Real-world Performance of a New Strategy for Off-Label Use of Guselkumab in Moderate to Severe Psoriasis: Super-Responder Patients as the Epitome of Efficacy and Optimisation.

BACKGROUND: Guselkumab is a drug used to treat moderate to severe plaque psoriasis. However, real-life clinical data on its off-label use are limited, especially regarding the optimal drug dosage regimen for different patient profiles. OBJECTIVE: The main objective of this real-world, single-centre, retrospective study was to identify the off-label guselkumab dosing regimen used in clinical practice. The study also aimed to evaluate the drug's efficacy, safety, and survival, as well as the proportion of super-responders (SR) based on a newly proposed definition. METHODS: The study included 69 patients who started treatment with guselkumab between March 2019 and July 2021. Patients were followed up until April 2022, during which time their efficacy, safety, persistence, and use of guselkumab were recorded. Patients were aged ≥  18 years and had moderate to severe plaque psoriasis. RESULTS: The mean disease duration was 18.6 years, and 59% of patients had received at least one biologic treatment before guselkumab with a mean of 1.3 biologics per patient. The initial absolute Psoriasis Area and Severity Index (PASI) was 10.1 and decreased to 2.1 between Week 11-20 without significant changes in the PASI value throughout the 90 weeks of follow-up. The cumulative probability of drug survival was 93.5% at Week 52. No differences were found in terms of efficacy and survival associated with the off-label drug dosage regimens compared to the doses described in the Summary of Product Characteristics (SmPC). The greatest adjustments in the drug administration regimen were achieved in the subgroups of bio-naïve and SR patients, with a reduction in the number of administrations by 40% and 47% compared to the regimen described in the SmPC. Super-response to guselkumab was mainly associated with patients naïve to previous biologic treatment. CONCLUSION: The study demonstrated that off-label use of guselkumab was safe and effective in real-life clinical practice. The findings suggest that adjustments to the drug administration regimen may be necessary to optimise its use in different patient profiles, especially in SR and bio-naïve patients. Further studies are needed to confirm these findings.

Long-Term Omalizumab in Elderly Patients with Chronic Urticaria: Is It a Safe Therapy?

BACKGROUND: Biologics have revolutionized the treatment of many diseases. In this regard, omalizumab (OMA), an anti-IgE monoclonal antibody, is the recommended therapeutic option for patients with chronic spontaneous urticaria (CSU) refractory to second-generation H1-antihistamines. Several studies confirm the efficacy and safety of the drug. However, the literature focusing on the elderly population is scarce, as this age group is often excluded from clinical trials. Therefore, the pharmacological treatment of CSU in elderly patients is a challenge that is increased by their comorbidities and consequent polypharmacy. OBJECTIVES: We describe the real-life safety profile of OMA in elderly patients (≥70 years) with CSU and chronic inducible urticaria (CIndU). We aimed to provide data for daily clinical practice in this vulnerable patient group. METHOD: A retrospective review was performed of the records of patients with CSU/CIndU from May 2003 to December 2019 in the Hospital Universitario La Paz. We describe qualitative and quantitative data according to measures of central tendency. Comparisons between qualitative and quantitative data were performed with the Mann-Whitney U test and the Fisher's test for qualitative variables. A p value <0.05 was considered statistically significant. RESULTS AND CONCLUSIONS: Eighty-nine patients were included, divided into two groups (<70 vs. ≥70 years). The overall rate of adverse events (AEs) was 48%, mainly mild. No association between age and AE was found (p = 0.789). No serious AE such as anaphylaxis was detected. CSU predominated in both groups. CIndU was less prevalent in the elderly (p = 0.017). There was no association between age and the other variables. Although the frequency of neoplasms was slightly higher in the elderly with OMA, we found no difference compared to the incidence of neoplasms in the general population. Therefore, our data suggest that OMA may be a safe treatment in elderly people with CSU/CIndU for prolonged periods of treatment, although further studies with larger samples are needed to corroborate our observations.

