Drug survival of secukinumab, ustekinumab, and certolizumab pegol in psoriasis: a 2-year, monocentric, retrospective study.

OBJECTIVE: To investigate the drug survival of secukinumab (SEC), ustekinumab (UST), and certolizumab pegol (CZP) in real-world conditions and to identify the predictors and reasons for treatment discontinuation. METHODS: We performed a 2-year retrospective single-center analysis of 110 treatment courses in 98 patients with moderate to severe plaque-type psoriasis and/or psoriatic arthritis (SEC n = 68; UST n = 29; and CZP n = 13). Drug survival was examined using the Kaplan-Meier analysis and the influence of demographic factors on drug survival with Cox regression analysis. RESULTS: Drug survival rates at 12 and 18 months were respectively 68.5% and 59% for the entire study population, 85% and 69% for UST, 68% and 59% for SEC, and 34% for CZP. Both UST and SEC showed a significantly longer survival rate compared to CZP (p<.05), but not between each other. A total of 30 treatment discontinuations were observed, predominantly due to loss of efficacy and adverse events. Treatment selection predicted the survival rate. Other predictors could not be identified. CONCLUSIONS: Drug survival is the resultant of many factors such as long-term effectiveness, safety, compliance, and convenience of use. UST and SEC had higher retention rates in comparison with CZP.

Exploring the Potential of Nitric Oxide and Hydrogen Sulfide (NOSH)-Releasing Synthetic Compounds as Novel Priming Agents against Drought Stress in Medicago sativa Plants.

Land plants are continuously exposed to multiple abiotic stress factors like drought, heat, and salinity. Nitric oxide (NO) and hydrogen sulfide (H2S) are two well-examined signaling molecules that act as priming agents, regulating the response of plants to stressful conditions. Several chemical donors exist that provide plants with NO and H2S separately. NOSH is a remarkable novel donor as it can donate NO and H2S simultaneously to plants, while NOSH-aspirin additionally provides the pharmaceutical molecule acetylsalicylic acid. The current study aimed to investigate the potential synergistic effect of these molecules in drought-stressed Medicago sativa L. plants by following a pharmacological approach. Plants were initially pre-treated with both donors (NOSH and NOSH-aspirin) via foliar spraying, and were then subsequently exposed to a moderate water deficit while NO and H2S inhibitors (cPTIO and HA, respectively) were also employed. Phenotypic and physiological data showed that pre-treatment with NOSH synthetic compounds induced acclimation to subsequent drought stress and improved the recovery following rewatering. This was accompanied by modified reactive-oxygen and nitrogen-species signaling and metabolism, as well as attenuation of cellular damage, as evidenced by altered lipid peroxidation and proline accumulation levels. Furthermore, real-time RT-qPCR analysis revealed the differential regulation of multiple defense-related transcripts, including antioxidant enzymes. Overall, the present study proposed a novel role for NOSH compounds as efficient plant priming agents against environmental constraints through the coordinated regulation of multiple defense components, thus opening new horizons in the field of chemical priming research toward the use of target-selected compounds for stress tolerance enhancement.

Melatonin systemically ameliorates drought stress-induced damage in Medicago sativa plants by modulating nitro-oxidative homeostasis and proline metabolism.

Recent reports have uncovered the multifunctional role of melatonin in plant physiological responses under optimal and suboptimal environmental conditions. In this study, we explored whether melatonin pretreatment could provoke priming effects in alfalfa (Medicago sativa L.) plants subsequently exposed to prolonged drought stress (7 days), by withholding watering. Results revealed that the rhizospheric application of melatonin (10 µmol L-1 ) remarkably enhanced the drought tolerance of alfalfa plants, as evidenced by the observed plant tolerant phenotype, as well as by the higher levels of chlorophyll fluorescence and stomatal conductance, compared with nontreated drought-stressed plants. In addition, lower levels of lipid peroxidation (MDA content) as well as of both H2 O2 and NO contents in primed compared with nonprimed stressed plants suggest that melatonin pretreatment resulted in the systemic mitigation of drought-induced nitro-oxidative stress. Nitro-oxidative homeostasis was achieved by melatonin through the regulation of reactive oxygen (SOD, GR, CAT, APX) and nitrogen species (NR, NADHde) metabolic enzymes at the enzymatic and/or transcript level. Moreover, melatonin pretreatment resulted in the limitation of cellular redox disruption through the regulation of the mRNA levels of antioxidant and redox-related components (ADH, AOX, GST7, GST17), as well via osmoprotection through the regulation of proline homeostasis, at both the enzymatic (P5CS) and gene expression level (P5CS, P5CR). Overall, novel results highlight the importance of melatonin as a promising priming agent for the enhancement of plant tolerance to drought conditions through the regulation of nitro-oxidative and osmoprotective homeostasis.