Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Effect of Photobiomodulation on Atrophic-Erosive Clinical Forms of Oral Lichen Planus: A Systematic Review.

INTRODUCTION: Oral lichen planus is a chronic autoimmune inflammatory disease of unknown origin, characterized by various clinical forms of which the atrophic-erosive causes patients the greatest symptomatology. For this reason, there are different treatments that improve the associated signs and symptoms. One of these therapies is photobiomodulation (PBM), which, although new, has a high level of acceptance in dentistry based on evidence. However, there are inconsistent results in its application against lichen planus. The aim of this review was to evaluate the effect of photobiomodulation and its effectiveness as a therapeutic alternative for atrophic-erosive lesions. MATERIAL AND METHODS: The databases PubMed, Google Scholar and Cochrane Library were searched to identify studies investigating the photobiomodulation treatment in atrophic-erosive lesions of oral lichen planus. A total of 294 articles were identified, published between 2017 and 2022, and then evaluated; 7 articles that met all the inclusion criteria were included in this study. RESULTS: The type of laser light source used in PBM was the diode laser (four cases), the Nd-YAG laser at the same wavelength of 1064 nm (two cases) and the He-Ne laser (one case). The minimum and maximum wavelengths used were 630 nm and 1064 nm, respectively. Most studies used lesions treated with topical corticosteroids as a control group. The follow-up times of the studies were highly variable. CONCLUSIONS: Photobiomodulation is a treatment that competently combats oral lichen planus lesions by improving signs and symptoms, with no known adverse reactions so far, which makes it more beneficial compared to more conventional therapies, such as corticosteroids, for which side effects have been found.

Study of the Effect of Photobiomodulation on a Skin Repair Model in SKH-1 Mice.

Background and objective: Laser applied at low power (400-1100 nm), currently named photobiomodulation (PBM), is a noninvasive therapy to speed up wound healing. The purpose of this study was whether two different laser PBM delivery protocols would impact the skin wound healing in a mouse model. Materials and methods: A total of 24 SKH-1 mice were divided into three groups: Group 1 (control: untreated ulcers), Group 2 (a single postsurgical laser application), and Group 3 (laser each other day for 10 days; total five applications). Laser parameters were 940 nm, 0.4 W, 10 mm spot size, 0.008 J/cm2, 300 sec/wound. Each animal received two skin wounds which were photographed on days 0, 5, and 10 to determine wound closure (ImageJ). Half of the animals in each group were sacrificed on day 5 and the other half on day 10. Samples were routinely processed for histological analysis (re-epithelization, angiogenesis, granulation tissue formation, inflammation, and collagen deposition). Results: The closure of the wounds at the end of the experiment in the animals photobiostimulated each other day was more advanced than in the controls and in those treated only once, in both the macroscopic and microscopic studies. Angiogenesis was higher in both treated groups than in the control in the first study time (day 5). However, inflammation, maturation of the granulation tissue, and collagen deposition only improved when the laser was applied each other day. Conclusions: In our study, with the parameters used, PBM improved the healing of skin wounds when applied every other day and not in a single dose.

Effect of mesoporous silica and its combination with hydroxyapatite on the regeneration of rabbit's bone defects: A pilot study.

BACKGROUND: Bone volume augmentation is a routine technique used in oral implantology and periodontology. Advances in the surgical techniques and the biomaterials field have allowed a greater accessibility to these treatments. Nevertheless, dehiscence and fenestrations incidence during dental implant procedures are still common in patients with bone loss. OBJECTIVE: The main objective is to evaluate in a pilot experimental study the biological response to mesoporous silica (MS) hybrid scaffolds and its regenerative capacity in different formulations. METHODS: Two defects per rabbit tibia were performed (one for control and other for test) and the biomaterials tested in this study have been used to fill the bone defects, prepared in two different formulations (3D hybrid scaffolds or powdered material, in 100% pure MS form, or 50% MS with 50% hydroxyapatite (HA). Euthanasia was performed 4 months after surgery for bone histopathological study and radiographic images were acquired by computerized microtomography. RESULTS: Results showed that radiographically and histopathologically pure MS formulations lead to a lower biological response, e.g when formulated with HA, the osteogenic response in terms of osteoconduction was greater. CONCLUSIONS: We observed tolerance and lack of toxicity of the MS and HA, without registering any type of local or systemic allergic reaction.

Chemopreventive effect of pomegranate and cocoa extracts on ultraviolet radiation-induced photocarcinogenesis in SKH-1 mice.

