Uso de recursos y costes sanitarios en pacientes con vejiga hiperactiva que inician tratamiento con mirabegrón o un antimuscarínico en monoterapia en Cataluña: estudio MIRACAT / Resource use and healthcare costs in patients with overactive bladder who initiate treatment with mirabegron or antimuscarinic monotherapy in Catalonia: the MIRACAT study

Introducción y objetivo La vejiga hiperactiva (VH) impacta negativamente en la calidad de vida de los pacientes y puede asociarse a un elevado consumo de recursos. Nuestro objetivo fue describir el uso de recursos, costes y persistencia asociados al tratamiento de la VH con mirabegrón (MB) o antimuscarínicos (AM).Materiales y métodos Estudio observacional retrospectivo en registros médicos en adultos que iniciaron tratamiento para VH con MB o AM en Cataluña. Se analizó el uso de recursos sanitarios (visitas, hospitalizaciones, pruebas, medicación, absorbentes para incontinencia) en el primer año tras el inicio del tratamiento, estimando sus costes asociados (€, 2019) y la persistencia terapéutica. Se definió abandono como la falta de prescripción durante ≥ 45 días o el cambio de tratamiento.Resultados El coste medio por paciente (desviación estándar [DE]) con MB fue 1.640,20 € (1.227,60) vs. 2.159,20 € (2.264,60) con AM; el coste asociado al uso de recursos sanitarios fue inferior en MB vs. AM, exceptuando el coste del tratamiento farmacológico con MB. La persistencia al tratamiento a los 12 meses fue superior en MB (42,1 vs. 33,0%), así como el tiempo (mediana) hasta el abandono del tratamiento: 299 (IC 95%: 270,11-327,89) vs. 240 días (IC 95%: 230,46-249,54).Conclusiones Los pacientes tratados con MB mostraron menor uso de recursos, resultando en un coste medio por paciente/año más bajo, a pesar del mayor coste del fármaco respecto a AM. La mayor persistencia al tratamiento y el uso racional de las terapias disponibles mejoran el manejo de la VH y la calidad de vida de los pacientes (AU)

Introduction and aim Overactive bladder (OAB) negatively impacts patient quality of life and may be associated with high resource use. Our aim was to describe the resource use, costs and persistence associated with mirabegron (MB) or antimuscarinic (AM) treatment in patients with OAB.Materials and methods Observational retrospective study of medical records in adult patients initiating OAB treatment with MB or AM in Catalonia. Healthcare resource use (visits, hospital stays, tests, medication, absorbent pads) in the first year after treatment initiation was collected. Associated costs were estimated (€, reference year 2019), as well as treatment persistence. Treatment discontinuation was defined as the absence of prescription for at least 45 days or treatment change.Results The mean cost per patient (SD) was € 1,640.20 (€ 1,227.60) with MB and € 2,159.20 (€ 2,264.40) with AM; the associated healthcare resource use cost was lower with MB compared to AM, except for OAB drug costs. Persistence after 12 months of treatment initiation was higher in MB (42.1%) compared to AM (33.0%), as was the median time until treatment discontinuation: 299 (95% CI: 270-328) vs 240 days (95% CI: 230-250).Conclusions Lower healthcare resource use was observed with MB compared to AM in the first year of index treatment, resulting in a lower mean direct cost per patient and year, despite its higher acquisition cost. Increased treatment persistence, as well as rational use of available treatments improves OAB management and, in return, patients’ quality of life (AU)

Resource use and healthcare costs in patients with overactive bladder who initiate treatment with mirabegron or antimuscarinic monotherapy in Catalonia: the MIRACAT study.

INTRODUCTION AND AIM: Overactive bladder (OAB) negatively impacts patient quality of life and may be associated with high resource use. Our aim was to describe the resource use, costs and persistence associated with mirabegron (MB) or antimuscarinic (AM) treatment in patients with OAB. MATERIALS AND METHODS: Observational retrospective study of medical records in adult patients initiating OAB treatment with MB or AM in Catalonia. Healthcare resource use (visits, hospital stays, tests, medication, absorbent pads) in the first year after treatment initiation was collected. Associated costs were estimated (є, reference year 2019), as well as treatment persistence. Treatment discontinuation was defined as the absence of prescription for at least 45 days or treatment change. RESULTS: The mean cost per patient (SD) was є 1,640.20 (є 1,227.60) with MB and є 2,159.20 (є 2,264.40) with AM; the associated healthcare resource use cost was lower with MB compared to AM, except for OAB drug costs. Persistence after 12 months of treatment initiation was higher in MB (42.1%) compared to AM (33.0%), as was the median time until treatment discontinuation: 299 (95% CI: 270-328) vs 240 days (95% CI: 230-250). CONCLUSIONS: Lower healthcare resource use was observed with MB compared to AM in the first year of index treatment, resulting in a lower mean direct cost per patient and year, despite its higher acquisition cost. Increased treatment persistence, as well as rational use of available treatments improves OAB management and, in return, patients' quality of life.

Multiple components in the agonist concentration-response relationships of neuronal nicotinic acetylcholine receptors.