Encuesta a profesionales sanitarios y pacientes sobre el papel del farmacéutico en la Unidad de Enfermedades Inflamatorias Inmunomediadas / The role of the pharmacist within an immune-mediated inflammatory disease unit: Results of a survey of healthcare providers and patients

Objetivo: Evaluar el interés y necesidad de que el farmacéutico desarrolle nuevas actividades propuestas, y potenciar o mantener otras que yase realizaban, antes de que la futura Unidad de Enfermedades Inflamatorias Inmunomediadas inicie su actividad en nuestro hospital. Además,priorizar la incorporación de las nuevas actividades en base a los resultados obtenidos.Método: Diseño observacional transversal unicéntrico mediante unaencuesta realizada en enero de 2020 a todos los profesionales sanitarios de los servicios clínicos implicados y a una muestra de pacientes, yestructurada en dos categorías: Acciones orientadas a la atención farmacéutica al paciente y Acciones orientadas a los profesionales de dichaUnidad. Cada ítem se puntuó de 0 a 10, siendo 10 el máximo interés/necesidad. Se aplicó una matriz de priorización para cuantificar y evaluar cada actividad e implantar las nuevas por orden de priorización.Resultados: Se completaron 90 encuestas (30 de pacientes y 60 deprofesionales). Se analizaron las medianas obtenidas de cada una de las20 actividades propuestas, alcanzándose valores entre 8 y 10. Se compararon valores: en el grupo de farmacéuticos versus médicos se obtuvieron más ítems con diferencias estadísticamente significativas que en elgrupo farmacéuticos versus enfermería, o farmacéuticos versus pacientes. (AU)

Objective: To evaluate the importance and need for pharmacists toexpand their role to new activities and to promote and maintain othersthey already carried out prior to the implementation of a new Immunemediated Inflammatory Diseases Unit to be created in our hospital; toprioritize the new activities incorporated based on the results obtained.Method: This was a single center cross-sectional based on a survey administered during January 2020 to all clinical healthcare providers due to bepart of the new unit, as well as to a sample of patients. It was structuredinto two categories: actions related to patients’ pharmaceutical care, andactions related to practitioners of the Immune-mediated Inflammatory Diseases Unit. Each item was assigned a score from 0 to 10, where 10 indicatedmaximum interest or need. A prioritization template was applied to quantifyand evaluate each activity and implement the new ones in order of priority.Results: A total of 90 responses were obtained (30 from patients and60 from healthcare workers). An analysis was performed of the medianscores of each of the 20 activities proposed, which ranged between 8 and10 points. When comparing the scores obtained, it was observed thatmore statistically significant differences were obtained in the pharmacists vsdoctors group than in the pharmacists vs nurses group, or the pharmacistsvs patients one. After prioritization, the first action taken was to implement electronic prescriptions for outpatients with immune-mediated inflammatorydiseases. (AU)

The role of the pharmacist within an immune-mediated inflammatory disease unit: Results of a survey of healthcare providers and patients.

OBJECTIVE: To evaluate the importance and need for pharmacists to expand  their role to new activities and to promote and maintain others they already  carried out prior to the implementation of a new Immunemediated Inflammatory Diseases Unit to be created in our hospital; to prioritize the new activities incorporated based on the results obtained. METHOD: This was a single center cross-sectional based on a survey  administered during January 2020 to all clinical healthcare providers due to be part of the new unit, as well as to a sample of patients. It was structured into two categories: actions related to patients' pharmaceutical  care, and actions related to practitioners of the Immune-mediated  Inflammatory Diseases Unit. Each item was assigned a score from 0 to 10,  where 10 indicated maximum interest or need. A prioritization template was  applied to quantify and evaluate each activity and implement the new ones in  order of priority. RESULTS: A total of 90 responses were obtained (30 from patients and 60 from  healthcare workers). An analysis was performed of the median scores of each  of the 20 activities proposed, which ranged between 8 and 10 points. When  comparing the scores obtained, it was observed that more statistically  significant differences were obtained in the pharmacists vs doctors group than  in the pharmacists vs nurses group, or the pharmacists vs patients one. After  prioritization, the first action taken was to implement electronic prescriptions  for outpatients with immune-mediated inflammatory diseases. CONCLUSIONS: The survey revealed the expectations of healthcare providers and patients regarding the role pharmacists should play in the newly created unit and provided an insight into the most valued activities. This information will be useful in prioritizing the implementation of the new activities to be carried out by the unit.

