Articulos Científicos Neurociencias

Efficacy and Safety of Guselkumab in Real-World Evidence: A Systematic Review and Meta-Analysis

Mon, 11 May 2026 00:00:00 GMT

Efficacy and Safety of Guselkumab in Real-World Evidence: A Systematic Review and Meta-Analysis Dodero-Anillo, Jose Manuel; Fernandez-Pujol-Marzo, Marta; Pedrosa Martínez, María José; Ruiz-Villaverde, Ricardo; Armario Hita, José Carlos Background: Guselkumab, a selective anti-IL-23p19 monoclonal antibody, has shown high efficacy in randomized trials for moderate-to-severe psoriasis and active psoriatic arthritis (PsA). Real-world evidence is essential to assess treatment performance in broader and more heterogeneous patient populations. Objectives: To synthesize the available real-world evidence on the effectiveness and safety of guselkumab in psoriasis and PsA, and to quantify pooled clinical responses across clinically relevant follow-up windows. Methods: A systematic review and meta-analysis was conducted according to PRISMA 2020. PubMed/MEDLINE, MEDLINE, and Web of Science were searched for observational real-world studies of guselkumab in adults with psoriasis and/or PsA. Primary pooled outcomes were PASI 90 and PASI 100 in psoriasis and DAPSA < 14 in PsA. Random-effects meta-analysis of proportions was performed using a logit transformation. Cohort overlap was explicitly assessed and overlapping publications were not allowed to contribute concurrently to the same pooled estimate. Results: Thirty-four studies were included (29 psoriasis, 5 PsA). In psoriasis, pooled PASI 90 response rates were 50.8% (95% CI 46.8–54.8) at 12–16 weeks, 68.4% (95% CI 66.3–70.4) at 20–28 weeks, 71.2% (95% CI 64.9–76.8) at 36–60 weeks, and 77.1% (95% CI 74.9–79.3) at ≥96 weeks. Pooled PASI 100 response rates were 49.8% (95% CI 47.5–52.2) at 20–28 weeks and 49.7% (95% CI 47.1–52.3) at 36–60 weeks. In PsA, pooled DAPSA < 14 response rates were 56.9% (95% CI 23.0–85.3) at 20–28 weeks and 69.5% (95% CI 62.5–75.7) at 48–60 weeks. Safety reporting was heterogeneous, but serious adverse events and discontinuations due to adverse events were uncommon. Conclusions: Real-world evidence supports guselkumab as an effective treatment for psoriasis and a clinically useful option for PsA, with a safety profile broadly consistent with the known trial experience. Interpretation remains limited by observational designs, heterogeneous denominators, and inconsistent safety reporting.

Optimising Therapeutic Intervals for Anti-TNF Biologics in Rheumatoid Arthritis: A Retrospective Real-World Study

Fri, 24 Apr 2026 00:00:00 GMT

Optimising Therapeutic Intervals for Anti-TNF Biologics in Rheumatoid Arthritis: A Retrospective Real-World Study Dodero-Anillo, Jose Manuel; Rosety Rodríguez, Manuel; Pedrosa Martínez, María José Background: Therapeutic drug monitoring (TDM) of anti-TNF biologics may help optimise treatment in rheumatoid arthritis (RA), but current therapeutic ranges do not always reflect clinical response in routine practice. Methods: We conducted a retrospective observational study including 224 adults with RA treated with infliximab (IFX), adalimumab (ADL), or etanercept (ETN) during the maintenance phase at Hospital Universitario Puerto Real between May 2016 and May 2023. Drug and anti-drug antibody levels were measured by sandwich ELISA and analysed against clinical response using DAS28. Demographic and clinical variables, associations between drug levels and response, the effect of antibodies, correlations between serum concentrations and DAS28, and the performance of current and proposed therapeutic ranges were evaluated. Results: The cohort was mainly female (62.1%), with a mean age of 57.7 years, BMI of 28.5 kg/m2, and mean DAS28 of 3.33. ETN was most frequently used (62.5%), followed by ADL (21.9%) and IFX (15.6%). Drug levels were significantly associated with response (p < 0.001). Anti-drug antibodies were strongly linked to non-response, especially with IFX and ADL. Serum drug levels correlated inversely with disease activity for IFX and ADL, but not for ETN. Current therapeutic ranges showed low sensitivity, while lower proposed ranges improved sensitivity considerably. Conclusions: Current anti-TNF therapeutic ranges have limited ability to identify responders in real-world RA. Lowering the lower bound improves sensitivity and supports more individualised TDM, particularly for IFX and ADL, pending prospective validation.