Non-melanoma skin cancer (NMSC) has a high and increasing incidence all over the world. Solar radiation is the main aetiology for humans. Although most research into photocarcinogenesis uses UVB as a source of radiation, UVA is also carcinogenic in long term. Pomegranate (PGE) and cocoa (CE) extracts have been used for medicinal purposes for time immemorial. Recently, it has been claimed that some of their properties may be an effective preventative measure against photocarcinogenesis and photoaging, but to date in vivo models have not been tested using RUVA, the objective of the present work. A lower incidence of lesions was observed in SKH-1 mice treated with PGE (p<0.001), and lower incidence of invasive squamous carcinoma in both treatment groups (p<0.001 for PGE and p<0.05 for CE); the PGE group also showed a lower level of cell proliferation than the control group (p<0.001). Significantly greater p53 alteration was observed in the control group than the treatment groups (p<0.001 for PGE and p = 0.05 for CE). No significant differences were found in relation to TIMP-1 and MMP-9. Taken together, the results suggest that oral feeding of PGE and CE to SKH-1 mice affords substantial protection against the adverse effects of RUVA, especially PGE.

Long-term evaluation of quality of life and satisfaction between implant bar overdentures and conventional complete dentures: A 23 years retrospective study.

BACKGROUND: Dental implants have been used in edentulous jaws to improve the retention and stability of complete dentures. Attachment to the implants improves stability and function of the prostheses and increases patient satisfaction. PURPOSE: The aim of this study was to evaluate quality of life and satisfaction between patients with implant overdentures and complete dentures for more than 20 years. METHODS: Forty patients with overdentures and 40 patients with conventional complete dentures were included in this study. Both groups are carriers of their prosthesis more than 20 years. All patients completed an OHIP-14 and perception and satisfaction questionnaire related their implant prothesis. RESULTS: Follow-up mean in patients with overdentures were 23.27 ± 1.87 years and 23.20 ± 3.91 years for conventional prosthesis group. A worse quality of life was shown in the group of patients with conventional dentures in the 7 dimensions and in the total value, with statistically significant differences in 6 dimensions and in the total value (P ≤ .05). Patients with implants overdenture were more satisfied than patients with conventional dentures, with statistically significant differences (P < .001). CONCLUSIONS: Implant overdentures on cobalt chrome and gold bars offer an excellent long-term solution for edentulism compared with conventional denture.

Infections in Moderate to Severe Psoriasis Patients Treated with Biological Drugs Compared to Classic Systemic Drugs: Findings from the BIOBADADERM Registry.

Information regarding the safety of biological drugs prescribed to psoriasis patients on daily and long-term bases is insufficient. We used data from the BIOBADADERM registry (Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases) to generate crude rates of infection during therapy with systemic drugs, including biological drugs (infliximab, etanercept, adalimumab, and ustekinumab) and nonbiological drugs (acitretin, cyclosporine, and methotrexate). We also calculated unadjusted and adjusted risk ratios (RRs) (with propensity score adjustment) of infection, serious infections, and recurrent infections of systemic therapies compared with methotrexate, using Poisson regression. Our study included records of 2,153 patients (7,867.5 person-years). The adjusted RR of overall infection was significantly increased in the groups treated with adalimumab with methotrexate (adjusted RR = 2.13, 95% confidence interval [CI] = 1.2-3.7), infliximab (adjusted RR = 1.71, 95% CI = 1.1-2.65), cyclosporine (adjusted RR = 1.58, 95% CI = 1.17-2.15), ustekinumab with methotrexate (adjusted RR = 1.56, 95% CI = 1.08-2.25), and etanercept (adjusted RR = 1.34, 95% CI: 1.02-1.76) compared with methotrexate alone. Cyclosporine had a significant risk of serious infection (adjusted RR = 3.12, 95% CI = 1.1-8.8), followed by adalimumab combined with methotrexate (adjusted RR = 3.28, 95% CI = 0.8-13.5). Adalimumab in combination with methotrexate had the highest risk of infection recurrence (adjusted RR = 4.33, 95% CI = 2.27-8.24).

Risk of serious adverse events associated with biologic and nonbiologic psoriasis systemic therapy: patients ineligible vs eligible for randomized controlled trials.

OBJECTIVE: To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients. DESIGN: A registry inception cohort was used. SETTING: Thirteen dermatology departments in Spain participated. PATIENTS: A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included. EXPOSURE: Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease. MAIN OUTCOME MEASURES: Serious adverse events as defined by the International Conference on Harmonization were evaluated. RESULTS: In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs. CONCLUSIONS: Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.