Objetivo: Evaluar el interés y necesidad de que el farmacéutico desarrolle nuevas actividades propuestas, y potenciar o mantener otras que ya se realizaban, antes de que la futura Unidad de Enfermedades Inflamatorias Inmunomediadas inicie su actividad en nuestro hospital. Además, priorizar la incorporación de las nuevas actividades en base a los  resultados obtenidos.Método: Diseño observacional transversal unicéntrico mediante una encuesta  realizada en enero de 2020 a todos los profesionales sanitarios de los servicios  clínicos implicados y a una muestra de pacientes, y estructurada en dos  categorías: Acciones orientadas a la atención farmacéutica al paciente y  Acciones orientadas a los profesionales de dicha Unidad. Cada ítem se puntuó  de 0 a 10, siendo 10 el máximo interés/necesidad. Se aplicó una matriz de  priorización para cuantificar y evaluar cada actividad e implantar las nuevas  por orden de priorización.Resultados: Se completaron 90 encuestas (30 de pacientes y 60 de profesionales). Se analizaron las medianas obtenidas de cada una de las 20  actividades propuestas, alcanzándose valores entre 8 y 10. Se compararon valores: en el grupo de farmacéuticos versus médicos se  obtuvieron más ítems con diferencias estadísticamente significativas que en el grupo farmacéuticos versus enfermería, o farmacéuticos versus pacientes. Tras la priorización, la primera acción fue implantar la prescripción electrónica en pacientes externos con enfermedades inflamatorias inmunomediadas.Conclusiones: La encuesta ha permitido conocer las expectativas de los  profesionales sanitarios y pacientes sobre la actividad del farmacéutico en  dicha Unidad, cuantificar las actividades más valoradas y priorizar la  implantación de nuevas actividades.

Real-World Experience with Two-Drug Regimens in HIV-1-Infected Patients Beyond the Indication of Clinical Trials: 48 Weeks' Results.

Data on two-drug regimens (2DRs) have shown high efficacy and tolerability in treatment-naive and treatment-experienced HIV-1 patients. Current guidelines recommend 2DRs as alternative to three-drug regimens (3DRs) to reduce long-term drug exposure and costs. Nevertheless, real-world experience with 2DR is limited. This study assessed the use of 2DR in routine clinical practice in a tertiary hospital. A retrospective, observational, descriptive study was performed on the use of dual therapy in adult HIV-1 patients. Individuals on antiretroviral treatment (ART) with dolutegravir plus lamivudine or dolutegravir plus rilpivirine who started 2DR between November 1, 2018, and April 30, 2019, were eligible for our study. Follow-up period was 48 weeks. Overall, 112 patients started 2DR; median age was 51 years and 88.4% were men. Most patients (97.3%) were treatment experienced before dual therapy, with 9.6 ± 8.0 years of prior ART on average. Around 96.4% of patients were virologically suppressed before 2DR. Most common reasons to start dual therapy were treatment simplification (49.5%), avoidance of long-term toxicities (21.1%), and intolerance to previous ART (18.3%). The main regimen used in dual therapy was dolutegravir plus lamivudine (98.2%). Only eight patients discontinued dual therapy; the main reason for discontinuation was toxicity. All patients who did not discontinue 2DR were virologically suppressed at week 48. ART simplification saved €130,117.58 during the study period. In our cohort, dual therapy was mainly used for virologically suppressed patients, before availability of the single-tablet 2DR. Switching to a 2DR may be a key option for treatment simplification and avoidance of long-term toxicities. Furthermore, 2DR could provide a more cost-effective alternative to 3DR.

Persistence of biological agents over an eight-year period in rheumatoid arthritis and spondyloarthritis patients / Persistencia de medicamentos biológicos durante ocho años en pacientes con artritis reumatoide y espondiloartritis

Objective: To calculate the persistence, over a period of eight years, the retention rate of first and second-line of treatment with biological agents in patients with rheumatoid arthritis, spondyloarthritis and psoriatic arthritis and to compare retention rates of the various drugs for each pathology. Method: Retrospective observational study that included patients affected by rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, who started treatment with biological agents between January 2009 and December 2012 and followed until December 2016. Results: 132, 87 and 33 patients were included in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, respectively. The median retention duration of all biological agents for the first and second-line, was 30.9 months and 14.0 months, respectively for rheumatoid arthritis; 63.06 months and 25.6 months, respectively in spondyloarthritis. Psoriatic arthritis did not reach the median (> 70 months in first-line) (first line p = 0.002). Individual drug survival in first line: the median retention duration of tocilizumab was 58.3 months, followed by etanercept (p = 0.79) in rheumatoid arthritis. For spondyloarthritis, golimumab and etanercept had greater retention than the other drugs (they did not reach the median): adalimumab was 63.0 months and for infliximab was 50.1 months. In psoriatic arthritis, golimumab, infliximab and etanercept not reach the median and they had greater retention than adalimumab (59.4 months). Individual drug survival in second line: tocilizumab was the most persistent drug (median 22.1 months) in rheumatoid arthritis, and golimumab for spondyloarthritis and psoriatic arthritis. Conclusions: Tocilizumab and etanercept in rheumatoid arthritis, and golimumab in spondyloarthritis and psoriatic arthritis also, were the most persistent drugs in first-line and second-line treatment

