G. Carretero

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.

Risk of adverse events in psoriasis patients receiving classic systemic drugs and biologics in a 5-year observational study of clinical practice: 2008–2013 results of the Biobadaderm registry

Biobadaderm is the Spanish registry of psoriasis patients receiving systemic treatment in clinical practice.

Spanish Evidence-Based Guidelines on the Treatment of Psoriasis With Biologic Agents, 2013. Part 1: On Efficacy and Choice of Treatment

Biologic therapy is a well-established strategy for managing moderate and severe psoriasis. Nevertheless, the high cost of such therapy, the relatively short span of clinical experience with biologics, and the abundance of literature now available on these agents have made evidence-based and consensus-based clinical guidelines necessary. The ideal goal of psoriasis treatment is to achieve complete or nearly complete clearing of lesions and to maintain it over time. Failing that ideal, the goal would be to reduce involvement to localized lesions that can be controlled with topical therapy. Although current evidence allows us to directly or indirectly compare the efficacy or risk of primary or secondary failure of available biologics based on objective outcomes, clinical trial findings cannot be directly translated to routine practice. As a result, the prescribing physician must tailor the treatment regimen to the individual patient. This update of the clinical practice guidelines issued by the Spanish Academy of Dermatology and Venereology (AEDV) on biologic therapy for psoriasis incorporates information from the most recent publications on this topic.

Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis.

Few reported studies compare drug survival in moderate‐to‐severe psoriasis vulgaris.

Risk of serious infections, cutaneous bacterial infections, and granulomatous infections in patients with psoriasis treated with anti–tumor necrosis factor agents versus classic therapies: Prospective meta-analysis of Psonet registries

Background: Anti–tumor necrosis factor (TNF) therapy in psoriasis has been associated with an increased risk of serious infections compared with nonbiologic systemic therapies. Objective: We sought to quantify the risk of: (1) serious infections (leading to hospitalization, sequelae, or death); and (2) “any infection,” bacterial cutaneous infections, and granulomatous infections among patients receiving anti–TNF therapy compared with nonbiologics (acitretin, methotrexate, cyclosporine). Methods: We used prospective meta‐analysis to combine data from the Psocare registry (Italy), Biobadaderm registry (Spain), and Clalit Health Services database (Israel), including 17,739 patients and 23,357.5 person‐years of follow‐up. Results: For serious infections, age, gender, and Charlson morbidity index adjusted hazard ratio of exposure to anti–TNFs compared with nonbiologics was 0.98 (95% confidence interval 0.80‐1.19), for bacterial cutaneous infections it was 1.00 (95% confidence interval 0.62‐1.61), and for granulomatous infections it was 1.23 (95% confidence interval 0.82‐1.84). Using methotrexate as comparator and comparing first year of exposure with later exposure did not modify the results. For any infectious episode, risks and relative risks were heterogeneous among registries, probably because of different definitions of outcome. Limitations: There was lack of power to describe risk of single drugs. Conclusion: In current clinical practice, treatment with anti–TNF drugs was not associated with a higher risk of serious infections than treatment with nonbiologic systemic therapy.

Safety of classic and biologic systemic therapies for the treatment of psoriasis in elderly: an observational study from national BIOBADADERM registry.

Psoriasis patients over 65 years‐old (elderly) constitute a growing group, underrepresented in clinical trials, and likely to be more prone to adverse events.

Metotrexato en psoriasis moderada-grave: revisión de la literatura y recomendaciones de experto

Methotrexate (MTX) is the most frequently used conventional systemic drug in the treatment of psoriasis. Despite over 50years of experience in this setting, certain aspects of the use of this drug in clinical practice are still little standardized and poorly understood. For this reason, a group of 15 experts took part in a consensus development conference to achieve consensus on a series of recommendations on the use of MTX in psoriasis. The guidelines, which were developed on the basis of a systematic review of the literature, were validated by 2 rounds of voting and categorized by level of evidence and grade of recommendation. Before MTX can be used to treat moderate to severe psoriasis, the patient must be evaluated to assess the suitability of the treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy. The recommended starting dose for a patient with no risk factors is 10 to 20mg/wk, the therapeutic dose for most patients is 15mg/wk, and the maximum dose is 20mg/wk. Most patients who respond to treatment will show improvement within 8weeks. Parenteral administration of MTX is desirable when there is a risk of erroroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally. Noninvasive methods are preferred for monitoring hepatotoxicity. MTX is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitisB infection or individuals who are seropositive for human immunodeficiency virus.

Riesgo de reactivación de hepatitis B pasada en pacientes con psoriasis tratados con biológicos. Análisis retrospectivo de 20 casos. Registro de BIOBADADERM

INTRODUCTION AND OBJECTIVES A 5% risk of reactivation of hepatitis B virus (HBV) infection has been reported in patients with diseases other than psoriasis treated with tumor necrosis factor inhibitors. The aim of this study was to investigate the risk of HBV reactivation in patients with a past history of HBV infection who were receiving biologic therapy for psoriasis. MATERIAL AND METHODS This was a multicenter study of 20 patients with psoriasis who were treated with at least 1 biologic agent. All the patients had serologic evidence of past HBV infection (positive total hepatitis B core antibody and negative hepatitis B surface antibody). We analyzed the clinical, serological, and liver function variables recorded before, during, and at the end of follow-up. The viral load at the end of follow-up was also analyzed for all patients. RESULTS None of the patients fulfilled the criteria for HBV reactivation at the end of a median follow-up period of 40 months. Combining our data with data from other studies of psoriasis patients with a past history of HBV infection who were treated with a biologic, we calculated a maximum estimated risk of HBV reactivation for a mean follow-up period of 30 months of 2.7 reactivations per 100 patients. CONCLUSIONS Biologic therapy did not cause HBV reactivation in our series of patients. Nonetheless, because of the potentially serious complications associated with HBV reactivation, it is important to measure viral load in patients with a history of HBV infection prior to initiation of biologic therapy to rule out occult carriage. These patients should also be monitored regularly in conjunction with a hepatologist.

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

Abstract 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.

Adverse events associated with discontinuation of the biologics/classic systemic treatments for moderate-to-severe plaque psoriasis: data from the Spanish Biologics Registry, Biobadaderm

Little is known about the adverse events (AEs) that lead to suspension of systemic treatments for psoriasis in clinical practice.