Modelo de fotocarcinogénesis cutánea en ratones SKH-1 por radiación ultravioleta / An experimental model of ultraviolet radiation-induced cutaneous photocarcinogenesis in SKH-1 mice

Antecedentes. La exposición crónica a las radiaciones solares provoca el envejecimiento patológico de la piel (fotoenvejecimiento) y es uno de los principales factores etiológicos implicados en el desarrollo del cáncer cutáneo. Métodos. Para el presente experimento, hemos expuesto 20 ratones SKH-1 a radiaciones ultravioleta, que se aplicaban tres veces a la semana durante 60min (80 sesiones). Las zonas expuestas a las radiaciones han sido estudiadas macro y microscópicamente. Resultados. El 100% de los animales tratados desarrollaron neoplasias malignas, así como los signos típicos del fotoenvejecimiento. Conclusiones. Debido a la gran similitud de las lesiones desarrolladas por los animales, con las que tienen lugar en la piel humana tras la exposición crónica a las radiaciones ultravioleta, consideramos este modelo, idóneo para el estudio del fotoenvejecimiento y la fotocarcinogénesis, así como para el ensayo de sustancias antioxidantes y fotoprotectoras(AU)

Introduction. Chronic exposure to solar radiation leads to pathological aging of the skin (photoaging) and is one of the principal etiological factors of skin cancer. Methods. For the present experiment, twenty SKH-1 mice were exposed to ultraviolet radiation three times a week for 60min (a total of 80 sessions). The areas exposed to radiation were subsequently examined macroscopically and microscopically. Results. All the experimental animals developed malignant neoplasias (skin carcinomas) as well as signs typical of photoaging. Conclusions. Given the great similarity between the lesions found in the experimental animals and those appearing in human skin following extensive exposure to ultraviolet radiation, we consider this model suitable for the study of photoaging and photocarcinogenesis and for the assessment of antioxidants and photoprotectors(AU)

Estudio comparativo de la aplicación del hidrocarburo aromático policíclico 7, 12-dimetil-1, 2-benzatraceno (DMBA) sobre la mucosa oral del hámster y del cobaya / A comparative study of the effect of applying polycyclic aromatic hydrocarbon, 7,12-dimethyl-1,2-benzanthracene (DMBA), to the oral mucosa of hamsters and guinea-pigs

Introducción: El carcinoma oral de células escamosases una neoplasia maligna con mal pronóstico y baja tasa desupervivencia, en cuya etiología están fuertemente implicadosel tabaco y el alcohol, entre otros factores. En 1954,Salley describió un modelo experimental de carcinogénesisen la mucosa yugal del hámster mediante la aplicación delagente DMBA. Métodos: Hemos desarrollado dos modelosexperimentales diferenciados, basados en la aplicación delDMBA sobre cobayas y hámster respectivamente. Resultados:En el primer modelo (cobayas) no ocurrió el fenómenode la carcinogénesis con el tiempo y las dosis administradas.Solamente observamos áreas de displasia epitelial,que era más severa en los animales que, además del tratamientocon DMBA, ingerían etanol. En el segundo modelo(hámster), se desarrollaron neoplasias malignas, que eranmás numerosas y con un comportamiento biológico másagresivo cuando se administraba el DMBA combinado conel etanol. Conclusiones: El etanol se ha comportado comoagente promotor de la carcinogénesis(AU)

Introduction: Oral squamous cell carcinoma is a malignantneoplasm with a bad prognosis and low survival rate.Tobacco and alcohol are among the most important causativefactors. In 1954, Salley described an experimental modelof carcinogenesis, applying the agent DMBA to the jugalmucosa of hamsters. Methods: we have developed two differentexperimental models based on the application ofDMBA to guinea pigs and hamsters. Results: No carcinogenesiswas seen in the guinea pigs at the administereddoses of DMBA, only areas of epithelial dysplasia, whichwere more severe in the animals that were also given alcohol.Malignant neoplasias developed in the hamsters andwere more numerous and more aggressive when DMBAwas administered together with ethanol. Conclusions: Inthe present study, ethanol acted as an enhancer of carcinogenesis(AU)

Modelo experimental de fotoenvejecimiento cutáneo por radiación ultravioleta A / Experimental model of UVA-induced cutaneous photoageing

