), Secukinumab (Sec) and Apremilast (Apr). Materials & methods: Data from an observational study were used to calculate adherence using the Proportion of Days Covered (PDC) method and persistence. Results & conclusion: Treatment adherence was found to be good for all the drugs studied across all years of analysis, while persistence was suboptimal, showing a marked decrease from the third year of study onward. In the treatment of PsO, greater attention needs to be paid to treatment persistence.

This summary explains that when a patient follows their doctor's medication instructions and continues using the same medication over time to treat a condition like psoriasis, they can expect safer and more effective outcomes. This study examined these aspects to assess how different medications perform over the long term and to explore ways to improve their prescription. The findings highlight that the main issue is not so much in following instructions but in continuing to use the same medication throughout the treatment duration. Raising awareness among healthcare professionals about these issues is crucial to help patients maintain consistent therapy over time and improve their care pathway.

ADA_ETA_BIO2021: real-world evaluation of adherence, persistence, and cost-effectiveness of originator and biosimilar biologic drugs in the treatment of rheumatoid arthritis: a multicenter study in Italy.

OBJECTIVES: The objective was to assess the adherence, persistence, and costs of bDMARDs through a multicentre study of nine Italian hospital pharmacies. METHODS: The drugs analysed were Abatacept, Adalimumab, Certolizumab, Etanercept, Golimumab and Tocilizumab.Adult subjects with Rheumatoid Arthritis were considered in the analysis.In this study, we calculated the following metrics: Adherence to treatment was evaluated as dose-intensity, which is the ratio between the amount of medication received and probably taken by the patient at home (Received Daily Dose, RDD) and the amount prescribed by the clinician (Prescribed Daily Dose, PDD). Persistence was calculated as the number of days between the first and last dispensing of the same drug. Lastly, costs were assessed based on persistence to treatment and normalized for adherence. RESULTS: Adherence to treatment was found to be above 0.8 for all drugs studied. The median persistence for a 5-year treatment period was 1.4 years for Abatacept, 1.7 years for Adalimumab, 1.8 years for Certolizumab, 1.4 years for Etanercept, 1.3 years for Golimumab, and 1.6 years for Tocilizumab. CONCLUSIONS: This multicentre retrospective observational study of bDMARDs used in the treatment of RA showed that, for all the drugs studied, there was no problem with adherence to treatment but rather a difficulty in maintaining treatment with the same drug over time.

Peroxisome proliferator-activated receptor gamma and spermidine/spermine N1-acetyltransferase gene expressions are significantly correlated in human colorectal cancer.

BACKGROUND: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor that regulates adipogenic differentiation and glucose homeostasis. Spermidine/spermine N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) are key enzymes involved in the metabolism of polyamines, compounds that play an important role in cell proliferation. While the PPARgamma role in tumour growth has not been clearly defined, the involvement of the altered polyamine metabolism in colorectal carcinogenesis has been established. In this direction, we have evaluated the PPARgamma expression and its relationship with polyamine metabolism in tissue samples from 40 patients operated because of colorectal carcinoma. Since it is known that the functional role of K-ras mutation in colorectal tumorigenesis is associated with cell growth and differentiation, polyamine metabolism and the PPARgamma expression were also investigated in terms of K-ras mutation. METHODS: PPARgamma, ODC and SSAT mRNA levels were evaluated by reverse transcriptase and real-time PCR. Polyamines were quantified by high performance liquid chromatography (HPLC). ODC and SSAT activity were measured by a radiometric technique. RESULTS: PPARgamma expression, as well as SSAT and ODC mRNA levels were significantly higher in cancer as compared to normal mucosa. Tumour samples also showed significantly higher polyamine levels and ODC and SSAT activities in comparison to normal samples. A significant and positive correlation between PPARgamma and the SSAT gene expression was observed in both normal and neoplastic tissue (r = 0.73, p < 0.0001; r = 0.65, p < 0.0001, respectively). Moreover, gene expression, polyamine levels and enzymatic activities were increased in colorectal carcinoma samples expressing K-ras mutation as compared to non mutated K-ras samples. CONCLUSION: In conclusion, our data demonstrated a close relationship between PPARgamma and SSAT in human colorectal cancer and this could represent an attempt to decrease polyamine levels and to reduce cell growth and tumour development. Therefore, pharmacological activation of PPARgamma and/or induction of SSAT may represent a therapeutic or preventive strategy for treating colorectal cancer.

Expression analysis of a subset of coregulators and three nuclear receptors in human colorectal carcinoma.

In human colorectal tissue samples, the gene expressions of 4 coactivators, p300, pCAF, TIF-2 and TRAP 220, and 7 corepressors, N-CoR, REA, MTA1, MTA1L1, HDAC1, HDAC2 and HDAC3, linked to estrogen receptors (ER), were revealed by traditional RT-PCR. Cofactors ERalpha, ERbeta and ERRalpha mRNA levels were then measured in 40 tumor tissue samples matched with respective normal mucosa by real-time PCR. The decline of mRNA levels of all coactivators and the increase of NCoR, HDAC1, HDAC2 and MTA1 were observed from normal to tumor tissue, whereas REA, HDAC3 and MTA1L1 expressions were similar in both tissue compartments. The gene expression of ERbeta correlated with those of p300, TIF-2 and REA in normal mucosa, and with that of REA in tumor tissue only. No association was found between ERalpha and coregulators and between each coregulator and different clinical parameters. Our findings suggest that the co-induction of ERbeta and some cofactors may play an important role during the development of human colorectal carcinoma.

Oestrogen receptor-related receptor alpha (ERRalpha) and oestrogen receptors (ERalpha and ERbeta) exhibit different gene expression in human colorectal tumour progression.

We have investigated the presence of oestrogen receptor-related (ERR) mRNA in human colorectal tumour tissues and adjacent normal mucosa by reverse transcriptase and nested-polymerase chain reaction. ERRalpha was found in 100% of the patients and ERRgamma in approximately 30% while ERRbeta was not detected at all. The multiplex PCR analysis showed elevated levels of ERRalpha mRNA in tumour tissue compartment as compared to normal mucosa, whereas ERRgamma mRNA was found in lower levels but in both tissue compartments. In contrast, oestrogen receptor (ERalpha and ERbeta) mRNA levels were shown to be decreased in tumour tissues. A positive correlation was observed between ERalpha and ERbeta and between ERalpha and ERRalpha, respectively, in normal mucosa but not in tumour tissue. ERRalpha expression in tumour tissues significantly increased from TNM stages II to IV, whereas both ERs progressively declined. These findings suggest that ERRalpha, as well as the two ERs, might play a critical role in the progression of the colorectal cancer.