Associations of cardiorespiratory fitness and muscular fitness with plasma levels of endocannabinoids and their analogues in adults with diagnosed depression: SONRIE study

Wed, 01 Jan 2025 00:00:00 GMT

Associations of cardiorespiratory fitness and muscular fitness with plasma levels of endocannabinoids and their analogues in adults with diagnosed depression: SONRIE study Ruiz Muñoz, Manuel; Ortega Gómez, Sonia; Espinosa Nogales, María del Mar; Valmisa Gómez de Lara, Eulalio Juan; Rosety Rodríguez, Miguel Ángel; España Romero, Vanesa Background: Depression is a leading cause of global disability, affecting approximately 280 million individuals worldwide. Emerging evidence suggests that both physical fitness and endocannabinoids system play significant roles in the pathophysiology and management of depressive disorders. Purpose: To examine the associations between physical fitness, in terms of cardiorespiratory fitness (CRF) and muscular fitness (MF), with plasma levels of endocannabinoids (eCBs) and their analogues, in adults diagnosed with depression. Methods: The study involved 80 adults (ages 25-65) with a psychiatric diagnosis of mild-to-moderate depression based on the International Classification of Diseases 10th Revision (ICD-10) criteria. Physical fitness was assessed through tests measuring CRF (6-Minute Walk Test) and MF (Handgrip, Arm Curl, Chair Stand, Standing Long Jump Test). Fasting plasma levels of eCBs, such as anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), and their analogues were measured using liquid chromatography-tandem mass spectrometry. Linear regression analyses were conducted or the associations between fitness variables and plasma levels of eCBs and their analogues using three models. Results: CRF and jump performance were inversely associated with plasma levels of the eCBs AEA (β range: - 0.302 to - 0.237 for CRF, - 0.315 to - 0.370 for jump; All p < 0.05) and 2-AG (β range: - 0.308 to - 0.326 across all models). eCBs analogues correlated negatively with CRF [2-linoleoylglycerol, 2-oleoylglycerol, docosatetraenoylethanolamide (DEA)] and jump (linoleylethanolamine, stearoylethanolamine, DEA); findings persisted after lean mass normalization. Conclusion: Our findings indicated that higher physical fitness was associated with lower plasma levels of eCBs and their analogues.

Deep brain stimulation changes locus coeruleus responses to social stress from activation to inhibition

Wed, 01 Jan 2025 00:00:00 GMT

Deep brain stimulation changes locus coeruleus responses to social stress from activation to inhibition Torres-Sanchez, Sonia; Curtis, Andre L.; Valentino, Rita J.; Berrocoso Domínguez, Esther María Deep Brain Stimulation (DBS) of the subgenual cingulate cortex (SCC) stands as an innovative therapeutic approach for treatment-resistant depression. Previous preclinical investigations utilizing DBS targeted at the ventromedial prefrontal cortex (vmPFC), considered the rodent equivalent of the human SCC, have demonstrated antidepressant-like effects, as well as enhancement in the activity of the locus coeruleus (LC)-norepinephrine (NE) system and pontine-cortical network oscillations. Given the association between social stress and depression and other psychiatric disorders, we assessed the impact of vmPFC DBS on social stress-induced changes in LC neuronal activity in awake rats. Spontaneous and auditory-evoked LC single unit activity were compared between control and DBS male rats during the first (acute) and fifth (repeated) day of social defeat stress. In stark contrast to LC activation observed in controls, both acute and repeated stress robustly inhibited LC neurons of DBS rats. While both groups experienced an acute stress-induced reduction in auditory-evoked LC discharge, the duration of the evoked response was only decreased in control animals. LC auditory-evoked activity was increased after repeated stress and DBS effectively counteracted these stress-induced alterations. These findings suggest that DBS treatment shifts stress-induced regulation of LC activity such that it favors the engagement of inhibitory modulation. This may serve to promote resistance of the LC-NE system to stress-induced excitation and contribute to the mitigation of neuropsychiatric consequences of stress.