Antecedentes: La piel puede sufrir, además del envejecimiento cronológico, el fotoenvejecimiento, secundario a las radiaciones ultravioletas, las cuales se consideran el carcinógeno ambiental más potente. Material y métodos: Hemos utilizado 32 ratones Swiss en 4 grupos: I. control; II. TPA (102 sesiones); III. UVA (102 sesiones, 120 minutos/sesión); IV. TPA y UVA (32 sesiones, 120 minutos/sesión). Al final realizamos la necropsia. La piel del lomo y orejas fueron incluidas en parafina por el método habitual, seccionadas a 5 μm y teñidas con H.E. Valoramos diversos criterios histológicos epidérmicos y dérmicos (+, ++ o +++), por dos observadores distintos. Resultados: Hemos establecido un modelo de fotoenvejecimiento en los dos grupos tratados con UVA que presentaban lesiones de displasia moderada a severa en el grupo irradiado con UVA y carcinomas invasores en el grupo con UVA y TPA, mientras que en el grupo de TPA sólo observamos múltiples áreas de hiperplasia epitelial. Conclusiones: La exposición crónica a UVA asociada al promotor tumoral TPA ha desarrollado un modelo de fotocarcinogénesis cutánea en ratones Swiss

Introduction: Chronological ageing aside, skin may also experience photoageing as a result of exposure to ultraviolet radiation, considered to be the most potent environmental carcinogen. Materials and Methods: 32 Swiss mice (divided into 4 groups) were treated as follows: I (Control); II (TPA: 102 sessions); III (UVA: 102 sessions at 120 minutes/session); IV (TPA & UVA: 32 sessions at 120 minutes/session). Finally, necropsies were performed. The skin from the back and ears was included in paraffin via the usual method, sectioned at 5 μm and stained using H-E. Diverse dermal and epidermal histological criteria were evaluated (+, ++, +++), by two different observers. Results: A model for photoageing was established for both groups treated with UVA, which displayed moderate to severe dysplasia in the case of those treated with UVA alone and invasive carcinoma in the case of those treated with UVA and TPA, whilst only (multiple) areas of epithelial hyperplasia were observed in the group treated with TPA alone. Conclusions: Chronic exposure to UVA in conjunction with the tumour promoter TPA has provided a model for cutaneous photocarcinogenesis in Swiss mice

Modelo experimental de fotoenvejecimiento cutáneo por radiación ultravioleta A / Experimental model of UVA-induced cutaneous photoageing

Antecedentes: La piel puede sufrir, además del envejecimiento cronológico, el fotoenvejecimiento, secundario a las radiaciones ultravioletas, las cuales se consideran el carcinógeno ambiental más potente. Material y métodos: Hemos utilizado 32 ratones Swiss en 4 grupos: I. control; II. TPA (102 sesiones); III. UVA (102 sesiones, 120 minutos/sesión); IV. TPA y UVA (32 sesiones, 120 minutos/sesión). Al final realizamos la necropsia. La piel del lomo y orejas fueron incluidas en parafina por el método habitual, seccionadas a 5 μm y teñidas con H.E. Valoramos diversos criterios histológicos epidérmicos y dérmicos (+, ++ o +++), por dos observadores distintos. Resultados: Hemos establecido un modelo de fotoenvejecimiento en los dos grupos tratados con UVA que presentaban lesiones de displasia moderada a severa en el grupo irradiado con UVA y carcinomas invasores en el grupo con UVA y TPA, mientras que en el grupo de TPA sólo observamos múltiples áreas de hiperplasia epitelial. Conclusiones: La exposición crónica a UVA asociada al promotor tumoral TPA ha desarrollado un modelo de fotocarcinogénesis cutánea en ratones Swiss

Introduction: Chronological ageing aside, skin may also experience photoageing as a result of exposure to ultraviolet radiation, considered to be the most potent environmental carcinogen. Materials and Methods: 32 Swiss mice (divided into 4 groups) were treated as follows: I (Control); II (TPA: 102 sessions); III (UVA: 102 sessions at 120 minutes/session); IV (TPA & UVA: 32 sessions at 120 minutes/session). Finally, necropsies were performed. The skin from the back and ears was included in paraffin via the usual method, sectioned at 5 μm and stained using H-E. Diverse dermal and epidermal histological criteria were evaluated (+, ++, +++), by two different observers. Results: A model for photoageing was established for both groups treated with UVA, which displayed moderate to severe dysplasia in the case of those treated with UVA alone and invasive carcinoma in the case of those treated with UVA and TPA, whilst only (multiple) areas of epithelial hyperplasia were observed in the group treated with TPA alone. Conclusions: Chronic exposure to UVA in conjunction with the tumour promoter TPA has provided a model for cutaneous photocarcinogenesis in Swiss mice