Assessing the potential of nicotinic agonists as therapeutic agents has frequently relied upon single component EC(50) values obtained from studies of nicotinic receptors expressed in Xenopus oocytes. We have evaluated the validity of this approach using voltage clamp techniques. In general, agonist concentration-response plots for the alpha3beta2, alpha3beta4, alpha4-1beta2, alpha4-1beta4 and alpha7 combinations were poorly fitted by a single component Hill-equation. Improved fits were obtained with the sum of two components, although only in the case of alpha3beta4 and alpha4-1beta2 was the improvement significant regardless of the weighting method used. For the acetylcholine (ACh) concentration-response relationships of the alpha4-1beta2 combination, the two EC(50) values were 0.3 and 58.3 microM. For the alpha3beta4 combination, the two EC(50) components were 39 and 2919 microM. The 39 microM component of alpha3beta4 represented 36% of the sum of the maximum responses of both curves. This shows that for some combinations, the secondary components represent a well-separated, major population of receptors. Therefore, published EC(50) values which assume that only a single subtype of functional receptor is present may not accurately describe agonist action may therefore need to be re-evaluated.

Agonist activation and alpha-bungarotoxin inhibition of wild type and mutant alpha7 nicotinic acetylcholine receptors.

The properties of wild type and mutant rat nicotinic alpha7 receptors expressed in Xenopus oocytes were investigated using electrophysiology and site-directed mutagenesis. When compared at individual agonist concentrations, neither the normalised nicotinic, nor acetylcholine, responses of the wild type receptors were significantly different from the corresponding responses obtained from a first extracellular domain mutant, phenylalanine(189)tyrosine (P0.05). The dissociation constants (K(D)) of the wild type (4.7 nM) and Phe(189)Tyr mutant (5.2 nM) receptors for alpha-bungarotoxin were estimated by an electrophysiological approach. The similarity of the results suggests that the mutation did not lead to a widespread disruption of structure-function relationships, although a slight change in nicotine sensitivity may have occurred. In contrast, the mutations (Tyr(190)Gln, first extracellular domain), (Glu(261)Ala, M2 region) severely compromised receptor function. An additional mutation was made in a negatively charged motif of the second extracellular domain which is conserved in homomeric nicotinic receptors. This mutation, Asp(268)Ala, also caused a loss of function. Thus the structure-function relationships in nicotinic alpha7 receptors have parallels with heteromeric nicotinic receptors, but there may also be some marked differences.

Differential modulation of rat neuronal nicotinic receptor subtypes by acute application of ethanol.

1. We have studied the effects of acute ethanol (EtOH) exposure on the agonist responses of rat neuronal nicotinic receptors expressed in Xenopus oocytes by means of voltage clamp techniques. 2. In some cells, agonist-induced current responses with the alpha 3 beta 4 subunit combination could be either significantly potentiated or inhibited (range 25% to 237% of control response) by low ethanol concentrations (1-30 mM). At high ethanol concentrations (100-300 mM) robust potentiations were observed (range 135% to 305% of control). 3. The low EtOH concentration effects on the alpha 3 beta 4 subtype exhibited tolerance with repeated EtOH exposure. 4. In general, the alpha 3 beta 2, alpha 4-1 beta 2 and alpha 4-1 beta 4 subunit combinations were less sensitive to low concentrations of ethanol, but respectively showed potentiations of up to 178%, 226% and 154% at high EtOH concentrations. 5. The alpha 7 homomeric receptor was also relatively insensitive at low EtOH concentrations. At high EtOH concentrations, potentiations, inhibitions or no alteration of control agonist response were observed (range 88% to 141% of control). 6. We conclude that all the neuronal nicotinic receptor subunit combinations tested here can be modulated by high concentrations of EtOH in a rapidly reversible manner. This modulation may underlie some of the behavioural effects of ethanol. The alpha 3 beta 4 subunit combination may be especially sensitive to modulation by low EtOH concentrations. This remarkable sensitivity and plasticity of nicotinic receptors may contribute to a process of mutual reinforcement in nicotine and alcohol addiction.

Comparison of neuronal nicotinic receptors in rat sympathetic neurones with subunit pairs expressed in Xenopus oocytes.

1. The agonist sensitivity of nicotinic acetylcholine receptors in rat superior cervical ganglion (SCG) neurones was compared with that of cloned receptors expressed in Xenopus oocytes by pairwise injections of alpha 3-beta 2 or alpha 3-beta 4 neuronal nicotinic subunit combinations. 2. Agonist responses in rat SCG neurones indicated that cytisine was the most potent agonist and lobeline the least potent (rank order of potency: cytisine > dimethylphenylpiperazinium iodide (DMPP) > nicotine > ACh > carbachol > lobeline). 3. Receptors expressed in oocytes by injection of alpha 3 and beta 2 subunits had a relatively high sensitivity to DMPP and low sensitivity to cytisine (rank order of potency: DMPP > ACh > lobeline > carbachol > nicotine > cytisine), whereas receptors composed of alpha 3 and beta 4 subunits had a high sensitivity to cytisine and low sensitivity to DMPP (rank-order of potency: cytisine > nicotine approximately ACh > DMPP > carbachol > lobeline). 4. With the exception of responses to DMPP, agonist sensitivity measurements suggest that nicotinic receptors in the rat SCG are composed of alpha 3 and beta 4 subunits. The results are discussed in terms of the receptor subunit mRNAs known to be expressed in the rat SCG and previous evidence of functional heterogeneity of rat SCG nicotinic acetylcholine receptors.