Objetivo: Calcular y analizar la persistencia global y por medicamento, en primera y segunda línea de tratamiento, en pacientes con artritis reumatoide, espondiloartritis axial radiográfica y no radiográfica y artritis psoriásica durante un periodo de ocho años. Método: Estudio retrospectivo observacional de persistencia en pacientes que iniciaron su terapia con medicamentos biológicos entre enero de 2009 y diciembre de 2012 en seguimiento hasta diciembre de 2016. Resultados: Se analizaron 132, 87 y 33 pacientes con artritis reumatoide, espondiloartritis y artritis psoriásica, respectivamente. La persistencia mediana global para los biológicos en primera y segunda línea fueron: 30,9 meses y 14 meses, respectivamente, en artritis reumatoide; 63,06 meses y 25,6 meses en espondiloartritis. No se alcanzó la persistencia mediana en los ocho años de seguimiento en artritis psoriásica (> 70 meses) (p = 0,002 para la función de supervivencia entre patologías en primera línea). Persistencia mediana alcanzada en primera línea por medicamento: tocilizumab (58,3 meses), seguido de etanercept (44 meses) en artritis reumatoide (p = 0,79); en espondiloartritis golimumab y etanercept fueron los más persistentes (no alcanzaron la mediana), seguidos de adalimumab (44 meses) e infliximab (50,1 meses). En artritis psoriásica, golimumab seguido de infliximab y etanercept fueron los más persistentes (no alcanzaron la mediana), y adalimumab (59,4 meses). Persistencia mediana alcanzada en segunda línea por medicamento: tocilizumab (22,1 meses) en artritis reumatoide. Golimumab fue el más persistente en espondiloartritis y artritis psoriásica (sin alcanzar la mediana). Conclusiones: Tocilizumab y etanercept fueron los medicamentos más persistentes en artritis reumatoide, y golimumab en espondiloartritis y artritis psoriásica en primera y segunda línea de tratamiento

Persistence of biological agents over an eight-year period in rheumatoid arthritis and spondyloarthritis patients.

OBJECTIVE: To calculate the persistence, over a period of eight years, the retention rate of first and second-line of treatment with biological agents in  patients with rheumatoid arthritis, spondyloarthritis and psoriatic arthritis and to compare retention rates of the various drugs for each pathology. METHOD: Retrospective observational study that included patients affected by  rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, who started  treatment with biological agents between January 2009 and December 2012 and followed until December 2016. RESULTS: 132, 87 and 33 patients were included in rheumatoid arthritis, spondyloarthritis and psoriatic arthritis, respectively. The median  retention duration of all biological agents for the first and second-line, was 30.9 months and 14.0 months, respectively for rheumatoid arthritis; 63.06  months and 25.6 months, respectively in spondyloarthritis. Psoriatic arthritis did  not reach the median (> 70 months in first-line) (first line p = 0.002). Individual drug survival in first line: the median retention duration of tocilizumab was 58.3 months, followed by etanercept (p = 0.79) in rheumatoid arthritis. For spondyloarthritis, golimumab and etanercept had greater retention than the other drugs (they did not reach the median): adalimumab was 63.0 months and for infliximab was 50.1 months. In psoriatic arthritis, golimumab,  infliximab and etanercept not reach the median and they had greater retention than adalimumab (59.4 months). Individual drug survival in second  line: tocilizumab was the most persistent drug (median 22.1 months) in  rheumatoid arthritis, and golimumab for spondyloarthritis and psoriatic arthritis. CONCLUSIONS: Tocilizumab and etanercept in rheumatoid arthritis, and golimumab in spondyloarthritis and psoriatic arthritis also, were the most persistent drugs in first-line and second-line treatment.

