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.

Mapping exercise and status update of eight established registries within the TREatment of ATopic eczema Registry Taskforce.

BACKGROUND: The TREatment of ATopic eczema (TREAT) Registry Taskforce is a collaborative international network of registries collecting data of atopic eczema (AE) patients receiving systemic and phototherapy with the common goal to provide long-term real-world data on the effectiveness, safety and cost-effectiveness of therapies. A core dataset, consisting of domains and domain items with corresponding measurement instruments, has been developed to harmonize data collection. OBJECTIVES: We aimed to give an overview of the status and characteristics of the eight established TREAT registries, and to perform a mapping exercise to examine the degree of overlap and pooling ability between the national registry datasets. This will allow us to determine which research questions can be answered in the future by pooling data. METHODS: All eight registries were asked to share their dataset and information on the current status and characteristics. The overlap between the core dataset and each registry dataset was identified (according to the domains, domain items and measurement instruments of the TREAT core dataset). RESULTS AND CONCLUSIONS: A total of 4702 participants have been recruited in the eight registries as of 1st of May 2022. Of the 69 core dataset domain items, data pooling was possible for 69 domain item outcomes in TREAT NL (the Netherlands), 61 items in A-STAR (UK and Ireland), 38 items in TREATgermany (Germany), 36 items in FIRST (France), 33 items in AtopyReg (Italy), 29 items in Biobadatop (Spain), 28 items in SCRATCH (Denmark) and 20 items in SwedAD (Sweden). Pooled analyses across all registries can be performed on multiple important domain items, covering the main aims of analysing data on the (cost-)effectiveness and safety of AE therapies. These results will facilitate future comparative or joint analyses.

Primary cutaneous lymphomas in children: A prospective study from the Spanish Academy of Dermatology and Venereology (AEDV) Primary Cutaneous Lymphoma Registry.

BACKGROUND/OBJECTIVES: Primary cutaneous lymphomas are rare in pediatric patients. The clinical and histopathological manifestations may differ from those in adults. Due to their low frequency and the insidious clinical picture, the diagnosis is usually delayed. The Spanish Primary Cutaneous Lymphoma Registry was initiated in 2016 as a multicenter registry that would allow better insight into the epidemiological, clinical, histopathological, and treatment response characteristics of patients with primary cutaneous lymphomas. METHODS: We conducted a prospective observational cohort study of primary cutaneous lymphomas in pediatric patients participating in the Spanish Academy of Dermatology and Venereology (AEDV) Primary Cutaneous Lymphoma Registry. RESULTS: At the time of the analysis, 10 patients under 18 years of age out of 799 all-age cases (1.25%) had been included in the registry (7 males, 3 females). The mean age at diagnosis was 9.7 years (SD: 4.8). Seven (70%) had mycosis fungoides, 2 of them had the folliculotropic variant; and 3 (30%) had primary cutaneous marginal zone B-cell lymphoma. CONCLUSIONS: Primary cutaneous lymphomas are extremely rare in pediatric patients and usually have a good prognosis. Therefore, a high level of suspicion is necessary for the diagnosis. We suggest management by experienced physicians and follow-up into adulthood.

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.

Development of clinical prediction models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis, based on the BIOBADADERM cohort.

BACKGROUND: Identifying patients likely to have very good or bad results from systemic psoriasis therapy could improve efficiency of therapy. OBJECTIVE: To develop prognostic models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis. METHODS: Multivariable logistic regression of a prospective multicenter cohort of psoriatic patients in clinical practice (6449 person-years of follow-up). We used as possible predictors demographic characteristics, comorbidities, characteristics of the psoriasis (type, PASI, arthritis), history of past therapy at entry in the cohort, and history of response to previous cycles while in the cohort. We defined good response to a treatment cycle as either cycle end due to disease remission or a cycle longer than 2 years that does not end later due to inefficacy in the follow-up period. Bad response to a treatment cycle was defined as a cycle that is finished due to inefficacy, based on the physician judgment, after more than 3 months of treatment. RESULTS: Patients with fewer previous therapies, lower body mass index, older at start of therapy, and with previous history of good responses to therapy are more likely to have positive results of therapy. However, the predictive characteristics of models are poor. CONCLUSION: Predictive models of clinical response to systemic drugs in psoriasis with the studied variables do not seem to outperform drug selection by a dermatologist.

Use of off-label doses is frequent in biologic therapy for moderate to severe psoriasis: A cross-sectional study in clinical practice.

INTRODUCTION: Biologic medications increase dramatically the burden of a chronic and high prevalent disease like psoriasis. The objective of the study was to quantify the use of dose reduction or dose escalation strategies, not reflected in the drug summary of product characteristics, in clinical practice. METHODS: An observational, cross-sectional study of a subset of patients from the Spanish Registry for Systemic Treatments in Psoriasis (BIOBADADERM) treated for over six consecutive months with the same biologic agent. RESULTS: The study included 637 patients. At the cut-off date, the initial dose had been reduced in 223 patients (35%; 95% CI: 31.3-38.9%) and escalated in 46 (7.2%; 95% CI: 5.3-9.5%). When compared with the patients treated with standard doses, the patients on reduced doses had a lower PASI score at the cut-off date (a mean 2.6 versus 1; -1.6 points) and exhibited greater improvement in PASI since the start of biologic therapy (mean reduction over baseline 75% versus 87%). By contrast, the patients receiving an escalated dose had higher PASI scores (2.6 versus 8.0) and showed less improvement in PASI (75% versus 46.8%). CONCLUSION: Off-label doses of biologic agents for psoriasis are frequent in clinical practice. This information is especially relevant for pharmacoeconomic models.

