Mercè Alsina

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.

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.

Calciphylaxis in a Hemodialysis Patient: Appearance After Parathyroidectomy During a Psoriatic Flare

Chronic renal failure patients are prone to soft tissue calcifications. A phenomenon of acute ischemic skin necrosis and dermohypodermic arteriolar medial calcification has been described recently in patients with chronic renal failure and secondary hyperparathyroidism (HPT). This phenomenon, termed calciphylaxis, occurs in response to certain factors, the most important of which appears to be an elevated blood calcium-phosphate product. Accordingly, parathyroidectomy in addition to normalization of calcium-phosphate product has been proposed as the only effective therapeutic approach for this condition. We describe a case of chronic renal failure with severe secondary HPT in which the patient developed calciphylaxis 4 days after the appearance of a psoriatic flare. Four months before, a subtotal parathyroidectomy was performed for severe HPT and at the time the ulcerations appeared, blood calcium-phosphate product was correct. Etiological and physiopathological aspects of calciphylaxis are discussed.

PRIMARY LOCALIZED CUTANEOUS AMYLOIDOSIS AND FAMILIAL MEDULLARY THYROID CARCINOMA

We have studied a family with an autosomai dominant Inheritance of primary localized cutaneous amyloidosis (PLCA) and familial medullary thyroid carcinoma (MTC). Ten family members were screened for multiple endocrine neoplasia (MEN) 2; five were found to have MTC and two had C‐cell hyperplasia. None had evidence of phaeochromocytoma or parathyroid abnormalities. Five of these seven patients presented characteristic inter‐scapular hyperpigmented lesions, showing dermal amylold deposits In two of the four patients In which a biopsy was performed. The data are analysed In the light of two recent reports of MEN 2A associated with Identical lesions. We conclude that PLCA should be sought in MTC patients, even If no other endocrinopathies are present. This may be Informative of the familial character of MTC in Index cases and also of the tumour gene status in family members who are being screened

An open-label, multicenter study of the combination of amorolfine nail lacquer and oral itraconazole compared with oral itraconazole alone in the treatment of severe toenail onychomycosis

Abstract Background: Data indicate that combination therapy may provide enhanced clinical and economic benefits over monotherapy in the treatment of onychomycosis. Objective: The aim of this study was to compare the efficacy of 2 topical amorolfine/oral itraconazole combination regimens with oral itraconazole alone in the treatment of severe toenail onychomycosis. Cost implications of all treatments were assessed in a pilot pharmacoeconomic analysis. Methods: In this multicenter, open-label, 24-week study, patients were randomized to 3 parallel treatment groups: 5% solution of amorolfine nail lacquer applied once weekly for 24 weeks plus itraconazole 200 mg once daily for either 6 weeks (group AI-6) or 12 weeks (group AI-12), or itraconazole alone for 12 weeks (group I-12). Results: Mycologic cure at week 12 was achieved in 93% of patients in group AI-6, 83% in group AI-12, and 41% in group I-12. Combination therapies were significantly more effective than itraconazole monotherapy ( P P Conclusions: Our results show that topical amorolfine combined with oral itraconazole was more effective in treating severe toenail onychomycosis than was itraconazole monotherapy. Combination with a short course of oral therapy had a marked pharmacoeconomic advantage over the other regimen, suggesting that switching from the current 12-week itraconazole monotherapy to the 6-week combination therapy would cure more patients for a lower cost.

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.

BIOBADADERM, the Spanish Registry of Adverse Events Associated With Biologic Drugs in Dermatology: First Report

Abstract Background and objectives The Working Group on Psoriasis of the Spanish Academy of Dermatology and Venereology has initiated BIOBADADERM, a registry of patients with psoriasis receiving treatment with biologic drugs, in order to assess the long-term risk of adverse events (AEs). Material and methods A multicenter study was undertaken in 2 cohorts of patients with psoriasis: patients receiving biologic therapy and patients receiving nonbiologic systemic therapy other than phototherapy. Similar numbers of patients were included in each group. Information was recorded on demographic and clinical variables, treatment, and relevant AEs. The risk of specific AEs was determined by comparison of the frequencies for those events in the 2 cohorts. Results Data on the 2 cohorts were evaluated for the period from October, 2008 to November, 2009 alongside retrospective data on patients treated with biologics since 2005. Thirteen Spanish hospitals participated in the study. A total of 632 patients were included in the analysis: 417 treated with biologic drugs and 215 controls. Suspension of biologic therapy due to AEs was rare (72 cycles, 10%). A total of 232 AEs were reported in patients receiving biologic therapy. The majority were not serious. The most frequent AEs were infections (mostly upper respiratory tract infections and nasopharyngitis), followed by conditions affecting the skin or subcutaneous tissue. Forty-three AEs were reported in control subjects. The most frequent events were metabolic and nutritional abnormalities and abnormal transaminase levels. Comparison of the incidence of any AE in patients treated with biologics compared with control subjects revealed a relative risk of 2.2 (P Conclusions Patients treated with biologic drugs had a greater number of AEs, particularly infections and skin conditions. Definitive conclusions, however, are difficult to draw due to the small number of patients included in the registry, particularly in the control cohort, and the short follow-up period. Differences in the percentages of events reported by the different hospitals reveal the difficulties associated with the concept of AEs in clinical practice and highlight the need to harmonize criteria in the future. Since the problems identified in this analysis should be overcome in future years, we expect BIOBADADERM to become an important source of information on the safety profile of biologic drugs in dermatology.

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.