Objetivo: Calcular y analizar la persistencia global y por medicamento, en  primera y segunda línea de tratamiento, en pacientes con artritis reumatoide, espondiloartritis axial radiográfica y no radiográfica y artritis  psoriásica durante un periodo de ocho años.Método: Estudio retrospectivo observacional de persistencia en pacientes que  iniciaron su terapia con medicamentos biológicos entre enero de 2009 y  diciembre de 2012 en seguimiento hasta diciembre de 2016. Resultados: Se analizaron 132, 87 y 33 pacientes con artritis reumatoide, espondiloartritis y artritis psoriásica, respectivamente. La  persistencia mediana global para los biológicos en primera y segunda línea  fueron: 30,9 meses y 14 meses, respectivamente, en artritis reumatoide; 63,06 meses y 25,6 meses en espondiloartritis. No se alcanzó la persistencia mediana en los ocho años de seguimiento en artritis psoriásica (>  70 meses) (p = 0,002 para la función de supervivencia entre patologías en primera línea). Persistencia mediana alcanzada en primera línea por  medicamento: tocilizumab (58,3 meses), seguido de etanercept (44 meses) en  artritis reumatoide (p = 0,79); en espondiloartritis golimumab y etanercept fueron los más persistentes (no alcanzaron la mediana), seguidos deadalimumab (44 meses) e infliximab (50,1 meses). En artritis psoriásica, golimumab seguido de infliximab y etanercept fueron los más persistentes (no alcanzaron la mediana), y adalimumab (59,4 meses).  Persistencia mediana alcanzada en segunda línea por medicamento: tocilizumab (22,1 meses) en artritis reumatoide. Golimumab fue el más persistente en espondiloartritis y artritis psoriásica (sin alcanzar la mediana).Conclusiones: Tocilizumab y etanercept fueron los medicamentos más persistentes en artritis reumatoide, y golimumab en espondiloartritis y  artritis psoriásica en primera y segunda línea de tratamiento.

Analysis of antiretroviral therapy modification in routine clinical practice in the management of HIV infection.

OBJECTIVES: The main goal was to assess the reasons for antiretroviral therapy (ART) change in patients with HIV in a hospital setting in routine clinical practice. The economic impact of ART modification was also analysed. METHODS: Patients with HIV who changed their ART between 24 November and 24 December 2014 were registered. Length of initial therapy, type of ART before and after therapy modification, and reasons for the ART change were analysed. To assess the economic impact, antiretroviral drug costs at the time of the study were recorded. RESULTS: Of a cohort of 3850 patients with HIV, 1976 attended for pharmaceutical care consultation at Hospital Universitario La Paz during the study period. Ninety-two patients (4.7%) had their ART modified. The median length of the previous therapy was 26 months (range 1-144). The most common initial therapy regimen was 2 nucleoside reverse transcriptase inhibitors (NRTI)+1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (29.4%), and the most common one after modification was 2 NRTI+1 integrase strand transfer inhibitor (INSTI) (40.2%). Forty-three modifications were made because of toxicity and adverse effects (46.7%), 25 because of therapy simplification (27.2%), 16 because of treatment failure (17.4%), and 8 because of drug-drug interactions (8.7%). ART costs increased by a mean of €14 (SD €216; range -€528 to +€831) per month per patient after therapy modification at the time of study. CONCLUSIONS: Toxicity and adverse effects were the most common reason for ART alteration in patients with HIV in routine clinical practice in a hospital setting. Better knowledge about factors that motivate these changes may contribute to decreased toxicity and increased treatment success. ART modification had a variable but not very substantial economic impact.

Polyarteritis nodosa resistant to conventional treatment in a pediatric patient.

OBJECTIVE: To report the case of a child diagnosed with polyarteritis nodosa (PAN) that was unresponsive to conventional treatment alone but improved with the addition of iloprost and bosentan to her drug regimen. CASE SUMMARY: A 3-year-old girl who had been diagnosed with PAN was referred to our hospital from another region. With conventional treatment of high doses of a corticosteroid and cyclophosphamide, her condition resolved. Six months later, our patient had a relapse that required hospital admission. In this second hospital stay, some cutaneous lesions evolved into digital necrosis. Offlabel therapeutic alternatives, including a single dose (2 g/kg) of intravenous immunoglobulin (IVIG), intravenous iloprost 2 ng/kg/min over 6 h for 5 days and, approximately 4 wk later, oral bosentan 37.25 mg twice daily for 4 wk followed by 62.5 mg twice daily for 8 wk, were added to the conventional regimen to treat the serious cutaneous manifestations. Her fingers improved very slowly, and she was discharged on gradually tapered doses of oral corticosteroids, bosentan, and monthly pulsed injections of cyclophosphamide. The digital necrosis and other cutaneous lesions had resolved completely 6 months after the second discharge. DISCUSSION: The dosages of IVIG and iloprost were based on those used for PAN, Raynaud's phenomenon, and digital necrosis in children. The use of bosentan for vasculitis had not been reported in children before the treatment of our patient, so its dosage was based on that used to produce vasodilation in children with pulmonary hypertension. CONCLUSIONS: Digital necrosis and cutaneous manifestations not resolved with conventional PAN treatment improved within 5 days with iloprost and 12 weeks with bosentan.