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.

Estudio comparativo del tratamiento de la psoriasis en placas con baño de PUVA y UVB de banda estrecha (311 nm) / Comparative study of the treatment of psoriasis plaques with PUVA baths and narrow-band UVA (311 nm)

Introducción. Los estudios realizados hasta la fecha comparan el tratamiento con baño de psoraleno y radiación ultravioleta A (PUVA) y radiación ultravioleta B de banda estrecha (UVBBE) en la psoriasis muestran mejores resultados con UVBBE. Ciertas características de los protocolos pueden interferir en los resultados. Material y métodos. Estudio prospectivo en una unidad de psoriasis, con asignación del tratamiento según disponibilidad. De 167 pacientes con psoriasis en placas, 32 recibieron baño de PUVA (fotosensibilizante 8-metoxipsoraleno a concentración 2,6 mg/l) y 135 radiación UVBBE. Se consideró como buena respuesta un blanqueamiento superior al 70 %. Se realizó descripción de los datos y comparación entre los dos grupos, incluyendo técnicas de análisis multivariante, para poder controlar estadísticamente los efectos del sexo, el número de sesiones necesarias para el éxito, la dosis fototóxica mínima (DFM) y la dosis eritematosa mínima (DEM). Resultados. Se obtuvo buena respuesta en el 87,5 % de los casos con baño de PUVA (intervalo de confianza del 95 % [IC 95 %]: 71,0-96,5) y en el 87,4 % de los casos con UVBBE (IC 95 %: 80,6-92,5). No se encontraron diferencias significativas en los porcentajes de éxitos o de abandonos. Entre los pacientes que respondieron al tratamiento no se encontraron diferencias en el número de sesiones ni en la dosis acumulada. El sexo, la dosis acumulada o los valores de la DFM y la DEM tampoco se asociaron con la respuesta a los tratamientos. Conclusiones. En la psoriasis en placas, cabe esperar unos porcentajes de respuesta similar con ambos tratamientos empleando los protocolos propuestos. La respuesta es independiente del sexo, la dosis acumulada y los valores de la DFM y la DEM

Introduction. Studies carried out to date comparing treatment with PUVA baths and narrow-band UVB (NBUVB) in psoriasis show that better results are obtained with NBUVB. Certain features of the protocols may interfere with the results. Material and methods. Prospective study in a psoriasis unit, with treatment assigned according to availability. Of 167 patients with psoriasis plaques, 32 received PUVA baths (photosensitizer 8-methoxypsoralen at a concentration of 2.6 mg/l) and 135 received NBUVB radiation. A clearing rate of over 70 % was considered a good response. The data were described and compared between the two groups, including multivariate analysis techniques, in order to statistically control the effects of gender, number of sessions necessary for success, minimum phototoxic dose and minimum erythema dose. Results. A good response was obtained in 87.5 % of the cases with PUVA baths (95 % CI: 71.0-96.5) and in 87.4 % of the cases with NBUVB (95 % CI: 80.6-92.5). No significant differences were found in the success and abandonment percentages. Among the patients who responded to the treatment, no differences were found in the number of sessions or in the cumulative dose. Gender, cumulative dose or minimum phototoxic dose and minimum erythema dose values were not associated with the response to the treatments either. Conclusions. With psoriasis plaques, similar response percentages can be expected with both treatments, using the proposed protocols. The response is regardless of gender, cumulative dose and minimum phototoxic dose and minimum erythema dose values

[Comparative study of the treatment of psoriasis plaques with PUVA baths and narrow-band UVA (311 nm)]. / Estudio comparativo del tratamiento de la psoriasis en placas con baño de PUVA y UVB de banda estrecha (311 nm).

INTRODUCTION: Studies carried out to date comparing treatment with PUVA baths and narrow-band UVB (NBUVB) in psoriasis show that better results are obtained with NBUVB. Certain features of the protocols may interfere with the results. MATERIAL AND METHODS: Prospective study in a psoriasis unit, with treatment assigned according to availability. Of 167 patients with psoriasis plaques, 32 received PUVA baths (photosensitizer 8-methoxypsoralen at a concentration of 2.6 mg/l) and 135 received NBUVB radiation. A clearing rate of over 70 % was considered a good response. The data were described and compared between the two groups, including multivariate analysis techniques, in order to statistically control the effects of gender, number of sessions necessary for success, minimum phototoxic dose and minimum erythema dose. RESULTS: A good response was obtained in 87.5 % of the cases with PUVA baths (95 % CI: 71.0-96.5) and in 87.4 % of the cases with NBUVB (95 % CI: 80.6-92.5). No significant differences were found in the success and abandonment percentages. Among the patients who responded to the treatment, no differences were found in the number of sessions or in the cumulative dose. Gender, cumulative dose or minimum phototoxic dose and minimum erythema dose values were not associated with the response to the treatments either. CONCLUSIONS: With psoriasis plaques, similar response percentages can be expected with both treatments, using the proposed protocols. The response is regardless of gender, cumulative dose and minimum phototoxic dose and minimum erythema dose values.